Obat Pare

ANALISA ARTIKEL
“TANAMAN PARE SEBAGAI TERAPI UNTUK DIABETES”
Disusun untuk memenuhi tugas mata kuliah Farmakologi dalam Keperawatan
Dosen Pembimbing: Ns. Nur Widayati, S.Kep., MN
Disusun oleh :
Dhea Cristina Damaiyanti Saragih (172310101071)
Della Kharisma Putri (172310101100)
PROGRAM STUDI ILMU KEPERAWATAN
UNIVERSITAS JEMBER
2017
ANALISA ARTIKEL
“TANAMAN PARE SEBAGAI TERAPI UNTUK DIABETES”
Disusun untuk memenuhi tugas mata kuliah Farmakologi dalam Keperawatan
Dosen Pembimbing: Ns. Nur Widayati, S.Kep., MN
Disusun oleh :
Dhea Cristina Damaiyanti Saragih (172310101071)
Della Kharisma Putri (172310101100)
PROGRAM STUDI ILMU KEPERAWATAN
UNIVERSITAS JEMBER
2017
ii
HALAMAN PENGESAHAN
Tugas Analisa Pemanfaatan Hasil-hasil Pertanian dalam Pengobatan dengan Judul
“TANAMAN ALPUKAT SEBAGAI TERAPI UNTUK DIABETES”
yang disusun oleh:
Dhea Cristina Damaiyanti 172310101071
Della Kharisma Putri 17231010101100
telah disetujui untuk diseminarkan dan dikumpulkan pada:
hari/tanggal:……………….
Makalah ini disusun dengan pemikiran sendiri, bukan hasil jiplakan atau reproduksi ulang
makalah yang telah ada.
Ketua,
Dhea Cristina Damaiyanti
NIM 172310101071
Mengetahui,
Penanggung jawab mata kuliah Dosen Pembimbing
Ns. Wantiyah, S.Kep., M.kep Ns. Nur Widayati, S.Kep., MN
NIP 198107122006042001 NIP 198106102006042001
iii
PRAKATA
Puji syukur ke hadirat Allah SWT, atas segala rahmat dan karunia-Nya sehingga
penulis dapat menyelesaikan makalah yang berjudul “Tanaman Pare Sebagai Terapi Untuk
Diabetes” Makalah ini disusun untuk memenuhi tugas mata kuliah Farmakologi dalam
Keperawatan pada Program Studi Ilmu Keperwatan Universitas Jember.
Penulis menyusun makalah ini dengan judul “Analisa Artikel Pemanfaatan buah pare
(Momordica charantia L.) untuk Terapi Diabetes”. Makalah ini disusun dengan tujuan untuk
memenuhi tugas mata kuliah Farmakologi dan juga untuk menjadi salah satu sumber bacaan
mahasiswa dalam mempelajari obat dan pengobatan tradisional.
Penyusunan makalah ini tidak lepas dari bantuan berbagai pihak. Oleh karena itu,
penulis menyampaikan terima kasih kepada:
1. Ns. Wantiyah, M.Kep., selaku dosen pengampuh dan penanggung jawab mata kuliah
Farmakologi dalam Keperawatan;
2. Ns. Nur Widayati, S.Kep., MN selaku dosen pembimbing umum;
3. Semua pihak yang telah membantu dalam menyelesaikan makalah ini.
Penulis juga menerima segala kritik dan saran dari semua pihak demi kesempurnaan
makalah ini. Akhirnya penulis berharap semoga makalah ini dapat bermanfaat.
Jember, 09 April 2018
Penulis
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DAFTAR ISI
Halaman
HALAMAN SAMPUL ........................................................................................ i
HALAMAN JUDUL .......................................................................................... ii
HALAMAN PENGESAHAN ........................................................................... iii
PRAKATA ........................................................................................................ iv
DAFTAR ISI ...................................................................................................... v
BAB 1. PENDAHULUAN .................................................................................. 1
1.1 Latar Belakang ............................................................................... 1
1.2 Tujuan Pembuatan Makalah ......................................................... 1
BAB 2. KONSEP DASAR OBAT TRADISIONAL .......................................... 3
2.1 Obat Tradisional ............................................................................. 3
2.1.1 Definisi............................................................................. 3
2.1.2 Macam-macam Obat Tradisional..................................... 3
2.1.3 Ciri-Ciri Obat Tradisional................................................ 5
2.2 Tingkatan obat tradisional ............................................................ 6
2.3 Syarat-Syarat Obat Tradisional (Safety Drug) ............................ 7
2.4 Peraturan terkait obat dan pengobatan tradisional ..................... 8
BAB 3. ANALISA ARTIKEL............................................................................... 9
3.1 Jenis Tanaman Obat ...................................................................... 9
3.1.1 Nama Ilmiah Tanaman........................................................ 9
3.2.2 Ciri-Ciri............................................................................... 9
3.1.3 Nama Produk yang Sudah Dibuat Obat............................ 10
3.2 Kandungan Dalam Obat Tradisional ........................................ 11
3.3 Farmasetika ................................................................................ 11
3.4 Farmakokinetik .......................................................................... 14
3.5 Farmakodinamik ......................................................................... 15
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3.6 Dosis......................................................................................................................15
3.7 Indikasi dan Kontraindikasi.......................................................................16
3.8 Efek Samping Obat 16
3.9 Hal-hal yang harus diperhatikan.............................................................17
3.10 Implikasi Keperawatan 17
BAB 4. PENUTUP...................................................................................................................19
4.1 Kesimpulan........................................................................................................19
4.2 Saran....................................................................................................................19
DAFTAR PUSTAKA..............................................................................................................21
LAMPIRAN...............................................................................................................................23
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BAB 1. PENDAHULUAN
1.1 Latar Belakang

Penyakit Diabetes Melitus saat ini hampir merambah seluruh dunia, Menurut data
Organisasi Kesehatan Dunia (WHO), Indonesia menempati urutan keenam dunia sebagai
negara dengan jumlah penderita DM terbanyak setelah India, China, Uni Soviyet, Jepang
dan Brazil. Tercatat pada tahun 1995, jumlah penderita DM di Indonesia mencapai 5
juta. Pada tahun 2000 yang lalu saja, terdapat sekitar 5,6 juta penduduk Indonesia yang
mengidap diabetes. Namun, pada tahun 2006 diperkirakan jumlah penderita diabetes di
Indonesia meningkat tajam menjadi 14 juta orang, jika peningkatan penderita Diabetes
Mellitus pertahunnya 230.000 orang, maka bisa kita bayangkan berapa banyak jumlah
penderita Diabetes Mellitus pada tahun 2017 (Hady, 2011).
Penyakit diabetes adalah penyakit gangguan metabolisme yang merupakan suatu
kumpulan gejala yang timbul pada seseorang karena adanya peningkatan kadar glukosa
darah di atas nilai normal. Berbagai peneitian epidemologi yang dilakukan, penderita
diabetes selalu meningkat dari tahun 1980-an. Data hasil riskesdas tahun 2013
menunjukkan peningkatan dari data hasil riskesdas tahun 2007, yaitu dengan proporsi
dari 5,7% menjadi 6,9% pada penduduk usia 15 tahun ke atas (Riskesdas, 2013).
Sedangkan menurut IDM (International Diabetes Federation) tahun 2015 jumlah
penderita diabetes di dunia mencapai 415 juta orang yang tersebar di setiap benua.
Diabetes yang tidak terkontrol dapat menyebabkan komplikasi akut dan kronis, yaitu
seperti hipoglikemia, sering terjadi pada penderita diabetes tipe 1 karena lupa atau
sengaja meninggalkan makan, atau karena olahraga terlalu berat. Selain itu, penderita
diabetes juga berpotensi terkena komplikasi lain seperti hiperglikemia, makrovaskular
dan mikrovakular (Dirjen Bina Farmasi Komunitas dan Klinik, 2005). Diabetes juga
dapat menyebabkan meningkatnya risiko penyakit jantung dan stroke, neuropati, dan
menjadi penyebab utama terjadinya gagal ginjal bahkan kematian (Kemenkes, 2014).
Pengobatan tradisional merupakan upaya kesehatan yang dilakukan secara turun
temurun yang dipercaya masyarakat untuk dapat menangani berbagai penyakit. Hal ini
menjadi familier kembali di kalangan masyarakat modern dikarenakan banyaknya
penelitian ilmiah untuk menunjukkan potensi berbagai tumbuhan alami dalam mengatasi
permasalahan kesehatan manusia. Oleh karenanya muncullah berbagai bentuk sediaan
obat dari tanaman obat sehingga mempermudah masyarakat dalam mengonsumsinya
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(Suprapto, 1992). Kelebihan dari tanaman obat seperti mudah didapat, murah dan
rendahnya efek samping membuatnya lebih menarik dari obat kimia. Namun, terdapat
juga kelemahan dari obat tradisional yaitu efek farmakologisnya masih relative lemah,
belum teruji klinik dan masih mudah tercemar mikroorganisme (Katno, 2004)
Berdasarkan penelitian secara in –vitro , pare (Momorcadia charantia) memiliki
aktivitas menghambat enzim a-glukosidase dan a- amylase (Zuraini Ahmad,2012).
Terdapat beberapa zat aktif utama yang terkandung dalam buah pare yaitu phyto-nutrient,
polypeptide-p, dan charantine. Senyawa ini secara structural mirip dengan insulin hewan
(Antinio Miguel dkk, 2006). Sementara zat yang memiliki potensi antidiabetes yaitu
alkaloid, saponin, flavonoid, polifenol dan glikosida cucurbitacin, zat – zat inilah yang
membuat buah pare memiliki aktivitas antiglikasi (Fernandes, 2007)
Dari hasil penelitian menunjukkan beberapa data yang signifikan terkait potensi dan
efek samping dari penggunaan Pare sebagai antidiabetes diantaranya peningkatan
alkaline-phospatase dan gamma glutamyl transferase di tikus (Tennekon KH dkk, 1994),
hipotensi pada anjing (Feng PC, 1962), sterilitas pada tikus betina, perdarahan uterus
pada tikus hamil dan kelinci (Dixit, 1996), dan peningkatan kolesterol serum dan
nonesterifikasi asam lemak pada anjing (Dixit, 1996). Dalam uji coba manusia, yang
paling umum efek samping yang dilaporkan adalah sakit perut dan diare (Sharma
VN,1960). Efek hipoglikemik yang berpotensi fatal sering terjadi pada anak-anak setelah
pemberian sediaan teh daun sebelum sarapan (Hulin A,1988). Selain itu, individu dengan
kekurangan glukosa-6-fosfat beresiko terkena defisiensi G6PD (Basch E, 2003). Dari
penjelasan diatas maka dapat ditarik kesimpulan bahwa Momordica charantia berpotensi
dalam aktivitas antidiabetes.
1.2 Tujuan
1.2.1 Mengetahui pengaruh pemberian ekstrak pare terhadap penderita Diabetes Melitus
1.2.2 Mengetahui manfaat pengobatan non-farmakologi menggunakan bahan alami buah
pare
1.2.3 Mengetahui farmasetika, farmakokinetik, farmakodinamik, dosis, indikasi dan
kontraindikasi, serta efek samping obat pada obat tradisional pare
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BAB 2. KONSEP DASAR OBAT TRADISIONAL
2.1 Obat Tradisional
2.1.1 Pengertian
Obat tradisional adalah obat yang didapat dari bahan alam (mineral, tumbuhan atau
hewan), terolah secara sederhana atau dasar pengalaman yang digunakan dalam pengobatan
tradisional (Syamsuni, 2006). Obat tradisional adalah bahan atau ramuan bahan yang berupa
bahan tumbuhan, bahan hewan, bahan mineral, sediaan sarian (galenik) atau campuran dari
bahan tersebut yang secara turun temurun telah digunakan untuk pengobatan, dan dapat
diterapkan sesuai dengan norma yang berlaku di masyarakat (Peraturan Kepala BPOM No.
12 Th. 2014). Obat tradisional merupakan obat-obatan yang dibuat dari bahan alami secara
tradisional dan merupakan resep yang berdasarkan nenek moyang atau sudah ada sejak jaman
dahulu (Redaksi Kesehatan, 2015).
2.1.2 Macam – Macam Obat Tradisional
Menurut Peraturan Kepala BPOM RI No. 12 Tahun 2014 Tentang Persyaratan Mutu
Obat Tradisional, macam – macam obat tradisional adalah sebagai berikut :
1. Sediaan Galenik yang selanjutnya disebut ekstrak adalah sediaan kering, kental atau cair
dibuat dengan menyari Simplisia nabati atau hewani menurut cara yang cocok, di luar
pengaruh cahaya matahari langsung.
2. Simplisia adalah bahan alam yang telah dikeringkan yang digunakan untuk pengobatan dan
belum mengalami pengolahan, kecuali dinyatakan lain suhu pengeringan tidak lebih dari
60oC.
3. Rajangan adalah sediaan Obat Tradisional berupa satu jenis Simplisia atau campuran
beberapa jenis Simplisia, yang cara penggunaannya dilakukan dengan pendidihan atau
penyeduhan dengan air panas.
4. Serbuk Simplisia adalah sediaan Obat Tradisional berupa butiran homogen dengan derajat
halus yang sesuai, terbuat dari simplisia atau campuran dengan Ekstrak yang cara
penggunaannya diseduh dengan air panas.
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5. Serbuk Instan adalah sediaan Obat Tradisional berupa butiran homogen dengan derajat
halus yang sesuai, terbuat dari Ekstrak yang cara penggunaannya diseduh dengan air panas
atau dilarutkan dalam air dingin.
6. Kapsul adalah sediaan Obat Tradisional yang terbungkus cangkang keras.
7. Kapsul Lunak adalah sediaan Obat Tradisional yang terbungkus cangkang lunak.
8. Tablet adalah sediaan Obat Tradisional padat kompak, dibuat secara kempa cetak, dalam
bentuk tabung pipih, silindris, atau bentuk lain, kedua permukaannya rata atau cembung,
terbuat dari Ekstrak kering atau campuran Ekstrak kental dengan bahan pengering dengan
bahan tambahan yang sesuai.
9. Efervesen adalah sediaan padat Obat Tradisional, terbuat dari Ekstrak, mengandung
natrium bikarbonat dan asam organik yang menghasilkan gelembung gas (karbondioksida)
saat dimasukkan ke dalam air.
10. Pil adalah sediaan padat Obat Tradisional berupa masa bulat, terbuat dari serbuk
Simplisia dan/atau Ekstrak.
11. Dodol/Jenang adalah sediaan padat Obat Tradisional dengan konsistensi lunak tetapi liat,
terbuat dari Serbuk Simplisia dan/atau Ekstrak.
12. Pastiles adalah sediaan padat Obat Tradisional berupa lempengan pipih, umumnya
berbentuk segi empat, terbuat dari Serbuk Simplisia dan/atau Ekstrak.
13. Cairan Obat Dalam adalah sediaan Obat Tradisional berupa minyak, larutan, suspensi
atau emulsi, terbuat dari Serbuk Simplisia dan/atau Ekstrak dan digunakan sebagai obat
dalam.
14. Cairan Obat Luar adalah sediaan Obat Tradisional berupa minyak, larutan, suspensi atau
emulsi, terbuat dari Simplisia dan/atau Ekstrak dan digunakan sebagai obat luar.
15. Salep dan Krim adalah sediaan Obat Tradisional setengah padat terbuat dari Ekstrak yang
larut atau terdispersi homogen dalam dasar Salep/Krim yang sesuai dan digunakan sebagai
obat luar.
16. Parem adalah sediaan padat atau cair Obat Tradisional, terbuat dari Serbuk Simplisia
dan/atau Ekstrak dan digunakan sebagai obat luar.
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17. Pilis dan Tapel adalah sediaan padat Obat Tradisional, terbuat dari Serbuk Simplisia
dan/atau Ekstrak dan digunakan sebagai obat luar.
18. Koyo/Plester adalah sediaan Obat tradisional terbuat dari bahan yang dapat melekat pada
kulit dan tahan air yang dapat berisi Serbuk Simplisia dan/atau Ekstrak, digunakan sebagai
obat luar dan cara penggunaannya ditempelkan pada kulit.
19. Supositoria untuk wasir adalah sediaan padat Obat Tradisional, terbuat dari Ekstrak yang
larut atau terdispersi homogen dalam dasar supositoria yang sesuai, umumnya meleleh,
melunak atau melarut pada suhu tubuh dan cara penggunaannya melalui rektal.
20. Film Strip adalah sediaan padat Obat Tradisional berbentuk lembaran tipis yang
digunakan secara oral.
2.1.3 Ciri – Ciri Obat Tradisional
Menurut Eraherbs, 2016, obat tradisional memiliki ciri – ciri yang berbeda dengan
obat modern, yaitu :
1. Obat tradisional terbuat dari bahan – bahan tradisional dan alami yaitu tanaman obat atau
dikenal dengan apotek hidup.
2. Dalam meracik obat tradisional, tumbuhan obat yang digunakan tidak perlu dilakukan
pengujian laboratorium terlebih dahulu.
3. Resep obat tradisional yang digunakan untuk menyembuhkan penyait biasanya diperoleh
dari resep nenek moyang. Dengan kata lain, resep racikan obat tradisional diperoleh secara
turun-temurun.
4. Obat tradisional umumnya memiliki efek samping yang lebih kecil dibanding obat modern.
Karena dosis yang digunakan langsung memilki efek positif pada orang yang mengkonsumsi.
Meskipun ukuran dosis obat tradisional tidak ditentukan secara kuantitatif, namun biasanya
dosis obat tradisional tidak terlalu tinggi.
5. Dalam mengkonsumsi obat tradisional diperlukan dalam waktu lama, karena obat
tradisional memiliki dosis yang rendah dibanding obat modern. Jadi obat tradisional harus
dikonsumsi secara teratur.
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6. Obat tradisional biasanya tidak hanya dapat menyembuhkan satu penyakit. Misalnya satu
tanaman dapat digunakan sebagai obat antikanker dan hipertensi juga dapat untuk mengontrol
diabetes.
7. Obat tradisional umumnya memiliki harga lebih murah karena mudah dijumpai.
2.2 Tingkatan Obat Tradisional
Berdasarkan Keputusan Kepala Badan Pengawas Obat dan Makanan Republik

Indonesia Nomor HK.00.05.4.2411 Tahun 2004 Tentang Ketentuan Pokok Pengelompokan
dan Penandaan Obat Bahan Alam Indonesia, obat tradisional di Indonesia dikelompokkan
menjadi Jamu, Obat Herbal Terstandar dan Fitofarmaka.
1. Jamu (Empirical Based Herbalmedicine) Jamu merupakan bagian dari obat tradisional
yang digunakan secara turun temurun dan baru memiliki klaim penggunaan sesuai
dengan jenis pembuktian tradisional (secara empiris/turun temurun) dan telah
melewati 3 generasi. Artinya jika satu generasi rata – rata umur adalah 60 tahun, maka
ramuan tersebut sudah bertahan 180 tahun. Sebagai contoh, masyarakat telah
menggunakan rimpang temulawak untuk mengatasi hepatitis selama ratusan tahun.
Pembuktian khasiat tersebut baru sebatas pengalaman, selama belum ada penelitian
ilmiah yang membuktikan bahwa temulawak sebagai antihepatitis. Jadi Curcuma
xanthorriza itu tetaplah jamu. Jadi, ketika dikemas dan dipasarkan, produsen dilarang
mengklaim produk tersebut sebagai obat dan harus tertera logo berupa ranting daun
berwarna hijau dalam lingkaran. Sediaan jamu dapat berupa simplisia sederhana,
seperti rimpang, daun atau akar kering (Azrim, 2013).
Gambar 2.1 Logo jamu. (Azrim, 2015)
2. Obat Herbal Standar (Scientificbased Herbal Medicine) OHT adalah sediaan obat bahan
alam yang sediaannya berupa ekstrak yang telah dibuktikan keamanan dan khasiatnya secara
ilmiah dengan uji praklinik dan bahan bakunya telah distandarisasi. Disamping itu herbal
terstandar harus melewati uji pra klinis seperti uji toksisitas (keamanan), kisaran dosis,
farmakodinamik (kemanfaatan) dan teratogenik (keamanan terhadap janin). Uji praklinis
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meliputi uji in vivo dan in vitro. Uji in vivo dilakukan terhadap mencit, sedangkan uji in vitro
dilakukan terhadap sebagian organ yang teriolasi, kultur sel atau mikroba (Azrim, 2013).
Gambar 2.2 Logo Obat Herbal Terstandar (OHT). (Azrim, 2015)
3. Fitofarmaka (Clinical Basedherbal Medicine) Adalah sediaan obat bahan alam yang telah
dibuktikan kemanan dan khasiatnya secara ilmiah dengan uji praklinik dan uji klinik, bahan
baku dan produk jadinya telah distandarisasi. Fitofarmaka merupakan tingkatan tertinggi dari
bahan alami sebagai “obat”. Uji klinik sudah dilakukan terhadap manusia dengan dosis yang
disesuaikan. Setelah lulus uji fitofarmaka, produk dapat dikatakan sebagai obat dengan syarat
tidak menyimpang dari materi uji klinis sebelumnya. Artinya, jika uji klinis hanya sebagai
antikanker, maka produk tidak boleh diklaim sebagai antikanker dan antidiabetes (Azrim,
2013).
Gambar 2.3 Logo Fitofarmaka. (Azrim, 2015)
2.3 Syarat-Syarat Obat Tradisional

Menurut Badan Pengawas Obat dan Makanan (BPOM) tahun 2012
menyebutkan persyaratan yang harus dipenuhi dalam memproduksi obat tradisional
yaitu :
a. Personalia
Personalia hendaklah mempunyai pengetahuan, pengalaman, ketrampilan dan
kemampuan yang sesuai dengan tugas dan fungsinya, dan tersedia dalam jumlah
yang cukup.
b. Bangunan
Bangunan industri obat tradisional hendaklah menjamin aktifitas industri dapat
berlangsung dengan aman, syarat bangunan industri obat itu sendiri yaitu:
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1) Bangunan industri obat tradisional hendaklah berada di lokasi yang terhindar
dari pencemaran, dan tidak mencemari lingkungan.
2) Bangunan industri obat tradisional hendaklah memenuhi persyaratan hygiene.
3) Bangunan untuk pembuatan obat tradisional hendaklah memiliki rancangan,
konstruksi, dan pekerja yang memadai.
c. Peralatan
Peralatan yang digunakan dalam pembuatan produk hendaklah memiliki rancang
bangun konstruksi yang tepat, ukuran yang memadai serta ditempatkan dengan
tepat, sehingga mutu yang dirancang bagi tiap produk terjamin secara seragam, serta
untuk memudahkan pembersihan dan perawatannya. Sarana pengolahan produk
hendaklah dilengkapi dengan peralatan sesuai dengan proses pembuatan dan bentuk
sediaan yang akan dibuat.
d. Sanitasi dan Hygiene
Dalam pembuatan produk hendaklah diterapkan tindakan sanitasi dan hygiene yang
meliputi bangunan, peralatan dan perlengkapan, personalia, bahan dan wadah serta
faktor lain sebagai sumber pencemaran produk.
e. Penyiapan Bahan Baku
Setiap bahan baku yang digunakan untuk pembuatan hendaklah memenuhi
persyaratan yang berlaku.
f. Pengolahan dan Pengemasan
Pengolahan dan pengemasan hendaklah dilaksanakan dengan mengikuti cara yang
telah ditetapkan oleh industri sehingga dapat menjamin produk yang dihasilkan
senantiasa memenuhi persyaratan yang berlaku:
1. Menjalankan verifikasi
2. Tidak menimbulkan pencemaran
3. Melakukan system penomeran kode produksi
4. Penimbangan dan penyerahan
5. Waktu pengolahan dan pengemasan.
2.4 Peraturan Terkait Obat dan Pengobatan Tradisional
Peraturan terkait obat dan pengobatan tradisional tercantum dalam :
1. Keputusan Menteri Kesehatan Republik Indonesia Nomor

1076/Menkes/SK/VII/2003 Tentang Penyelenggaraan Pengobatan Tradisional
Menteri Kesehatan Republik Indonesia
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2. Peraturan Pemerintah Republik Indonesia Nomor 103 Tahun 2014 Tentang
Pelayanan Kesehatan Tradisional
3. Peraturan Menteri Kesehatan Republik Indonesia Nomor 007 Tahun 2012 Tentang
Registrasi Obat Tradisional
4. Peraturan Kepala Badan Pengawas Obat Dan Makanan Republik Indonesia Nomor
12 Tahun 2014 Tentang Persyaratan Mutu Obat Tradisional
5. Keputusan Menteri Kesehatan RI No. 661/Menkes/SK/VII/1994 tentang

Persyaratan Obat Tradisional
BAB 3. ANALISA ARTIKEL
3.1 Jenis Tanaman Obat
3.1.1 Nama Ilmiah Tanaman
Menurut Krisnakai, 2017 tanaman buah pare (Momordica charantia) memiliki

klasifikasi ilmiah sebagai berikut:
Kingdom: Plantae
Devisio: Spermatophyta
Sub-Devisio: Angiospermae
Classis: Dicotyledoneae
Ordo: Cucurbitales
Familia: Cucurbitaceae
Genus: Momordica
Spesies: Momordica Charantia L.
3.1.2 Ciri-ciri
Menurut Santoso (2008), Pare adalah tanaman yang rasanya pahit namun
memiliki khasiat yang berbuah manis. Nama ilmiahnya adalah Momordica charantia.
Adapun ciri-ciri dari tanaman obat ini ialah :
a. Termasuk tanaman herbal dari famili Cucurbitaceae
b. Tanaman semak semusim yang hidup menjalar dengan sulur berbentuk spiral
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c. Batang tidak bulat sempurna, berusuk lima, berambut saat muda dan gundul
setelah tua, dan warnanya hijau
d. Daun tunggal, berbentuk lekuk tangan, berbulu, panjang tangkai 7-13 cm, dan
warnanya hijau
e. Bunga tunggal, berkelamin satu, kelopak berbentuk lonceng, berusuk banyak,
panjang 5-15 cm, mahkota berbentuk bulat telur dan warnanya kuning muda
f. Buah buni, berbentuk bulat memanjang, berusuk, berwarna hijau saat muda dan
berwarna jingga setelah tua, rasanya pahit, renyah serta teksturnya berair
g. Biji berada di dalam buah, berbentuk pipih, keras, warna coklat kekuningan
h. Akar tunggang, warna putih kotor
Gambar 3.1 Momordica charantia
3.1.3 Nama Produk yang Sudah Dibuat Obat (Jika Ada)
Salah satu produk obat tradisional yang memanfaatkan buah pare yaitu karela tablet yang
dikonsumsi dalam bentuk tablet. Telah banyak produk kapsul maupun tablet yang berasal dari
buah pare yang memang mampu sebagai obat tradisional untuk diabetes. Teh daun tin juga
dapat diproduksi sendiri di rumah apabila memiliki tanaman buah tin ini.
Gambar 3.2 Produk Tablet buah Pare
10
3.2 Kandungan dalam Obat Tradisional
Analisis gizi buah pare menunjukkan bahwa buah ini kaya akan karbohidrat, protein,
vitamin dan serat. Buah pare memegang nilai gizi tertinggi di antara semua famili
Cucurbitaceae (Kwarta, et. all, 2016). Memanfaatkan pare untuk diabetes dikenal sebagai
bantuan pengobatan yang sangat efektif karena memiliki kandungan zat yang berperan aktif
sebagai penurun gula darah dalam tubuh, diantaranya adalah sebagai Antiradang, sifatnya
dingin. Charantin dan polypeptide-P di dalam pare merangsang sel beta pankreas untuk
mengeluarkan insulin dan juga meningkatkan cadangan glikogen di hati.. (Febryan, 2016)
Pare juga tinggi zat besi, dan dua kali lipat kalium dari pisang dan dua kali kalsium dari
bayam. Untuk membantu diabetes tipe 2, pare bisa dimakan mentah setiap hari. Hal ini akan
membantu memberikan nutrisi yang anda butuhkan untuk mengalahkan resistensi insulin atau
diabetes tipe 2. Anda juga bisa menggunakan pare untuk mengatasi diabetes tipe 1, karena
pare dianggap melawan proses penghancuran sel oleh sistem kekebalan tubuh menjadi bagian
dari gangguan autoimun. (Anah, 2015)
Berikut ini Kandungan Buah Pare tiap 100 gramnya :
Gambar 3.3 Kandungan Buah Pare tiap 100 gram
3.3 Farmasetika
Buah pare (Momordica charantia L.) apabila dikonsumsi secara langsung dalam bentuk
segar kemungkinan kurang disukai oleh masyarakat karena rasa pahit dari buah pare tidak
bisa dihindari. Sehingga untuk meningkatkan kepraktisan dalam penggunaannya serta
11
meningkatkan nilai ekonomisnya perlu dikembangkan dalam bentuk sediaan lain yaitu tablet
ekstrak buah pare. Bentuk sediaan tablet sangat menguntungkan karena mudah untuk
dikonsumsi, praktis, takarannya tepat, dikemas secara baik, praktis transportasi dan
penyimpanannya (stabilitasnya terjaga dalam sediaannya) serta mudah ditelan, sehingga
diharapkan masyarakat dapat tertarik untuk mengkonsumsi sediaan tablet ekstrak buah pare.
Buah pare telah banyak dimanfaatkan sebagai obat tradisional karena kandungannya
yang banyak memberikan manfaat bagi kesehatan. Saat ini ada beberapa bentuk sediaan buah
pare yang dapat dikonsumsi sebagai obat, yaitu dalam bentuk kapsul ataupun tablet.
Sedangkan dalam penelitian yang dilakukan oleh Fitri Arum, Sunyoto, Nurul Hidayati, 2015
bentuk sediaan yang digunakan adalah berbentuk ekstrak yang dicampur dengan aspartam.
Tujuan penelitian ini adalah untuk membuat tablet ekstrak buah pare (Momordica
carantia L.) dengan bahan pemanis aspartam dengan berbagai konsentrasi yang dapat
menutupi rasa pahit dan memenuhi persyaratan mutu fisik tablet. Formula tablet ekstrak buah
pare ( Momordica charantia L.) dengan bahan pemanis aspartam pada konsentrasi 0,5% dan
0,625% mampu menghasilkan tablet yang memenuhi persyaratan. Sedangkan pada
konsentrasi 0,75% belum mampu menghasilkan tablet yang memenuhi persyaratan.
Konsentrasi pemanis aspartam memberi pengaruh terhadap sifat fisik granul dan sifat fisik
tablet yaitu pada kekerasan dan waktu hancur tablet. Konsentrasi pemanis aspartam yang
paling baik sebagai bahan pemanis tablet ekstrak buah pare (Momordica charantia L.) adalah
formula I yaitu dengan konsentrasi bahan pengikat 0,5%.
Untuk mendapatkan zat aktif yang terdapat dalam pare (Momordica charantia L.)
tersebut dilakukan penyarian zat aktif dengan metode maserasi. Metode ini sangat sesuai
dengan zat berkhasiat yang tidak tahan terhadap pemanasan tinggi, mudah dilakukan dan
sederhana. Pelarut yang digunakan adalah pelarut etanol 70%, hal ini dikarenakan kandungan
senyawa yang akan diambil dari buah pare (Momordica charantia L.) adalah senyawa
triterpenoid dan polisakarida yang pada umumnya larut dalam etanol.
Kandungan zat aktif ekstrak pare tidak tahan panas, tidak tahan terhadap tekanan
tinggi, sifat alir jelek apabila menggunakan granulasi kering. Berdasarkan sifat-sifat tersebut
maka metode pembuatan tablet ini dapat menggunakan metode granulasi basah. Metode
granulasi basah dapat memperbaiki sifat alir dan kompaktibilitas bahan sehingga menjadi
lebih mudah di tablet. Bahan tambahan pemanis yang digunakan pada penelitian ini adalah
aspartam dengan konsentrasi 0,5% - 0,75% yang diharapkan dapat menutupi rasa pahit dari
12
buah pare (Momordica charantia L.) dan kita dapat mengetahui tablet dengan konsentrasi
pemanis aspartam yang sesuai dengan standar sifat fisik.
Proses pembuatan Tablet ekstrak buah pare :
1. Pengambilan Sampel Bahan utama yang akan digunakan dalam penelitian ini adalah buah
pare (Momordica charantia L.) jenis pare pare gajih. Pare gajih berdaging tebal, warnanya
hijau muda, bentuknya besar, panjang dan rasanya tidak begitu pahit yang diambil dari
perkebunan di daerah Jatinom, Klaten Utara dengan umur 2 bulan sejak berbuah.
2. Determinasi Sampel Dilakukan untuk menetapkan kebenaran sampel tanaman pare

(Momordica charantia L.) dan dibuktikan di Laboratorium Biologi Universitas Ahmad
Dahlan.
3. Pembuatan Simplisia dan Serbuk Buah pare segar dicuci bersih, Dipotong-potong tipis
dengan diameter 2-3 mm, Simplisia diletakkan dalam loyang yang terbuat dari alumunium
dan dikeringkan dalam oven pada suhu 40o C sampai kering selama 48 jam (2 hari) hingga
memenuhi kadar air kurang dari 10%. Diserbukkan, kemudian diayak dengan ayakan ukuran
40 mesh.
4. Pembuatan Ekstrak Pare Serbuk buah pare kering sebanyak 300 gram dimaserasi dengan
cairan penyari 2000 ml etanol 70%. Maserasi dilakukan selama 5 hari sambil digojok sekali-
kali, kemudian disaring menggunakan kain flannel dengan tujuan untuk memisahkan sari
dengan ampas buah pare. Selanjutnya disaring menggunakan kain flanel. Sari yang didapat
dicampur dengan sari yang pertama agar homogen. Sari dipekatkan menggunakan rotary
evaporator dengan tekanan rendah dan suhu 50°C sehingga didapatkan ekstrak kental buah
pare (Momordica charantia L.).
5. Pembuatan Tablet Ekstrak kental pare ditambah Aerosil 5% diaduk hingga kering
kemudian ditambah Avicel PH 101 dan Eksplotab diaduk sampai homogen. Tambahkan
gelatin sebagai bahan pengikat. Adonan diayak dengan ayakan no.16 membentuk granul
basah. Dikeringkan dalam oven pada suhu 60˚ C. Granul kering diayak dengan ayakan no.18
kemudian dilakukan pengujian granul kering. Granul + Aspartam + Mg stearat dicampur
hingga homogen. Tablet dikempa dengan berat 600 mg. Pengujian sifat fisik tablet.
Tabel 1. Formulasi Tablet Ekstrak Pare
13
Formula 1 (mg) Formula 2 (mg) Formula 3 (mg)
Komposisi Aspartam 0,5% Aspartam 0,625% Aspartam 0,75%
Zat aktif 400 400 400
Avicel PH 111 110,25 109,5
Eksplotab 30 30 30
Gelatin 30 30 30
Aspartam 3 3,75 4,5
Mg stearat 6 6 6
Aerosil 20 20 20
Bobot Tablet 600 600 600
3.4 Farmakokinetik
Farmakokinetik merupakan fase yang meliputi waktu selama obat diangkut
menuju organ sasaran, yaitu setelah obat dilepas dari bentuk sediaan kemudian
diabsorpsi ke dalam darah dan segera didistribusikan ke semua jaringan tubuh
(Syamsuni, 2006).
Pare dalam sediaan tablet diberikan melalui oral seperti kebanyakan obat pada
umumnya. Obat oral akan diabsorbsi melalui saluran cerna karena merupakan cara yang
paling mudah, ekonomis dan aman. Obat per oral absorbsinya terjadi di usus halus.
Setelah itu di distribusikan ke seluruh tubuh melalui sirkulasi darah. Karena bentuk
sediaan obat dalam bentuk tablet maka distribusinya akan melintasi membran sel dan
langsung terdistribusi ke dalam otak sebab kapsul ini sifatnya mudah larut. Setelah di
distribusikan, maka lanjut ke proses metabolisme yaitu proses perubahan struktur kimia
obat yang terjadi di dalam tubuh dan di katalis oleh enzim khususnya CYT 45. Pada
proses ini molekul obat diubah menjadi lebih polar, artinya lebih mudah larut dalam air
dan kurang larut dalam lemak sehingga lebih mudah disekresi melalui ginjal. Kemudian,
obat dikeluarkan dari tubuh melalui berbagai organ ekskresi dalam bentuk metabolis
hasil biotransformasi atau dalam bentuk asalnya. Eksresi obat dapat terjadi melalui
keringat, dan air liur (Tripathi, 2003). Gejala-gejala reaksi metabolisme setelah
mengonsumsi ekstrak daun pare, diantaranya adalah bau nafas tidak sedap, diare, kepala
sakit ringan, dan sering buang angin. Charantin yang ada di dalam daun pare yang
memiliki aktivitas mirip insulin dapat menurunkan kadar glukosa darah dengan
14
menghambat terjadinya aborbsi glukosa oleh usus. Dan obat diekskresi melalui
urine/ginjal karena bentuk sediaan obat ini (kapsul) dapat larut dalam air. (Doble dan
Prabhakar, 2008)
3.5 Farmakodinamik
Charantin dan polypeptide-p yang terkandung dalam daun pare dapat
meningkatkan sensitivitas insulin dengan mempengaruhi aktivitas postreseptornya, yaitu
pada fosforilasi tyrosine IRS-1. Perbaikan dari fosforilasi tyrosine IRS-1 ini sangat
penting karena berpotensi dalam menyebabkan resistensi insulin. Hal ini akan
menyebabkan terjadinya transport glukosa pada sel otot dan adiposa, sehingga kadar
glukosa pada darah dapat kembali turun mendekati normal. Penurunan kadar glukosa ini
akan menekan mekanisme kompensasi tubuh untuk memproduksi insulin dalam jumlah
yang tinggi sehingga hal tersebut akan menghalangi terjadinya kondisi hyperinsulinemia
dan kadar insulin akan kembali normal. (Zahirah, 2015). Penurunan kadar glukosa
dimulai setelah 30 menit, mencapai maksimum 4 jam dan berakhir dalam 12 jam.
(Peraturan Menteri Kesehatan Republik Indonesia (PERMENKES RI) no 6 tahun 2016)
3.6 Dosis
Terdapat berbagai pendapat tentang ketentuan dosis pare untuk diabetes
milletus. Menurut departemen kesehatan Filipina, dosis normal penggunaan Pare
sebanyak 100mg/kgBB setara dengan 2,5mg/kg dari obat antidiabet glibenklamid
(Charantia product information. Las Pinas City, Philippines; Herbcare Corporation.
April 2002). Menurut Peraturan Menteri Kesehatan Republik Indonesia
(PERMENKES RI) no 6 tahun 2016 tentang Formulasi Obat Herbal Asli Indonesia,
dosis lazim obat pare ini 2 x 2 kapsul (100-200 mg ekstrak)/hari.
Dosis toksik senilai 2000mg/kgBB dapat menyebabkan pusing dan depresi
dalam 30 menit pertama. Hal ini terjadi karena jumlah sel darah merah mengalami
penurunan secara signifikan terutama hemoglobin pada hati. Selain itu penggunaan
dalam dosis ini juga memprovokasi efek racun pada darah, jaringan dan organ vital
lainnya. (Nurul Husna, dkk, 2013). Penggunaan dalam dosis diatas 2000g/kgBB dapat
bersifat letal.
3.7 Indikasi dan Kontraindikasi

3.7.1 Indikasi
Diabetes Mellitus
15
3.7.2 Kontraindikasi
1. Ibu Hamil
Mengkonsumsi momordica charantia dapat menyebabkan keguguran karena
kandungan momorcharin pada tanaman ini memiliki efek antifertilitas. Selain
itu dampak lain juga dapat terjadi seperti pendarahan vagina, aborsi dan
kontraksi prematur. (Rae Uddin, 2017)
2. Defisiensi G6PD
G6PD merukapakan kondisi dimana seseorang mengalami masalah herediter
terkait aktivitas eritrosit dimana kekurangan enzim glukosa-6-fosfat
dehydrogenase. Kandungan vicine yag terdapat pada tanaman ini tidak dapat
dicerna oleh penderita defisiensi G6PD sehingga tidak dianjurkan untuk
menggunakan terapi obat dari momordica charantia. (Rae Uddin,2017)
3. Menyusui
4. Anak – anak
3.8 Efek Samping

1. Sakit perut
Iritasi saluran pencernaan seperti diare dapat terjadi apabila penggunaan ekstrak
Momordica charantia (pare) dikonsumsi secara berlebihan terutama pada anak – anak.
Kandungan yang menyebabkan efek samping ini adalah arils merah atau panutup
pada biji pare.Hal ini dapat menyebabkan seseorang mengalami dehidrasi akibat
kekurangan elektrolit.
2. Hipoglikemia
Kandungan charantin dari Momordica charantia berpotensi untuk penderita diabetes.
Jika dikonsumsi oleh seseorang dengan kadar gula darah normal maka akan
mengakibatkan penurunan kadar gula darah secara drastis sehingga menyebabkan
hipoglikemia. Hal ini ditandai dengan rasa sakit kepala, lapar, berkeringat, lemas dan
rasa cemas.
3. Keguguran
Kandungan momorcharin pada tanaman ini telah terbukti memiliki efek antifertilitas.
4. Hepatotoksisitas
Seseorang yang mengonsumsi obat ini juga berdampak terkena toksisitas hati
dikarenakan keracunan. Gelaja dari kasus ini yaitu demam dan koma.
16
5. Konvulsi pada anak (Peraturan Menteri Kesehatan Republik Indonesia
(PERMENKES RI) no 6 tahun 2016)
6. Peningkatan kadar glutamil transferase dan fosfatase alkali (Peraturan Menteri
Kesehatan Republik Indonesia (PERMENKES RI) no 6 tahun 2016).
7. Sakit kepala (Peraturan Menteri Kesehatan Republik Indonesia (PERMENKES RI) no
6 tahun 2016)
3.9 Hal – hal yang perlu diperhatikan
Pare memiliki efek toksisitas yang tinggi pada anak – anak jika arils merah
disekitar biji pare tercampur dalam formula obat. Namun pada orang dewasa efek
toksisitas pare masih dapat ditoleransi dengan baik. Hanya beberapa efek samping
pare yang perlu diwaspadai seperti diare dan perut kembung yang sering terjadi.
Berdasarkan uji klinis terkait pengaruh pare pada gula darah, tanaman ini tidak
dianjurkan sebagai pengganti maupun dikombinasi dengan obat –obat antidiabetik
lain yang diresepkan dokter karena memiliki efek aditif yang menyebabkan terjadinya
hipoglikemia (Rae Uddin, 2017). Efek penurunan fertilitas pada perempuan maupun
laki-laki juga perlu diperhatikan (Peraturan Menteri Kesehatan Republik Indonesia
(PERMENKES RI) no 6 tahun 2016)
3.10 Implikasi Keperawatan
Ada beberapa implikasi keperawatan yang dapat diterapkan seorang perawat
dalam menanggapi manfaat Momorcadia charantia sebagai obat herbal ini, yakni :
1. Sebagai pendidik
Seorang perawat diharapkan mampu mendorong masyarakat untuk menjaga
kesehatannya dengan mengonsumsi obat – obatan herbal melalui edukasi sehingga
pemakaiannya tepat aturan. Perawat dapat menjelaskan berbagai manfaat dari pare
terutama untuk penderita diabetes. Hal ini dilakukan agar masyarakat dapat
meminimalisir penggunaan obat kimia yang cenderung berakibat buruk bagi tubuh
jika dikonsumsi terus menerus. Selain itu, perawat merupakan pemantau ketika
klien sudah menggunakan obat herbal terkait prosedur penggunaan, efek samping
dan hal – hal lain yang perlu diperhatikan dalam terapi obat herbal tersebut.
2. Sebagai Advokat
Dalam hal ini perawat diharapkan dapat melakukan pembelaan apabila terjadi
kesalahan pemberian obat dalam kolaborasi dengan tenaga kesehatan lain.
Pengetahuan tentang efek samping, indikasi dan kontraindikasi tentang
17
pengggunaan obat herbal dapat menjadi landasan seorang perawat dalam memberi
perlindungan kepada pasiennya terkait penggunaan obat – obatan.
3. Sebagai peneliti
Perawat dapat melakukan penelitian lebih lanjut terkait manfaat pare sehingga
dapat berfikir kritis menangani segala permasalahan klien dari segi keperawatan.
Inovasi baru tentang manfaat obat – obatan herbal akan semakin membantu
perawat dalam menyelesaikan permasalahan klien.
4. Sebagai konsultan
Perawat memberikan solusi kepada setiap permasalahan klien mengenai
penggunaan obat – obatan herbal tanpa mengesampingkan kebutuhan akan obat –
obatan kimia. Memberi pandangan tentang dampak positif dan negative tentang
penggunaan obat herbal juga sangat penting dilakukan.
18
BAB 4. PENUTUP
4.1 Kesimpulan
Pare adalah salah satu jenis sayuran yang memiliki rasa yang khas, yaitu rasa
pahit adalah salah satu sifat yang dimiliki pare. Nama ilmiahnya adalah Momordica
charantia. Tanaman pare (Momordica charantia L.) berasal dari kawasan Asia Tropis.
Pare dapat dikemas menjadi tablet agar dapat ditelan secara mudah dan absorbsinya
lancar ke usus. Mula-mula obat diabsorbsi melalui oral kemudian masuk ke dalam
pembuluh darah lalu melalui tahap pendistribusian. Charantin yang merupakan saponin
steroid yang diisolasi dari biji pare yang memiliki aktivitas mirip insulin dengan
menstimulasi pengeluaran insulin di pancreas dan menekan gluconeogenesis di hati dan
polipeptida-p yang merupakan polipeptida yang kerjanya mirip insulin yang dapat
menstimulasi pengeluaran insulin dari sel beta pancreas serta glikosida asam oleanol
yang dapat menurunkan kadar glukosa darah dengan menghambat terjadinya aborbsi
glukosa oleh usus. Dan obat diekskresi melalui urine/ginjal karena bentuk sediaan obat
ini (kapsul) dapat larut dalam air. Charantin dan polypeptide-p yang terkandung dalam
daun pare dapat meningkatkan sensitivitas insulin dengan mempengaruhi aktivitas
postreseptornya. Perbaikan dari fosforilasi tyrosine IRS-1 ini sangat penting karena
berpotensi dalam menyebabkan resistensi insulin. Hal ini akan menyebabkan terjadinya
transport glukosa pada sel otot dan adiposa, sehingga kadar glukosa pada darah dapat
kembali turun mendekati normal. Penurunan kadar glukosa dimulai setelah 30 menit,
mencapai maksimum 4 jam dan berakhir dalam 12 jam.
4.2 Saran
Menurut WHO obat tradisional memiliki sedikit efek samping dan bahkan tidak
ada. Maka dari itu, akan baik jika lebih banyak tanaman obat yang dikembangkan dalam
pemanfaatannya untuk kesehatan. Selain sediaannya banyak, secara tidak langsung akan
menjadi alasan seseorang melestarikan tanaman tersebut. Untuk perawat juga tidak
hanya dapat menjalankan pengobatan dengan hasil yang sudah ada, tetapi dapat juga
melakukan penelitian terhadap tanaman obat lain.
19
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Indonesia Nomor : HK.00.05.41.1384 Tentang Kriteria Dan Tata Laksana
Pendaftaran Obat Tradisional, Obat Herbal Terstandar Dan Fitofarmaka. Jakarta :
BPOM RI. http://sireka.pom.go.id/requirement/HK.00. 05.41.1384-
2005.pdf[diakses pada tanggal 23 Maret 2018].
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1076/Menkes/SK/VII/2003 Tentang Penyelenggaraan Pengobatan Tradisional
Menteri Kesehatan Republik Indonesia. Jakarta : Menkes RI. http://pelayan
an.jakarta.go.id/download/regulasi/keputusan-menteri-kesehatan-republik-
indo nesia-no-1076-menkes-sk-vii-2003-tentang-penyelenggaraan-
pengobatan-tradi sional.pdf[diakses pada tanggal 20 Maret 2018].
Kwarta, D., dkk. (2016). Bitter Melon as a Therapy for Diabetes, Inflammation and Cancer:
a Panacea. Topical Collection (Dapat diakses pada :
21
https://www.semanticscholar.org/paper/Bitter-Melon-as-a-Therapy-for-Diabetes-
Kwatra-Dandawate/ab1b856d65d05b06d7e11dad4f5f4dd27172dde0/abstract)
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Levels During the Postprandial State Among Patients with Type 2 Diabetes
Mellitus. Philippine journal of international medicine. 48(2): 1-7.
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Obat Herbal Asli Indonesia no 6 tahun 2016.
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Pelayanan Kesehatan Tradisional. Jakarta : Kemenkes.
http://tradkom.depkes.go.id/wp-content/uploads/2015/1-PP%20No.%20103%
20Th%202014%20ttg%20Kesehatan%20Tradisional.pdf [diakses pada tanggal
20 Maret 2018].
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Nomor 007 Tahun 2012 Tentang Registrasi Obat Tradisional. Jakarta : Menkes.
http://sireka.pom.go.id/requirement/PMK-7-2012-Registrasi Obat-
Tradisional.pdf [diakses pada tanggal 25 Maret 2018].
Sayoeti, A.Z. 2015. Effect Of Decocta In Bitter Melon Fruit (Momordicacharantial.) For
Decrease Blood Glucose Levels. J Majority. 4(4): 1-5.
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Tripathi. 2003. Essentials of Medical Pharmacology. 5th Edition. New Delhi : Jaypee
Zahirah, Azatu. (2015). Effect of Deccota in Bitter Melon Fruit (Momordica charantia L.)
For Descrease Blood Glucose Levels. J Majority (Dapat diakses pada :
http://juke.kedokteran.unila.ac.id/index.php/majority/article/view/573)
22
Halaman Pengesahan
Tugas Analisa Pemanfaatan Hasil-hasil Pertanian dalam Pengobatan dengan Judul
“BUAH PARE UNTUK DIABETES MELITUS”
yang disusun oleh:
Dhea Cristina Damaiyanti Saragih (NIM 172310101071)
Della Kharisma Putri (NIM 17231010100)
telah disetujui untuk diseminarkan dan dikumpulkan pada:
hari/tanggal: ..........
Makalah ini disusun dengan pemikiran sendiri, bukan hasil jiplakan atau reproduksi ulang dari
makalah yang telah ada.
Ketua,
Dhea Cristina D.S
NIM 172310101071
Mengetahui,
Penanggung Jawab Mata Kuliah Dosen Pembimbing
Ns. Wantiyah, S.Kep., M.Kep Ns. Nur Widayati, S.Kep., MN
NIP 198107122006042001 NIP 198106102006042001

See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/23458791
A Target Based Therapeutic Approach Towards

Diabetes Mellitus Using Medicinal Plants
Article in Current diabetes reviews · December 2008
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Current Diabetes Reviews, 2008, 4, 291-308 291
A Target Based Therapeutic Approach Towards Diabetes Mellitus Using

Medicinal Plants
Pranav K. Prabhakar and Mukesh Doble*
Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology Madras,
Chennai-600 036, India
Abstract: Diabetes mellitus (DM) is not one disease but is a heterogonous group of syndromes. Contrary to the popular
belief DM is a metabolic disorder characterized by increased blood glucose level (hyperglycemia) and this is because of
insufficient or inefficient insulin secretary response. Glucose is the main energy source for the body, and in the case of
DM, management of glucose becomes irregular. There are around 410 experimentally proven medicinal plants having an-
tidiabetic properties but the complete mechanism of action is available only for about 109. There are several medicinal
plants whose extract modulate glycolysis, Krebs cycle, gluconeogenesis, HMP shunt pathway, glycogen synthesis and
their degradation, cholesterol synthesis, metabolism and absorption of carbohydrates, and synthesis and release of insulin.
This paper provides a comprehensive review of the mode of action of medicinal plants that exhibit anti-diabetic proper-
ties.
Keywords: Diabetes mellitus, Hyperglycemia, Ayurveda, Anti-diabetic, Insulin.
1. INTRODUCTION mg/dL), glucose appears in the urine (glucouria). This causes

an increased loss of water from the body and triggers a com-
Diabetes mellitus (DM) is the most common endocrine pensatory adjustment that leads to an increase in thirst
disorder, which is characterized by a defective or deficient (polydipsia) [3]. The inability of glucose to enter some tis-
insulin secretary process, glucose underutilization, and in- sues increases the need for alternate sources of energy, such
creased blood sugar (hyperglycemia). It is a congenital or as ketone bodies (acetoacetate, acetone and 3-beta-
acquired inability to transport sugar from the bloodstream hydroxybutyrate) [4].
into the cells. DM is a major health problem, affecting 5% of
the total population in the US and 3% of the population Humankind has a long history in the use of herbal medi-
worldwide [1]. It causes about 5% of all deaths globally each cines. Well-known Ayurvedic physicians Maharshi Charaka
year. DM can be divided into two major categories- Insulin (600 BC) and Sushruta (400 BC) correctly described almost
dependent diabetes mellitus (IDDM) or type 1 (an autoim- all the symptoms of this disease [5]. The present review dis-
mune disease of younger patients with a lack of insulin pro- cusses the mechanism of action of medicinal plants to com-
duction causing hyperglycemia and a tendency towards keto- bating diabetes. World ethnobotanical information about
sis) and noninsulin-dependent diabetes mellitus (NIDDM) or medicinal plants reports that about 800 plants are used in the
type 2 (a metabolic disorder resulting from the body’s inabil- control of diabetes mellitus [6, 7]. There are around 410 ex-
ity to produce enough or properly utilize insulin hence pa- perimentally proven medicinal plants having antidiabetic
tients have hyperglycemia but are ketosis resistant). Over properties but complete mechanism of action is available
90% of patients with diabetes have type 2 and the remainder only for about 109 plants.
has type 1 diabetes [2]. The complications associated with
2. THERAPEUTIC STRATEGIES
diabetes are neuropathy, nephropathy, retinopathy, diabetic
foot, and ketoacidosis. The management of diabetes without any side effect is
All tissues have energy requirement that is usually met by still a challenge to the medical system. Herbal drugs are pre-
metabolizing glucose. The entry of glucose from the blood scribed widely because of their effectiveness, fewer side
into the cells, liver, skeletal muscle, and adipose tissue is effects and relatively low cost. Wide array of plant derived
promoted by insulin. In the case of diabetics, these tissues active principles have demonstrated antidiabetic activity. The
cannot normally assimilate glucose, and hence it accumu- main active constituents of these plants include alkaloids,
lates within the blood. As the blood glucose concentrations glycosides, galactomannan gum, polysaccharides, pepti-
increases, osmotic forces come into play that tends to in- doglycan, hypoglycans, guanidine, steroids, carbohydrates,
crease the blood volume and urine output (polyuria). As the glycopeptides, terpenoids, amino acids and inorganic ions.
blood glucose level exceeds its renal threshold (i.e., 180 These affect various metabolic cascades, which directly or
indirectly affect the level of glucose in the human body [8].
Previous work, which has been published in non-indexed and
obscure journals, may have been missed out in this re-view
*Address correspondence to this author at the Bhupat and Jyoti Mehta as citations for the present article were predominantly taken
School of Biosciences, Department of Biotechnology, Indian Institute of from Diabetes Medicinal Plant Database “DiaMed-Base”
Technology Madras, Chennai-600 036, India; Tel: +914422574107; Fax:
+914422574102; E-mail: mukeshd@iitm.ac.in (http://www.progenebio.in/DMP/DMP.htm) [9].
1573-3998/08 $55.00+.00 © 2008 Bentham Science Publishers Ltd.

292 Current Diabetes Reviews, 2008, Vol. 4, No. 4 Prabhakar and Doble
Table 1. Medicinal Plants that Regulate Glycolysis and Krebs Cycle
S. No. Plant Constituent Activity References
Aegle marmelose L. Correa e- Aegelin, & -Sitosterol, Marmelosin, Mar-

1. 1 gm/kg/day [11, 43]
xRoxb(Rutaceae) mesin.
S-methyl cysteine sulfoxide,

2. Allium cepa L. (Liliaceae) 100-200 mg/kg [27, 28]
S-allyl cysteine sulfoxide.
Allicin, Apigenin, Alliin, S-allyl cysteine

3. Allium sativum L. (Alliaceae) 200 mg/kg [25, 26]
sulfoxide.
Leucopelargonidin, Dulcitol,
4. Casearia esculenta Roxb. (Flacourtaceae) [19]
Beta sitosterole.
Coscinium fenestratum
5. Berberine, saponin. [29]
Colebr(Menispermaceae)
Curcumin, Turmerone,
6. Curcuma longa L. (Zingiberaceae) 0.08 g/kg body Wt. [30, 37, 48, 66]
-Sitosterol, Zingiberene.
Wedelolactone, Demethyl wedelolactone,

7. Eclipta alba L. (Asteraceae) [20]
Eclipticine.
Mallic acid, Gallic acid, Oxalic acid, Tan-

8. Eugenia jambolana Lam. (Myrtaceae) 100 mg/kg [24, 30, 76]
nins.
Isoquercitrin, Quercetin3-O- -l-

9. Eucommia ulmoides Oliv. (Eucommiaceae) arabinopyrano syl -(1, 2)- -d- [14]
glucopyranoside, Astragalin.
Gongronema latifolium Benth (Asclepiad-

10. 100 mg/Kg [15]
aceae)
[24, 30, 44, 53, 63,

11. Momordica charantia L. (Cucurbitaceae) Charantin, Momordicoside. 200 mg/kg /day
77]
Mucunine, Mucunadine,
12. Mucuna pruriens L. (Fabaceae) 200 mg/kg /day [77]
-Sitosterol, Mucuadinine.
13. Murraya koenigii L. Speng (Rutaceae) 80 mg/kg /day [11, 31]
Eugenol, Carvacrol, Linalool, Caryophylline,

14. Ocimum sanctum L. (Lamiaceae) [11, 62, 78]
-Sitosterol.
Quinquenoside L3 & L9, Vina-Ginsenoside

15. Panax quinquefolius L. (Araliaceae) [79]
R3.
16. Piper betleL. (Piperaceae) -phenol, Chavicol, Cadinene. 75 mg/kg [21]
17. Plumbago zeylanica Linn. (Plumbaginaceae) [80]
Pterostilbene, Liquiritigerin, Isoliquiritigerin,

18. Pterocarpus marsupium Roxb. (Fabaceae) 1g/kg [8, 30]
Epicatechin.
Tinospora cordifolia Hook. f. & Thomson

19. Berberine. [30, 32, 60, 76]
(Meninspermaceae)
20. Trigonella foenumgraecum L. (Leguminosae) Trigonelline, Choline, Galactomannan. 1g/kg [22, 81]
3. BIOCHEMICAL PATHWAYS, MEDICINAL substrate or liberated as a product and the medicinal plants
PLANTS AND THEIR TARGET SITES that inhibit or activate one of these regulatory steps in the
pathways are listed.
Most of the tissues metabolize glucose for their energy
requirement and other purposes such as glucosylation of pro- 3.1. Glycolysis and Krebs Cycle
tein. In mammals, glucose is the only fuel that the brain uses
under nonstarvation conditions and the fuel that red blood Glycolysis is the most important metabolic pathway in all
cells use [10]. In the following sections the important bio- the cells of the human body through which the 6-carbon glu-
chemical pathways where glucose is involved, either as a cose molecule is oxidized to two molecules of pyruvic acid.
A Target Based Therapeutic Approach Towards Diabetes Current Diabetes Reviews, 2008, Vol. 4, No. 4 293
Fig. (1). Medicinal plants which regulate the glycolysis and Krebs cycle (see Table 1). {Plant No. 95 = Panax ginseng C. Meyer [13]}.
Glycolysis is the main energy producing pathway in some ents of medicinal plants which regulate the enzyme
specific tissues which lack mitochondria such as mature hexokinase/ glucokinase are listed in Table 1 (Plants No.1-
RBC and cells under low oxygen conditions such as heavily- 20). Plants No: 9-12, 15 and 17-22 activate phosphofructo-
exercising muscle. In glycolysis, the reactions catalyzed by kinase (Table 1, Fig. 1). However, last regulatory step of the
hexokinase, phosphofructokinase, and pyruvate kinase are glycolytic pathway which is catalysed by pyruvate kinase is
irreversible, and hence, these enzymes would be expected to not regulated by any medicinal plant. In the case of anaero-
have regulatory as well as catalytic roles [10]. bic respiration and in tissues which lack mitochondria, pyru-
Krebs cycle is the central pathway for energy production vate is converted to lactic acid by the enzyme lactic acid
dehydrogenase. The plants that regulate the conversion of
in which pyruvate is oxidized to CO 2 and H2O via acetyl pyruvate to lactate by inhibiting lactate dehydrogenase
CoA with the synthesis of energy equivalent, NADH. The (LDH) in the anaerobic glycolysis step are plants No: 1, 3, 5,
latter gets oxidized and produces ATP through the electron 13-14, 17, 19 and 20 respectively (Table 1, Fig. 1). Plants
transport chain. There are seven enzymes involved in this such as Aegle marmelose L. Correa ex Roxb [11], Catharan-
cycle, of which only two enzymes, succinate dehydrogenase
thus roseus (L.) G. Don. [12] and Panax ginseng C. Meyer
and malate synthase are regulated by plants and their respec-
tive constituents [10]. [13] (Plant No: 1, 27 and 95 respectively) activate succinate
dehydrogenase, while Catharanthus roseus (L.) G. Don. [12]
Several medicinal plants control the glycolysis and the and Panax ginseng C. Meyer [13], activate malate dehydro-
Krebs cycle (Fig. 1). The activity and the principal constitu- genase (Plant No: 27 and 95 respectively) (Table 1, Fig. 1).
Fig. (2). Medicinal plant that modulate gluconeogenesis pathway (see Table 3).
Table 2. Medicinal Plants (in Addition to Plant No. 1-5, 7, 9, 11, 13-14, 16, 19-20) that Inhibit Gluconeogenesis (Glucose-6-
phosphatase)
Aconitum carmichaeli Songoramine, Hypaconitine, Karakanine,

21. [33]
Debeaux(Renunculaceae) Songorine
Coccinia indica Weigh & Arn

22. Taraxerone, Taraxerol 2 gm/kg [23, 24]
(Cucurbitaceae)
Enicostemma littorale Blume

23. 2 gm/kg [30, 34]
(Gentianaceae)
Syzygium aromaticum (L.) Merr. & Perry

24. Isoflavones 50 mg/kg [17, 46, 47]
(Myrtaceae)
3.2. Gluconeogenesis decreasing the expression of phosphoenol pyruvate car-

boxykinase gene (Fig. 2) [18].
Gluconeogenesis is the pathway that generates glucose
from non-sugar carbon substrates like pyruvate, lactate, The last regulatory enzyme in this pathway is glucose-6-
glycerol, and glucogenic amino acids (primarily alanine and phosphatase, which is inhibited by Aegle marmelose L. Cor-
glutamine). Gluconeogenesis cannot be considered to be rea ex Roxb [11], Allium sativum L. [25, 26], Allium cepa L.
simply a reverse process of glycolysis, as the three irreversi- [27, 28], Casearia esculenta Roxb. [19], Coscinium
ble steps in glycolysis are bypassed here with four irreversi- fenestra-tum Colebr. [29], Eclipta alba L [20], Eugenia
ble and regulatory steps which are catalyzed by pyruvate jambolana L. [24, 30], Eucommia ulmoides Oliv [14],
carboxylase; PEP carboxykinase; Fructose-1, 6-bisphos- Momordica charan-tia L. [24, 30], Murraya koenigii (L.)
phatase and glucose-6-phosphatase. The medicinal plants [11,31], Ocimum sanc-tum L. [11], Piper betle L. [21],
Eucommia ulmoides Oliv [14], Gongronema latifolium Pterocarpus marsupium Roxb. [8], Tinospora cordifolia
Benth. [15], Panax quinofolium L. [16], Syzygium aromati- (Willd.) Hook. f. & Thom-son [32], Aconitum carmichaeli
cum (L.) Merr. & Perry [17] and Camellia sinensis (L.) Debeaux. [33], Coccinia indica Weigh & Arn [23, 24],
Kuntze. [16, 18] inhibit phosphoenol pyruvate carboxykinase Enicostemma littorale Blume
(Plant No: 9-10, 14-15, 24 and 93 respectively); and Aegle [34] and Syzygium aromaticum (L.) Merr. & Perry [17]
marmelose L. Correa ex Roxb [11], Casearia esculenta (Plant No: 1-5, 7-9, 11, 13-14, 16, 18-19 and 21-24 respec-
Roxb. [19], Eclipta alba L. [20], Murraya koenigii (L.) [11], tively) (Table 2, Fig. 2).
Ocimum sanctum L. [11], Piper betle L. [21], Trigonella
foenum-graecum L. [22] and Coccinia indica Weigh & Arn 3.3. Hexose Monophosphate (HMP) Shunt
[23, 24] inhibit fructose-1, 6-bisphosphatase (Plant No: 1, 4, HMP Shunt is an alternative pathway to glycolysis and
7, 13-14, 16, 20 and 22 respectively). Green tea flavonoid Krebs cycle for the oxidation of glucose. It generates two
epigallocatechin gallate (I) has glucose lowering effect by important products namely pentoses (ribose-5-phosphate)
and NADPH. It is an anabolic pathway that utilizes the six
Fig. (3). Medicinal plants affecting HMP shunt.
Table 3. Medicinal Plants (in Addition to Plant No. 1, 5, 10-11, 13-14, 21-22, 24) that Regulate HMP Shunt (Glucose-6-phosphate
dehydrogenase)
Sapogenin, Diosgenin, Yamogenin,

25. Balanites roxburghii (Balanitaceae) 1.5 g/kg [82]
-sitosterol.
26. Casearia esculenta Roxb. (Flacourtaceae) Resin, Sterol, Flavonoid. 300 mg/kg [19]
Catharanthus roseus (L.) G.Don Vinblastine, Vineristine, Vinine, Vincamine,

27. 500 mg/kg [12, 61]
(Apocynaceae) Alstonine.
28. Dioscorea cayenensis Lam. (Dioscoreaceae) [35, 36]
Fig. (4). Glycogen synthesis and medicinal plants involved in its regulation. Plant No. 96 = Brassica juncea (L.) Czem. [31].
carbons of glucose to generate five carbon sugars (Fig. 3). 3.4. Glycogen Synthesis
The regulatory and irreversible step in HMP shunt pathway
is catalyzed by enzyme glucose-6-phosphate dehydrogenase. Synthesis of glycogen from unused glucose is a multistep
Hence, regulation of enzyme glucose-6-phosphate dehydro- process carried out by the enzyme glycogen synthase in the
genase in the case of diabetes is a very important issue. liver. This enzyme utilizes UDP-glucose and the non-
There are several plants which regulates this enzyme. Aegle reducing end of glycogen as another substrate and progres-
marmelose L. [11], Coscinium fenestratum Colebr. [29], sively lengthens the glycogen chain. The activation of glu-
Gongronema latifolium Benth [15], Momordica charantia L. cose to be used for glycogen synthesis is carried out by the
[24, 30], Murraya koenigii (L.) [11, 31], Ocimum sanctum L. enzyme UDP-glucose pyrophosphorylase (Fig. 4). In the
[11], Aconitum carmichaeli Debeaux. [33], Coccinia indica case of diabetes the glucose is not properly converted to gly-
Weigh & Arn [23, 24], Colocassia esculenta (L.) Schott [35], cogen and as a result of which blood glucose level increases.
Catharanthus roseus (L.) G.Don [12] and Dioscorea Several plants affect the enzyme glycogen synthase action
cayenensis Lam. [36], affect the enzyme glucose-6- and they are Aegle marmelose L. [11], Curcuma longa L.[30,
phosphate dehydrogenase in the HMP shunt pathway (Plant 37], Dioscorea esculenta (Lour.) Burk. [37], Momordica
No: 1, 5, 10-11, 13-14, 21-22 and 24-28 respectively) (Table charantia L [24, 30], Murraya koenigii (L.) [11, 31] Ocimum
3, Fig. 3). sanctum L. [11], Piper betle L. [21], Coccinia indica Weigh
Fig. (5). Medicinal plants which repress the glycogenolysis process.
Fig. (6). Mechanism of action of medicinal plant in the digestion and absorption of carbohydrate (see Table 4).
& Arn [23, 24], Catharanthus roseus (L.) G. Don [12] and of starch and sugar produces glucose, which is absorbed in the
Brassica juncea (L.) Czem [31] (Plant No: 1, 6, 11, 13-14, blood stream through the walls of the intestine, and fi-nally
16, 22, 27 and 96 respectively) (Fig. 4). carried to the liver (Fig. 6). This process maintains the glucose
level in the blood. Several enzymes take part during the
3.5. Glycogenolysis carbohydrate digestion process, which primarily include
Glycogenolysis is the degradation of glycogen to glucose -Glucosidase, maltase, sucrase, amylase, lactase, isomaltase etc
which leads to increase in glucose level in the blood. Glyco- of which -glucosidase is the most important. Hence, inhibition
gen phosphorylase (GP) is the primary enzyme involved in of -glucosidase can be the effective treatments of DM. There
the glycogen breakdown. Plants like Aegle marmelose L are a number of medicinal plants known to sup-press this
[11], Murraya koenigii (L.) [11, 31], Ocimum sanctum L. activity (Plant No: 18 and 29-48 respectively) (Ta-ble 4) and
[11] and Brassica juncea (L.) Czem [31], inhibit the enzyme some of the plants decrease the absorption of car-bohydrates via
GP, thereby regulating the gluconeogenolysis pathway and the brush border cell of the intestine. The two active
components, (-)-3-O-galloylepicatechin and (-)-3-O-
hence decrease the glucose level in the blood (Plant No: 1,
galloylcatechin, from Bergenia ciliata Haw have demon-strated
13-14 and 96 respectively) (Fig. 5). It is reported that leaf
inhibition of inhibit rat intestinal -glucosidase and porcine
extract of Azadirachta indica is able to block the reduction in
pancreatic -amylase [39]. Alstonia scholaris (L.) R. Br.
the peripheral utilization of glucose and glycogenolysis in
containing quercetin 3-O-b-D-xylopyranosyl (1’’’ 2’’)-b-D-
diabetic rabbits [38]. galactopyranoside and (-)-lyoniresinol 3- O-b-D-
3.6. Digestion and Absorption of Carbohydrates glucopyranoside [40], also inhibits -glucosidase. These
inhibitors are known as "diabetes pills" however they are not
Carbohydrates are the major energy producing compo- technically hypoglycemic agents because they do not have a
nents of the normal diet, supplying more than 80% of the direct effect on insulin secretion or its sensitivity, but they slow
quick requirement of the body. The main constituents of car- the digestion of starch in the small intestine. The glucose
bohydrates are starch and sucrose. Starch is first decomposed comesfrom the starch present in daily intake food enter the
into oligosaccharides by the enzyme -amylase present in bloodstream slowly and can be matched to an impaired insulin
saliva and various pancreatic juices. -Glucisidase (EC response or low production. Miglitol and Acarbose are two
3.2.1.20), which is a membrane-bound enzyme located at the commercially available synthetic drugs which inhibits the
epithelium of the small intestine, catalyzes the cleavage of activity of -glucosidase.
glucose from disaccharides and oligosaccharides. Digestion
Table 4. Medicinal Plants (in Addition to Plant No. 18) that Inhibit -Glucosidase Activity and Glucose Absorption
Anemarrhena asphodeloides Bunge. (As-

29. Sarsasapogenin, mangiferin, neomangifrin. [83]
phodelaceae)
Alstonia scholaris
30. Chlorogenic Acid. [40]
(Apocynaceae)
Angylocalyx pynaertii de Wild (Legumino- 1,4-dideoxy-1,4-imino-D-ribitol, 2,5-dideoxy-

31. [84]
sae) 2, 5-imino-D-fucitol.
Artemisia pallens Wall ex. DC. T-Cadinol, -urunene,

32. 100 mg/kg [85]
(Compositae) -Eudesmol, -Ubebene.
Astragalin, Kaempferitrin, Astragalin, Bauhi-

33. Bauhinia candicans Link. (Leguminosae) [86, 87]
noside.
Bergenia ciliata Haw ( )-3-O-galloylepicatechin, ( )-3-O-

34. [12]
(Saxifragaceae) galloylcatechin.
35. Cassia auriculata L. (Leguminoceae) Di-(2-ethyl) hexyl phthalate. IC50 =0.023 mg/mL [30, 88]
Hydnocarpus wightiana Blume.

36. Hydnowightin, Hydnocarpin, Neohydnocarpin. [89]
(Flacourtaceae)
-Sitosterol, Ursolic acid, Moracin

37. Morus insignis Bur. (Moraceae) [90]
M,MulberrofuranU.
Mulberrofuran U, Moracin M3-O--D-

38. Myrtus communis L. (Myrtaceae) [91]
glucopyranoside.
Isoquercitrin, Astragalin, Scopolin, Roseoside

39. Morus alba L. (Moraceae) 200 mg/kg [92]
II.
40. Morus bombycis Koide. (Moraceae) 3-Epifagomine, Fagomine, Castanospermine. IC50 = 0.1 mg/ml [92]
Myrciaphenones A & B, Myrciacitrins I-V,

41. Myrcia multiflora DC. (Myrtaceae) [93]
Kotalanol.
42. Phylanthus embelica L. (Euphorbiaceae) Pterostilbene, Epicatechin, Liquiritigerin. [88]
Mangiferin, Salacinol, Kotalanol, Epigalloca-

43. Salacia reticulata Wight. (Celastraceae) 1 ml/day/rat [94]
techin.
Mangiferin, Salacinol, Kotalanol, Epigalloca-

44. Salacia oblonga (Celastraceae) 250 mg/kg [94]
techin.
Taraxacin, Acrystalline, Inulin,Taraxacerin,

45. Taraxacum officinale Weber. (Compositae) IC50 = 38 g/mL [91, 90]
Laevulin.
46. Urtica dioica L. (Urticaceae) Quercetin, Kaempferol, Glucoquinone. [91]
Lectins, Misteloe lectin I, II, III, Viscotoxins,

47. Viscum album L. (Loranthaceae) [91]
Cyclitols.
4. INSULIN MIMETIC NATURAL DRUGS The mechanism of insulin release from -cells in re-sponse
to changes in blood glucose concentration is a com-plex
Insulin is the most important peptide hormone in the hu-
process (Fig. 7). The release of insulin from insulin stored
man body. It not only regulates the carbohydrate metabo-
granules involves closure of ATP-gated potassium channels
lism, but also stimulates lipogenesis, diminishes lipolysis,
and activation of voltage-gated calcium channels [41].
and increases amino acid transport into the cells. This is se-
creted from the -cells of the islets of Langerhans in re-sponse
Many medicinal plants modulate this expression, synthe-
to hyperglycemia. Presently, all focus is targeted to increase sis and degradation of insulin (Table 5a). There are a few
the expression of insulin genes, increase secretion of insulin plants which act on the Sulfonylurea binding site 1 (SUR1)
from secretary granules, and inhibit their degrada-tion. and close the ATP-sensitive potassium channel (KATP), due
Fig. (7). Mechanism of action of exocytosis of insulin and of sulfonylurea (Table 5a).
to which the cell membrane gets depolarized leading to the gamma ligand-binding activity [46, 47]. PPAR gamma is one
influx of Ca2+ [41]. Plants which directly act on the Ca 2+ of the most important targets for Curcumin (IX), extracted
channels affecting insulin secretion are listed in Table 5a from curcuma longa and 6-gingerol (X), a natural analog of
(Plant No: 12, 14-15, 18, 40 and 49-89) and those which curcumin derived from the root of ginger (Zingiber officinale
increase the activity of insulin and decrease their degradation Roscoe.). The latter compound exhibits biological activity
by inhibiting insulinase are listed in Table 5b (Plant No: 14, profile similar to that of curcumin [48].
51 and 90-92). Cyclic AMP is one of the second messengers that medi-
Peroxisome proliferator-activated receptors (PPARs) are ate intracellular signaling networks triggered by membrane
a group of nuclear receptor transcription factors that induce receptor stimulation, eventually leading to alteration of cell
the proliferation of peroxisomes in the cells, which are also functions including metabolic activities. The synthesis of
involved in the cellular metabolism of carbohydrates, protein cAMP is catalyzed by adenylate cyclase, which has a short
and lipids [41]. There are three types of PPAR, namely, half life as the enzyme cAMP phosphodiesterase cleaves it.
alpha, delta/ beta and gamma. Among these, alpha This eventually leads to a decrease in the intensity of insulin
participates in the metabolism of lipids and peroxisome [49]. Several medicinal plants which include Orthosiphon
proliferation, beta has been implicated to be involved in aristatus Blume.[50], Passiflora edulis Sims. f [51], Hylo-
some disorder such as cancer, infertility and dislipidemis cereus undatus (Haworth) Britton & Rose [52], Luffa cylin-
whereas gamma participates in the insulin resistance [42]. drical (L.) Roem [53], Momordica charantia L. [53] and
Medicinal plants such as Aegle marmelose (L.) Correa ex Panax ginseng L. [13] possess cAMP phosphodiesterase
Roxb (Rutaceae) [43], Momordica charantia L. [44], inhibitory activity, as a result of which the action of insulin is
Helicteres isora L. (Sterculiaceae) [45], and Syzyzium retained.
cumini (L.) Skeel [43], increase the expression of PPAR
Glucose transporters (GLUT) which are present on the
gamma and decrease the insulin resistance (Plant No: 1, 11,
vesicles in the cytoplasm help in transporting glucose in and
72 and 94 respectively). Thiazolidinedione class of drugs
out of the cells. On excitation by glucose, GLUT comes to
which include roziglitazone, troglitazone and piaglitazome
the membrane and performs its required function. In the case
also target PPAR gamma. DehydroglyasperinC (II), dehy-
of DM the transportation of GLUT to the plasma membrane
droglyasperinD (III), glyasperinB (IV), glycycoumarine (V),
does not takes place (Fig. 8). A group of medicinal plants,
glycyrin (VI), and glyasperinD (VII), isolated from Glycyr-
such as Aegle marmelose (L.) Correa ex Roxb [11, 43], Al-
rhiza uralensis and neolgnan dehydroeugenol (VIII) isolated
lium sativum L. [25, 26], Canna indica L. [54], Lagerstro-
from Syzygium aromaticum exhibit significant PPAR-
Table 5a. Medicinal Plants (in Addition to Plant No. 12, 14-15, 18, 40) that Increase Insulin Secretion and Potentiates its Action
-Sitosterol, Ambrettelide, Myricetin-3-

48. Abelmoschus moschatus L. (Malvaceae) 1.0 mg/kg [95]
glucoside.
49. Abies pindrow Royle. (Pinaceae) -Sitosteral, Terpenoids, Flavonoids. 10 μg/ml [96]
Acacia arabica (Lam.) Muhl. ex Willd. m-Digallic acid, Chlorogenic acid, (+)-
50. 4 gm/kg [97, 98]
(Mimosaceae) Catechin.
Betaine, Achyranthine, Aschyranthes -

51. Achyranthes aspera L. (Amaranthaceae) 4 mg/kg [99]
aponins (B3).
Agaricus campestris L..

52. -Terpineol, Hexanol, Furfural, Captylic acid. 1 mg/mL [100]
(Agaricaceae)
Artemisia roxburghiana Besser. (Composi- 1,8-Cineole, Camphor,

53. 1 g/mL [66, 85, 96]
tae) -Thujone.
Isobarbalin, Aloe-emodin, Aloetic acid,

54. Aloe barbadensis L. (Aloaceae) 500 mg/kg [62]
Barbaloin.
Asparagus adscendens
55. 3-Hepatadecanone, Steroidal glycosides. [101]
Roxb.(Asparagaceae)
56. Azorella compacta Lam. (Umbelliferae) Mulinol, Azorellanol, Mulinolic acid. [102]
Astragalin, Kaempferitrin, Bauhinoside, 25.9%

57. Bauhinia forficata Link. (Leguminosae) [103]
-sitosterol. decrease
58. Biophytum sensitivum auct. (Oxalidaceae) Shamimin (flavonol glucoside). [104]
59. Bauhinia variegata L. (Caesalpiniaceae) Quercetin, Quercetrin, Apigenin, Rutin. 20 g/ml [105]
60. Bergenia himalaica Boriss. (Saxifloriaceae) Bergenin. 20 g/ml [96]
Caesalpinia bonducella L. Roxb. (Cesalpi- Bargenin, Caeselpinine A,

61. 30 mg/kg [106]
naceae) & -Amyrin, Lupeol.
Centaurea iberica Trev. ex Spreng

62. 10 g/mL [96]
(Asteraceae)
63. Cinnamomum cassia Lour. (Lauraceae) Melilotic acid, Cinnamaldehyde 0.1 mg/ml [107]
Cinnamomum zeylanicum Blume. L-arabino-D-xylan, D-glucan, Cinnzeylanin,

64. [107]
(Lauraceae) Cinnzeylanol,
Citrullus colocynthis L. Schrad.

65. Citrullol, Elaterin, Elatericin B, Colosynthetin. [108]
(Cucurbitaceae)
Linalool, Geraniol, -Pinene, p-Cymene, Li-

66. Coriandrum sativum L. (Umbelliferae) [109]
monene.
67. Eugenia uniflora Lam. (Myrtaceae) [110]
68. Euphorbia helioscopiaL. (Euphorbiaceae) 10 g/mL [96]
69. Ficus religiosa L.(Moraceae) Leucopelargonidin, Pelargonidine. [111]
Gynostemma pentaphyllum Thumb.

70. [112]
(Cucurbitaceae)
Gymnemosides,
71. Gymnema sylvestre Retz. (Asclepiadaceae) [30, 65]
Gymnemic acid I-IV.
72. Helicteres isora L. (Sterculiaceae) Cucurbitacin B, Isocucurbitacin B. 100 mg/kg [45]
Hylocereus undatus Britton & Rose. -Sitosterol, Vit-B1, B2, B3, C, Stigmasterol,
73. [52]
(Cactaceae) Ca, P, Fe.
Table 5a. contd…
74. Luffa cylindrica (L.) Roem (Cucurbitaceae) Momordin-a, Luffin-a. [53]
75. Musa sapientum L. (Musaceae) 2-heptyl acetate, 2-methylbutyl acetate. 150 mg/kg [113]
76. Marrubium vulgare L. (Lamiaceae) [114]
77. Monstera deliciosa Liebm. (Areceae) 1 g/mL [96]
Orthosiphon aristatus Neoorthosiphols A & B,

78. [50]
Blume. (Lamiaceae) 3-hydroxy-2methyl-4-pyrone
Panax notoginseng (Burk.) F.H.Chem Saponin, Dencichine, Flavonoid, Polysaccha-

79. [115]
(Araliaceae) ride.
Quinquenoside L3 & L9, Vina-Ginsenoside

80. Panax quinquefolium L. (Araliaceae) [79, 116]
R3.
81. Salvia coccinia Salmon & Red. (Lamiaceae) 1 g/mL [96]
82. Scoparia dulcis L. (Scrophulariaceae) [117]
Swertia chirayita Roxb. ex Fle- Amarogentin, Swerchirin, Chirantin, Gentio-

83. 100 mg/kg [118]
ming.(Gentinaceae) picrin.
84. Stevia rebaudiana Bertoni (Compositae) Sstevioside. [119]
85. Teucrium polium L. Labiaceae) [120]
Cordifole, Cordifolide,
86. Tinospora crispa L. (Menispermaceae) [121]
-Sitosterol, Tinosporine.
87. Vinca rosea (L.) G. Don (Apocyanaceae) Vinblastine, Vincristine, Reserpine, Vinceine. 500 mg/kg [12, 61]
88. Viburnum foetens Decne (Caprifoliaceae) 40 g/mL [96]
Xanthocercis zambesiaca (Baker) Harms Castanospermine, Fagomine, Epifagomine, -

89. 50 mg/ml [122]
(Leguminoceae) Homono jirimycin, Deoxynojirimycin.
Table 5b. Medicinal Plants (in Addition to Plant No. 14 and 51) that Potentiates Insulin Action by Inactivating Insulinase Enzyme
Arctostaphylos uva-ursi (L.) Arbutin, Ericolin, Ellagic acid, Myricetin,

90. 6.25% by weight [123]
Spreng.(Ericaceae) Ursone.
Camphor, Eugenol, Juvocimene I & II, Trans-

91. Ocimum canum L. (Lamiaceae) 0.03 mg/ml [124]
ß-ocimene, Linalool.
emia speciosa (L.) Pers. [55], Syzyzium cumini (L.) Skeel. gallate (I), a green tea flavonoid, mimics insulin by increas-
[43], and Cornus officinalis Siebold. & Zucc. [56] help in the ing the PI3 Kinase activity [18].
effective transportation of GLUT to the plasma membrane,
as a result of which glucose gets transported into the cells 5. PHYTOCOSTITUENTS HAVING HYPOGLYCE-
and its concentration in the blood decreases. MIC POTENTIAL
Several phytochemicals including alkaloids, flavonoids,
Insulin modulates several metabolic pathways through a
glycosides, glycolipid, polysaccharides, peptidoglycans, car-
cascade of steps by activating PI3 Kinase (Fig. 8) [57].
bohydrates, amino acids and saponin obtained from plant
However, when its action is insufficient then these steps do
sources have been reported to posses hypoglycemic activity
not take place. Plants, such as Aegle marmelose (L.) Correa
(Fig. 9) [8]. Many of them may be found in a single plant
ex Roxb [11, 43], Helicteres isora L. [45], catharanthus
and their combined synergistic action may be giving the ob-
roseus (L.) G. Don [12], Camellia sinensis (L.) Kuntze. [16,
served behaviors. First three groups of phytochemical, which
18] and Hericium erinaceus Persoon. (Fungi) [58] have PI3
are explained below, can be considered as insulin mimetic
kinase activating capacity thereby affecting all the metabolic
natural drugs. They either increase the serum insulin level or
pathways inspite of inefiicient insulin (Table 5c, and Plant
increase the activity of insulin. The remaining groups either
No: 1, 72, 86-87 and 92-94 respectively). Epigallocatechin
suppress glucose production or enhance glucose metabolism.
Fig. (8). Mechanism of action of insulin (Tables 5b and 5c).
Table 5c. Medicinal Plants (in Addition to Plant 1, 72, 86-87) that Activate PI3K
Epicatechin Epigallocatechin gallate, Epigallo-

92. Camellia sinensis (L.) Kuntze. (Theaceae) [16, 18]
catechin.
Hericium erinaceus Persoon.

93. [58]
(Fungi)(Hericiaceae)
94. Syzyzium cumini (L.) Skeel. 200 mg/kg [43]
5.1. Alkaloids serum insulin, reduce blood glucose level and improve toler-
ance of glucose [62].
Alkaloids are naturally occurring amines and they have
pharmacological effects on human and animals. Resveratrol 5.3. Saponins
is a phytoalexin, a class of antibiotic compounds produced as
Saponins are glycosides of steroids, steroid alkaloids
part of a plant's defense system against disease. It increases (steroids with a nitrogen function) or triterpinoids found in
glucose uptake in STZ-induced type 1 diabetic rat mediated
plants. Charantin (XV), a steroidal saponin, isolated from
through nitric oxide [59]. Berberine (XI) is known to have Momordica charantia L. is reported to posses an insulin-like
potent hypoglycemic activity and it is found in Tinospora
activity [63], by enhancing the release of insulin and slowing
cordifolia (Willd.) Hook. f. & Thomson [60]. Alkaloids such down the glucogenesis. -Sitosterol (XVI), a steroid found in
as Catharanthine (XII.), vindoline (XIII) and vindolinine
Azadirachta indica A.Juss. andrographolide (XVII), a diter-
(XIV) isolated from Catharanthus roseus (L.) G. Don have penoid lactone, isolated from Andrographis paniculata Nees.
been reported to lower blood sugar level [61].
[64] and saponin gymnemic acid IV (XVIII) isolated from
Gymnema sylvestre R, exhibit potent hypoglycemic activity
5.2. Polysaccharides in animal models [65].
Medicinal plants which include Aloe vera L., Ocimum 5.4. Ferulic Acids
sanctum L., and Alpinia galanga (L.) Willd. contain poly-
sachharides which increases the insulin level and showing Ferulic acid (4-hydroxy-3-methoxycinnamic acid) (XIX)
hypoglycemic properties [62]. A protein-bound polysaccha- is a flavonoid which is a highly abundant phenolic photo-
ride isolated from pumpkin is shown to increase the levels of chemical present in cell walls of many plants that include
OH
OH
HO O
OH HO O OH
O
HO Me2C HC H2C
OH
OMe OH
O
Dehydroglyasperin C [II]
OH
OH
Epigallocatechin gallate [I]
MeO O
MeO O OH
Me2C HC H2C
Me2C C H2C OH O
H
HO OH
OMe OH
Dehydroglyasperin D [III] Glyasperin B[IV]
O O
HO O OH MeO O OH
Me2C C H2C Me2C C H2C

H
H
OMe OH OMe OH
Glycycoumarin [V] Glycyrin [VI]
MeO O
OH
Me2C HC H2C
O
OMe O
HO OH
Dihydroeugenol [VIII]
Glyasperin D [VII]
O O
CH3
(CH2)4
HO OH
OMe OMe 6-Gingerol [X]
Curcumin [IX]
O
N Et
N+
O H
OCH3 N
H
MeO O
OCH3
Catharanthine [XII]
Berberine [XI]
Fig (9). Hypoglycemic phytochemicals. (Contd…)

Fig (9). Contd….
N N
H CH3
N N
H3CO CH3 COCH3
H COOCH3
HO COOCH3
Vindolinine [XIV]
Vindoline [XIII]
CH3
H
CH(CH3)2 CH3
H3C H
CH3
H3C H
H H
Glucose Beta O
HO
Charantin [XV]
B-Sitosterol[XVI]
O H3C CH3
O O-Toqloyl
HO
OH
H3C H3C
H3C H CH2OH
CH2 HOOC OH
O CH3
O
HO HC
H CH OH
HOH2C CH HO 3 2
3
OH
Andrographolide [XVII]
Gymnemic acid [XVIII]
OH
H3CO OH
OH HO O
COOH
Ferulic acid [XIX] OH

OH O
Quercetin [XX]
O
OH O
H3CO OH
O HO
O
O
HO O O
O HO O
CH3 O O
OH CH3 O
OH
HO OH HO
OH HO OH HO
OH
Hespiridin [XXI]
Naringin [XXII]
Fig (9). Hypoglycemic phytochemicals. (Contd…)
Fig (9). Contd….
OH
HO O HO O
OH
OH
OH O
OH OH
Genistein [XXIII] (-) Epicatechin [XXIV]
+
HO O HO O+ OH
OH OH
OH OH
OH OH OH
- -
.Cl .Cl
Pelargonidin [XXV] Delphinidin [XXVI]
O
H 3C O
H 3C
N N
N N
H N N
H
CH3 H
Harmane [XXVII] Norharmane [XXVIII] Pinoline [XIX]
O
H
2 O O
HC CH CH S S C C C H2
CH S S C C
2 2
H2C CH2 CH2

OH H
H2 N H
S-allyl cysteine sulfoxide [XXX] Allicin(Diallyl thiosulfinate) [XXXI]
Fig (9). Hypoglycemic phytochemicals.
Curcuma longa L, Artemisia arborescens L (Compositeae), when tested on obese Zucker rats (type II diabetes model)
A. herba habla L (Compositeae) and it may have significant significantly improved lipid and glucose metabolism by act-
health benefits through its antioxidant, anti-cancer properties ing as a hypoglycemic on PPAR [70]. Green tea flavonoid,
and blood glucose lowering activity [66]. epigallocatechin gallate (I) has a glucose-lowering effect in
animals [18]. It is reported to decrease hepatic glucose pro-
5.5. Flavonoids duction and increase tyrosine phosphorylation of the insulin
Flavonoides is a group of naturally occurring compounds receptor and insulin receptor substrate-1 (IRS-1), similar to
which possess hypoglycemic as well as antioxidant proper- insulin. It also reduces phosphoenolpyruvate carboxykinase
ties. They are also a class of plant secondary metabolites. gene expression in a phosphoinositide 3-kinase-dependent
Flavonoids can be widely classified into flavanols, flavones, manner and mimics insulin by increasing PI3K, MAP kinase
catechins, flavanones, etc. Some flavonoids have hypogly- [18]. Another flavonoid, ( )-epicatechin (XXIV), has been
cemic properties because they improve altered glucose and reported to possess insulin-like activity [71] which acts on
oxidative metabolisms of the diabetic states [67]. Quercetin erythrocyte membrane-bound acetylcholinesterase in Type II
(XX) is an important flavonoid known to increase hepatic diabetic patients [72]. Pelargonidin (XXV) and delphinidin
glucokinase activity, probably by enhancing the insulin re- (XXVI) have also shown good hypoglycemic activity [73].
lease from pancreatic islets [68]. It also exerts stimulatory 5.6. Imidazoline Compounds
effect on insulin secretion by changing Ca2+ concentration
[69]. Supplimentation of (0.2 g/kg) citrus bioflavonoids, Pancreatic beta cells have imidazoline-I binding sites on
namely hesperidin (XXI) and naringin (XXII), in the diet of them and imizoline derivatives found in some of the plants
the male C57BL7KsJ-db/db mice (Type II diabetes model) have stimulatory action on insulin secretion by activating this
lead to reduction in the blood glucose levels, increase in he- binding site [74]. -carbolines which include harmane
patic glucokinase activity and glycogen concentration. Nar- (XXVII), norharmane (XXVIII) and pinoline (XXIX), ob-
ingin lowers the activity of hepatic glucose-6-phosphatase tained from Tribulus terrestris L. have found to increase
and phosphoenolpyruvate carboxykinase and the plasma insulin secretion two- to three-folds in isolated human islets
insulin, C-peptide. Genistein (XXIII) and soy isoflavonoids of Langerhans [75].
5.7. Sulfur Containing Compounds PPAR = Peroxisome proliferator-activated rece-

ptors
Administration of sulfur containing amino acids namely
S-methyl cysteine sulfoxide (XXX) and Diallyl thiosulfinate SUR = Sulfonylurea binding site 1
isolated from the plants Allium sativum L. [25, 26] and Al-
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Received: 22 January, 2008 Revised: 17 March, 2008 Accepted: 15 May, 2008

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Curr Pharmacol Rep (2016) 2:34–44
DOI 10.1007/s40495-016-0045-2
CANCER CHEMOPREVENTION (R AGARWAL, SECTION EDITOR)
Bitter Melon as a Therapy for Diabetes, Inflammation,

and Cancer: a Panacea?
1,2 1 3 1,2
Deep Kwatra & Prasad Dandawate & Subhash Padhye & Shrikant Anant
Published online: 21 January 2016

# Springer International Publishing AG 2016
Abstract Natural products have been used for centuries for cures . . .
Keywords Herbal remedy Anticancer Antidiabetic Anti-
prevention, treatment, and cure of multiple diseases. Some . . .
inflammatory Drug resistance Dietary agent Obesity
dietary agents are present in multiple systems of medi-cines as
proposed treatments for chronic and difficult to treat diseases.
Once such natural product is Momordica charantia or bitter Introduction
melon. Bitter melon is cultivated in multiple regions across the
world, and various parts of the plant, such as fruit, leaves seed, Nature is full of deadly poisons as well as life-saving entities.
etc. have been shown to possess medicinal prop-erties in ancient In natural products such as medicinal plants, their extracts
literature. Over the last few decades, multiple well-structured have been used for thousands of years in traditional medicine
scientific studies have been performed to study the effects of throughout the world. In the past century, new drug develop-
bitter melon in various diseases. Some of the properties for which ment is mainly being carried out using combinatorial chemis-
bitter melon has been studied include: antioxidant, antidiabetic, try and targeted drug design. However, phytochemicals and
anticancer, anti-inflammatory, anti-bacterial, antifungal, antiviral, their analogs have also started to garner a lot of attention in
anti-HIV, anthelmintic, hypo-tensive, anti-obesity, immuno- drug discovery because of their relatively better safety profile,
modulatory, antihyperlipidemic, hepato-protective, and neuro- possible multi-targeted activities, and potential to treat wide
protective activities. This review attempts to summarize the range of diseases. A report from the World Health Organiza-
various literature findings regarding medicinal properties of bitter tion (WHO) had reported that about 80 % of the world’s pop-
melon. With such strong scien-tific support on so many medicinal ulation utilizes traditional system of medicine as their first
claims, bitter melon comes close to being considered a panacea. line of therapy [1]. Multiple countries in Asia, Africa, and the
Middle East have long-standing and still prevailing systems of
traditional medicines, most containing within them large
compilations of therapeutic plants and related products [2].
Some of the medicinal plants described in Ayurveda (the tra-
This article is part of the Topical Collection on Cancer Chemoprevention ditional Indian system of medicine), viz. bitter melon (BM)
[3–5], turmeric [6, 7], and stone apple [8, 9], have
* Shrikant Anant demonstrat-ed their importance in recent years for treatment
sanant@kumc.edu of various diseases including diabetes and cancer. With
advancement in science and technology, it is now a lot more
1 Department of Surgery, University of Kansas Medical Center,
feasible to dis-cover the active constituents present in these
3901 Rainbow Boulevard, Kansas City, KS 66160, USA plants and estab-lish their pharmacology for developing them
2 The University of Kansas Cancer Center, University of Kansas into safer and more efficient therapeutics.
Medical Center, 3901 Rainbow Boulevard, Kansas City, KS The current review discusses and summarizes the potential
66160, USA
biological activities of BM or Momordica charantia (MC).
3 Interdisciplinary Science and Technology Research Academy,
Abeda Inamdar College, University of Pune, Pune 411001, India BM, though a medicinal plant in Ayurveda and Chinese
sys-tems of medicine, is often consumed as a cooked
vegetable in
Curr Pharmacol Rep (2016) 2:34–44 35
both these countries as well as other parts of Southeast Asia. It Morphological Characteristics
is known as bitter melon, bitter gourd, balsam pear, bitter
cucumber, and Karela [10]. All parts of the plant, including MC is an herbaceous plant with tendril-bearing vines that
the fruit, taste bitter. The shoot and leaves of bitter melon are grows up to 5 m in length. It has simple and al-ternate
used as vegetables for cooking, while fruit extracts are also leaves, which are 4–12 cm across. These leaves bear 3–7
utilized in tea preparations [11, 12]. Since the bitterness of the deeply separated lobes. The plant has two different kinds
vegetable is considered desirable, hence, the bitter flavor has of flowers separated based on sex. MC has easily
been preferentially selected during domestication [13]. differentiable male and female, yellow-colored flowers,
In Ayurveda, MC is claimed to possess antidiabetic, owing to its monecious qualities. The male flowers grow at
abortifacient, anthelmintic, antimalarial, and laxative prop- the end of thin, long stems, whereas the female flowers
erties. Additional indications include dysmenorrhea, em- have a small fruit at the base of flower stem. The fruit is
menagogue, eczema, gout, galactagogue, kidney (stone), oblong in shape with
jaundice, leucorrhea, leprosy, pneumonia, piles, rheuma-tism, a distinct warty on exterior. The cross-sections of the fruit
and psoriasis [14]. In recent years, MC and its various extracts show hollow interior with thin layer of flesh cov-ering a
have been studied for biological activities including central seed cavity filled with large, flat seeds as well as
antioxidant [15], antidiabetic [16], anticancer [3, 4], anti- pith. Often, fruit is eaten when it is green or just starts
inflammatory [17], antibacterial [18], antifungal [19], anti-v i turning yellow in color. At this stage, the fruit is crunchy as
ral[20],anti-HIV[21],anthelmintic[22], well as watery in texture. As the fruit progress to ripening,
antimycobacterial [23], hypotensive [24], anti-obesity [25], the rind becomes tough and with sometimes increased
Immuno-modulatory [26], antihyperlipidemic [27], hepato- bitterness, while pith becomes sweet in taste and red in
protective [28], and neuro-protective activities [29]. Numer- color. After full ripening, fruit turns orange in color,
ous chemical constituents such as curcubitane-type mushy, and often splits into seg-ments, that curl back to
triterpenoids, curcubitane-type glycosides, triterpene sapo- expose seeds covered in bright red pulp (Fig. 1).
nins, phenolic and flavonoid compounds, and protein com-
ponents [30] have been identified and studied for various MC is available commercially in a variety of shapes and
therapeutic activities. In the present review, we are summa- sizes. The Chinese variety is 20–30 cm long, ob-long with
rizing some of the important reports dealing with antioxi-dant, bluntly tapering ends, and pale green colored with a gently
anti-inflammatory, anticancer, and antidiabetic activi-ties of undulating, warty surface, whereas the Indian variety has a
MC. With so many health and therapeutic benefits, one can narrower shape with pointed ends and a surface covered
consider bitter melon to be as close to panacea as possible that with jagged, triangular Bteeth^ and ridges. Indian MC is
exists in nature. available in two varieties based on size, shape, color, and
surface texture of the fruit. The first variety is M.
charantia var. charantia having large fusiform of fruits
that are not tapered at both ends and possesses numerous
M. charantia triangular tubercles looking like a Bcrocodile’s back.^ The
second variety is M. charantia var. muricato (Wild),
The genus Momordica occurs to subtribe Thladianthinae, which produces small and round fruits with tubercles, and
tribe Joliffieae, subfamily Cucurbitoideae, of the more or less tapering at both ends [36].
Cucurbitaceae family [31]. The genus Momordica includes
45 plant species domesticated in Asia and Africa [32]. The
plant grows in tropical areas of Asia, Amazon, east Africa, and
the Caribbean. The core of MC domestication is mainly in Nutritional Values
eastern Asia, with greater proportion in India and southern
China [33]. Other countries of prominent cultivation include The nutritional analysis of MC fruits shows that it is a rich
Brazil, Colombia, Cuba, Ghana, Haiti, Mexico, Malaya, New in carbohydrates, proteins, vitamins, fibers, and min-erals
Zealand, Nicaragua, Panama, and Peru [34, 35]. MC has been (Table 1). MC holds the highest nutritive value among all
mentioned in Ayurvedic books from 2000 to 200 BCE [32], cucurbits [37]. Vitamin C content of Chinese MC differs
providing reference of early cultivation of MC in India. The significantly (440–780 mg/kg edible portion).
Chinese written reference to MC was documented in 1370 Considerable variation in nutrients, including protein, car-
[33]. Both the domesticated and putative wild progenitors of bohydrates, iron, zinc, calcium, magnesium, phosphorous,
MC are recorded in floras of India, tropical Africa, and Asia and ascorbic acid, has been observed in MC [37, 38]. The
as well as Brazil, where it first came and then spread into pulp around the seeds of the mature ripe fruit is a major
Central America [13]. source of the carotenoid lycopene.
36 Curr Pharmacol Rep (2016) 2:34–44
Fig. 1 Raw and ripened fruit of

bitter melon
Biological Activities of Bitter Melon sulfation. There results showed that polysaccharides with high
degree of sulfation exhibited better antioxidant activities as
Antioxidant Activity and Antidiabetic Activity compared to native polysaccharides from MC in vitro [28].
Different ingredients in MC have found to be responsible
Oxidant production as normal metabolic by-products or their for its potential antioxidant and antidiabetic properties. Lin et
exposure from environment often leads to effects such as ag- al. in 2011 isolated a number of new compounds including a
ing or other degenerative disorders. Consumption of novel cucurbitane-type triterpene glycoside, taiwacin A,
antioxidant-rich foods can help alleviate such issues. Multiple taiwacin B, a known cucurbitane-type triterpene glycoside,
reports using different extracts of BM have shown potential and a known steroid glycoside from the stems and fruits of
antioxidant properties of the fruit. Lu and group have studied MC. They further proposed the structure of the new com-
the protective effects of the ethanolic extracts of MC fruit, pounds by utilizing spectroscopic methods. All four com-
against chronic alcohol-induced hepatic injury in C57BL/6 pounds were shown to exhibit ABTS radical cation scaveng-
mice. It is believed that the protective effects are facilitated by ing activity with IC50 values of 119.1 ± 4.3, 204.5 ± 1.2,
improving levels of liver antioxidant enzymes (GSH, GPx, 159.7 ± 11.0, and 98.1 ± 2.4 μM respectively [40]. In a study
GRd, CAT, and SOD), decreasing lipid peroxidation (MDA), comparing the antioxidant activities of various herbal agents,
and lowering expression of pro-inflammatory cytokines the highest free radical scavenging activity was observed with
(TNF-α, IL-1β, and IL-6) [28]. Similarly, antioxidant po- the extracts of MC and Eugenia jambolana [41]. Kumar et al.
tential of MC extract was studied in ammonium chloride- also carried out the evaluation of the antioxidant activity of
induced (AC) hyperammonemic rats. Treatment with MC the total aqueous extract (TAE) and total phenolic extract
extract normalized the abovementioned chang-es by reversing (TPE) of MC fruits. The antioxidant activities were measured
the oxidant–antioxidant imbalance dur-ing AC-induced by using radical-scavenging methods. Further, the
hyperammonemia [39]. cytoprotective effects of the extracts on hydrogen peroxide
The antioxidant activity of MC extracts may vary, depend- (H2O2)- and hypoxanthin-xanthin oxidase (HX-XO)-induced
ing on the method of extraction. Wei and coworkers have damage to various cell types were also measured. At 200 and
shown that the free radical scavenging activity of MC extract 300 μg/ mL, TPE showed dose-dependent cytoprotection
was significantly increased by using heat drying process for against the used oxidants [42]. Dhar et al. have studied the in
extraction. The extract was found to exert higher proliferation vitro anti-oxidant activity of MC seed oil containing
activity on NIT-1 beta cells, thus resulting in possibly better conjugated octadecatrienoic fatty acid and alpha-eleostearic
antidiabetic activity of the fruit [15]. Liu et al. developed sul- acid. Alpha-eleostearic acid also decreased the lipid
fated polysaccharide from MC with variable degrees of peroxidation level in a dose-dependent manner [43 ].
Table 1 Nutritional values of Momordica charantia raw leafy tips, raw pods, and their cooked forms
Nutrients Leafy tips, raw Leafy tips, cooked, Pods, raw Pods, cooked, boiled,
boiled, drained, no salt drained, no salt
Proximates Water (g) 89.25 88.69 94.03 93.95

Energy (Kcal) 30 34 17 19
Proteins (g) 5.30 3.60 1 0.84
Total lipids (fats) (g) 0.69 0.20 0.17 0.18
Carbohydrate, by difference (g) 3.29 6.68 3.70 4.32
Fiber, total dietary (g) – 1.9 2.8 2.0
Sugars, total 1.04 1.95
Minerals Calcium, Ca (mg) 84 42 19 9
Iron, Fe (mg) 2.04 1.02 0.43 0.38
Magnesium, Mg (mg) 85 94 17 16
Phosphorus, P (mg) 99 77 31 36
Potassium, K (mg) 608 602 296 319
Sodium, Na (mg) 11 13 5 6
Zinc, Zn (mg) 0.30 0.30 0.80 0.77
Vitamins Vitamin C, total ascorbic acid (mg) 88 55.6 84.0 33.0
Thiamin (mg) 0.181 0.147 0.040 0.051
Riboflavin (mg) 0.362 0.282 0.040 0.053
Niacin (mg) 1.110 0.995 0.040 0.280
Vitamin B-6 (mg) 0.803 0.760 0.043 0.041
Folate, DFE (μg) 128 88 72 51
Vitamin A, RAE (μg) 87 121 24 6
Vitamin A, IU (IU) 1734 2416 471 113
Vitamin E (mg) 1.45 0.14
Vitamin K (μg) 163.1 4.8
Lipids Fatty acids, total saturated (g) 0.032 0.014
Fatty acids, total monounsaturated (g) 0.005 0.033
Fatty acids, total polyunsaturated (g) 0.083 0.078
The detailed nutritional information can be found from the United States Department of Agriculture, Agricultural research services websites at
the following weblinks. For leafy tips, raw: http://ndb.nal.usda.gov/ndb/foods/show/2867; for pods, raw:
http://ndb.nal.usda.gov/ndb/foods/show/2869; for pods, cooked, boiled, drained, without salt: http://ndb.nal.usda.gov/ndb/foods/show/2870
The antioxidant and α-glucosidase inhibitory activity of the the heart, kidney, and liver tissues and TBARS levels were
methanolic and ethyl acetate extracts of MC was studied by also improved [46]. These authors also studied the effect of
Sulaiman et al. The reducing power was found to be 692.56 ± MC on antioxidant levels and lipid peroxidation in heart
43.38 and 221.97 ± 17.20 mM AscAE/g extract re-spectively, tissue of non-diabetic and alloxan-induced diabetic rats.
and the α-glucosidase inhibitory activities were 18.04 ± 0.47 They found that MC treatment reduced the elevated levels
and 66.64 ± 2.94 %, respectively [44]. Ching et al. evaluated of fasting blood glucose, decreased lipid peroxida-tion and
the effects of maternal high-fructose intake on the offspring increased antioxidant enzyme activity in heart tissue of
and if metabolic control in the offspring could improve from diabetic rats [47]. These results all suggest that some
supplementing bioactive food components to the maternal portion of the antidiabetic benefits of MC also come from
diet. Their results showed that MC supplementa-tion to dams its antioxidative properties, which supplement the
could offset the adverse effects arising from the maternal hypoglycemic effects with the reversal of oxidant-induced
high-fructose intake in adult offspring [45]. Tripathi and damage.
Chandra further studied the antihyperglycemic and anti- Further studies in diabetic animal models showed that MC
oxidative activities of MC aqueous extracts and found that it extracts possess not only the hypoglycemic properties but can
improved fasting blood glucose levels in rats. In addition, also alleviate diabetes-related adverse effects. A study by
antioxidant activities such as the levels of superoxide dismut- Chaturvedi and George in alloxan-induced diabetic rats sub-
ase, catalase, glutathione, and glutathione-s-transferase within jected to a sucrose load showed that MC maintained the
normal glucose levels in all experimental groups. It also re-duced The protective effects of MC extract on lipid peroxidation
triglyceride and low-density lipoprotein levels and in-creased induced by immobilization stress in rats were studied. Here
high-density lipoprotein levels. It further improved the too, MC inhibited stress-induced lipid peroxidation in rats,
antioxidant status by lowering the levels of thiobarbituric acid- which was in part due to increasing levels of reduced gluta-
reactive substances and normalizing the levels of reduced thione and increased catalase activity [55]. The anti-oxygenic
glutathione [48]. Teoh et al. studied the nephro protective effect activity of MC pulp and seed powders as well as their various
of MC extract in streptozotocin-induced diabetes in rats. The MC solvent extracts were evaluated. Overall, the MC pulp and
extract was found to reverse streptozotocin-induced thickening of seed powders exhibited stronger anti-oxygenic activity than
the basement membrane of the Bowman’s cap-sule, edema, and other solvent extracts. However, MC pulp and its extracts
hypercellularity of the proximal tubules, ne-crosis, and hyaline showed little higher activity when compared to MC seeds and
deposits. The MC extract also exerted nephro-protective activity its extracts [56]. De et al. determined the effects of fresh
by preventing the oxidative damage involved in the diabetic juices of MC and tomato separately as well as together in
kidney [49]. In a separate study, the livers of the diabetic rats had repairing DNA damage. They found that the combination
hepatocytes showing features of inflammation. These signs of could protect from DNA damage, but not as effectively as
liver damage were found to re-verse with administration of the either agent alone [57].
MC extract [50].
Another important study was to determine the potential cell
reparative effects of MC boiling water extract (MCE) on the HIT- Anti-inflammatory Activity
T15 Hamster Pancreatic beta cells by Xiang and col-leagues. The
high molecular weight fraction of MCE (MHMF, MW > 3 kDa) Immune cells are involved in inflammation-based responses.
exhibited better repairing in alloxan-damaged cells than the low Bitter melon is known to interact with immune cells. Multiple
molecular weight fraction (MLMF, MW < or =3 kDa). Contrary studies have shown that various extracts of MC can act as
to the cell proliferation improve-ments, it was observed that immunomodulators and, hence, can also act as anti-
MLMF showed higher overall activity through the increase in inflammatory agents. Bao et al. looked at the effects of MC
insulin secretion of both nor-mal and damaged cells. Their results treatment in C57BL/6 mice administered with HFD. Once
indicated MCE has sig-nificant repairing activity against again, MC-containing diets reduced the HFD-induced obesity
superoxide anion radicals. Further, their data shows that different as well as insulin resistance. MC was also shown to decrease
components of the extracts may elicit different aspects of macrophage infiltration into epididymal adipose tis-sues
response when it comes to its antidiabetic properties [51]. (EAT) and brown adipose tissues (BAT). MC further reduced
Antioxidant activities of the aqueous extract of seeds of two IL-6 and TNF-α expression in EAT and normalized serum
varieties of MC (MCSEt1 and MCSEt2) were studied in levels of cytokines, suggesting the potential anti-inflammatory
streptozotocin-induced diabetes in rats. The extracts were shown role of MC in obese rats [58]. Further, Xu et al. studied the
to possess protective effects against lipid peroxidation by effects of MC on mitochondrial function during the
scavenging of free radicals, thus reducing the risk of diabetic development of obesity-linked fatty liver in C57BL/6 mice.
complications. The effect was more pronounced in MCSEt1 The mouse model involved feeding with high fat diet (HFD)
compared to MCSEt2 [52]. supplemented with two doses of MC powder {0.5 (HFD +
Kavitha and colleagues evaluated the effects of ethanolic 0.5MC) and 5 (HFD + 5MC) g/kg}. The mice in HFD + 5MC
fruit extract of MC on stress-induced changes in Wister albino group showed less body and tissue weight gain and less
rats. MC pretreatment significantly coun-tered acute stress- hyperglycemia and hyperlipidemia compared to con-trol HFD
induced changes in plasma corticosterone levels and brain group. In both treatment groups, serum interleukin-6
monoamine levels (5-hydroxy tryptamine, norepinephrine, concentration was lower than that in HFD group, though the
epinephrine, and dopamine) [53]. Nerurkar et al. have also serum C-reactive protein concentration was lower only in
investigated the neuroprotective effects of MC on high-fat diet HFD + 5MC group [59].
(HFD)-associated changes in C57BL/ 6 female mice. MC Hsieh et al. suggested that the anti-adiposity effects of
treatment ameliorated HFD-associated changes in BBB MC seed oil is linked to white adipose tissue delipidation,
permeability. The treatment also normal-ized HFD-induced inflam-mation, and browning [60].
glial cells activation and expression of neuroinflammatory The triterpene, EMCD extracted from wild variant of
markers such as NF-κB1, IL-16, IL-22 as well as IL-17R in MC WB24 have been shown to suppress TNFα-induced
brains of MC-dosed mice. Brain oxidative stress was expres-sion of inflammatory markers including inducible
significantly reduced by MC along with reduction in FoxO, nitric oxide synthase (iNOS), NF-κB, protein-tyrosine
normalization of Sirt1 protein expression, and upregulation of phosphatase-1B, and interleukin-1β in FL83B cells.
Sirt3 mRNA expression [54]. Moreover, EMCD exerted more pronounced anti-
inflammatory activity in combination with EGCG [61].
The protective effect of MC in tibial and sural nerve tran- Fang et al. have isolated and characterized a 14-kDa ribo-
section (TST)-induced neuropathic pain were studied in rats. TST nuclease (RNase MC2) from MC seeds. RNase MC2 showed
induce significant development of cold allodynia, me-chanical both cytostatic and cytotoxic properties against MCF-7 breast
and heat hyperalgesia, dynamic mechanical allodynia, and cancer (BC) cells causing nuclear damage, leading to either
functional deficit in walking along with increase in TBARS and early or late apoptosis. Additionally, RNase MC2 induced
TNF-α levels. Administration of MC at vari-ous doses activation of MAPKs such as p38, JNK, and ERK as well as
significantly reduced TST-induced behavioral and biochemical Akt, caspases 8, 9, and 7, enhanced Bax and cleaved PARP
changes [62]. Hsu et al. showed that ethyl acetate extract of MC levels, further contributing to apoptosis [67].
fruit and its saponofiable as well as nonsapon-ifiable fractions In another study, the anticancer activity of MC extract was
reduced pro-inflammatory cytokine and ma-trix studied in MCF-7 and MDA-MB-231 human BC cells as well
metalloproteinase (MMP)-9 levels in Propionibacterium acnes- as in primary human mammary epithelial cells. MC treatment
stimulated THP-1 cells. The intradermal injection of MC extract reduced cell proliferation and induced apoptosis in BC cells
in mice effectively attenuated P. acnes-induced ear swelling and tested, which was accompanied by increased levels of cleaved
granulomatous inflammation [63]. poly (ADP-ribose) polymerase and caspase activation. The
In further studies, Lii and group have shown that the treatment also inhibited the expression of survivin and
etha-nol extracts of MC exerted the greatest decrease of claspin. MC-treated MCF-7 cells accumulated during the G2-
lipopoly-saccharide treatment (LPS)-induced production of M phase of the cell cycle. MC treatment enhanced p53, p21,
nitric oxide and prostaglandin E2 as well as iNOS and pro- and pChk1/2 expression and inhibited cyclin B1 and cyclin
interleukin-1beta expression in RAW264.7 macrophages D1 expression, suggesting a further mechanism involving cell
[64]. Similarly, Kobori et al. also showed that the butanol- cycle regulation [68]. Nagasawa et al. have shown that SHN
soluble fraction of MC extract decreased LPS-induced virgin mice supplimented with free access to hot water extract
TNF-α production in RAW 264.7 cells [65]. of MC (0.5 %) in drinking water developed significantly less
breast tumors. The treatment also inhibited uterine
Anticancer Activities adenomyosis. Moreover, there were no adverse effects ob-
served with MC treatment [69].
In the previous three decades, the research with MC was fo- Eleostearic acid (α-ESA) is a conjugated form of linolenic
cused on its antidiabetic, anti-inflammatory, and anti- acid (CLN) that constitutes up to 60 % of MC seed oil.
oxidative properties. Over the last 10 years, the interest in Grossmann and group have studied the effects of α-ESA on
studying MC in the prevention or treatment of cancer has estrogen receptor (ER)-negative MDA-MB-231 (MDA-wt)
increased. The Warburg effect, which deals with the shift in and ER-positive MDA-ERalpha7 human BC cells. Their stud-
metabolic profile of tumor cells by increasing their depen- ies found that α-ESA inhibited proliferation of MDA-wt and
dence on glycolysis and lactic acid fermentation, also MDA-ERalpha7 cells. α-ESA treatment also induced apopto-
regained prominence during this time. MC was found to be sis in both cell lines (70 %–90 %), whereas CLN resulted in
effective in multiple cancers by affecting multiple pathways only 5 to 10 % apoptosis. Moreover, the addition of α-ESA
including metabolic pathways. In the following section, we also caused loss of mitochondrial membrane potential and
have sum-marized the potential activities of MC and its translocation of apoptosis-inducing factor as well as endonu-
chemical con-stituents against numerous cancers including clease G from the mitochondria to the nucleus. α-ESA treat-
breast, colon, pancreatic, liver, prostate, and skin cancers. ment also caused a G(2)-M arrest in the cell cycle [70].
Lee-Huang et al. have studied the efficacy of a peptide
Breast Cancer MAP30 found in MC on estrogen-independent and highly
metastatic human breast tumor MDA-MB-231. The treatment
Weng et al. have studied a cucurbitane-type triterpene DMC resulted in inhibition of cancer cell proliferation and inhibition of
isolated from wild MC. DMC was found to activate PPAR-γ. HER2 gene expression in vitro. When MDA-MB-231 cells were
The pharmacological inhibition of PPAR-γ protected cells transferred into SCID mice, they developed extensive metastases
from DMC’s anti-proliferative effect, further confirming its and all mice succumbed to tumor by day 46. Treat-ment of the
mechanism of action. DMC suppressed the expression of BC-bearing mice with MAP30 injections resulted in significant
PPAR-γ targets, such as cyclin D1, CDK6, Bcl-2, XIAP, cy- increases in survival, with 20–25 % of the mice remaining tumor
clooxygenase-2, NF-κB, and estrogen receptor-α. It induced free for 96 days [71].
ER stress, as manifested by GADD153 and GRP78 induction.
DMC also inhibited mTOR-p70S6K signaling by downregu- Colon Cancer
lating Akt and activating AMPK. The study suggested in-
volvement of PPAR-γ signaling in the antitumor activity of The utilization of multiple food agents with potential cancer
MC [66]. preventive properties in the daily diet has been attributed to
relatively lower incidence rate of colon cancer in South and Kupradinun et al. examined effect of MC against
East Asian countries. MC is one such food, and hence, it has clastogens, cyclophosphamide (CYP), and DMBA using in
also been studied for its potential role in preventing/treating vivo erythrocyte micronucleus assay in mice and
colon cancer. We have evaluated the potential of methanolic azoxymethane (AOM)-induced colon carcinogenesis in rats.
extracts of MC (whole fruit and skin) on colon cancer stem The study demonstrated that mice fed with MC containing
and progenitor cells. Both the whole fruit and the skin extracts diets showed potential anticancer activity against clastogens.
significantly inhibited cell proliferation and colony formation, Surprisingly, the MC extracts did not show any preventive
where the whole fruit extract showed greater efficacy. In these effects in AOM model with treatment resulting in increased
studies, the cells were arrested at the S-phase of cell cycle. incidence and multiplicities of colon tumors than control [74].
The extracts induced the cleavage of LC3B, but not caspase Fan et al. showed that proliferation of LoVo cells was sup-
3/7, indicating that the cells were undergoing autophagy and pressed by MAP30 in both time- and dose-dependent manner.
not apoptosis. Autophagy was further confirmed by reduced MAP30-induced the apoptotic nuclei observed in LoVo cells.
Bcl-2 and increased Beclin-1, Atg 7, and 12 expression after Additionally, genomic degradation was detected in treated
MC treatment. The treatment also led to reduced cellular ATP cells by using single-cell gel electrophoresis (comet assay).
levels and activation of AMPK. Exogenous additions of ATP Upregulation of Bax and downregulation of Bcl-2 were also
led to revival of cell proliferation even in the presence of MC. observed [75]. Yasui et al. investigated the effects of free fatty
Treatment with MC resulted in decrease in the num-ber, and acids prepared from the MC seed oil in Caco-2 cells. The
size of colonospheres coupled with decreased expres-sion of expression of Bcl-2 was found to be decreased by the treat-
DCLK1 and Lgr5 suggested the activity of extracts on colon ment. Apoptosis regulators GADD45 and p53 were also re-
cancer stem cells [3]. The effects of the same MC extract on markably upregulated by the treatment [76].
anticancer activity and bioavailability of doxorubicin (DOX) Konishi et al. observed that MC fraction extracted with 40
was also studied. MC extract enhanced the effect of DOX on % methanol showed the greatest increase of rhodamine-123
proliferation and sensitized the cancer cells toward DOX upon accumulation in Caco-2 cells. Inhibitory compound in the MC
pretreatment. This synergism was attributed to both an fraction was identified as 1-monopalmitin. They hypoth-
increase in drug uptake and reduction in drug efflux. Reduced esized that that certain types of monoglyceride might modu-
expression of multidrug resistance conferring pro-teins late the bioavailability of drugs by inhibiting efflux mediated
(MDRCP) P-glycoprotein, MRP-2, and BCRP was also by P-gp, which matched the MDR-based claims of Kwatra et
observed. Suppression of DOX efflux in MDCK cells over- al. [77]. The inhibitory activity of 1-monopalmitin and re-
expressing the three MDRCP individually suggests that MC lated compounds suggested that the P-gp inhibition activity
extract is a potent inhibitor of MDR function. MC extract also was independent of degree of unsaturation of fatty acid
suppressed PXR (a xenobiotic sensing nuclear receptor that instead depending on chain length, with the monoglyceride
controls the expression of MDRCP) promoter activity. These structure deciding the ultimate inhibition of P-gp efflux.
results suggested that MC can enhance efficacy of Monoglycer-ides could therefore alter drug pharmacokinetics
convention-al cancer chemotherapy [4]. by inhibiting efflux [78].
Li et al. also showed that the methanolic extracts of MC Deep et al. tested MC fruit extract (2.5 % and 5 % of
exerted cytotoxic activity on Hone-1 (nasopharyngeal carci- standard mice feed) against 3,4 benzo(a)pyrene [B(a)P]-in-
noma), AGS (gastric adenocarcinoma), HCT-116 (colorectal duced forestomach papillomagenesis in Swiss albino mice. A
carcinoma), and CL1-0 lung adenocarcinoma in a time- significant decrease in tumor burden was observed after MC
dependent manner. MC treatment induced apoptosis by acti- treatment. Also, total tumor incidence reduced by 80 % to 90
vation of caspase-3, enhanced cleavage of downstream DFF45 % in short-term treatment and close to 75 % in long-term
and PARP, resulting in DNA fragmentation and nucle-ar treatment [79]. Kohno et al. studied the effects of MC contain-
condensation. Bax expression was increased, whereas Bcl-2 ing diet in AOM-induced colonic neoplasms in male F344
was decreased in all treated cells, indicating the involvement rats. The treatment reduced both the incidence and the multi-
of mitochondrial pathway in MC activity [72]. Another study plicity of colonic adenocarcinoma. The inhibition was associ-
identified a resistance-like protein P-B from MC by using ated with increased content of CLN in colonic mucosa and
high-speed counter-current chromatography (HSCCC) liver [80]. In another study, Kohno et al. had studied the die-
coupled with a reverse micelle solvent system. Fractions I and tary effects of CLN isolated from the seeds of MC against
III were identified as resistance-like protein P-B and AOM - induced colonic aberrant crypt foci (ACF) in male
pentatricopeptide repeat-containing protein, respectively. F344. Dietary administration of CLN caused a significant re-
However, fraction II, which is thought to be a new protein, duction in the frequency of ACF, lowered the PCNA index,
has not yet been identified. The fraction II had excellent anti- and induced apoptosis in ACF. The possible mechanism of
cancer activity (IC50 value 0.116 mg/ml for 48 h treatment) chemo-preventive activity was hypothesized to be modulation
on human gastric cancer cell line SGC-7901 [73]. of cryptal cell proliferation activity and/or apoptosis [81].
Pancreatic Cancer Pitchakarn et al. have shown that MC leaf extract and
Kuguacin J (KuJ) exerted growth inhibition through a G1-
The efficacy of MC juice against pancreatic carcinoma cells arrest of cell cycle and induced apoptosis in androgen-
both in culture and MiaPaCa-2 tumors in nude mice was independent LNCaP cells. MC leaf extract and KuJ also reduced
vestigated. Their results showed that MC (2–5 % v/v) de- the expression levels of prostate-specific antigen (PSA) and
creased cell viability in all tested cell lines by inducing strong androgen receptor (AR). These two together induced P53 pro-
apoptotic cell death caused by activation of caspases. It was tein level upon treatment. Additionally, the inhibition of p53
also found to activate AMPK, alter expression of Bcl-2 family by RNAi confirmed the mechanism partially to be p53-depen-
members, and release cytochrome-c into the cytosol. Addi- dent. MC leaf extract and KuJ were less toxic in normal pros-
tionally, the treatment with MC juice resulted in reduced tate cells (PNT1A); hence, these effects were prostate cancer
survivin and XIAP expression but increased p21, CHOP, and specific [86]. In another study, the same group studied the
phosphorylated MAP kinases levels. Oral administration of anti-invasive effects of MC on a rat prostate cancer cell line
lyophilized MC juice inhibited MiaPaCa-2 tumor xenograft (PLS10) and found that MC leaf extract significantly reduced
growth by 60 % without noticeable toxicity in nude mice. IHC the migration and invasion ability of cells in vitro. The MC
analyses of xenografts suggested that MC also inhibits prolif- extract successfully inhibited MMP-2, MMP-9, and uPA se-
eration, induces apoptosis, and activates AMPK in mouse cretion from PLS10. It also markedly increased the mRNA
model [82]. expression of TIMP-2. The collagenase type IV activity was
also partially inhibited by MC leaf extract. Intravenous inoc-
ulation of PLS10 to nude mice resulted in 20 % deaths, but a
Liver Cancer
100 % survival rate in the mice given MC leaf extract. The
treatment did not affect the incidence rate of lung metastasis
Fang et al. have shown that RNase MC2 restricted cell prolif-
but reduced the percentage of lung area occupied by metasta-
eration and induced apoptosis in HepG2 cells. RNase MC2
tic lesions [87].
caused S-phase cell cycle arrest, induced phosphorylation of
Xiong et al. also isolated a protein from MC seeds, which
ERK and JNK as well as caused activation of both caspase-8
they called MCP30. MCP30 - induced apoptosis in PIN and
and caspase-9 mediated apoptosis. RNase MC2 treatment also
PCa cells in vitro and also suppressed the PC-3 growth in vivo
reduced Bcl-2 and enhanced Bak expression. RNase MC2
with minimal effects on normal prostate cells. MCP30
suppressed tumor growth by inducing apoptosis in the HepG2
inhibited HDAC-1 activity and promoted histone-3 and
xenograft-bearing nude mice. RNase MC2 mediated apopto-
histone-4 protein acetylation. The treatment also induced
sis was confirmed by enhanced number of caspase-3-, PARP-,
PTEN expression in both cell lines, resulting in inhibition of
and TUNEL-positive cells in the tumor tissues of HepG2
Akt phosphorylation. MCP30 inhibited Wnt signaling by re-
xenograft-bearing nude mice [83]. Further studies have been
duced nuclear accumulation of β-catenin and decreased the
performed to establish the efficacy of MAP30 against human
levels of c-Myc and Cyclin-D1 [88].
hepatocellular carcinoma HepG2 cells and HepG2-bearing
mice. The mechanistic studies showed the involvement of
Skin Cancer
both extrinsically (caspase-8) as well as intrin-sically
(caspase-9) induced apoptosis in MAP30-treated cells. The
Agrawal and Beohar have shown that the treatment with MC
peptide was also found to be effective in HepG2 tumor-
fruit and leaf extract in Swiss albino mice resulted in reduced
bearing nude mice [84].
tumor incidence, tumor burden, and cumulative number of
papillomas when compared to untreated controls. In a mela-
Prostate Cancer noma model, the mice receiving either fruit or leaf extracts
showed improved life spans and reduced tumor volumes [89].
Ru et al. have evaluated the of MC against human prostate Further, Ganguly et al. have also evaluated the anticar-
cancer (PC3 and LNCaP) cells. The cancer cells treated with cinogenic effect of aqueous extract of MC fruit in skin carci-
MC extract got arrested during the S-phase of the cell cycle. nogenesis mouse model. Though high doses of extract had an
MC treatment also modulated cyclin D1, cyclin E, and p21 adverse effect on the health of the animals, but on reducing
expression within the cells. The treatment also increased Bax the dose by half, the extract reduced the development of skin
expression and induced PARP cleavage. Oral gavage of MC tumors and increased life expectancy. Hence, this study
extract in TRAMP mice delayed the progression to high-grade showed both the potential positive effects and potential toxic
prostatic intraepithelial neoplasia by 31 %. Prostate tissue effects upon overdosing [90].
from MC extract-fed mice displayed approximately 51 % re- Singh et al. have studied the potential of different MC plant
duction in the expression of proliferating cell nuclear antigen parts (peel, pulp, seed, and whole fruit) extracts on mouse model
(PCNA) [85]. of skin papillomagenesis. Topical use of MC against
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Philippine Journal of Internal Medicine Original Article
The MOCHA DM study: The Effect Of MOmordica CHArantia

Tablets on Glucose and Insulin Levels During the Postprandial
State Among Patients with Type 2 Diabetes Mellitus*
Sheila T. Lim, M.D.1 Cecilia A. Jimeno, M.D.2
Elvie B. Razon-Gonzales, M.D.3 and Marie Ellaine N. Velasquez, M.D.4
Abstract
Background: The worldwide prevalence of diabetes is rising both tablets, and d) placebo. Subjects were fasted for 8 hours and given
in developed and developing countries like the Philippines where standardized meal after taking assigned drug. Fasting blood sugar
4.6% of the population has the disease. Because of the high cost of and plasma insulin were determined at 0 minute, 15 minutes, 30
medications, the use of dietary supplements has also increased. minutes, 1 hour, 2 hours, and 4 hours after the given dose.
Momordica charantia (ampalaya), is a well known plant with Statistical analysis was done using analysis of variance (ANOVA),
glucose-lowering properties which have been demonstrated by Kruskal-Wallis, Bonferroni and Ranksum pairwise comparison tests.
previous clinical studies. Its mechanism of action and
pharmacologic properties are not yet well understood, and hence
continues to be used as a supplement rather than as a standard Results: 40 participants completed the study with no adverse
drug for the treatment of Type 2 diabetes. events. There is significantly higher insulin levels (p value = 0.0756)
and significantly lower plasma glucose levels (p value = 0.024) for
the 100 mg/kg/day ampalaya group (but not with the other dose
groups) versus placebo after 15 minutes.
Objective: To compare the effect of Momordica charantia (MC) and
placebo on insulin and glucose among type 2 diabetic patients
using different doses Conclusion: In this single dose study in type 2 diabetic patients,
100 mg/kg/day of ampalaya showed incremental dose effect and
Methodology: A double-blind, placebo-controlled, randomized trial provided more rapid and shorter-lived stimulation of insulin
was conducted on 40 diabetic subjects who randomly received secretion than placebo, resulting in lower meal-related glucose
single oral doses of either: a) 60 mg/kg/day, b) 80 mg/kg/day, c) excursions.
100 mg/kg/day MC
Introduction of these complications are possible by adequate control of blood

glucose using different pharmacologic agents.
Diabetes mellitus is the new epidemic. The prevalence of There are currently many classes of pharmacological agents
diabetes for all age groups worldwide was estimated to be 2.8% in for type 2 diabetes mellitus such as sulfonylureas, biguanides,
2000, and to rise to 4.4% by the year 2030. 1 The total number of thiazolidinediones and alpha glucosidase inhibitors. However, these
people with diabetes is projected to increase from 171 million in drugs have also shown adverse effects, including hypoglycemia,
2000 to 366 million in 2030, with the Philippines ranking 9 th among lactic acidosis, and diarrhea.5 Studies of functional food
the top most countries with the greatest number of diabetic components with blood glucose-controlling effects are in progress,
patients.1 According to local data, the prevalence rate of diabetes in and many useful components have been discovered in plants.6-7 In
the Philippines is 4.6%, based on fasting blood sugar (FBS) > 125 the Philippines, and other Asian and developing countries, the uses
mg/dL or a previous history of diabetes.2 of natural drugs, such as plants and herbal remedies to treat
diseases is very common. These populations are linked with the
Manypatientsdevelopmicrovascularand use of traditional medicines, due to their efficacy or due to the high
macrovascular complications that can cause significant morbidity cost of pharmaceutical production.5-7
and mortality.3,4 The prevention or slowing down
The annual prevalence of dietary supplement use increased
*Presented at the 15th Congress of the ASEAN Federation of Endocrine from 14.2% in 1998 – 1999 to 18.8% in 2002 based on data from
Societies November 2009 at Bangkok, Thailand; Best Poster in Clinical Science,
National Institute of Health, February 2009 the United States.8 In a local study done by Tanchoco et al., it was
estimated that 23% use nutraceutical products,9 and ampalaya
1Fellow, Section of Endocrinology, Diabetes and Metabolism, Department of
Medicine, UP-Philippine General Hospital

supplements are among the top five of the most commonly used
herbal medication.10,11,12,13,14
2Consultant, Section of Endocrinology, Diabetes and Metabolism, Department
of Medicine, UP-Philippine General Hospital

Momordica charantia, is a well known plant for its glucose-
3Resident, Department of Medicine, UP-Philippine General Hospital lowering properties.15,16 However, the sample sizes of the
investigations were small, with vaguely described
4Resident, Department of Medicine, UP-Philippine General Hospital
Volume 48 Number 2 July-

September, 2010
19
Lim S T, et al charantia tablets has not been determined, especially as it relates
to blood glucose and insulin levels at different doses. It has only
been shown that Momordica charantia has insulin-like properties
without the documentation of the actual levels of insulin. It is the
purpose of this study to provide physicians with significant data on
the comparative efficacy of Momordica charantia tablets and
placebo as glucose lowering agents among subjects, emphasizing
its effect on blood glucose and insulin levels. This research seeks to
integrate the existing data on Momordica charantia and offer
additional inputs to fill in the gaps in knowledge, thereby improving
its clinical use.
Objectives
The objective of this study was to compare the effect of
Momordica charantia tablets and placebo on insulin secretion and
glucose excursions among type 2 diabetic patients using different
doses. Specifically, this study aimed
18-19
statistical analysis. Some of the researches did not even have

control groups. There were no randomized trials that were included.
Subsequently, no conclusions on effectiveness were made.
The mechanism of action of the hypoglycemic effect brought

about by Momordica charantia has been variedly described.
According to experimental evidence, whole plant-aqueous extract
contains a hypoglycemic principle, which is an insulin-like peptide
(polypeptide p-insulin) or an alkaloid, variously called foetidin,
momordicin, or charantin.17 It is hypothesized that this plant extract
mimics or improves insulin action at the cellular level, and may
even have an extra-pancreatic mode of action. 17 Theoretical
mechanisms have also been proposed. These include increased
insulin secretion, tissue glucose uptake, liver muscle glycogen
synthesis, glucose oxidation, and decreased hepatic
gluconeogenesis.15
The leaves of Momordica charantia, particularly of the Makiling variety, produced the most consistent hypoglycemic properties with acceptable safety profiles compared
to other parts of the plant. It has undergone
several clinical trials.18, 20, 21 Based on these studies, it was

determined that the mean difference in fasting blood sugar of
40.8% from baseline compared to 36.8% for the glibenclamide
group at 12 weeks using a dose of 100mg/ kg/day of ampalaya
tablets. Mean HbAic also showed a 4.8% decrease from baseline
using Momordica charantia, compared to 4.2% for the
glibenclamide group.21
Clinical Significance
Despite these clinical trials however, the joint position
statement of the Philippine Society of Endocrinology and
Metabolism, Philippine Diabetes Association, Institute for Studies
on Diabetes Foundation, and Philippine Center for Diabetes
Education Foundation still does not consider ampalaya-derived
products as part of the standard care for diabetes in the absence of
more research data. The pharmacodynamics of the Momordica
The MOCHA DM 2. Newly diagnosed diabetes mellitus AND is drug naïve
study
OR is NOT on anti-diabetic agents for the past 3 months
to: a) indirectly demonstrate the mechanism of action of 3. Glycemic criteria: Glycosylated hemoglobin
Momordica charantia by determining its effect in insulin levels since (HbA1c) ≥ 6.5% and ≤ 9.0% and fasting blood glucose
theoretically, ampalaya extracts have been shown to improve of ≥126 mg/dL but ≤ 205 mg/dL
insulin levels; and b) determine the time of peak effect and onset of 4. Patient is ≥ 21 years old but ≤ 65 years old
efficacy of Momordica charantia tablets versus placebo using
different doses of 60 mg/kg/ day, 80 mg/kg/day and 100 mg/kg/day Exclusion criteria included:
among patients with type 2 diabetes mellitus during the 1. Unstable co-morbidities
postprandial state. This will be significant in establishing the 2. Significant acute illness in the previous 2 weeks before
dosage intervals of Momordica charantia tablets in maximizing its the start of the study
medical use. 3. History of diabetic emergency
4. History of corticosteroid use, herbal medications or any
Methodolgy other drugs that may affect glucose metabolism within
the preceding 6 months
Research Design 5. Hypersensitivity to the drug
This study was a double-blind, placebo-controlled, 6. Presence of conditions affecting compliance, e.g.,
randomized trial conducted in the Philippine General Hospital, from drug or alcohol abuse or psychiatric illness
June to December 2008. 7. Recipient of another investigational drug during and
preceding 6 months
Study population 8. Pregnancy
Subjects were recruited from the outpatient clinics of the 9. Unwillingness to participate in the study
University of the Philippines-Philippine General Hospital and were
enrolled to the study after fulfilling the following inclusion criteria: Materials and Methods
1. Data collection
1. Type 2 diabetes mellitus based on the American Diabetes
a. Determination of clinical data. Volunteers were asked to sign a
Association (ADA) Criteria for Diabetes Mellitus, 2007
written consent after explaining the objectives and procedures
(APPENDIX B)
involved in the study. They were then interviewed upon entry to the
study for demographic data, risk factors
20 Volume 48 Number 2 July-September, 2010

The MOCHA DM study Lim S T, et al
for coronary artery diseases such as smoking, family history of d. Discontinuation of testing. Study therapy was immediately
diabetes, presence or absence of sedentary lifestyle (being on discontinued for the following reasons:
his/her feet for <4 hours a day), and frequency of regular exercise • Withdrawal of informed consent (subject’s decision to
(30 minutes of exercise 3-4x/week). withdraw for any reason)
• Hypoglycemia
b. Physical examination and determination of baseline
- defined as symptoms suggestive of hypoglycemia (e.g. sweating,
measurements. Subjects underwent a standard physical
shaky, increased heart rate, confusion, dizziness, lightheadedness,
examination. Vital signs were measured, including the blood
or hunger) in the absence of environmental factors known to
pressure.
contribute to hypoglycemia (i.e. excess physical activity, concurrent
A non-elastic tape measure was used to measure waist
illness, or missed or delayed meal) and/or documented fasting
circumference at the level of the iliac crest, and hip circumference
blood glucose values ≤
at the level of the largest circumference or the greater trochanters.
50mg/dL (2.8 mmol/L)
The waist-to-hip ratio was used as an index of upper-body versus
lower-body adiposity. Body mass index (BMI) was calculated as
Outcome measures
weight (in kilograms) divided by height (in meters) squared.
1. The primary outcome was the change in glucose and insulin
level 4 hours after administration of treatment.
c. Screening laboratory tests. Blood was extracted for baseline 2. Adverse events were monitored and recorded based on
serum HbAic, FBS, blood urea nitrogen (BUN), creatinine, AST, spontaneous reporting by subjects and direct interview both of
ALT, complete blood count (CBC) levels and were analyzed using which will be conducted by the investigating physician (Appendix
the COBAS Integra 400 Plus Chemistry Analyzer. C). Tolerability parameters and tablet acceptability by subjects was
based on the organoleptic qualities of the tablet and ease of
swallowing conducted by the physician-investigator (Appendix D).
2. Randomization. Random allocation was done using a computer- Subjects were evaluated upon entry to the study, and at the end of
generated sequence of random numbers (Stata® version 6.0). To the study.
conceal allocation, medications were prepared by a third party. The
treatment and placebo tablets were matched in appearance and
Statistical analysis. The intent-to-treat analysis was the primary
packaged in unpackaged blisters.
analysis for this study. Only protocol-compliant subjects were
included in the secondary analysis. The primary variables for the
study were change in glucose and insulin levels. The end points
3. Study Proper
were summarized using proportions and analyzed using one way
a. Test Drug. Momordica charantia tablets, from dried ampalaya and repeated measures ANOVA and Kruskal Wallis tests.
leaves of the Makiling variety, was obtained from a local licensed Bonferroni and Ranksum pairwise comparison tests were also used
pharmacy in Manila. Commercially, it is available as Amargozin for the statistical analyses.
tablets. The dosage form was 500 mg/tablet. The dummy placebo
Ethical considerations. Ethical approval for this study was obtained
tablets were formulated by an industrial pharmacy to simulate the
from the Ethics Committee of the University of the Philippines
500 mg Momordica charantia tablets.
(Research Implementation and Development Office, College of
Medicine-Philippine General Hospital, University of the Philippines).
b. Study Protocol. The study was conducted at the Medical
Research Laboratory of UP-PGH under the supervision of trained
personnel. Volunteers were randomly allocated to one of four
groups according to single oral doses of Momordica charantia
tablets at 60, 80, or 100 mg/kg/day and placebo. Subjects were 20
21
17-21
fasted for 8 hours before each treatment period. At time 0, they

were given either one of the three doses of Momordica charantia or The main ethical issue for this study was the possible adverse effects of the intervention of Momordica charantia tablets. Based on the previous toxicity studies done in
animal and human subjects , the following adverse effects were
placebo after which they were then given a standard meal

consisting of 56.6 g carbohydrate, 19.5 g protein, 11.5 g fat and 395 noted: gastric pain, nausea, vomiting, diarrhea, dyspnea,
kcal. The subjects were permitted only water and minimal physical headache, dizziness, and rashes. These adverse effects were
activity for 4 hours. observed during the third week of the study with no interventions or
medical treatment being needed to address the adverse effects.
c . Study evaluations . Plasma glucose and insulin concentrations

Any adverse event that was incurred during the study period,
were measured at multiple time-doses from pre-dose to 4 hours
was addressed immediately and was compensated by the
post-dose: namely 0 minute, 15 minutes, 30 minutes, 1 hour, 2
investigators.
hours, and 4 hours after the given dose. Fasting blood sugar and
blood insulin levels were determined using standardized kits.
Results
A total of 40 Filipino healthy Type 2 diabetic patients
participated in the study, of which 18 males and 22 females.
September, 2010
21
Lim S T, et al The MOCHA DM
study
Table I. Baseline demographic characteristics of the subjects in the study population.

University of the Philippines-Philippine General Hospital, 2009 (N = 40).
Variable Placebo Momordica charantia Momordica charantia Momordica charantia p value

(Mean, S.D.) (n = 10) 60mg/kg 60mg/kg 100mg/kg
(n = 10) (n = 10) (n = 10)
Age (years) 55.7 ± 4.9 55.3 ± 5.0 57.8 ± 4.8 57.8 ± 4.8 0.74
Weight (kg) 60.9 ± 5.7 63.1 ± 7.0 62.4 ± 7.7 65.5 ± 7.6 0.74
Height (m) 1.55 ± 0.08 1.57 ± 0.07 1.58 ± 0.10 1.59 ± 0.11 0.40
Waist circumference (cm) 90.4 ± 6.8 93.45 ± 7.0 90.2 ± 6.2 93.85 ± 6.5 0.86
Waist-to-hip ratio 0.94 ± 0.05 0.96 ± 0.03 0.95 ± 0.03 0.95 ± 0.05 0.33
Body Mass Index (BMI) (kg/m2) 25.55 ± 2.05 25.60 ± 2.25 25.60 ± 2.25 26.00 ± 2.4 0.15
HbAic (%) 7.72 ± 0.8 7.44 ± 1.0 8.08 ± 0.8 7.86 ± 1.1 0.83
Fasting blood sugar (mg/dl) 174.8 ± 8.8 171.9 ± 16.7 172 ± 20.4 170.1 ± 16.5 0.14
Serum insulin (uIU/ml) 22.12 ± 11.7 22.45 ± 6.7 25.11 ± 6.5 24.65 ± 9.6 0.27
Table II. Analysis of variance of average insulin levels of subjects using different
doses of Momordica charantia tablets and placebo 4 hours after treatment.
Average Insulin Levels

Group Baseline 15 mins 30 mins 1 hr 2 hr 4 hr
(uIU/ml) (uIU/ml) (uIU/ml) (uIU/ml) (uIU/ml) (uIU/ml)
Placebo 22.12 38.81 45.82 44.26 40.12 28.93
60 mg/kg/day 22.45 37.29 46.63 42.55 38.65 29.97
80 mg/kg/day 25.11 40.3 51.09 42.92 40.55 31.82
100 mg/kg/day 24.35 48.49 53.43 45.71 39.72 29.11
Kruskal Wallis 0.8109 0.0402 * 0.2657 0.3365 0.3151 0.2852
p-value
*Significant difference across groups if p-value < 0.05
The mean age of the participants is 56.6 ± 1.28 years with majority Table 2 shows that there is a significant difference in average
being overweight or obese with mean body weight of 62.98 ± 1.92 insulin levels across the four groups at the 15 minute observation
kg, BMI of 25.6 ± 0.23 kg/m2 and WHR of 0.95 point. The pairwise comparison test showed that the insulin levels
± 0.01, respectively. Baseline HbA1c, FBS and insulin levels were using the 100 mg/kg/day dose are significantly higher than that of
also determined as follows: 7.78 ± 0.27 %, 172.2 ± 1.8 mg/dl, and the 60 mg/kg/day dose (Ranksum test p value = 0.0091) at 5%
23.51 ± 1.52 uIU/ml. Table 1 summarizes the other demographic level of significance. There is also significantly higher insulin levels
characteristics of the subjects. for the 100 mg/ kg/day group versus placebo (Ranksum test p
Table 1 shows no significant difference in the baseline value = 0.0756) at 10% level of significance. In analyzing the insulin
characteristics of the subjects. All 40 participants completed the levels, Kruskal Wallis test was used rather than ANOVA because
study. No clinically meaningful changes in vital signs were reported the variances across groups are significantly different at 5% level of
during the study or at the end-of-study evaluations. No reports of significance for each observation period.
adverse events were noted. The placebo and ampalaya tablets
were generally acceptable and well-tolerated by the subjects. Mean plasma insulin concentrations peaked at 30 minutes
postdose for both the placebo and the three treatment groups. After
All active drug treatments increased plasma insulin levels in reaching the peak concentrations, mean plasma insulin decreased
response to a standardized breakfast relative to placebo. During in all groups and was similar to placebo by 1 hour postdose (Figure
the initial 15-minute postmeal interval, 100 mg/kg/day dose of 1).
Momordica charantia tablets significantly produced a more The rapid effects of the 100 mg/kg/day dose of ampalaya
increased induction of insulin secretion than 80 mg/ kg/day, 60 tablets resulted in significantly higher average plasma insulin over
mg/kg/day and placebo (p ≤ 0.10) (Table 2), with mean rates of rise the early 0- to 0.25-h postdose intervals (36.42 ± 15.40 uIU/ml)
in insulin secretion of 48.49 ± 9.26, 40.3 compared with ampalaya doses of 80 mg/kg/day (32.70 ± 9.96
± 6.28, 37.29 ± 6.47, and 38.81 ± 16.76 uIU/ml, respectively. uIU/ml), 60 mg/kg/day (29.87 ± 9.95

was significantly lower with the 100 mg/kg/day dose of Momordica

Figure 1. Mean plasma insulin concentrations after treatments with charantia tablets (210.50 ± 51.61 mg/dl) than with either the 80
60 mg/kg/day, 80 mg/kg/day, 100 mg/kg/day ampalaya tablets and mg/kg/day (232.50 ± 39.16 mg/dl) or 60 mg/ kg/day doses (239.80
placebo administered postprandially. ± 20.61 mg/dl) and placebo (240.10
± 67.91 mg/dl) (Figure 2). Plasma glucose concentrations relatively
returned to predose levels by 4 hours with ampalaya treatment
using the 80 mg/kg/day and 100 mg/ kg/day, whereas the 60
mg/kg/day dose ampalaya-treated groups and placebo did not
reach the predose glycemic levels.
Compared with ampalaya tablets at 80 mg/kg/day, 60

mg/kg/day, and placebo, Momordica charantia at 100 mg/kg/day
Figure 2. Mean plasma glucose concentrations after treatments produced lower average plasma glucose concentrations (188.48 ±
with 60 mg/kg/day, 80 mg/kg/day, 100 mg/kg/day ampalaya 35.97 mg/dl) over the 0- to 4-hour postdose interval (Figure 2;
tablets and placebo administered postprandially. 197.83 ± 33.88 mg/dl versus 80 mg/kg/day dose, 204.27 ± 31.39
mg/dl versus 60 mg/kg/day dose at 207.03 ± 43.82 mg/dl versus
placebo).
Discussion
Recently, emerging data have looked into the significance of
meal time glycemia on overall glycemic control and cardiovascular
risk for mortality.22, 23 Studies show that early insulin secretion plays
uIU/ml) and placebo (30.46 ± 16.48 uIU/ml). Late average plasma a critical role in maintaining normal glucose homeostasis. 24 Thus,
insulin levels (1 – 4 hour postdose) after Momordica charantia at all loss of early insulin secretion initially leads to post-prandial
doses were similar to levels observed with placebo. The average hyperglycemia which, as the disease progresses, worsens to
insulin response over the entire 0- to 4- hour postdose interval was clinical hyperglycemia.25 Strategies that enhance early insulin
8.6% higher with ampalaya tablets using the 100 mg/kg/dose than secretion improve glucose tolerance and represent a novel and
placebo (40.14 ± 14.10 vs 36.68 ± 26.05 uIU/ml). more physiologic approach to improving glycemic control in patient
with type 2 diabetes mellitus. However, most oral anti-diabetic
Mean plasma glucose concentrations rose after breakfast and agents have little or no effect on meal-related glucose excursions. 26
reached peak levels 1 hour postdose after all treatments and In contrast, this study shows that Momordica charantia tablets
placebo (Table 3). appear to increase the first phase of insulin secretion in response to
Table 3 shows that there is a significant difference in average a meal.
plasma glucose levels after 15 minutes. The 100 mg/kg/day group
has the lowest average plasma glucose levels after 15 minutes.
The Bonferroni Pairwise comparison test shows that doses at 100 The results of this study compared the effects Momordica
mg/kg/day and 60 mg/kg/day (p value = 0.048), 100 mg/kg/day and charantia tablets at different doses versus placebo on the early and
placebo (p value = 0.024) are significantly different. extended profiles of mealtime insulin secretion in individuals with
type 2 diabetes mellitus, as well as the associated effects on the
The peak of the mean glucose postdose concentration glycemic response to a meal. In
Table III. Analysis of variance of average plasma glucose levels of subjects using different doses of
Momordica charantia tablets and placebo 4 hours after treatment.
Average plasma glucose levels

Diff Diff
Group Baseline 15 mins 30 mins 1 hr 2 hr 2 hr
Base - Base-
(uIU/ml) (uIU/ml) (uIU/ml) (uIU/ml) (uIU/ml) (uIU/ml)
Placebo 174.8 200.1 224.2 240.1 218.1 184.9 25.3 49.4
60 mg/kg/day 171.9 198 221.1 239.8 214.3 180.5 26.1 49.2
80 mg/kg/day 172 184.8 208.4 232.5 207.6 179 12.8 36.4
100 mg/kg/day 170.1 175.5 196 210.5 200.9 177.9 5.4 25.9
Anova F p- 0.933 0.0121* 0.036* 0.4804 0.8206 0.9255 0.0032* 0.0338*
*Significant difference across groups if p-value < 0.05

September, 2010
23
Lim S T, et al The MOCHA DM
study
these subjects, ampalaya tablets using the 100 mg/kg/day dose

Activities. Biol. Pharm. Bull. 29 (6): 1126 – 1131 (2006).
showed higher insulin levels compared to lower doses of ampalaya 6. Oishi, Yuichi. Sakamoto, Tatsuaki. Udagawa, Haruhide.
and placebo. Plasma insulin concentrations also comparatively Taniguchi, Hironobu. Kobayashi-Hattori, Kazuo. Ozawa, Yoshio.
returned to pre-prandial levels more promptly with the 100 Takita, Toshichika: Inhibition of Increases in Blood Glucose and
mg/kg/day dose of ampalaya, resulting in lower overall insulin Serum Neutral Fat by Momordica charantia Saponin Fraction.
Biosci. Biotechnol. Biochem., 71 (3), 735 – 740, 2007.
exposure relative to lower doses and placebo.
7. Harinantenaina, Liva. Tanaka, Michi. Takaoka, Shigeru. Oda,
The ampalaya tablets showed a consistent effect with the Munehiro. Mogami, Orie. Uchida, Masayuki. Asakawa,
onset of action within 15 to 60 minutes. This is similar to previous Yoshinori: Momordica charantia Constituents and Antidiabetic
studies done on extracts of Momordica charantia.19 However, the Screening of the Isolated Major Compounds. Chem. Pharm. Bull., 54
relative increase in insulin levels was short-lived as it was only able (7): 1017, 2006.
8. Kelly, Judith P. Kaufman, David W. Kelley, Katherine.
to significantly increase insulin levels during the first 15 minutes
Rosenberg, Lynn. Anderson, Theresa E. Mitchell, Allen A. Recent
with an increasing trend until the 1 st hour postdose, as compared Trends in Use of Herbal and Other Natural Products. Arch Intern
with the duration of 4 to 12 hours noted in other studies. 27,28 But it is Med., 165: 281, 2005
worth mentioning that the substances used in the previous studies 9. Tanchoco, CC. Cruz, AJ. Survey on the Awareness, Perceptions
were that of plant extracts from different parts of the ampalaya plant and Extent of Usage of Nutraceuticals and Dietary Supplements in
Metro Manila. DOST Food and Nutrition Research Institute. 1998.
and not in a constituted tablet form solely from the leaves of
Momordica charantia. 10. Bilano, Ver Luanni. Margallo, Divine J. Vistal, Kristine A.
Beliefs and Practices re: Herbal Supplements of Consumers in
The importance of early insulin secretion in the control of Barangay 59 Zone 6, District 2, Caloocan City. 2006. Unpublished.
mealtime glucose excursions was evident in the early postdose 11. Baldo, Sarah Jane. Calvo, Aileen. An Assessment of the Use of
Herbal Medicines Among Informal Sectors in Paco, Manila. 2004.
glycemic profiles and the average overall glucose exposure
Unpublished.
resulting from each drug treatment. Aside from demonstrating 12. Conde, May Flor. Mercado, Janette. Rebruriano-Bon, Beryl. An
greater overall insulin levels, 100 mg/kg/day dose of ampalaya was Assessment of the Use of Herbal Medicines Among Informal Sectors
more effective than lower doses of Momordica charantia and in Malate, Manila. 2004. Unpublished.
placebo in reducing mealtime glycemic excursions within the 4 hour 13. De los Reyes, Jo-Ann. Santiago, Menina Barbara. An Assessment
of the Use of Herbal Medicines Among Informal Sectors in San
postdose, with a more rapid return to pretreatment plasma glucose
Andres, Manila. 2004. Unpublished.
levels. 14. Francisco, Charlene. Sison, Karina. An Assessment of the Use of
Herbal Medicines Among Informal Sectors in Intramuros, Port Area
conclusion and Ermita, Manila. 2004. Unpublished.
15. Yeh, Gloria Y. Eisenberg, David M. Kaptchuk, Ted J. Phillips,
In conclusion, in this study involving 40 adult type 2 diabetics, Russell S. Systematic Review of Herbs and Dietary Supplements for
Momordica charantia tablet given as a single dose using the 100 Glycemic Control in Diabetes. Diabetes Care 26: 1277 – 1294, 2003.
mg/kg/day dose (12 tablets of 500 mg/ tab), showed an incremental
16. Dans, Antonio Miguel Limcaco. Villarruz, Maria Vanessa C.
dose effect and provided
Jimeno, Cecilia A. Javelosa, Mark Anthony U. Chua, Joel.
a more rapid (15 minutes) and shorter-lived (30 minutes) Bautista, Rhida. Velez, Gywneth Giselle. The Effect of Momordica
stimulation of insulin secretion than placebo, resulting in lower charantia capsule preparation on glycemic control in Type 2 Diabetes
meal-related glucose excursions. This herbal product has the Mellitus. Journal of Clinical Epidemiology.
potential to be used for reducing post-meal hyperglycemia. 17. Ojewole, John AO. Adewole, Stephen O. Olayiwola, Gbola.
Hypoglycemic and hypotensive effects of Momordica charantia
aqueous extract in rats. Cardiovasc J. South Afr 2006; 17: 227 – 232.
References 18. Purificacion, Jaime M. Cortes-Maramba, Nelia P. Ho, Herbert.

Phase 3 Clinical Trial: Comparative efficacy and safety study of
1. Wild, Sarah. Roglic, Gojka. Green, Anders. Sicree, Richard. Momordica charantia (ampalaya) leaf tablet and glibenclamide
King, Hilary: Global Prevalence of Diabetes. Estimates for the year among type 2 diabetes mellitus patients (2000 – 2004). Unpublished.
2000 and projections for 2030. Diabetes Care 27: 1407 – 1053, 2004.
19. Rosales, Reynaldo F. Fernando, Ricardo E. An Inquiry to the
2. Dans, Antonio L. Morales, Dante D. Velandria, Felicidad. Abola, Hypoglycemic Action of Momordica charantia among Type 2
Teresa B. Roxas, Artemio, Jr. Punzalan, Felix Eduardo R. Sy, Diabetic Patients. Phil. J. Internal Medicine. 39: 213 – 216. July
Rosa Allyn G. Paz-Pacheco, Elizabeth. Amarillo, Lourdes. – August, 2001.
Villarruz, Maria Vanessa: for the NNHeS: 2003 Group. Philippine 20. Cortes-Maramba, Nelia R. Ruiz, Ma. Cristina. Rebosura, Anita.
Journal of Internal Medicine, 43:103-115, May-June 2003 De Leon, Dina. Comparative efficacy and safety study of
3. Nathan, David M: Long-Term Complications of Diabetes Mellitus. Momordica charantia L. left tablet and glibenclamide among patients
New England Journal of Medicine. Volume 328: 1676. Number with non-insulin dependent type 2 diabetes mellitus. 1996.
23: June 10, 1993. Unpublished.
4. Bailey, Clifford J. Turner, Robert C: Metformin. The New 21. Cortes-Maramba, Nelia P. Purificacion, James, M. Comparative
England Journal of Medicine. February 29, 1996. efficacy and safety clinical trials of Momordica charantia L.
5. Yibchok-Anun, Sirintorn. Adisakwattana, Sirichai. Yu Yao, (ampalaya) left and glibenclamide tablets among type 2 diabetes
Cheng. Sangvanich, Polkit. Roengsumran, Sophon. Haw Hsu, mellitus patients. 1998 - 1999. Unpublished.
Walter: Slow Acting Protein Extract from Fruit Pulp of Momordica 22. The DECODE Study Group. Glucose Tolerance and
charantia with Insulin Secretagogue and Insulinomimetic Cardiovascular Mortality – Comparison of Fasting and 2-Hour
Diagnostic Criteria. Arch Intern Med. 2001; 161: 397, 2001.

23. Levitan, Emily B. Song, Yiqing. Ford, Earl S. Liu, Simin. Is

Nondiabetic Hyperglycemia a Risk Factor for Cardiovascular
Disease? – A Meta-analysis of Prospective Studies. Arch Intern
Med., 162: 2147, 2004.
24. Weyer, Christian. Bogardus, Clifton. Mott, David M. Pratley,
Richard E. The natural history of insulin secretory dysfunction and
insulin resistance in the pathogenesis of type 2 diabetes mellitus. J.
Clin. Invest., 104: 787, 1999.
25. Pratley, Richard E. Weyer, Christian. The role of impaired early
insulin secretion in the pathogenesis of type 2 diabetes mellitus.
Diabetologia, 44: 929, 2001.
26. Bolen, Shari. Feldman, Leonard. Vassy, Jason. Wilson, Lisa. Yeh,
Hsin-Chieh. Marinopoulos, Spyridon. Wiley, Crystal. Selvin,
Elizabeth. Wilson, Renee. Bass, Eric. Brancati, Frederick. Ann
Intern Med., 147: 386, 2007
27. Baldwa VS. Bhandau, CM. Pangaria, A.: Clinical Trial in Patients
with Diabetes Mellitus of an Insulin-like Compound obtained from a
Plant Source. Upsala Journal of Medicine; 82: 39, 1977.
28. Khanna, Pushpa and Jain, SC: Hypoglycemic Activity of
Polypeptide-P from a Plant Source. Journal of National Products,
Volume 44, No. 6, Nov – Dec, 1981.

September, 2010
25
FORMULASI TABLET EKSTRAK BUAH PARE
DENGAN VARIASI KONSENTRASI AVICEL SEBAGAI
BAHAN PENGIKAT
1 2
Puspita Septie Dianita , Tiara Mega Kusuma
Abstrak
Penelitian ini bertujuan untuk mengetahui pengaruh variasi konsentrasi avicel sebagai
bahan pengikat terhadap sifat fisik tablet ekstrak buah pare serta untuk mengetahui
konsentrasi yang dapat digunakan sebagai bahan pengikat yang optimal dalam formulasi
pembuatan tablet ekstrak buah pare. Penelitian ini merupakan penelitian eksperimental. Data
diambil dengan menggunakan tiga formulasi dengan konsentrasi avicel yang berbeda,
kemudian dilakukan pengujian sifat fisik tablet yang meliputi uji keseragaman bobot,
keseragaman ukuran, kekerasan tablet, kerapuhan tablet, dan waktu hancur tablet.
Hasil penelitian ini menunjukkan bahwa semakin tinggi avicel maka kekerasan akan semakin
besar dan kerapuhan akan semakin rendah. Bahan pengikat akan berpengaruh terhadap sifat fisik
tablet yang dihasilkan dengan konsentrasi maksimal terdapat pada formula II. Kesimpulan dari
penelitian ini yaitu dari ketiga formulasi yang dilakukan, formulasi yang paling optimal yaitu
formulasi II karena memiliki nilai kerapuhan dan kekerasan tablet yang sesuai.
Kata kunci : Avicel, Bahan Pengisi, Tablet
Abstract
Momordica charantia L. tablets Formulation With Variation of Concentration Avicel As a Binder.
The purpose of this study was to determine the effect of variations in the concentration of Avicel
as a binder on the physical properties of tablets and to determine the concentration of avicel can be
used as a binder optimal in tablets momordica charantia L. formulation. This study is an
experimental study. This study has 3 formulas with different concentration of avicel, then testing
the physical properties of the tablet which include test weight uniformity, size uniformity, tablet
hardness, friability tablet, and tablet disintegration time.
The results of this study showed that the higher the Avicel then greater hardness and brittleness
would be lower. Binder will affect the physical properties of the resulting tablet with a maximum
concentration found in formula II. The conclusion of this study is of the three formulations, the most
optimal formulation is a formulation II because it has a tablet hardness, fragility and appropriate.
Keywords : Avicel, Binder material, Tablets
1
Prodi DIII Farmasi Universitas Muhammadiyah Magelang
2
Prodi DIII Farmasi Universitas Muhammadiyah Magelang
Jurnal Farmasi Sains dan Praktis, Vol. II, No. 1, September 2016 | 41
Puspita Septie Dianita, Tiara Mega Kusuma
PENDAHULUAN hingga obat sampai di tangan konsumen.

Tablet merupakan bentuk sediaan yang
paling banyak dan sering digunakan oleh METODE PENELITIAN
masyarakat, karena tablet memiliki beberapa Metode pembuatan tablet
keuntungan yaitu mempunyai ketetapan dosis, Formula tablet ekstrak buah pare ini dibuat
cara penggunaannya yang mudah, stabil dalam dengan variasi pada bahan pengikat dari tablet
penyimpanan, mudah dalam transportasi, serta
dengan bobot total 500 mg. Tiap tablet yang
lebih murah bila dibandingkan dengan bentuk
(1)
akan dibuat mengandung paracetamol dengan
sediaan obat yang lainnya . Salah satu berat 280 mg. Terdapat tiga variasi konsentrasi
tanaman yang telah banyak dikenal dan Avicel sebagai bahan pengikat, yaitu 5%, 7,5%
digunakan secara luas oleh masyarakat dan 10% (Tabel 1).
Indonesia adalah buah pare.
Buah pare memiliki banyak kandungan kimia Tabel 1. Desain formulasi tablet ekstrak buah pare
di dalamnya, salah satu kandungan kimia yang
(1) Formula Formula Formula
terdapat dalam buah pare yaitu steroid . Para Bahan I II III
peneliti terdahulu membuktikan bahwa ekstrak (mg) Avicel Avicel Avicel
buah pare mempunyai efek hipoglikemik dan (5%) (7,5 %) (10%)
senyawa yang terkandung dalam buah pare yang Ekstrak buah pare 280 280 280
memiliki aktivitas tersebut adalah steroid Avicel 32,5 48,75 65
(2,3) . Primojel 32,5 32.5 32,5
Salah satu bahan tambahan yang Amprotab 116 99,75 83,5
diperlukan dalam suatu formulasi tablet adalah Talkum 13 13 13
bahan pengikat. Bahan pengikat memberikan Magnesium stearate 26 26 26
daya adhesi pada masa serbuk ketika granulasi
dan pada tablet kempa langsung dapat Metode pembuatan yang digunakan pada
menambah daya kohesi yang telah ada pada pembuatan tablet ekstrak buah pare dengan
bahan pengisi. Bahan pengikat dapat variasi konsentari avicel sebagai bahan pengikat
ditambahkan dalam bentuk kering, tetapi lebih yaitu dengan metode kempa langsung. Ekstrak
efektif jika ditambahkan dalam bentuk larutan. buak pare ditambahkan dengan avicel,
Avicel digunakan sebagai bahan pengikat kemudian ditambahkan dengan primojel dan
dalam formulasi tablet paracetamol pada amprotab. Semua bahan kemudian diayak dan
penelitian ini karena avicel merupakan salah satu ditambahkan magnesium stearate dan talcum
golongan derivate selulosa yang terdepolimerisasi sebagai bahan pelincir. Setelah semua bahan
parsial berwarna putih, tidak berasa, tidak berbau, tercampur kemudian langsung dilakukan
serbuk Kristal yang terdiri atas partikel porous, penabletan dan selanjutnya dilakukan evaluasi
tidak larut dalam asam encer dan sebagian pelarut pada tablet yang telah dihasilkan.
organik. Avicel merupakan produk aglomerasi
dengan distribusi ukuran partikel yang besar dan 1. Pemeriksaan Sifat fisik tablet
menunjukkan sifat alir serta kompaktibilitas yang
a. Keseragaman bobot
(2)
baik . Sebagai bahan pengikat, avicel memiliki Dari 20 tablet, jika ditimbang satu per satu
kelebihan karena dapat menghasilkan tablet yang tidak boleh lebih dari 2 tablet yang masing-
(3) masing bobotnya menyimpang lebih besar
keras namun masih dapat hancur di dalam air .
dari 5 % dan tidak boleh ada satu pun tablet
Diharapkan pada akhir penelitian ini dihasilkan yang bobotnya menyimpang lebih besar
tablet paracetamol yang memiliki daya ikat yang dari 10%.
kuat, sehingga tablet yang dihasilkan tidak mudah b. Keseragaman ukuran
rapuh dan tidak mudah pecah selama proses Diambil 20 tablet kemudian diukur
pembuatan, distribusi, ketebalannya menggunakan jangka sorong.
Diukur rata-rata diameter dan tebal tabletnya.
42 |
Jurnal Farmasi Sains dan Praktis, Vol. II, No. 1, September 2016
Formulasi Tablet Ekstrak Buah Pare dengan Variasi Konsentrasi Avicel Sebagai Bahan Pengikat
Diameter tidak lebih dari tiga kali dan tidak 2. Evaluasi Tablet
1 a. Keseragaman Bobot
kurang dari 1 /3 kali tebal tablet.
c. Kekerasan Keseragaman bobot merupakan salah satu
Sebanyak 20 tablet dimasukkan ke dalam parameter baik atau tidaknya produksi dari suatu
alat yang digunakan untuk mengukur tablet. Pemeriksaan atau evalusai keseragaman bobot
kekerasan tablet yaitu hardness tester, dilakukan dengan tujuan untuk melihat apakah tablet
kemudian dihitung berapa rata-rata yang dihasilkan mempunyai keseragaman bobot atau
kekerasan tablet yang dihasilkan. tidak. Keseragaman bobot tablet memberikan
d. Kerapuhan pengaruh yang sangat penting terutama pada
Sebanyak 20 tablet yang telah dibebas keseragaman kandungan zat aktifnya yang nantinya
debukan atau dibersihkan dari debu yang akan mempengaruhi efek terapi yang dihasilkan.
menempel pada tablet tersebut ditimbang
seksama, kemudian dimasukkan ke dalam Hasil dari pengujian keseragaman bobot
alat friabilator tester dan diputar selama 4 pada tablet ekstrak buah pare dengan variasi
menit atau 100 putaran. Setelah diputar avicel sebagai bahan pengisi dihasilkan bahwa
kemudian tablet diambil dan dibebas ketiga formulasi memenuhi persyaratan
debukan lagi kemudian ditimbang. keseragaman bobot. Persyaratan keseragaman
e. Waktu hancur bobot yang memenuhi yaitu dari 20 tablet, jika
Sebanyak lima tablet dimasukkan ke dalam ditimbang satu per satu tidak boleh lebih dari
keranjang pada alat untuk mengukur waktu 2 tablet yang masing-masing bobotnya
hancur yang disebut dengan disentrigation menyimpang lebih besar dari 5 % dan tidak
tester, kemudian dicelupkan ke dalam media boleh ada satu pun tablet yang bobotnya
0 menyimpang lebih besar dari 10%.
aquadest dengan suhu 37 C.
HASIL DAN PEMBAHASAN
1. Pembuatan tablet ekstrak buah pare
Buah pare merupakan tanaman yang
banyak tumbuh dan digunakan oleh
masyarakat Indonesia. Buah pare merupakan
salah satu tanaman yang bisa digunakan
sebagai obat. Salah satu zat yang terkandung di
dalamnya yaitun steroid, yang bisa digunakan
untuk menurunkan kadar gula dalam darah
6
atau sebagai obat untuk antidiabetes . Gambar 1. Grafik uji keseragaman bobot
Zat tambahan yang digunakan dalam
pembuatan tablet ekstrak buah pare yaitu avicel
Berdasarkan dari grafik di atas terlihat
yang digunakan sebagai bahan pengikat,
variasi keseragaman bobot tablet ekstrak buah
primojel sebagai bahan penghancur, amprotab
sebagai bahan pengisi, talcum dan magnesium pare dari masing-masing formula.Tablet yang
stearate sebagai bahan pelincir. dihasilkan dipengaruhi oleh tingkat kualitas
Metode pembuatan yang digunakan yaitu sifat alir dan kondisi peralatan yang digunakan.
metode kempa langsung, dimana serbuk buah Granul yang memiliki sifat alir yang baik akan
pare ditambahkan dengan avicel dan primojel mengalami transport yang konstan ke dalam
yang kemudian di ayak dan ditambahkan ruang kompressi selama proses pengempaan,
magnesium stearate dan talcum sebagai bahan sehingga akan diperoleh bobot tablet yang
pelincir. relatif sama.
b. Keseragaman ukuran
Keseragaman ukuran dapat ditunjukan
Puspita Septie Dianita, Tiara Mega Kusuma
dengan perbandingan diameter dan tebal tablet. dapat menghambat laju penetrasi air dalam
Pemeriksaan evaluasi keseragaman ukuran tablet sehingga waktu larutnya akan menjadi
dilakukan dengan tujuan agar pada saat lebih lama.
pengemasan primer ukurannya seragam sehingga
d. Uji Kerapuhan
dapat mempermudah pada saat pengemasan.
Kerapuhan merupakan gambaran dari
Tablet dikatakan memiliki keseragaman ukuran
kekuatan tablet dalam mempertahankan
apabila diameter tablet tidak loebih dari 3 kali dan
bentuknya, dimana yang berperan dalam
1
tidak kurang dari 1 /3 tebal tablet. pengujian ini adalah bagian luar permukaan
c. Uji kekerasan tablet tablet. Kerapuhan dinyatakan sebagai massa
Evaluasi kekerasan tablet dilakukan dengan seluruh partikel yang dilepaskan dari tablet
tujuan untuk menilai ketahanan tablet dalam akibat adanya beban penguji mekanis.
melawan kekuatan mekanik seperti goncangan
atau benturan dengan benda lain pada saat
proses penabletan, saat proses pengemasan atau
pada saat proses distribusi hingga obat sampai
ke tangan pasien atau konsumen. Evaluasi
kekerasan tablet dilakukan dengan
menggunakan jangka sorong.
Gambar 3. Uji kerapuhan tablet
Berdasarkan dari grafik di atas terlihat variasi

kerapuhan tablet ekstrak buah pare dari masing-
masing formula. Faktor-faktor yang berpengaruh
terhadap kerapuhan adalah kekerasan dan
keeratan ikatan antar partikel pada permukaan
tablet, dimana sifat dari kerapuhan berbanding
Gambar 2. Uji Kekerasan Tablet terbalik dari kekerasan tablet. Apabila nilai
kekerasan tablet tinggi maka kerapuhannya akan
Berdasarkan dari grafik di atas terlihat variasi rendah, begitu juga sebaliknya.
kekerasan tablet ekstrak buah pare dari masing- e. Uji waktu hancur
masing formula. Berdasarkan dari hasil uji kekerasan Proses hancurnya suatu tablet dapat
yang dihasilkan, ketiga formulasi mempunyai hasil disebabkan dengan adanya bahan penghancur
yang berbeda. Formulasi I diperoleh rata-rata hasil yang digunakan dalam formulasi proses
kekerasan tablet 5,23, formulasi II 5,72, dan formulasi pembuatan tablet. Bahan penghancur bekerja
III 7,115 (Gambar 2). Tablet yang baik hasrus dengan cara menarik air ke dalam tablet,
memiliki rentang nilai kekerasan tablet yaitu 4-7. Dari kemudian tablet akan mengembang, dan
hasil yang diperoleh dapat disimpulkan bahwa menyebabkan pecahnya tablet menjadi partikel-
formulasi yang sesuai dengan syarat uji kekerasan partikel kecil. Pengujian waktu hancur dilakukan
hanya pada formulasi I dan formulasi II. dengan memasukkan enam buah tablet ke dalam
ring yang terdapat pada alat desinteghration
Kekerasan tablet yang dihasilkan akan tester, dengan medium aquades yang bersuhu
berpengaruh pada pada kerapuhan tablet. 0
37 C. dari pengujian waktu hancur pada tablet
Semakin tinggi kekerasan tablet maka ikatan paracetamol diperoleh hasil yaitu 2.10 (dua menit
antar partikel penyusunnya semakin kuat 10 detik). Hasil tersebut sudah dapat
sehingga kerapuhannya akan kecil. Hal tesebut dikategorikan sebagai tablet yang baik dimana
Formulasi Tablet Ekstrak Buah Pare dengan Variasi Konsentrasi Avicel Sebagai Bahan Pengikat
syarat waktu hancur untuk tablet tidak bersalut dilakukan, formulasi yang paling optimal yaitu
yaitu kurang dari 15 menit. formulasi II karena memiliki nilai kerapuhan dan
Waktu hancur tablet merupakan merupakan kekerasan tablet yang sesuai. Variasi berat avicel
waktu yang dibutuhkan tablet untuk hancur menjadi memberikan pengaruh terhadap sifat fisik tablet.
partikel-partikel penyusunnya. Waktu hancur
menggambarkan cepat atau lambatnya tablet hancur DAFTAR ACUAN
dalam cairan pencernaan. Pengambilan air oleh tablet
Anonim, 1995, Farmakope Indonesia, edisi IV,
merupakan langkah awal dalam proses hancurnya
Departemen Kesehatan Republik Indonesia,
tablet. Semakin mudah air masuk ke dalam tablet
Jakarta, halaman 128
maka akan semakin pendek waktu yang dibutuhkan
Anonim, 1986, Handbook of Pharmaceutical
tablet untuk hancur. Hancurnya tablet merupakan
Exipients, USA, halaman 278, 309.
salah satu proses pelepasan zat aktif dari sediaannya,
Ansel, C. Howard, 2005, Pengantar Bentuk
walaupun tidak selalu diperoleh hubungan waktu Sediaan Farmasi, Universitas Indonesia
hancur tablet dengan kecepatan pelepasan zat aktif Press, Jakarta, halaman 201-303
dari sediaannya. Kibbe, H.A., and Araujo, E.O., 2006, Journal of
Pharmaceutical Sciences Volume 62, Willey-
Berdasarkan penelitian yang dilakukan oleh liss, New York.
Dwi Setyawan diperoleh hasil bahwa peningkatan Voigt, R., 1995, Buku Pelajaran Teknologi Farmasi,
konsentrasi avicel akan meningkatkan kekerasan diterjemahkan oleh Soendani Noerono
dan laju disolusi serta menurunkan kerapuhan Soewandhi, Gajah Mada University Press,
dan waktu disentegrasinya. Sedangkan penelitian Yogyakarta.
yang dilakukan oleh Hadi Cahyo, diperoleh hasil Srinivasan, R., Ramarao, P., 2007, Animal models in
bahwa semakin banyak avicel akan menurunkan type 2 diabetes research: An overview,
sudut diam, keseraganan bobot, kerapuhan tablet, Indian J Med Res 125; pp 451-472 Fernandes,
serta meningkatkan kekerasan tablet. N.P.C., Lagishetty, C.V., Panda, V.S.,
Naik, S.R., 2007, An Experimental
KESIMPULAN Evaluation of the Antidiabetic and
Formulasi tablet ekstrak buah pare yang Antilipidemic Properties of a Standardized
dihasilkan telah memenuhi persyaratan sifat Momordica charanthia Fruit Extract, BMC
fisik tablet yang baik, yang meliputi hasil uji Complementary and Alternative Medicine, 7:29
keseragaman bobot, keseragaman ukuran, Saubahar, T.S., 2004, Khasiat dan Manfaat Pare,
kekerasan tablet, kerapuhan tablet serta waktu Penerbit Agromedia Pustaka, Jakarta, halaman
hancur tablet. Dari ketiga formulasi yang 31-34.

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ANALISA ARTIKEL

“TANAMAN PARE SEBAGAI TERAPI UNTUK DIABETES”

Disusun untuk memenuhi tugas mata kuliah Farmakologi dalam Keperawatan

Dosen Pembimbing: Ns. Nur Widayati, S.Kep., MN

Dhea Cristina Damaiyanti Saragih (172310101071)

Della Kharisma Putri (172310101100)

PROGRAM STUDI ILMU KEPERAWATAN

“TANAMAN PARE SEBAGAI TERAPI UNTUK DIABETES”

Disusun untuk memenuhi tugas mata kuliah Farmakologi dalam Keperawatan

Dosen Pembimbing: Ns. Nur Widayati, S.Kep., MN

Dhea Cristina Damaiyanti Saragih (172310101071)

Della Kharisma Putri (172310101100)

PROGRAM STUDI ILMU KEPERAWATAN

Tugas Analisa Pemanfaatan Hasil-hasil Pertanian dalam Pengobatan dengan Judul

“TANAMAN ALPUKAT SEBAGAI TERAPI UNTUK DIABETES”

yang disusun oleh:

Dhea Cristina Damaiyanti 172310101071

Della Kharisma Putri 17231010101100

telah disetujui untuk diseminarkan dan dikumpulkan pada:

Dhea Cristina Damaiyanti

Penanggung jawab mata kuliah Dosen Pembimbing

Ns. Wantiyah, S.Kep., M.kep Ns. Nur Widayati, S.Kep., MN

NIP 198107122006042001 NIP 198106102006042001

Jember, 09 April 2018

HALAMAN JUDUL .......................................................................................... ii

HALAMAN PENGESAHAN ........................................................................... iii

DAFTAR ISI ...................................................................................................... v

BAB 1. PENDAHULUAN .................................................................................. 1

1.1 Latar Belakang ............................................................................... 1

1.2 Tujuan Pembuatan Makalah ......................................................... 1

BAB 2. KONSEP DASAR OBAT TRADISIONAL .......................................... 3

2.1 Obat Tradisional ............................................................................. 3

2.2 Tingkatan obat tradisional ............................................................ 6

2.3 Syarat-Syarat Obat Tradisional (Safety Drug) ............................ 7

2.4 Peraturan terkait obat dan pengobatan tradisional ..................... 8

BAB 3. ANALISA ARTIKEL............................................................................... 9

3.1 Jenis Tanaman Obat ...................................................................... 9

3.1.1 Nama Ilmiah Tanaman........................................................ 9

3.1.3 Nama Produk yang Sudah Dibuat Obat............................ 10

3.2 Kandungan Dalam Obat Tradisional ........................................ 11

3.3 Farmasetika ................................................................................ 11

3.4 Farmakokinetik .......................................................................... 14

3.5 Farmakodinamik ......................................................................... 15

3.7 Indikasi dan Kontraindikasi.......................................................................16

3.8 Efek Samping Obat 16

3.9 Hal-hal yang harus diperhatikan.............................................................17

3.10 Implikasi Keperawatan 17

1.1 Latar Belakang

2.1 Obat Tradisional

2.1.2 Macam – Macam Obat Tradisional

6. Kapsul adalah sediaan Obat Tradisional yang terbungkus cangkang keras.

2.1.3 Ciri – Ciri Obat Tradisional

2.2 Tingkatan Obat Tradisional

Berdasarkan Keputusan Kepala Badan Pengawas Obat dan Makanan Republik

Gambar 2.1 Logo jamu. (Azrim, 2015)

Gambar 2.2 Logo Obat Herbal Terstandar (OHT). (Azrim, 2015)

Gambar 2.3 Logo Fitofarmaka. (Azrim, 2015)

2.3 Syarat-Syarat Obat Tradisional

Peraturan terkait obat dan pengobatan tradisional tercantum dalam :

1. Keputusan Menteri Kesehatan Republik Indonesia Nomor

5. Keputusan Menteri Kesehatan RI No. 661/Menkes/SK/VII/1994 tentang

BAB 3. ANALISA ARTIKEL

3.1 Jenis Tanaman Obat

3.1.1 Nama Ilmiah Tanaman