Glycosides

Compounds on hydrolysis yields one or more sugars(glucose, rhamnose, digitoxose, cymarose) Chemically acetals
Non sugar component aglycone or genins Sugar component glycone F - forms occur in nature

Nomenclature is based on the name of plant where the glycoside is obtained Classification is based on therapeutic effect Hydrolytic enzymes are substrate specific
Except emulsin and myrosinase

Cardioactive Glycoside
Steroids in nature exerts powerful action on the cardiac muscle, as a glycoside the sugar moeity is attached to the #3 position of the steroid nucleus 2 types of steroid aglycone
1. Cardenolide (C23) C17 side chain -- E, F unsaturated 5 membered ring 2. Bufadienolide (C24) homolog of cardenolide, C17 unsaturated 6 membered lactone ring - origin prototype bufalin (Toad Bufo sp)

Cardioactive Glycoside
To obtain optimum cardiac activity aglycone must possess an E, F unsaturated lactone ring on C17 of the steroid nucleus and A/B and C/D on cis configuration (same side substituent) Sugar confers the molecule's solubility property, its absorption and distribution in the body (O- hydroxyl group rapid onset of action)

Cardioactive Glycoside

Action of Cardiac glycosides ability to increase the force of systolic contraction -- ventricle contraction and complete emptying and a shortening of the length of the systole which would allow more rest for the heart between contractions

Cardioactive Glycoside
Toxic concentration glycosides may increase cardiac automacity --- ectopic tachyarrhythmia
1. Inhibition of Na+, K+ ATPase ---- increase Na+, decrease K+ in the cell which stimulates a secondary Na+, Ca+ exchange mechanism, thus removing intracellular Na.

2. Increase intracellular Ca ----- positive inotropic action (muscle contraction)

Cardioactive Glycoside
Drug Interactions: Potassium depletion ---- increase susceptibility to cardiac glycoside
- low therapeutic index, no bioavailabilty- advise no changing of brands

Digitalis USP 23(1995)

Synonym: Foxglove, Ladys finger, Thimbles, Ladys Glove Origin: dried leaf of Digitalis purpurea (Scrphulariaceae)
- other species: D. ferruginea, D. grandiflora, D. lanata, D. lutea, D. mertonensis, D. nervosa, D. Alpina and D. thapsi

Constituents: digitoxin, gitoxin, gitaloxin

(amount varies with source and condition of growth) Digitoxin ----------- digitoxigenin + 3 molecules of digitoxose

Digitalis
Use: treatment of congestive heart failure, paroxysmal atrial tachycardia, atrial flutter, atrial fibrillation Digitalis lanata (Grecian Foxglove)
Dried leaves of D. lanata Source of digoxin and desacetyllanatoside C (deslanoside) Digoxin --------- digitoxigenin + 3 molecules of digitoxose - short acting, rapidly eliminated

Convallaria NF8 (1947)

Synonym: Lily of the valley, ladder to heaven, Ladys tears Origin: dried rhizomes and roots of Convallaria majalis (Liliaceae) Constituents: convallotoxin ----- K - strophanthin(strophantidin) + rhamnose (sugar of G -strophanthin)
convallatoxol, convalloside

Use: for mild exertional failure, age-related cardiac complaints, chronic cor pulmonale Note: herb not recommended for use (FDA)

Convallaria
Has a positive inotropic effect on the heart Contraindications: - F blockers, Ca channel blockers bradycardia or heart block - Ca salt, digoxin, glucocorticoids, laxatives, quinidine additive

Apocyanum

Synonym: black Indian hemp, dog bane, Canada hemp Origin: dried rhizome and roots of Apocyanum cannabinum or A. androsaemifolium (Apocynaceae) Constituent: apocannaoside, cyanocannoside

Adonis

Synonym: pheasants eye Origin: dried overground portion of Adonis vernalis (Ranunculaceae) Constituents: adonitoxin, cyamarin, K strophanthin

Cactus grandiflorus
Synonym: night - flowering cactus, night blooming cereus, vanilla cactus, sweet scented cactus Origin: fresh succulent stem of the wild growing Selenicereus grandiflorus (Cactaceae) Constituents: flavonoids, amines(digitalis effect) betacyans Action: Positive inotropic effect cardiac stimulation and coronary and peripheral dilatation Stimulates motor neurons of the spinal cord

Oleander
Synonym: Adelfa, rose laurel, rosebay Origin: leaves of Nerium oleander (Apocynaceae) Constituent: oleandrin (3 - glycosido - 16-acetyl derivative of gitoxigenin) Action: positive inotropic and chronotropic effects mimic digoxin (effectiveness not proven) Adverse: seizures, heart failure, respiratory paralysis

Black Hellebore
Synonym: Christmas rose Origin: dried rhizome and roots of Helleborus niger (Ranunuculaceae) Constituent: hellebrin (effect similar to digitalis) Use: cardiac stimulant Note: green hellebore (Veratrum viride) is a cardiac depressant (lowers arterial BP, heart and respiratory rates)

Strophanthus NF IX (1950)
Synonym: Onaya, Veneno de las Flechas Origin: ripe seed of Strophantus komber, S. hispidus (Apocynaceae) that is deprived for its awns. Constituent: K- strophantoside (strophoside) ----strophanthidin + cymarose + , glucose
Note: - seeds of Strophanthus gratus or wood of Acokanthera schimperi (Apocynaceae) - source of Ouabain (G-strophanthin) ----- ouabagenin + rhamnose

Squill NF X (1955)
Synonym: white squill bulb Origin: dried fleshy inner scales of the bulb of the white variety of Urginea maritima (white or mediterranean squill) or U. indica (Indian squill) (Liliaceae) Constituents: contains 16 glycosides scillaren A --- scillarenin + rhamnose +glucose glucoscillaren A ---- scillaren + rhamnose + 2 glucose proscillaren A ---- scillaren + rhamnose Use: expectorant, emetic, cardiotonic, diuretic
Note: red variety is used as a rodenticide (rat poison)

Squill
Interactions:
Ca, digoxin, diuretics, laxatives, quinidine

Adverse:
Seizures, coma, arrhythmias, bradycardia, hypotension

Other constituents present:

Silliglaucosidin anti cancer

Other uses:
Treatment of mild cardiac insufficiency, arrhythmia, reduces kidney capacity

Asclepias tuberosa butterfly weed source of cardenolide

Anthraquinone Glycosides
Aglycone is related to anthracene drugs are employed as cathartics or drastic purgatives aglycone can be a di-, tri-, tetrahydroxy anthraquinone
e.g. emodin, chrysophanic acid, aloe - emodin, rhein

free aglycone exhibit little therapeutic effect glycone facilitates absorption and translocation of the aglycone to the site of action

Anthraquinone Glycosides
plants with the glycosides are:
monocotyledonous - Liliaceae dicotyledonous - Rubiaceae, Fabaceae, Polygonaceae, Rhamnaceae, Ericaceae, Euphorbiaceae, Lythraceae, Saxifragaceae, Scrophulariaceae and Verbenaceae

natural anthraquinones are synthesized either via acetate - malonate pathway or derived from shikimate and mevalonate

Shikimate pathway

Cascara Sagrada USP 23 (1995)

Synonym: Sacred bark, Chittem bark, Bitter or yellow bark Origin: dried bark of Rhamnus purshianus (Rhamnaceae) Constituents: - cascaroside A & B - optical isomer of barbaloin - cascaroside C & D - optical isomer of chrysoloin ---------- rhamnose and glucose Use: cathartic or stimulant laxative (for habitual
constipation -- to restore the natural tone of the colon)

Cascara Sagrada
- purified water - soluble mixture of extract contains anthranol glycosides of Cascara sagrada - called Casanthranol and marketed as Lanes Pill - contains Cascaroside A Extracts treated with alkaline earth (Na, K, Li) or MgO have reduced bitter taste
Adverse Effect prolonged use causes arrhythmia Interactions: prolonged use hypokalemia And with digoxin increase digoxin toxicity

Frangula NF IX (1950) Synonym: Buckthorn bark, Alder bark Origin: dried bark of Rhamnus frangula (Rhamnaceae) Constituents: Frangulin A & B glucofrangulin A & B Use: laxative - orally treatment of cancer - topically - sunscreen

Frangula
Note: related drug - dried ripe fruits of R. catharticus - used as a laxative; small doses: tonic, diuretic, fresh emetic Interactions - anti arrhythmias - licorice - castor oil

Aloe USP 23 (1995)

Synonym: sabila, Lily of the desert Origin: dried latex(juice) of the leaves of Aloe barbadensis (A. vera) in commerce (Curacao aloe) or A. ferox, A. africana and A. spicata (Cape aloe) (Liliaceae) Constituent: barbaloin (C - glycoside) ----glucose + aloe - emodin anthrone + aloe emodin Uses: purgative pharmaceutical aid (Cpd. Benzoin Tincture)

Aloe
Note: Aloe vera gel obtained from the mucilaginous center portion of the leaf used as would healing agent, treatment of burns, abrasions and skin irritations (moisturizing effect) Bradykinase relieve pain and decrease swelling and redness Causes arrhythmia Interactions: anti arrhythmias, cardiac glycosides (digoxin), corticosteroids, diuretics and licorice

Rhubarb NF XI (1960)
Synonym: Rheum, Chinese Rhubarb, Himalayan Rhubarb Origin: dried rhizome and root deprived of periderm of Rheum officinale, R. palmatum (Polygonaceae) Constituents: anthraquinone (chrysophanol, emodin); rhein, anthrones and dianthrones Use: purgative, astringent May increase cardiac contractility with the polysaccharide inhibiting Ca+ influx into the myocardium Use in the treatment of jaundice, kidney stones, gout, headache, toothache, skin and mucous membrane inflammation

Rhubarb
Note: Indian Rhubarb (Himalayan rhubarb) - dried rhizome and roots of R. emodin (Polygonaceae) Interactions:
Ca+ ions oxalate crystals present in Rhubarb may form an insoluble compound and cause kidney stones

Senna USP 23 (1995)

Synonym: Sennae Folium, Hojas de Sen Origin: dried leaflets of Cassia senna (C. acutifolia) known as Alexandria or Khartoum senna and Cassia augustifolia (Tinnevelly senna) (Fabaceae) Constituents: - sennoside A and B ----------- sennidin A (dextrorotary) and B (mesoform) + 2 glucose
- sennoside A and B are pair of stereoisomers whose aglycones are rhein dianthrone

Use: cathartic

Senna fruit
Synonym: Sennae fructus Origin: dried fruits of C. senna and C. augustifolia (Fabaceae) Constituent: sennoside A (present in pericarp) Use: purgative for habitual constipation

Goa powder
Origin: the powder obtained from lysogenous cavities of the wood of Andira araroba (Fabaceae) Constituents: chrysophenolanthrone, emodinanthrone - monoethyl ether Use keratolytic agent (treatment of psoriasis, trichophytosis and chronic eczema) Note: replaced by synthetic anthracenetriol anthralin

Hypericum
Synonym: St. Johns wort Origin: aerial parts of Hypericum perforatum (Clusiaceae) Constituent: hypericin ( naphthodianthrone), pseudohypericin Use: treatment of mild to moderate depression antiviral and wound - healing activity
Note: rank second to ginkgo as herbal

Hypericum
Has an inhibitory effect on MAO inhibitors and uptake of serotonin Inhibit catechol o methyltransferase amd receptors for adenosine, benzodiazepine, inositol triphosphate Drug Herb interactions
- tyramine containing foods beer, cheese, dried meat, fava beans, liver, yeast and wine

Morinda
Synonym: Noni, Indian Mulberry Origin: fruit of Morinda citrifolia (Rubiaceae) Constituent: anthraquinone (alizarin -1 - methyl - ether); aglycone - morindone glycone - primeverose Use: traditionally used as antifungal property - treat diabetes, oBP and GI and liver conditions - sedative, and chronic fatigue syndrome Adverse: hyperkalemia (renal failure)

Saponin Glycosides
Compounds that form colloidal solutions in water upon shaking has a bitter acrid taste and exhibit sternutatory irritating to the mucous membrane, destroys RBC by hemolysis (toxic to cold-blooded animals - fish poison) aglycone (sapogenins are classified under 2 chemical classes 1. Steroid 2. Triterpenoid - widely distributed in nature

Saponin Glycosides
hydrophobic large molecules (C27 - 30) glycone(hydrophilic) makes the molecule capable of lowering surface tension plants with saponins are: (monocots)Liliaceae, Amaryllidaceae, Dioscoraceae; (dicot) Apocynaceae
saponins for cortisone production
1. Disocorea - diosgenin, botogenin 2. Agave - hecogenin, manogenin, gitogenin 3. Smilax - sarsapogeni, smilagenin 4. Strophanthus - sarmentogenin 5. Crude vegetable oil - sitosterol

Steroidal saponins

Less distributed in nature pharmaceutical importance is due to their relation to sex hormones, cortisone, diuretic steroids, Vitamin D and cardiac glycosides arise via the mevalonic acid pathway

Ginseng / Panax USP V (1873)

Origin: roots of a perennial heab, Panax quinquefolius (American ginseng), P. ginseng (Asian ginseng)(Araliaceae) Constituents: contains both steroidal and triterpenoid saponins glycosides are categorized into 3 series:
1. Ginsenoside - ginsenoside Rg (glycoside with a steroidal tripterpene aglycone 0 (20) protopanaxatriol) 2. Panaxoside A, B and C ---- oleanolic acid, panaxadiol and panaxatriol 3. chikusetsusaponin

Ginseng
Use: favorite remedy - tonic, stimulant, diuretic, carminative - possesses adaptogenic (antistress) activity (CNS, metabolism and endocrine) - use in the treatment of anemia, diabetes, insomnia, neurasthenia, gastritis, sexual impotence - aphrodisiac (performance and endurance enhancer (FDA, no evidence of such activity)

Ginseng
Interactions:
Anticoagulants, anti platelets - q effect Antidiabetes, insulin - o hypoglycemic effect Drugs metabolized by CYP 3A4 ginseng inhibits enzyme Warfarin - qINR MAO inhibitors

Dioscorea species NF VII (1942)

Synonym: mexican wild yam, devils bones, yuma Origin: Tubers or roots of Discorea mexicana and D. composita (Dioscoreaceae) Constituent: diosgenin ------- dioscin + 2 rhamnose + glucose -diosgenin is a steroid precursor Use: sole source for steroidal contraceptives, topical hormones, estrogens, progestogen, androgen and sex hormones - orally, natural alternative for estrogen replacement or relieve menopausal symptoms

Dioscorea species
Note: China export diosgenin (high quality ) due to absence of yamogennin Interactions: - disulfiram, metronidazole - estrogen containing drugs, progesterone o glucose level - indomethacin - qanti inflammatory effect

Sisal
Synonym: Maguey Origin: juice from the leaves of Agave sisalana (Agavaceae) Constituent: hecogenin Use: precursor for the manufacture of corticosteroids

Fenugreek
Synonym: birds foot, Greek hay seed Origin: seeds of Trigonella foenum - graecum ( Fabaceae) Constituent: diosgenin(embryo), trigonelline (pyridine alkaloid) Use: spice,source of diosgenin; lowers cholesterol, blood glucose, insulin, appetite stimulant and anticancer - topical skin inflammation, muscle pain and gout
Note: Adverse effect causes hepatotoxicity, causes angioedema ( inhalation or ingestion of topical anesthesia

Fenugreek
Note: Adverse effect causes hepatotoxicity, causes angioedema ( inhalation or ingestion of topical anesthesia Interactions: - adrenergic blockers, anticoagulants - o PT and o abnormal bleeding - anti diabetics (insulin) - q glucose level - probenecid - q uricosuric effect Intake: avoid fenugreek within 2 hrs after another drug

Sarsaparilla NF XI (1960)
Synonym: Maxican, Honduras, Ecuadorian sarsaparilla Origin: dried roots of varios species of Smilax (Liliaceae) S. aristochiafolia - Mexican (Vera Cruz or Grey) S. regelii - Honduras (Brown) S. febrifuga - Ecuadorian (Guayaquil) Constituents: sarsaponin ------ sarsapogenin + glucose smillagen -------- iso - sarsapogenin Use: treatment of syphilis, rheumatism, psoriasis, other urinary problems

Pentacyclic Triterpenoid Saponins

Rare in monocots but abundant in dicots: Caryophyllaceae, Sapindaceae, Polygalaceae, Sapotaceae and other 16 families sapogenin is attached to a chain of sugar or uronic units classified into three groups represented by - amyrin, - amyrin and lupeol

Quillaja
Synonym: Soap bark, Murillo, China bark, Panama wood Origin: dried inner bark of Quillaja saponaria (Rosaceae) Constituent: contains a mixture of saponins (quillaja-saponin) ------ sapogenin quillaic acid (hydroxygypsogenin) Use: medicine: detergent - cleaning wounds, emulsifying agent industry: metal polish, cleaning silk, fire extinguisher Pharmaceutical: emulsifier - volatile oils, tars

Quillaja
Note:
another saponin ------- quillaja sapotoxin (insoluble in water) - used as adjunct in ISCOM(ImmunoStimulating Complex) vaccines where they enhance the antibody response to an antigen Allied drug: Bark of Entada scandens (Fabaceae) - known as gogo, Gandoc, balogo(Tree)

Liquorice
Synonym: Liquorice root, Glycyrrhiza, sweet wood Origin: dried rhizome and roots of Glycyrrhiza glabra (Spanish licorice), G. glabra var. glandulifera (Russian licorice) (Fabaceae) Constituent: glycyrrhizin (glycyrrhizinic acid) ----glycyrrhetic acid (liquiritic acid) + 2 glucouronic acid
Glycyrrhizin is responsible for serous side - effects related to corticosteroid - like activity (Cushings syndrome) associated in large ingestion of licorice.

Liquorice
- other: flavonoid - liquiritin, isoliquirin etc. coumarin derivatives - herniarin, umbelliferone asparagine, dihydrostigmasterol, glucose, mannitol

Use:demulcent, expectorant, flavoring agent, surfactant commercial: added to gums, chocolate, candies, cigarette, smoking mixture chewing tobacco, snuff widely used as anti-ulcer, anti-inflammatory and anti-hepatoxic agent

Liquorice
Note: glycyrrhetic acid is an amyrin derivative - 50X sweeter than sucrose - topical - anti - inflammatory property increase foam in beer or rootbeer PRECAUTION: should not be consumed by patients with cardiac problem or hypertension ---- capability of licorice to increase fluids and sodium retention and promote potassium depletion

Liquorice
Interactions: - anti arrhythmics like procainamide, quinidine hypokalemia - antihypertensives less effective - corticosteroids additive - digoxin - o hypokalemia, o digoxin toxicity - diuretics worsen hypokalemia - lifestyle smoking reduced metabolism o licorice toxicity Adverse Effects: - membranes tingling, paralysis, hypertension, heart failure, arrhythia, hypernatremia, hypokalemia, myopathy, muscle cramps

Liquorice
Preparation in the market:
1. Pure glycyrrhiza extract (Pure licorice) - extract is a black pilular mass (sweet taste) - used as an ingredient in aromatic cascara sagrada 2. Pure glycyrrhiza fluidextract - sweetener (pharmaceutical aid) Substitute in the Philippines - leaves and roots Abrus precatorius (Fabaceae) - saga - saga, Indian or Wild Licorice - contains abrin (toxalbumin) - toxic

Senega
Synonym: Senega snakeroot, rattlesnake root Origin: dried root of Polygala senega (Polygalaceae) Constituent: senegin ------ senegenin + polygalic acid sterol - - spinasterol polygalitol (anhydride of mannitol) Use: stimulating expectorant (chronic bronchitis) prescribed with other expectorant (ipecac and Na2CO3) Interaction: disulfiram - Cloudy or forms gel on standing

Aralia
Synonym: Spignet, American Spikenard Origin: dried rhizome and roots of Aralia racemosa (Araliaceae) Constituent: saponinaraliin Use: alterative, expectorant, treatment of rheumatism and syphilis - official ingredient of the Compound White Pine syrup
Note: Aralin elata - treatment of liver disorders(japan patent) Aralia japonica - aralin ---- aralidin + 2 arabinose + glucouronic acid

Condurango
Synonym: Condor vine, Eagle vine Origin: dried bark of Marsdenia condurango (Asclepiadaceae) Constituent: condurangin, Use: bitter stomachic, astringent (gastro intestinal afflictions
Note: - used in folklore as arrow poison - alternative treatment of chronic syphillis - condurangin, not completely dissolves in water and precipitated by an aqueous solution

Condurango
- stimulates appetite, alleviate dyspepsia, promote diuresis, treat stomach cancer Adverse: vertigo, paralysis, visual changes Interactions: disulfiram, metromidazole

Other Pencyclic triterpenoids

1. Primula root - dried rhizome and roots of Primula veris (cowslip) or P. elatior (oxslip) (Primilaceae) - oleane type primulaverosdie --- primeverose + methyl - 5- methoxysalicylate (odor of drug) - aglycone - primulogenin - expectorant (bronchial conditions) Interactions: antihypertensive potentiate; diuretics potentiate, electrolyte depletion; sedatives - potentiate 2.Bupleurum falcatum - roots of B. falcatum(Apiaceae) - oleane type - saikosaponin - chinese medicine - treatment of hepato-biliary disorders; anti - inflammatory; auto immune diseases

Other Pencyclic triterpenoids

3. Centella (Indian Pennywort, Gotu Kola, Indian water navelport) - dried aerial parts of Centella asiatica (Apiaceae) - most active saponin: asiaticoside; bitter principle vallerin - brahminoside(sedative); madecassoid(anti inflammatory) - tonic - skin diseases I leprosy (India) - promotes fibroblast proliferation and collagen synthesis - anti - ulcer, mild diuretic, anti-rheumatic - Interactions: antidiabetics; cholesterol lowering drugs 4. Horse chestnut seed (buckeye, Spanish chestnut) - seeds of Aesculus hippocastannum (Hippocastanaceae) - principal component - aescin (escin) ---- aescigenin - Interactions: anticoagulants, anti - diabetics

Other Pencyclic triterpenoids

flavones(quercitin, kaempferol,; coumarins, tannins - weak diuretic - treatment of chronic venous insufficinecy, varicose veins, leg pain, hemorrhoids - considered unsafe by FDA due to aescin - Interactions: anticoagulants, anti - diabetics 5. Hedera helix (common ivy) - aerial parts of H. helix (Araliaceae) - hederacoside A(hederin) ------- hederagenin + glucose + rhamnose - research undergoing

Cyanophore (Cyanogenic) Glycosides

Glycosides that yield hydrocyanic acid (HCN) on hydrolysis common glycosides are derivatives of mandelonitrile (benzaldehyde - cyanohydrin)
1. Amygdalin ------- mandelonitrile (aglycone)
prunasin

2. Sambunigrin ------- S - mandelonitrile (aglycone)

accompanied by enzymes ( -glucosidases) that catalyze reactions

amygdalin p glucose + prunasin p glucose + mandelonitrile p HCN + benzaldehyde

Cyanophore (Cyanogenic) Glycosides

amygdalin p A glucose + prunasin p B glucose + mandelonitrile p C HCN + benzaldehyde
A - amygdalin hydrolase B - prunasin hydrolase C - mandelonitrile lyase

widely used as flavoring agent anti cancer claim ---- amygdalin (laetrile or Vit B17) - control of sickle cell anemia
not recognized by FDA as a cancer drug because of high HCN content, potential for overdose or poisoning

Cyanogenic Glycoside
aglycones are derived from nitrogen intermediates (amino acid)
Test: 1. Sodium picrate (yellow) --HCN-- Na isopurpurate (brick red) 2. Guaiacum resin (in methanol) + CuSO4 --HCN----blue coloration of paper 3. Quantitative analysis of glycoside plant in water + tartaric acid ---Steam distilled-----HCN(determine by AgCl) other methods GC, TMS

Wild Cherry USP XVIII (1970)

Synonym: wild black cherry, Virginian prune bark, rum or whisky bark Origin: carefully dried stem bark of Prunus serotina (Rosaceae) - also known as Prunus virginiana (wild black cherry tree) Constituent: prunasin ---partial H+---- HCN p-coumaric acid, trimethyl gallic acid Use: flavoring vehicle (cough remedies) sedative expectorant, antitussive, astringent used for colds, bronchitis, whooping cough Adverse: fatal poisoning when ingested in large amounts

Apricot pits

Kernel of various varieties of Prunus americana (Rosaceae) sold as a health food as source of laetrile or amygdalin - sold due to amygdalin but banned by FDA due to ineffectivity and potential danger

Other Cyanogenic glycosides

1. Linamarin Flax, linseed, lint bells Linum usitatissimum (Linaceae) - treatment of diarrhea, constitpation, gastritis; poultice skin inflammation - adverse effect: intestinal blockage - capable of qcholesterol and o bleeding time 2. Prulaurasin (Cherry - laurel leaves) Prunus laurocerasus (Rosaceae) 3. Manihotoxin(cassava) Manihot utilissima (Euphorbiaceae) 4. Dhurrin Sorghum vulgare (Poaceae)

Other Cyanogenic glycosides

5. Sambunigrin Sambucwas nigra (Caprifoliaceae) 6. Vicianin Vicia angustifolia (Fabaceae) 7. Phaseolunatin Phaseolus lunatus (Fabaceae) 8. Amygdalin Prunus amygdalus (Rosaceae) Prunus persica (Rosaceae) - peach
- constipation, cough, bad breath, blisters, bronchitis - abundant in persic oil, peach kernel oil , seed, bark, leaves and flowers

Isothiocyanate Glycosides
Also known as glucosinolates R represents: CH2 = CHCH2 (sinigrin) p-HOC6H4CH2 (sinalbin) abundant in dicot families: Brassicaceae, Capparidaceae, Resedaceae many glucosinolates have anti-thyroid and goiter - inducing effect in man in mustard vegetables
indolmethylglucosinolate (mammary cancer) -H+ -- indole 3 - carbinol 4 - methylsulfinyl isothiocyanate (broccoli) - induces anti-cancer enzymes

Isothiocyanate Glycosides

Black Mustard NF XI (1960)

Synonym: brown or chinese mustard, Sinapis nigra Origin: dried ripe seed of Brassica nigra or B. juncea (Brassicaceae) Constituent: sinigrin ---H+---- allyl isothiocyanate + KHSO4 + glucose - sinigrin (potassium myronate) - allyl isothiocyanate (mustard oil - volatile) Use: local irritant, emetic, externally: rubefacient, vesicant, pulmonary congestion, rheumatic arthritis commercial: condiment

Black Mustard
Interactions
Acetaminophen and other drugs metabolized by CYP 2E1 Anticoagulants, NSAID, prostacylin Antidiabetics Herb to Herb Anticoagulants feverfew, ginkgo Antihyperglycemic - glucomannan

White Mustard
Synonym: yellow or English mustard Origin: dried seeds of Brassica alba (Brassicaceae) Constituent: sinalbin --H+--- p - hydroxybenzylisothiocyanate Use: same use as black mustard Note: p-hydroxybenzylisothiocyanate (acrinyl isothiocyanate) is pungent tasting, almost odorless oil

Organosulfur drug (Garlic)

Synonym: bawang, garlic Origin: bulb of Allium sativum(Liliaceae) Constituent: alliin --H+-- allicin (diallyl thiosulfinate)-air and water ----- diallyl disulfide + dillyl trisulfide Use: - anti-hyperlipidemic activity - enhances blood fibrinolytic activity - inhibits platelet aggregation (antithrombotic agent)
Note: alliin - sulfur containing amino acid derivative of S - allyl - cysteine sulfoxide

Garlic
Aroma, flavor and medicinal properties sulfur containing cpds (aliin, ajoen, allicin) Inhibits lipid synthesis - q cholesterol Anticoagulant inhibit platelet aggregation
Allicin, ajoen

qblood glucose - oinsulin, oglycogen storage

Flavonol Glycosides
Flavonoids - widely distributed natural product in plants occurring both in the free state and as glycosides. Yellow pigments structural categories flavone, flavanone, flavonol, anthocyanidin, isoflavone general biosyntheis involves the central intermediate p -c coumaroyl CoA and 3 malonyl CoA to elongate t he side chain of the original phenylpropanoid unit

Rue USP V (1873)

Synonym: Garden Rue, Herb of Grace, herbygrass Origin: leaves of Ruta graveolens (Rutaceae) Constituent: Rutin (Vit. P factor) - rhamnoglucoside of the flavonoid (quercetin) Rutin --H+ --- quercetin + rhamnose + glucose Use: treatment of various conditions characterized by capillary bleeding and increased capillary fragility Uterine stimulant, insect repellant (topical)

Rue
Note: bark contains berberine anthelmintic, antispasmodic, antiepileptic, rubefacient, emmenagogue Adverse: bradycardia, severe kidney damage

hesperedin
Origin: rind of unripe citrus fruits synonym: hesperetin - 7 - rutinoside or hesperetin - 1 -rhamnoside - d -glucoside - methyl eriodictyol hesperedin --H+ --- hesperetin + rutinose Use: necessary for the retention of Vit C, catalyzes Vit C and protein to maintain normal capillary resistance (reduce capillary fragility) - for common colds

Phenolic Glycosides
Phenolic compounds possess alcohol, aldehyde and carboxylic groups glycosidic formation is very common phenolic compounds originate from shikimic acid Alcohol glycosides Poplar buds, Hamamelis bark, Aspidosperma, Viburnum prunifolium, Mezereum, Xanthoxylum Aldehyde glycosides

Ma. Asuncion S. Cobar:

Poplar Buds

Alcohol

Synonym: balm of Gilead Buds, Black Poplar buds, Willow buds, quaking aspen Origin: air - dried closed winter leaf buds of Populus candicans (balm of Gilead buds); P. tacamahacca (P. balsamifera) (balsam poplar buds) (Salicaceae) Constituents: volatile oil contains humulene, salicin, populin
salicin ---H+ --- saligenin (salicyl alcohol + glucose

Use: stimulating expectorant, anti-rheumatic, sluggish sores micturition, complaints in prostatic hyperplasia

Poplar buds
Salicin NF IX (1950) antiseptic, stimulate wound healing, gargle (laryngitis) Bark salicotin, salicin Adverse: depression of clotting factors, rash Interactions:
antiarthritics Feosol Aspirin Warfarin and other anticoagulants

Willow Barks
Synonym: weeping Willow, violet willow Origin: bark of Salix fragilis or S. purpurea (Salicaceae) Constituent: salicin Use: ancient remedy for its analgesic, antiinflammatory and febrifuge properties
Note: natural forerunner of aspirin salicn p salicylic acid Adverse: liver necrosis, kidney damage, bleeding episodes Interactions: anticoagulants, ibruprofen

Viburnum prunifolium NF X (1955)

Synonym: Black Haw, Sherry berry, Stugbush Origin: dried bark of the roots or stem of Viburnum prunifolium (Caprifoliaceae) Constituents: salicin, viburmin (bitter resinous principle), viburnic acid, isovaleric acid, tannin, oxalic acid scopoletin Use: uterine sedative, diuretic, astringent, tonic , dysmenorrhea, treatment of threaten abortion (uterine relaxant)
Note: Not official in any pharmacopoeia scopoletin is a uterine relaxant, anti-spasmodic

Viburnum prunifolium
Interactions:
Anticoagulants Anti platelets Dipyridamole, NSAID Herbs feverfew, garlic, ginger, ginkgo, ginseng

Ma. Asuncion S. Cobar:

Vanilla NF XVII (1990)

Aldehyde

Synonym: Vanilla pod or bean Origin: cured, full grown unripe fruit of Vanilla planifolia or V. fragrans(Mexican or Bourbon vanilla) or V. tahitensis (Tahiti vanilla) (Ochidaceae) Constituent: Green vanilla contains: glucovanillin (vanilloside) and glucovanillic alcohol
glucovanillin(avenein) ---H+ --- vanillic aldehyde + glucose glucovanillic alcohol ---H+ --- vanillic alcohol + glucose

Use: flavoring agent, perfumery

Vanilla
Vanillin can be obtained synthetically from: 1. Coniferin - glucoside from the cambium sap of Pine trees 2. Eugenol - phenol present in clove oil 3. Lignin - by-product of pulp industry Commercial varieties of Vanilla:
1. Mexican or Vera Cruz Vanilla - best grade 2. Bourbon Vanilla - blacker in color, usually covered with vanillin crystals and possesses coumarin - like odor 3. Tahiti Vanilla - reddish brown in color, odor - unpleasant, unsuitable for flavoring

Ma. Asuncion S. Cobar:

Uva Ursi NF VIII (1946)

Phenol Phenol

Synonym: Bearberry, Rockberry, sandberry Origin: dried leaf of Arctostaphylos uva - ursi var. coactylis or adenotricha (Ericaceae) Constituents: arbutin ---H+ ---- hydroquinone + glucose ericolin --decomposition ericonol(vol) + glucose resinous principle ursone (ursolic acid) Use: urinary antiseptic, diuretic, urethritis and cystitis, treatment of hepatitis effective against E. coli, Proteus mirabilis and vulgaris, P. aeroginosa, S. aureus and UTI bacteria

Uva ursi
Allied drug: dried leaves of Chimaphila umbellata (Ericaceae) - chimaphillin, arbutin, ericolin, ursone Excrete greenish brown or green urine (hydroquinone) Adverse: seizures, hepatoxic, inflammation, irritation to the bladder, UTI mucosa Interactions: desamethasone, prednisone, diuretics
drugs that can inhibit effects of Uva ursi
1. 2. drugs that can acidify urine and ouric acid levels

Lactone glycosides
coumarin Classified as a simple phenylpropanoid occurs in tonka beans, sweet vernal grass ( Anthoxanthum odoratum Poaceae), sweet clover (Melilotus albus/officinalis Fabaceae), etc. formerly used as flavoring agent, FDA banned the use of coumarin and coumarin containing materials as flavoring agent (cont)

Lactone glycosides
Bishydroxycoumarin (dicumarol) is obtained from improperly cured leaves and flowering tops of Melilotus officinalis (Fabaceae) anti - coagulant property (determine by PTT) as prophylaxis and treatment of venous thrombosis and pulmonary embolism interfere with Vit K action

Lactone glycosides
aside from coumarin (lactone of o-hydroxy cinnamic acid), other hydroxylated coumarin derivatives occurring in plants are: 1. Skimmin - Japanese star anise 2. Aesculin - horse chestnut tree 3. Daphnin - mezereum 4. Fraxin - ash bark (manna) 5. Scopolin - belladonna 6. Limettin - citrus trees

Santonica USP VIII (1905)

Synonym: levant, Aleppo, Alexandria Wormseed, Semen Cinae, sea wormseed Origin: dried unexpanded flower heads of Artemisia cinae (Asteraceae) Constituent: chief: - santonin(sesquiterpene lactone), artemisin(crystalline lactone) Use: anthelmintic (roundworm e.g. ascaris) little effect on threadworm,  no effect on Taenia

Santonica
- action is due to spasmodic contraction of the GIT rendering worm incapable of movement -excreted in bowel; should not be followed by a purgative

Allied drug in the Phillipines seeds of Quisqualis indica (Combretaceae) known as niog - niogan used as anthelmintic agent

Cantharides NF X (1955)
Synonym: Spanish flies, Russian flies, Blistering Flies Origin: dried insects of Cantharis vesicatoria (Meloidae) Constituent: cantharidin (lactone or anhydride of cantharidic acid) Use: irritant, vesicant, rubefacient removes warts (topically) internally: excreted by kidney, irritating to urinary tract --- resulting in priapism

Cantharides
Note: popular as aphrodisiac - dangerous and reported can cause death insect found in shrubs of Caprifoliaceae and Oleaceae mature insect - brilliant green with metallic luster

Psoralens
Photosensitizing furocoumarin common cause of phototoxicity 1. Methoxsalen (8-methoxypsoralen, xanthotoxin) - present in the cremocarp of Ammi majus (Apiaceae) - used to facilitate repigmentation in idiopathic vitiligo (leukoderma) - symptomatic control of severe, disabling psoriasis
CAUTION: therapy is carcinogenic, cataract development, actinic degeneration of skin

Psoralens
2. Trioxsalen (4,5,8 - trimethoxypsoralen) - synthetic furocoumarin - treatment of vitiligo 3. Khellin(Visnaga, khella)) - furochrome found in fruits of Ammi visnaga (Apiaceae) - aside from khellin vasodilator (bronchial asthma and angina pectoris, - visnagin, - visnadin mild inotropic dilate coronary vessels - used as urethral spasm and renal colic

Psoralens - potent coronary vasodilator, broncho dilator in the treatment of coronary insufficiency, angina pectoris, bronchial asthma - prototype for a synthetic mast -cell stabilizing drug (cromolyn solution) - anti-asthma, anti-allergic - applied by inhalation

Interactions
Hepatoxic herbs - additive St. John wort -ophotosensitivity Lifestyle alcohol leads to hepatotoxicity

Miscellaneous Glycosides

Bitter glycosides

Ma. Asuncion S. Cobar:

Gentian NF XI (1960)

bitter

Synonym: yellow gentian root, bitter root Origin: dried fermented root and rhizomes of Gentiana lutea (Gentianaceae) Constituents:
Gentiopicrin --H+ -- mesogentiogenin + glucose Gentiopicrin - seco - iridoid gentiopicroside gentiomarin (gentisin) xanthone (yellow color)

Use: bitter tonic stimulate appetite stimualte gastric secretions

Interactions : barbiturates, cephalosporins, disulfiram, metromidazole

Quassia NF X (1955)
Synonym: Bitter wood, Bitter ash, Corrales(Tag.) Origin: stem woord(heartwood) of Picrasma excelsa (Jamaican) or Quassia amara (Surinam) (Simarubaceae) Constituents: quassin (amaroid triterpenoid), neoquassin, 18 - hydrozyquassin, scopoletin, cathine - 6 -one(alakloid) Use: bitter tonic (beverages), insecticide, enema for expulsion of threadworms

Quassia
Note: Quassia amara (traditiona South American medicine) used as stomachic, antiamoebic, antimalarial and antianaemic

Researches: variety of diseases: cancer, amebic dysentery, and malaria others: anti- leukemia, antiviral, antiinflammatory, antifeed (insect)

Coloring glycosides
Essential subsidiary requirements of a medicinal colorant are: 1. Non-toxic 2. stable specific factors to be considered are: 1. Effect of pH on color (natural pigments are used as pH indicators 2. Solubility in water and oil 3. Stable to light, heat and sugar

Natural Colorants
1. Cochineal Dactylopius coccus BP, EU - red, soluble in water - precipitates below pH 3 2. Beetroot (Betanin) Beta vulgaris EU - red, soluble in water - fairly stable in acid, poor in alkali 3. Carmine powder Dactylopius coccus BPC(1988) EU - purplish red, soluble in alkali - precipitates below pH4

Natural Colorants
4. Paprika oleo resin Capsicum annuum EU - capsanthin, capsorubin - orange - red, soluble in oil, stable 5. Saffron Crocus sativus NF VII (1942) - crocin (crocetin) - yellow - orange, soluble in water 6. Carotenes Daucus carota - orange, soluble in oil or water - stable

Natural Colorants
7. Annattto Bixa orellana EU - bixin - yellow -orange, soluble in oil or water - good in alkali, precipitated in acid 8. Curcumin Curcuma longa EU - yellow, soluble in water - good in acid, poor in alkali

Natural Colorants
9. Chlorophyll and complexes EU - green, olive -green - soluble in oil, water , acid or alcohol depending on the preparation - fair in alkali, precipitated in acid

Red Saunders
Synonym: Red Sandal wood Origin: the heartwood of Pterocarpus santalinus (Fabaceae) Constituent: santalin or santalinic acid santalic acid Use: coloring matter (cabinets)

Haematoxylon
Synonym: logwood, redwoods Origin: heartwood of Haematoxylon campechianum (Fabaceae) Constituents: hematoxylin, hematein, tannin (gallotannic acid) Use: astringent, microscopic stain, indicator (volumetric analysis)

Cochineal
Synonym: Cochinella, Coccus Origin: dried female insect of Dactylopius coccus (Coccus cacti) Order Hemiptera containing eggs and larvae Constituent: carminic acid --H+ -- glucose + 1,3,4,6 OH and 5 - carboxylic acid, 8 - methyl (aglycone) Use: colorant (liquids and solids) and indicator
Note: carminic acid - carmine red and a C-glycoside anthraquinone)

Saffron NF VII (1942)

Synonym: crocus Origin: dried stigma and tops of the styles of Crocus sativus (Iridaceae) Constituents: crocin ---H+ --- gentiobiose +crocetin picrocrocin --H+ -- glucose + safranal(color
&taste)

Use: chiefly as coloring agent and flavor

Researches: anti- cancer, anti-arthritic, antihypertensive due to the powerful antioxidant property of constituents

Coloring Principles from Lichen

Biblical manna - Lecanora esculenta fixative in perfumery - Evernia prunastri (oak moss) lichens contain derivatives of orcinol, orcellic acid and lecanoric acid (compounds called depsides) phenolic acids lichen dyes are formerly used in textile industry e.g. litmus

Coloring Principles from Lichen

other to mask nauseous medicine e.g. Cetraria islandica (Iceland moss) Cladonia contains depsidone, cetraric acid for the treatment of cough and masked by Cetraria others are investigated for its cancer chemopreventive and cytotoxic activity (Iceland moss) Usnea - usnic acid

Cudbear
Synonym: Persio Origin: purplish red powder from the lichen thallus Lecanora acharius (Lecanoraceae) - other sources: Rochella, Parmelia Constituent: orccin Use: coloring for pharmaceuticals - tincture and elixirs

Litmus

Synonym: Turnsole Origin: blue pigment from lichen thallus Lecanora tartarea (Lecanoraceae) Constituent: potassium salt of Asolitmin Use: laboratory indicator (acid - base reaction)

Neutral glycosides
Cocculus NF VII (1942) Synonym: Ligtang, Balising, Fish berry, Indian berry , Cocculus indicus Origin: dried fruits of Anaminta cocculus (Menispermaceae) Constituents: pricrotoxin -- picrotoxinin + picrotin Use: intravenously in barbiturate poisoning and other narcotics fish poison - stupefy fish

Glycosides with volatile oil

Arnica Synonym: Mountain Tobacco, Talpica Origin: dried flower heads of Arnica montana (European arnica) or A. fulgens, sororia or cordifolia (American arnica)(Asteraceae) Constituents: helenalin (Eastern europe flower - 11,12-dihydrohelenalin (Spanish flower) - ussilagine and isoussilagine(pyrrolizidine
alkaloids)

Use: antirheumatic, antiarthritic, antihyperlipidaemic and respiratory analeptic, respiratory analgesic

Calamus
Synonym: Sweet flag, lubigan Origin: dried peeled rhizome of Acorus calamus (Araceae) Constituent: cadinene, acorane, acorin volatile oil(sesquiterpenes) and asarone (related to myristicin) Use: carminative, aromatic bitter and vermifuge toothache remedy, tonic, treatment of dysentery

Steroids Any compound that contains a cyclopentanoperhydrophenanthrene nucleus carbons are numbered and rings lettered (A,B,C,D) Widely distributed throughout the plant and animal kingdoms and are formed by identical or nearly identical biosynthetic pathways easily predictable physical and chemical properties due to their relatively rigid chemical structures. Have little similarity therapeutically

Steroids formed biosynthetically from isopentenyl pyrophosphate (active isoprene) intermediate precursor in steroid biosynthesis is squalene acetate squalene cholesterol pathway mevalonate isopentenyl pyrrophosphate

Steroids
first steroids isolated from nature - series of C27 C29 alcohols found in lipid tissues, solids and called sterols (Gk stereos - solid) most widely occurring sterol - cholesterol principal sterol in fungi - ergosterol (provitamin D2) arising from the transmethylation reaction of cholestane side chain involving S-adenosyl methionine common sterol in plants - - sitosterol (stigmast-5en- 3 -ol), a C29 compound present in wheat germ oil, rye germ oil, corn oil, cottonseed oil and other seed oils stigmasterol - first isolated from calabar bean and also found in soybean oil

Steroids Bile acids

isolated from liver with the degradation of the side chain of cholesterol to form C24 steroids collectively referred as bile acids primary bile acid in human liver - cholic acid and chenodesoxycholic acid in the GIT by the action of microorganisms on cholic acid - desoxycholic acid; chenodesoxycholic acid - lithocholic acid presence in bile is attributed to enterohepatic circulation conjugating glycine or taurine and discharged into the duodenum and act as emulsifiers to aid in the fat absorption in the intestine

Ox Bile Extract prepared by the evaporation of fresh ox bile, precipitation of mucus and albuminous matter with alcohol, filtered , washed and combined filtrates evaporated to dryness at a temperature of nlt 800C contains sodium salts of glycocholic acid and taurocholic acid equivalent to nlt 45% cholic acid Chenodesoxycholic acid suppresses hepatic synthesis of both cholesterol and cholic acid gradually replacing the cholic acid and desoxycholic acid in the expanded bile acid poll resulting in biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones ( no effect on calcified gallstones or blue pigment gallstones

Steroids

Steroid Hormones production is initiated by the releasing factors of the hypothalamus that travels to the anterior lobe of the pituitary gland to induce the release of tropic hormones in the blood ( gonads or adrenal cortex which in turn stimulate the synthesis of the hormone at the target site Divided to 2 classes 1. Sex hormones 2. Adrenocortical hormones

Sex Hormones
produced by the gonads mediates growth, development, maintenance and function of the reproductive tract and accessory sex organs divided into 3 chemically and physiologically distinct categories a. estrogens and progestins - regulates various functions of the female reproductive organs c. androgens - stimulate the development of the male reproductive organs

Adrenocortical Hormones
Produced from the outer cortical portion of the adrenal glands divided to 2 classes depending on biologic activity
a. mineralocorticoids - affecting the excretion of fluids and electrolytes with a subsequent sodium retention b. glucocorticoids - affect the intermediary metabolism

prolong use may cause irreversible atrophy of the adrenal cortex high levels may suppress the hypothalamus from secreting corticotropin - releasing factor lack of stimulating factor released by the pituitary gland may result in atrophy of adrenal cortex

Adrenal Cortex
Animals - Cortical deficiency is marked by loss of appetite,
vomiting, diarrhea, fall in temperature, metabolism and blood pressure loss of blood fluid - concentrated blood, q serum Na, oserum glucose and K kidney damage

Humans - development of Addisons disease (chronic

adrenocortical deficiency) - due to tuberculosis or tumor of adrenal cortex associated with the disease - degeneration of the gonads, marked oin capillary permeability and o sensitivity to insulib sodium loss with potassium retention as outstanding condition untreated - death due to hypoglycemia, dehydration, nutritional disturbances or secondary infection

Adrenal Cortex
Human - excessive activity
tumors or presence of accessory adrenal cortex (due to profound growth abnormalities observed in the external genitalia and the secondary sex characteristics children - precocious sexual development and desire and obesity or unusual muscular development. Females(adult) - virilism associated with a masculine appearance, often with homosexuality (bearded lady)

Drug interactions: barbiturates and phenytoin can induce the hepatic drug metabolizing enzymes degradation of corticosteroids - increase dose

Adrenal Cortex
Desoxycorticosterone or desoxycortisone
synthesized from stigmaterol classified as mineralocorticoid restores balance of sodium and potassium in the body and restore kidney function

Cortisone
glucocorticoid from the adrenal cortex used in the treatment of rheumatoid arthritis, other collagen diseases, Addisons disease, certain allergic and asthmatic conditions disadvantage : sodium retention

Cortisol (hydrocortisone)
Kendalls compound principal glucocorticoid of the adrenal cortex slightly more potent than cortisone and better overall effect disadvantage: sodium retention

Gonads
Ovaries and Testes are both exocrine and endocrine (hormonal) in function develops in the influence of the anterior pituitary hormones
FSH - follicle stimulating hormone - (female) develops the ovarian follicle to the formation of the ova and estrogen ; (male) development of testes and the maturation of the spermatozoa LH - luteinizing hormone (female) development of the corpora lutea in the ovarian follicle after ovulation, to the formation of progesterone by the corpora lutea; (male) production of androgen in the matured testis Androgens(male hormones) and estrogens (female follicular hormones) act to: 1. Develop and maintain the secondary characters of sex 2. Depress anterior pituitary function, leading to the depression of the testis or the ovary

Gonads
Progesterone (corpus luteum hormone)
depresses anterior pituitary function and presents a mixed antagonism - synergism with estrogenic activity

Gonad hyperactivity or excessive therapy may result in a precocious or excessive sexual development with generalized effects of anterior pituitary depression Hypoactivity occurs in menopause or surgical removal of gonads - results in sexual regression and enhanced anterior pituitary activity with psychic disturbance and involvement of other endocrine glands (thyroid)

Gonads
Testes
castration of male, sex organ atrophy, sexual activity diminishes restored by administration of testis hormone Hypogonadism (eunuchoidism) - inadequate development of the testis due to pituitary disorder, infection or other disease Hypergonadism (young males) - testis tumor due to precocious development of sex organs and male characteristics (therapy surgical)

Testosterone(not an aphrodisiac) - produce the general effects of anterior pituitary depression

prepared syntheically from cholesterol valued as a replacement therapy for castrates males and enunchoid states and treatment of certain female ovarian dysfunctions

Gonads
Ovaries
ova develops from a primitive ovarian follicle (graafian follicle) influence by the FSH ovulation occurs with the extrusion of one ovum each month during childbearing period ruptured folllicle undergoes cellular change to become corpus luteum under the influence of the LH of the anterior pituitary produced 2 types of hormones a. estrogen - developing graafian follicle and in the placenta during pregnancy b. progestin - development of corpus luteum and later half of pregnancy by the placenta

Gonads
Estrogens
deficiency - experienced in normal menopause or after surgical removal of ovaries or changes in the vaginal tissues or vulva necessary for:
1. Develop and maintain secondary female sex characteristics 2. Develop and maintain the uterus and the vagina 3. Presecretory development of the mammary glands 4. act as a growth hormone for uterine smooth muscle cells during pregnancy 5. Excite or sensitize the uterine muscle 6. Depress the anterior pituitary function

Gonads
Estrogens
employed in the management of:
1. Symptoms of the natural or surgical menopause 2. local atrophic and degenerative changes in the adult vagina and vulva 3. gonorrheal vaginitis in a young child, inducing adult type of vaginal epithelium that is resistant to gonorrhea 4. Suppress lactation in gorged, painful mammary glands 5. Prostatic cancer in the male, presumable to balance excessive androgen (principle of biochemical castration)

natural estrogen exhibit carcinogenic properties upon prolonged administration (mammary or genital cancer) 3 estrogen hormones - estradiol and its oxidation products, estriol and estrone

Gonads
Corpus luteum - Progestins
essential in the maintenance of pregnancy during the first trimester of pregnancy hormonal functions are:
1. Preparing the uterine mucosa in receiving the fertilized ovum 2. development of the maternal placenta 3. Continued development of mammary glands in preparation for lactogenic action of anterior pituitary 4. Suppression of ovulation for the duration of pregnancy 5. Antagonize the stimulating effect of estrogen on the uterine muscle and produce uterine relaxation

Gonads
Progesterone
active hormone of the corpus luteum used in the treatment of amenorrhea, dysmenorrhea, endometriosis, functional uterine bleeding, premenstrual tension and threatened or habitual abortion used in oral contraceptives with estrogenic substances included IUD (intrauterine device) - hormone dissolved in silicone oil in a flexible polymer