Journal of Integrative Medicine xxx (2018) xxx–xxx

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Review

Traditional and modern aspects of hemorrhoid treatment in Iran: A review

Sahar Dehdari a, Homa Hajimehdipoor b, Somayeh Esmaeili b,⇑, Rasool Choopani c, Seyed Alireza Mortazavi d
a
Student Research Committee, Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1516745811, Iran
b
Traditional Medicine and Materia Medica Research Center and Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical
Sciences, Tehran 1516745811, Iran
c
Department of Traditional Medicine, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1516745811, Iran
d
Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran 1991953381, Iran

a r t i c l e i n f o a b s t r a c t

Article history: Hemorrhoidal disease is a prevalent anorectal condition which is generally not managed well with cur-
Received 18 May 2017 rent pharmacologic interventions. However, in Iranian traditional medicine (ITM) there are numerous
Accepted 27 June 2017 plants with hemorrhoid-healing properties. The present research assembled plants with hemorrhoid-
Available online xxxx
healing properties in ITM; their related pharmacological effects, phytochemical constituents and mech-
anisms of action in the modern medicine were also gathered. For this purpose, leading ITM textbooks
Keywords: were searched for plants with hemorrhoid-healing effects. Further, in vitro, in vivo and clinical studies
Clinical study
on the most cited species were considered using scientific databases. Studying ITM textbooks revealed
Hemorrhoids
In vitro
37 medicinal plants with hemorrhoid-healing effects. Among the mentioned herbal medicines, six spe-
In vivo cies, including Allium ampeloprasum, Phyllanthus emblica, Aloe vera, Terminalia chebula, Vitis vinifera and
Plants Commiphora mukul, had the largest number of related pharmacological effects documented in scientific
Iranian traditional medicine databases. These herbs from ITM should be considered as important resources for producing novel drugs
for hemorrhoid treatment.

Please cite this article as: Dehdari S, Hajimehdipoor H, Esmaeili S, Choopani R, Mortazavi SA. Traditional
and modern aspects of hemorrhoid treatment in Iran: A review. J Integr Med. 2018; xx(x): xxx–xxx
Ó 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2. Traditional aspects of hemorrhoids treatment in ITM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.1. Body purification from sowda. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.2. Control the function of liver, spleen and gastrointestinal tracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.3. Phytotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.4. Operation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3. Modern aspect of hemorrhoid treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.1. Modern classification of hemorrhoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.2. Pathogenesis of hemorrhoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4. Modern treatment of hemorrhoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.1. Medical therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.2. Minimally invasive therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.2.1. Sclerotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.2.2. Rubber band ligation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.2.3. Infrared coagulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.2.4. Radiofrequency ablation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.2.5. Cryotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

⇑ Corresponding author.
E-mail address: sesmaeili@sbmu.ac.ir (S. Esmaeili).

https://doi.org/10.1016/j.joim.2018.01.002
2095-4964/Ó 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Please cite this article in press as: Dehdari S et al. Traditional and modern aspects of hemorrhoid treatment in Iran: A review. J Integr Med. (2018), https://
doi.org/10.1016/j.joim.2018.01.002
2 S. Dehdari et al. / Journal of Integrative Medicine xxx (2018) xxx–xxx

4.3. Operative therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

4.3.1. Hemorrhoidectomy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.3.2. Plication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.3.3. Doppler-guided hemorrhoidal artery ligation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5. Modern support for the most cited herbal medicines in ITM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
6. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Conflicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

1. Introduction
Hemorrhoidal cushions are normal anatomic structures located
in the anal canal. The vascular structures within these cushions aid
in maintaining anal continence by preventing damage to the
sphincter muscles [1,2]. Many risk factors are involved in the
pathological changes of normal hemorrhoidal cushions, such as
constipation, diarrhea, spicy diet, alcohol consumption, low-fiber
diet, aging and chronic straining. These risk factors lead to sliding
hemorrhoidal cushions, intensified pressure in the hemorrhoidal
plexus, and swelling and protrusion of the hemorrhoidal mass
[3–6]. Symptoms of hemorrhoid complaints may include bleeding,
pruritus, inflammation, discharge and pain; hemorrhoids are often
classified as internal or external, and graded into 4 categories [7,8].
Among adults (20–85 years old) in Austria, a prevalence of 39% is
reported for symptomatic hemorrhoids of grades I to IV [9]. Classi-
cal treatments for grades I and II, in order to reduce symptoms,
include increasing water intake, establishing a high-fiber diet and
applying topical therapies like steroids and anesthetics. Treatment
for grades III and IV may include non-surgical and surgical inter-
ventions [10,11]. Traditional medicine has been a valuable
resource for developing new clinical drugs [12,13]. Iranian tradi-
tional medicine (ITM) flourished under famous practitioners such
as Avicenna and Rhazes, in medieval times (865–1037 AD) [14–
17]. Bavasir, the traditional term for hemorrhoidal disease in ITM,
is classified into different types based on shape [18]. Hemorrhoid
shape is ascribed to improper distribution of humors in the body.
The role of these humors in development of Bavasir is also
explained in ITM [18–20]. For the management of this disease,
ancient practitioners have recommended various strategies,
including lifestyle optimization, phytotherapy and surgery. In the
first step, lifestyle modification is suggested. Among mentioned
treatments, phytotherapy was the main recommended remedy
for hemorrhoids [18,19,21,22]. In current medical approaches,
many complications of hemorrhoids are not managed well [2].
The medicinal herbs of ITM, having anti-inflammatory, anti-
bleeding, analgesic, wound healing and venotonic properties,
may be effective for hemorrhoid treatment [5]. This study is
designed to investigate the most cited herbs for their
hemorrhoid-healing effects by reviewing ITM textbooks and cur-
rent researches.
2. Traditional aspects of hemorrhoids treatment in ITM
Review of ITM textbooks revealed 37 plants with hemorrhoid-
healing properties. The traditional and scientific names, families,
temperaments, parts used and ITM doses are given in Table 1.
Persian scholars have divided Bavasir into six types based on
their shapes: wart form, grape seed form, berry form, palm form,
fig form and bubble form [18,19]. According to ITM, ailments are
due to improper distribution of Akhlat (humors) in the body. There
are four humors: dam (blood), sowda (black bile), safra (bile) and
balgham (phlegm) [18,19,21–33]. ITM textbooks have emphasized
that sowda is the main cause for the development of Bavasir
[18,21,22]. Other humors involved in the pathogenesis of the most
common types of Bavasir are blood in berry form, black bile/blood
in grape seed form and phlegm in bubble form.
The traditional treatments of Bavasir were body purification
from sowda, controlling the function of liver, spleen and gastroin-
testinal tracts, phytotherapy and surgery.
2.1. Body purification from sowda
Sowda is believed to be the primary and dominant cause in the
pathogenesis of the disease. So cleansing the body of this humor is
considered to be an important step in treatment. For this purpose,
Hijamat (cupping) and consumption of sowda-reducing plants like
Terminalia chebula and Phyllanthus emblica are suggested [18–22].
2.2. Control the function of liver, spleen and gastrointestinal tracts
Because of the special importance of the above organs in the
production of sowda, recovery of proper organ function is also an
objective of treatment [21,22].
2.3. Phytotherapy
Ancient physicians have prescribed different plants for various
purposes, such as reducing sowda level in the body and manage-
ment of Bavasir complications [18–27,34,35].
2.4. Operation
Removal of hemorrhoidal cushions was proposed when other
strategies had failed to treat Bavasir [18,19,21,23].
3. Modern aspect of hemorrhoid treatment
3.1. Modern classification of hemorrhoids
According to modern medicine, hemorrhoids are often classified
as internal or external. Internal hemorrhoids are classified into four
categories based on the progression of the disease (grades I–IV).
Grade I: bleeding of hemorrhoidal cushions without prolapse.
Grade II: hemorrhoidal cushions prolapse with straining and return
to their original position spontaneously. Grade III: hemorrhoidal
cushions prolapse during defecation and need assistance to return.
Grade IV: irreducible prolapse of hemorrhoidal cushions. External
hemorrhoids are usually asymptomatic except when they become
thrombosed [7,8].
3.2. Pathogenesis of hemorrhoids
Pathogenesis of the disease has not been completely under-
stood but mentioned risk factors make some pathological changes.
For example, intensified pressure in the hemorrhoidal plexus can

Please cite this article in press as: Dehdari S et al. Traditional and modern aspects of hemorrhoid treatment in Iran: A review. J Integr Med. (2018), https://
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 S. Dehdari et al. / Journal of Integrative Medicine xxx (2018) xxx–xxx 3

Table 1
The most frequent plants in Iranian traditional medicine with hemorrhoid-healing effect.

Scientific name Traditional Family Temperament Part used Dosage form

name
Phyllanthus emblica L. [18,20,23–27] Amlaj Euphorbiaceae Cold and dry Fruit Oral
Artemisia absinthium L. [18,20,25–27] Afsantin Asteraceae Hot and dry Aerial part Ointment
Ferula assa-foetida L. [18,20,23,25–27] Anjodan Apiaceae Hot and dry Fruit Lotion/liniment
Myrtus communis L. [18,20,23,25–27] As Myrtaceae Cold and dry Leaf Fumigation; ointment; oil
Solanum melongena L. [18,20,25–27] Badenjan Solanaceae Hot and dry Fruit Ointment; oil; topical powder
Portulaca oleracea L. [18,23,25–27] Baghlat-ol- Portulacaceae Cold and wet Aerial part Oral raw material
homgha
Anacardium officinarum Gaertn. [18,20,25,26] Belador Anacardiaceae Hot and dry Fruit Fumigation
Allium cepa L. [18,20,24–27] Basal Amaryllidaceae Hot and dry Bulb Oil
Potentilla reptans L. [18,25–27] Bentafalon Rosaceae Hot and dry Root Decoction
Cinnamomum zeylanicum Nees. [18,26,27] Darsini Lauraceae Hot and dry Bark Ointment
Vitis vinifera L. [18,20,23,25–27] Enab Vitaceae Hot and wet Leaf Oral raw material; ointment
Ocimum basilicum Willd. [18,20,23,25–27] Faranjamoshk Lamiaceae Hot and dry Aerial part Oral raw material; lotion/liniment
Bryonia alba L. [18,20,25–27] Fashara Cucurbitaceae Hot and dry Root Decoction
Lepidium draba L. [18,20,25–27] Ghonabari Brassicaceae Hot and dry Aerial part Oral raw material; lotion/liniment
Parietaria officinalis L. [18,20,25–27] Hashishat-ol- Urticaceae Cold and wet Aerial part Ointment
zujaj
Hypericum perforatum L. [18,24–27] Hofarighoon Hypericaceae Hot and dry Seed Oil
Trigonella foenum-graecum L. [20,23,26,27] Holbe Fabaceae Hot and dry Seed Decoction
Lycium afrum L. [18,23,25–27] Hozoz Solanaceae Mild and dry Seed; leaf Oral raw material
Terminalia chebula Retz. [18,20,23,25–27] Ihlilaj Combretaceae Cold and dry Fruit Oral raw material
Iris florentina L. [18,20,23,25–27] Irsa Iridaceae Hot and dry Root Oil
Capparis spinosa L. [18,20,23,25–27] Kabar Capparaceae Hot and dry Fruit Fumigation
Carum carvi L. [18,26,27] Korovya Apiaceae Hot and dry Seed Ointment
Allium ampeloprasum L. [18,20,23–27] Korrath Amaryllidaceae Hot and dry Leaf Fumigation; lotion/liniment; decoction
Plantago major L. [18,23,26,27] Lesan-ol-haml Plantaginaceae Cold and dry Root; leaf Oral
Colchicum variegatum L. [18,26,27] Lobat-e-barbari Colchicaceae Hot and dry Root Oral raw material
Arum italicum Mill.; Dracunculus vulgaris Schott. Luf Araceae Hot and dry Root Oral raw material; lotion/liniment;
[18,23,25–27] ointment
Armeniaca vulgaris L. [18,20,24,26,27] Meshmesh Rosaceae Hot and dry Seed Oil
Commiphora mukul (Hook. ex Stocks) Engl. [18,23–27] Moql Burseraceae Hot and dry Oleo gum Oral raw material; fumigation;
resin ointment
Cocos nucifera L. [18,20,23,26,27] Narjil Arecaceae Hot and dry Fruit Oral raw material; ointment
Rubus fruticosus L. [18,20,23,25–27] Olaygh Anacardiaceae Cold and dry Aerial part Ointment

lead to venodilation, vascular tone reduction and hyperperfusion
state of submucosal plexus [9]. Over expression of inducible-
nitric oxide synthase (iNOS) and matrix metallo proteinase-9
(MMP-9) in internal hemorrhoid tissue has been confirmed. The
direct degenerative performance of MMP-9 on supporting elastic
fiber structures in the hemorrhoidal cushions is one of the impor-
tant mechanisms [10]. The over expression of iNOS suggests that
inflammatory mediators are associated with the pathogenesis of
hemorrhoids, and that nitric oxide may play a role in the pathology
of hemorrhoids [10]. Additionally, the presence of some inflamma-
tory cells in hemorrhoidal tissue has been reported [36].
4. Modern treatment of hemorrhoids
4.2. Minimally invasive therapy
4.2.1. Sclerotherapy
In this method, chemicals are injected to shrink the hemor-
rhoids by damaging its blood vessels. This method is recom-
mended for grades I and II [6,8].
4.2.2. Rubber band ligation
An endoscope is inserted into anus. Then, a rubber band that is
placed around the hemorrhoids, cuts the blood supply and reduces
and kills the hemorrhoids. This procedure is effective, quick and
simple, and is recommended for grades I and II and some cases
of grade III [38,40].

There are three strategies for the treatment of hemorrhoids

4.2.3. Infrared coagulation
including medical, non-operative and operative treatments
In this method, infrared radiations can create scar tissue. The
[6,8,36–39].
scar tissue shrinks the hemorrhoids via reduction of its blood flow.
This method is quick and safe, but cannot be used for large, or pro-
4.1. Medical therapy lapsed hemorrhoids [2,7,10].

The medical therapy for hemorrhoids includes oral and topical

4.2.4. Radiofrequency ablation
treatment. For oral treatment, flavonoids and calcium dobesilates
In this treatment, a radiofrequency generator is connected to an
are the two main types. Flavonoids are venotonic agents that can
electrode and inserted on the hemorrhoidal cushions, coagulating
increase vascular tone, decrease vascular capacity and reduce cap-
blood, and killing venous tissue forming the hemorrhoid. This pro-
illary permeability [6,37]; calcium dobesilates can reduce capillary
cedure is a painless method. However, recurrent bleeding and pro-
permeability and tissue edema. In addition, venotonic properties
lapse of hemorrhoidal tissues have been reported [5,37,41].
are attributed to them both [6,36,39]. Topical application includes
suppositories and creams. These drugs can control symptoms but
other treatments are also required. These topical preparations 4.2.5. Cryotherapy
may contain additional active ingredients, such as analgesics, cor- In this process, freezing cryoprobe ablates hemorrhoidal tissues.
ticosteroids, anti-inflammatory agents and antibiotics [8,38]. This method is rarely used because of some disadvantages like

Please cite this article in press as: Dehdari S et al. Traditional and modern aspects of hemorrhoid treatment in Iran: A review. J Integr Med. (2018), https://
doi.org/10.1016/j.joim.2018.01.002
4 S. Dehdari et al. / Journal of Integrative Medicine xxx (2018) xxx–xxx

pain, malodorous discharges and high rate of persistent hemor- and tying a knot at the vascular pedicle. Disadvantages of this
rhoidal tissues [6,8]. method include bleeding and pelvic pain [5,6].

4.3. Operative therapy

Operative treatment is used when non-operative methods have
failed to manage hemorrhoid complications.
4.3.1. Hemorrhoidectomy
This surgery is the most effective approach for the treatment of
hemorrhoids. Hemorrhoidectomy is indicated in the case of unsuc-
cessful non-operative therapy, thrombosed hemorrhoids, patient
preference and third or fourth degree hemorrhoids [42–44].
4.3.2. Plication
This procedure relocates hemorrhoidal cushions to their normal
site without excision. Plication involves oversewing of cushions
4.3.3. Doppler-guided hemorrhoidal artery ligation
This method was presented in 1995 as an alternative to hemor-
rhoidectomy. This process is indicated for grades II and III hemor-
rhoids. This method cannot manage prolapsing symptoms of
hemorrhoids [2,36,44,45].
5. Modern support for the most cited herbal medicines in ITM
The most cited species, with vigorous support from in vitro,
in vivo and clinical studies, are summarized in Tables 2–4. Further-
more, active chemical components of the most cited herbs in ITM
are mentioned in Table 5. Further, botanical parts of the most cited
herbal medicines are illustrated in Fig. 1.

Table 2
In vivo studies on the most reported plants used in Iranian traditional medicine for hemorrhoid treatment.

Plant Part or chemical constituents Animal Animal model(s) Results

species
Allium Methanol extract of fresh bulb Mouse Carrageenan-induced paw edema Anti-inflammatory activity
ampeloprasum
var. porrum [46]
Aloe vera [47–49] Crude gel of leaf Rat Carrageenan-induced paw edema Protective and curative effect against
inflammation
Leaf aqueous extract Rat Carrageenan-induced paw edema Anti-inflammatory activity
Cotton pellet granuloma Anti-inflammatory activity
Formaldehyde-induced paw edema Anti-inflammatory activity
Hot plate Analgesic activity
Tail immersion Analgesic activity
Acetic acid-induced writhing response No significant analgesic activity
Leaf aqueous extract Rat Radiant heat method Analgesic activity
Hot plate Analgesic activity
Writhing induced with 4% sodium Analgesic activity
chloride
Phyllanthus emblica Water extract of the fruit Rat Ethyl phenylpropiolate-induced and Anti-inflammatory properties on
[50] arachidonic acid-induced ear edema ethyl phenylpropiolate-induced ear
edema, but not on arachidonic acid-
induced ear edema.
Carrageenan-induced paw edema Anti-inflammatory activity
Cotton pellet-induced granuloma Anti-inflammatory activity
Mouse Formalin test Analgesic activity
Terminalia chebula Aqueous-ethanolic extract of fruit Rat Carrageenan-induced rat hind paw Anti-inflammatory activity
[51–57] edema
Ethanol extract of fruit Mouse Acetic acid-induced writhing model Analgesic activity
Hot plate Analgesic activity
Rat Carrageenan-induced paw edema Anti-inflammatory activity
Incision wounds Wound healing activity
Excision wound Wound healing activity
The petroleum ether, chloroform, ethanol and Mouse Tail immersion model Analgesic activity of ethanolic extract
water extracts of T. bellerica and T. chebula fruit in both plant
Water extract of fruit Mouse Formalin test Analgesic activity
Rat Ethyl phenylpropiolate-induced ear Anti-inflammatory activity
edema
Arachidonic acid-induced ear edema No significant anti-inflammatory
activity
Carrageenan-induced paw edema Anti-inflammatory activity
Cotton pellet-induced granuloma No significant anti-inflammatory
activity
Vitis vinifera [58–62] Aqueous ethanol extracts of leaf Rat Acetic acid-induced vascular Anti-inflammatory activity
permeability test
Carrageenan-induced edema Anti-inflammatory activity
Ethanol extracts of the fruit Rat Carrageenan-induced left hind paw Anti-inflammatory activity
edema
Grape-skin powder Excision wound model Wound healing activity
Seed oil Excision wound model Wound healing activity
The methanol extract of leaf Mouse Formalin-induced paw licking Analgesic activity
Tail flick Analgesic activity
Rat Carrageenan-induced paw edema Anti-inflammatory activity
Histamine-induced paw edema Anti-inflammatory activity

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 S. Dehdari et al. / Journal of Integrative Medicine xxx (2018) xxx–xxx 5

Table 3
In vitro studies on the most reported plants used in Iranian traditional medicine for hemorrhoid treatment.

Plant Part or chemical constituents Model/method Result

Aloe vera [63–66] Aloesin, aleresin, p-coumaroylaloesin, COX-2 and TX-A2 synthase assay Anti-inflammatory, pain killer
feruloylaloesin, isorabaichromone, effect
isoaloeresin, isoaloeresin E and 7-methoxy-8-
glucosylaloesol
Fresh leaf Peripheral blood mononuclear cell Anti-inflammatory effect
Leaf Human colorectal mucosa Anti-inflammatory, pain killer
effect
Leaf gel Purified LOX and COX-2 Anti-inflammatory, pain killer
effect
Hexane fraction from methanolic extract of COX-1 of ram seminal vesicles and COX-2 of insect Anti-inflammatory, pain killer
gum resin cell lysate effect
Commiphora mukul [67] Leaf and fruit Human polymorphonuclear leukocyte and platelet Anti-inflammatory effect
Phyllanthus emblica Water extract of fruit Human umbilical vein endothelial cell Wound-healing effect
[68,69] Aqueous ethanol extract of fruit Human erythrocyte hemolytic assay Anti-inflammatory effect
Terminalia chebula Ethanol-water extract of fruit Chicken ileum intestinal section Anti-inflammatory effect
[52,70–72] Seed Inhibition of albumin denaturation Anti-inflammatory effect
Water extract of fruit Macrophage (RAW 264.7) Anti-inflammatory, pain killer
effect
Ethanol extract of root Cultured macrophage Anti-inflammatory effect
Vitis vinifera [73,74] Water extract of leaf Human gastric epithelial cell Anti-inflammatory effect

COX: cyclooxygenase; TX: thromboxane; LOX: lipoxygenase.

Table 4
Clinical studies on the most reported plants used in Iranian traditional medicine for hemorrhoid treatment.

Plant Part or chemical Dosage Study design Number of Duration of Result

constituents patients treatment
Allium ampeloprasum Subsp Aqueous extract Cream, twice daily Pilot study 34 3 weeks No significant difference
iranicum [75,76] of aerial part
Leaf extract — Double blind, 80 3 weeks Significant reduction in the
randomized bleeding severity in leek group
Aloe vera [77,78] Inner leaf juice Cream (0.5%), 3 Prospective, double 60 6 weeks Significant differences
times/day blind
Gel (97.5%), twice Prospective, 40 2 subsequent Reduction in skin inflammation
daily randomized, double- days
blind
Commiphora mukul [79] Crude resin 3 g/day Parallel-group, 105 4 weeks Significant decrease in the
controlled, randomized symptoms
Terminalia chebula [80] Aqueous extract Capsule (1000 Randomized, double 12 2 weeks Significant rise in pain threshold
of the fruit mg), single dose blind and pain tolerance time
Vitis vinifera [81] Leaf extract 360 mg/day Observational 65 6 weeks Significant improvement in
subjective symptoms

Table 5
clinical trial, potent antibleeding activity of leek has been con-
Responsible chemical compositions of medicinal herbs for hemorrhoids. firmed [76].
Aloe vera (L.) Burm.f. is a medicinal plant indigenous to hot
Scientific name Chemical constituents
countries and has been utilized by Egyptian, Indian, European
Allium ampeloprasum Saponin, flavonoids and Iranian cultures [63]. Phytochemical constituents such as
[46,75]
saponins and flavonoids may be responsible for its anti-
Aloe vera [47,65,66] Saponins, flavonoids, protein
Commiphora mukul [67] Steroids, terpenoids inflammatory effect. Oral consumption of leaf juice at the dose of
Phyllanthus emblica [50] Flavonoids, tannin, terpenes 20 mg/kg, once daily, revealed peak anti-inflammatory effects
Terminalia chebula [53] Tannins, flavonoids, triterpenes, phenolic in vivo [47]. A. vera inner leaf juice, at 1:50 dilution, inhibited pros-
phytoconstituents
taglandin E2 and interleukin-8 generations with no effect on
Vitis vinifera [58] Triterpenoids, alkaloids, flavonoids
thromboxane B2 synthesis in vitro [63]. Vijayalakshmi et al. [64]
found a potent MMP-9 (an inflammatory factor) inhibitory effect
when inner leaf gel was taken at the dose of 60 lg/mL. A 14 kD
Allium ampeloprasum L, or leek, is a member of Amaryllidaceae protein, isolated from A. vera leaf gel, demonstrated potent anti-
family with remarkable anti-hemorrhoid effects in ITM [18,20,23– inflammatory effects against lipoxygenase and cyclooxygenase-2
27]. Steroidal saponin compounds isolated from the methanol in vitro [65]. Phytochemicals such as p-coumaroyl and feruloyl-
extract of fresh leek bulbs showed significant anti-inflammatory aloesin are responsible for its anti-inflammatory property in vitro
effects similar to the reference drug dexamethasone [46]. Topical [66]. The aqueous extract of A. vera leaf exhibited significant
application of leek cream in patients with symptomatic hemor- anti-inflammatory effects in some in vivo models. Among various
rhoids has been studied by Mosavat et al. [75]. A pilot study found doses (100, 200, 400 and 600 mg/kg), administration of 600 mg/kg
that the topical application of A. ampeloprasum cream was as effec- dose revealed the most potent anti-inflammatory effect [48].
tive as a commercial anti-hemorrhoid cream [75], and in another Although a significant analgesic property was confirmed through

Please cite this article in press as: Dehdari S et al. Traditional and modern aspects of hemorrhoid treatment in Iran: A review. J Integr Med. (2018), https://
doi.org/10.1016/j.joim.2018.01.002
6 S. Dehdari et al. / Journal of Integrative Medicine xxx (2018) xxx–xxx
Phyllantus emblica fruit
Vitis vinifera leaf
Fig. 1. Part(s) used of the most cited herbal medicines in Iranian traditional medicine.
some in vivo models, in the acetic acid-induced writhing test no
significant analgesic effect was observed [48]. A. vera at the dose
of 300 mg/kg can be considered a potent analgesic agent in visceral
and somatic pain [49]. A clinical trial on A. vera confirmed that
pain, wound healing and hemorrhaging upon defecation were
improved after an average 7 days of administration [77]. In another
clinical trial, A. vera gel (97.5%), after 48 h of treatment, cured
ultraviolet-induced erythema (an inflammatory skin disease) in
patients with skin types II and III. The effect was lower than the
reference drug hydrocortisone 1% [78]. In addition, there are
numerous reports about the wound-healing action of the plant
[82–86]. The wound-healing activity of A. vera is due to increasing
the rates of collagen synthesis and epithelialization due to fibrob-
last stimulation by acemannan [82]. The plant has been utilized for
the treatment of post-hemorrhoidectomy complications as well
[87]. A. vera is contraindicated in some gastrointestinal diseases
such as Crohn’s disease, ileus, idiopathic abdominal pain and
appendicitis. This herb should not be used during pregnancy, lacta-
tion or in children. Prolonged use of A. vera may lead to potassium
loss. Therefore, concomitant use of this plant with cardiac glyco-
sides and antiarrhythmic medicines should be monitored. In addi-
tion, some drugs like loop and thiazide diuretics, corticosteroids
and licorice can increase the risk of potassium loss when taken
with A. vera. Further, taking A. vera increases the risk of hypo-
glycemia. Therefore, when aloe and antidiabetic drugs are taken
together, signs of hypoglycemia should be monitored [88].
Commiphora mukul (Hook. ex Stocks) Engl., also called triphala
and itrifal in ITM, is an important Ayurvedic poly-herbal formula-
tion for the treatment of various diseases, which contains 3 medic-
inal fruits, including Phyllanthus emblica L., Terminalia chebula
Retz., and Terminalia bellerica Retz. [89,90]. Among different types
of triphala, triphala guggulu contains C. mukul, and has a special
importance for hemorrhoid treatment [91]. Oleo gum resins of C.
Please cite this article in press as: Dehdari S et al. Traditional and modern aspects of hemorrhoid treatment in Iran: A review. J Integr Med. (2018), https://
doi.org/10.1016/j.joim.2018.01.002
Allium ampeloperasum leaf Commiphora mukul oleo-gum resin
Aloe vera inner leaf juice Terminalia chebula fruit
mukul have been utilized as efficient plant materials by Persian
practitioners, in various dosages and forms, for hemorrhoid treat-
ment [18,23–27]. Gugglusteroids and terpenoids are responsible
for its considerable anti-inflammatory activity [67]. A clinical trial
of patients suffering from uncomplicated internal grades I and II
hemorrhoids demonstrated that C. mukul can improve many hem-
orrhoid symptoms, including defecation discomfort, constipation
and bleeding severity [79]. Z-Guggulsterone, an isolated ketos-
teroid from C. mukul, has also shown thyroid-stimulating activity.
So, this point must be considered in susceptible patients [92].
Phyllanthus emblica L. is a component of the triphala formulation
that has been extensively used by traditional Persian physicians for
hemorrhoid treatment [18,20,23–27]. The plant, at the dose of 50
lg/mL, demonstrated antineutrophil and antiplatelet properties
that confirmed its anti-inflammatory activity in vitro [68].
Although its anti-inflammatory and analgesic effects were con-
firmed by different in vivo models, no significant anti-
inflammatory activity was seen in the arachidonic acid-induced
ear edema model [50]. Moreover, analgesic effects of the herb are
because of direct activity on the nociceptor and an inhibitory effect
on the synthesis and release of inflammatory mediators like pros-
taglandins [50]. The water extract of P. emblica displayed a wound-
healing effect at low concentration, but the opposite influence was
seen at high concentration in vitro [69]. This herb can increase
bleeding duration when it is administrated along with clopidogrel
and ecosprin as antiplatelet drugs [93].
Terminalia chebula Retz. is a member of the Combretaceae fam-
ily and is used for management of hemorrhoids in ITM
[18,20,23,25–27]. There are many reports about the anti-
inflammatory effects of the plant in both in vivo and in vitro studies
[51–53,70–72]. The analgesic activity of the species has been con-
firmed by some in vivo experiments [51,53–55]. Presence of tan-
nins, flavonoids, triterpenes and phenolic phytoconstituents in
 S. Dehdari et al. / Journal of Integrative Medicine xxx (2018) xxx–xxx
the ethanol extract of T. chebula may play an important role in
pharmacological properties of the plant [53]. In addition, T. chebula
can accelerate the wound-healing process [56]. Further, tannins
extracted from the species can improve cutaneous wound healing
in rats, probably due to potent anti-bacterial and angiogenic activ-
ities [57]. Moreover, the plant leads to a rise in pain threshold and
pain tolerance time in a clinical study using the hot air pain model.
T. chebula has an excellent safety profile, making it a good choice
for geriatric populations [80].
The leaves and roots of Vitis vinifera L. have exhibited anti-
inflammatory activity in both in vitro and in vivo assays [59–
61,73,74]. The methanolic extract of V. vinifera at 400 mg/kg exhib-
ited a major analgesic property (50% of inhibition), but this effect
was lower than that of the reference drug diclofenac (58.99% of
inhibition) [59]. In addition, Nayak et al. [62] using an in vivo
model demonstrated that the plant had potent wound-healing
effect. This effect is due to the simultaneous antimicrobial and
antioxidant properties of triterpenoids, alkaloids and flavonoids
[58]. Further, V. vinifera showed a potent venotonic property in
patients with grade I or II chronic venous insufficiency [81]. Fur-
thermore, the inhibitory effect of the plant on intestinal enzymes
was shown in an animal model, but this effect was reversible [69].
6. Discussion
Herbal medicines are a rich resource for identifying candidate
drugs with lower occurrence of side effects than current medicine
[94].
According to ITM, the plant parts which have been utilized for
hemorrhoid treatment include fruits, seeds, roots, aerial parts,
etc. As shown in Fig. 2, fruits appeared to be the most commonly
used plant part (20%). Among different dosage forms, raw materi-
als (29%) and ointments (23%) had the greatest frequency of use for
hemorrhoid treatment in ITM manuscripts (Fig. 3). Moreover, all of
the plants had a dry temperament except Portulaca oleracea L., Pari-
etaria officinalis L. and V. vinifera L. Further, most of the plants had
hot temperaments (75.67%; Table 1).
As shown in Tables 2–4, these plants can improve hemorrhoid
complications such as inflammation, bleeding, pain and defecation
discomfort, and have different mechanisms of action, like wound-
healing, analgesic and anti-bleeding properties. In addition, various
classes of phytocompounds, particularly flavonoids and terpenoids,
can be responsible for the hemorrhoid-healing effects of these
plants (Table 5). Through one meta-analysis by Alonso-coello
et al. [95], the efficacy of flavonoids in hemorrhoid treatment
was confirmed. They demonstrated that flavonoids can improve
major patient complaints, such as bleeding, anal itching and pain.
Flower
2%
Seed 17% Root 17%
Bark 5% Branch
Other 9% 2%
Oleo gum resin 5%
Aerial part 17%
Leave 10%
Fruit 20%
Fig. 2. Plant parts used in the treatment of hemorrhoids of Iranian traditional
medicine.
Please cite this article in press as: Dehdari S et al. Traditional and modern aspects of hemorrhoid treatment in Iran: A review. J Integr Med. (2018), https://
doi.org/10.1016/j.joim.2018.01.002
7
16
14
12
Frequency
10
8
6
4
2
0
aterial Ointme
nt
inimen
t Oil tion Decoction
Raw m Lotion/L Fumiga l powd
er
Topica
Dosage forms
Fig. 3. Frequency of use for different dosage forms prepared from Iranian
traditional medicine in hemorrhoid treatments.
Moreover, Rahimi et al. [96] have evaluated the published arti-
cles about plants used to treat hemorrhoids in different countries.
Finally, they introduced some important species with related phar-
macological properties along with their active constituents. In the
present study, all of the mentioned ITM herbs have been extracted
from selected textbooks. Then, the most cited plants were investi-
gated through scientific databases. Our study revealed that the
most important herbs in ITM have been shown to have potent,
related pharmacological effects in modern laboratory studies as
well. But, these herbs need to be evaluated by scientists and go
through clinical tests to confirm their efficacy and safety. The sec-
ond recommendation is to examine mixtures of these herbs due to
their possible synergism effects. One important point is that ITM
does not agree with the treatment of sign and symptoms alone,
but it emphasizes the treatment of the main cause of a disease
which is black bile, or sowda, in the case of hemorrhoids. The herbs
described above are able to control the signs and symptoms of
hemorrhoids until the main treatment is accomplished.
Recent investigations showed that there are many medicinal
plants with hemorrhoid-healing effect in ITM. Most of these
medicinal plants had dry and hot temperaments. Among the most
cited medicinal plants Allium ampeloprasum L., P. emblica L., A. vera
(L.) Burm.f., Terminalia chebula Retz., V. vinifera L. and Commiphora
mukul (Hook. ex Stocks) Engl. have received the most support from
scientific research. These medicinal plants may achieve their most
useful effects in hemorrhoid treatment through all or at least two
related biological effects like anti-inflammatory, anti-bleeding,
analgesic, wound-healing and venotonic properties, and they can
be considered to be an important resource for producing novel
drugs for hemorrhoid treatment.
Acknowledgements
This article was related to Ph.D. thesis (No. 171), Traditional
Bulb Pharmacy, School of Traditional Medicine, Shahid Beheshti
2%
University of Medical Sciences, Tehran, Iran.
Inner leaf
juice 3%
Conflicts of interest
There are no conflicts of interest.
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