A review of the efficacy of traditional Iranian medicine for inflammatory bowel disease

Table 1 In vitro studies on plants used in traditional Iranian medicine for the treatment of inflammatory bowel disease

Study	Plant	Part	Results
Watt et al[39]	Althaea officinalis	Whole plant ethanol extract	Antibacterial activity against E. coli
Yoshikawa et al[40]	Boswellia carterii	Mono- and triterpenes isolated from this oleogum resin	↓NO production in lipopolysaccharide-activated mouse peritoneal macrophages
Chevrier et al[41]	Boswellia carterii	Ethanol extract of oleogum resin	Immunomodulatory properties
Camarda et al[42]	Boswellia carterii	Essential oil isolated from oleogum resin	Antimicrobial activities against various microorganisms including fungi, Gram-positive and Gram-negative bacterial strains
Moghtader et al[43]	Bunium persicum	Essential oil of seed	Strong anti-bacterial effects
Shahsavari et al[44]	Bunium persicum	Essential oil of seed	Antioxidant properties
Kumar et al[45]	Cassia fistula	Crude extract of fruit	Significant antimicrobial activity
Francis et al[46]	Commiphora mukul	Terpenoids and guggulusteroids	↓Lipid peroxidation and Cox inhibitory activities
Manjula et al[47]	Commiphora mukul	Crude extract of gum resin	↓Proliferative response of peripheral blood mononuclear cells, ↓inflammatory mediators such as IFN-δ, IL-12, TNF-α, IL-1β and NO, ↓NO production in lipopolysaccharide-activated mouse peritoneal macrophages
Matsuda et al[48]	Commiphora mukul	Methanolic extract of gum resin
Saeed et al[49]	Commiphora mukul	The essential oil, chloroform extract and seven sesquiterpenoids compounds of oleogum resin	Wide range of inhibitory activity against both Gram positive and Gram negative bacteria
Fattouch et al[50]	Cydonia oblonga	Pulp and peel polyphenolic extract	Radical scavenging and antimicrobial activities
Silva et al[51]	Cydonia oblonga	Pulp and peel methanolic extract	Antioxidant activity
Hamauzu et al[52]	Cydonia oblonga	Pulp and peel phenolic extract	Superior antioxidant functions to that of chlorogenic acid and ascorbic acid as standard antioxidants
Kaur et al[53]	Foeniculum vulgare	Aqueous and organic seed extracts	Antibacterial activity comparable to standard antibiotics
De Marino et al[54]	Foeniculum vulgare	n-butanol and aqueous extract of fruit	Moderate antioxidant activity
Baliga et al[55]	Foeniculum vulgare	Aqueous extract	↓NO
Fukuda et al[56]	Juglans regia	Polyphenols	↓Lipid peroxidation, ↑antioxidant activity
Zhou et al[57]	Pistacia lentiscus	Oleogum resin	↓Pro-inflammatory substances such as NO and prostaglandin E2, ↓expression of iNOS and Cox-2 at both protein and mRNA levels, potent hydroxyl radical scavenging activity
Westerhof et al[58]	Plantago ovata	Mucopolysaccharides of seed	Wound cleansing and healing properties, limits scarring
Al-Fatimi et al[59]	Solanum nigrum	Methanolic extract of fruit	Free radical scavenging activities in the DPPH assay
Heo et al[60]	Solanum nigrum	A glycoprotein (SNL glycoprotein) isolated from fruit	Scavenging effects on both superoxide anion and hydroxyl radical
Aquil et al[61]	Terminalia chebula	Ethanolic extract of fruit	Broad-spectrum antibacterial activity, synergistic interaction with tetracycline, chloramphenicol and ciprofloxacin against S. aureus and/or E. coli
Kim et al[62]	Terminalia chebula	Butanol fraction of fruit	Profound growth-inhibitory activity against six intestinal bacteria especially Clostridium perfringens and E. coli
Moeslinger et al[63]	Terminalia chebula	Aqueous extract of fruit	↓Inducible nitric oxide synthesis

E. coli: Escherichia coli; NO: Nitric oxide; Cox: Cyclooxygenase; IFN: Interferon; IL: Interleukin; TNF-α: Tumor necrosis factor α; iNOS: Inducible nitric oxide synthase; mRNA: Messenger ribonucleic acid; DPPH: 1,1-diphenyl-2-picrylhydrazyl; SNL: Solanum nigrum L.; S. aureus: Staphylococcus aureus.

Table 2 In vivo studies on plants used in traditional Iranian medicine for the treatment of inflammatory bowel disease

Study	Model	Species	Plant	Part	Results
Wang et al[64]	Carrageenan- or dextran- induced paw edema	Rat	Althaea rosea	Ethanolic extract of flower	Anti-inflammatory and analgesic effect
Fan et al[65]	Complete Freund’s adjuvant-induced inflammation	Rat	Boswellia carterii	Gum resin extract	Lengthened paw withdrawal latency, ↓paw edema, ↓spinal Fos protein expression, no noticeable adverse effects observed
Banno et al[66]	TPA-induced inflammation	Mouse	Boswellia carteri	Compounds isolated from methanol extract of the resin	Marked anti-inflammatory activity
Kiela et al[67]	DSS- and TNBS-induced colitis	Mouse	Boswellia serrata	Gum resin extract	Ineffective in ameliorating colitis, ↑the basal and IL-1β-stimulated NF-κB activity in intestinal epithelial cells in vitro as well as reverse proliferative effects of IL-1β, hepatotoxicity effect with pronounced hepatomegaly and steatosis was observed
Mencarelli et al[68]	TNBS-induced colitis	Mouse	Commiphora mukul	Guggulsterone	↓Severity of disease and the fecal score and colon inflammation, ↓IL-2, IL-4 and IFN-γ as well as T cell proliferation
Cheon et al[69]	DSS-induced colitis	Mouse	Commiphora mukul	Guggulsterone	↓NF-κB signaling pathway, attenuates acute colitis
Birdane et al[70]	Ethanol-induced gastric lesions	Rat	Foeniculum vulgare	Aqueous extract	↓Gastric mucosal lesion, ↓lipid peroxidation, ↑antioxidant activity
Choi et al[71]	Carrageenan-induced paw edema, arachidonic acid-induced ear edema, formaldehyde-induced arthritis, DNFB-induced contact hypersensitivity reaction	Mouse	Foeniculum vulgare	Fruit methanolic extract	Anti-inflammatory and central analgesic effect, ↓lipid peroxidation, ↑antioxidant activity
Al-Yahya et al[72]	Carrageenan-induced paw edema	Rat	Lepidium sativum	Ethanolic extract of seed	Anti-inflammatory and analgesic activities, potentiate gastric ulcer induced by indomethacin
Kim et al[73]	DSS-induced colitis	Mouse	Pistacia lentiscus	Oleogum resin	Delayed the onset and progression of the disease, prevent weight loss
Al-Said et al[74]	Gastric mucosal damage induced by pyloric ligation, aspirin, phenylbutazone, and reserpine	Rat	Pistacia lentiscus	Oleogum resin	↓Intensity of gastric mucosal damage
Rodríguez-Cabezas et al[75]	TNBS-induced colitis	Rat	Plantago ovata	Seed	Ameliorated the development of colonic inflammation, ↓some of the pro-inflammatory mediators such as NO, leukotriene B4, and TNF-α;↑production of short chain fatty acids, butyrate and propionate
Rodríguez-Cabezas et al[76]	TNBS-induced colitis	Rat	Plantago ovata	Seed	↓Colonic myeloperoxidase activity, restoration of colonic glutathione levels
Joo et al[77]	DSS-induced colitis	Mouse	Solanum nigrum	A glycoprotein (SNL glycoprotein) isolated from fruit	↓NO production, ↓free radical formation, suppressive effect on activities of NF-κB, regulates the expression of iNOS and Cox-2
Jainu et al[78]	Acetic acid-induced gastric ulcers	Rat	Solanum nigrum	Fruit extract	↓Gastric lesions induced by cold restraint stress (76.6%), indomethacin (73.8%), pyloric ligation (80.1%) and ethanol (70.6%) with equal or higher potency than omeprazole, ↓gastric secretory volume and acidity and pepsin secretion, ↑rate of healing of ulcers, ↓H(+)K(+)ATPase activity, ↓gastrin secretion
Akhtar et al[79]	Aspirin-induced gastric ulcers	Rat	Solanum nigrum	Powder from aerial parts and its methanolic extract	↓Ulcer index, ↓acid and pepsin secretions
Mahesh et al[80]	-	Rat	Terminalia chebula	Aqueous extract of fruit	Modulate oxidative stress and enhance antioxidant status in the liver and kidney
Bhattacharya et al[81]	-	Rat	Terminalia chebula	Ethanolic extract of fruit	↑Rate of healing of gastric lesion induced by indomethacin, ↓lipid peroxidation

TNBS: 2,4,6-Trinitrobenzene sulfonic acid; DNBS: 2,4-dinitrobenzene sulfonic acid; DSS: Dextran-sulfate sodium, TPA: 12-O-tetradecanoylphorbol-13-acetate; IL: Interleukin; NF-κB: Nuclear factor κB; IFN: Interferon; DNFB: 2,4-dinitrofluoro benzene; NO: Nitric oxide; TNF-α: Tumor necrosis factor α; iNOS: Inducible nitric oxide synthase; SNL: Solanum nigrum L.; Cox: Cyclooxygenase.

Table 3 Clinical studies on plants used in traditional Iranian medicine for the treatment of inflammatory bowel disease

Study	Study design	No. of patients	Disease	Plant	Part of plant	Control group	Duration of treatment	Result
Kaliora et al[82]	Open, comparing CD patients with healthy volunteers	10 patients and 8 controls	CD	Pistacia lentiscus	Oleogum resin	-	4 wk	↓TNF-α secretion, ↑macrophage migration inhibitory factor release meaning that random migration and chemotaxis of monocytes/macrophages was inhibited
Kaliora et al[83]	Open, comparing CD patients with healthy volunteers	10 patients and 8 controls	CD	Pistacia lentiscus	Oleogum resin	-	4 wk	Significant reduction of CD Activity Index, ↓Plasma IL-6 and C-reactive protein, ↑total antioxidant potential, no side effects observed
Madisch et al[84]	Double-blind, randomized, placebo-controlled, multicenter	31	Collagenous colitis	Boswellia serrata	Gum resin extract	Placebo	6 wk	The proportion of patients in clinical remission was higher in the Boswellia serrata extract group than in the placebo group; Compared to placebo, Boswellia serrata extract treatment had no effect on histology and quality of life
Gupta et al[85]	Randomized	30	Chronic colitis	Boswellia serrata	Gum resin	Sulfasalazine	6 wk	Eighteen out of 20 patients treated with Boswellia gum resin showed an improvement in one or more of the parameters including stool properties, histopathology as well as scanning electron microscopy, hemoglobin, serum iron, calcium, phosphorus, proteins, total leukocytes and eosinophils; In the sulfasalazine group, 6 out of 10 patients showed similar results in the same parameters, 14 out of 20 patients treated with Boswellia gum resin achieved remission, while in the case of sulfasalazine the remission rate was 4 out of 10
Gupta et al[86]	Randomized	30	UC	Boswellia serrata	Gum resin	Sulfasalazine	6 wk	All tested parameters including stool properties, histopathology, scanning microscopy of rectal biopsies, and blood parameters including hemoglobin, serum iron, calcium, phosphorus, proteins, total leukocytes and eosinophils improved after treatment with Boswellia serrata gum resin. The rate of remission was similar in the two studies group (82% in the Boswellia serrata group vs 75% in the sulfasalazine group)
Al-Habbal et al[87]	Double-blind controlled	38	Duodenal ulcer	Pistacia lentiscus	Oleogumresin	Placebo	2 wk	Symptomatic relief in 80% of patients on oleogum resin from P. lentiscus and 50% in patients on placebo, endoscopically proven healing occurred in 70% of patients on oleogum resin from P. lentiscus and 22% of patients on placebo, no side effects observed
Fernández-Bañares et al[88]	Open label, multicenter, randomized	92	UC	Plantago ovata	Seed	Mesalamine	12 mo	40% relapse rate in the P. ovata seed group and 35% in the mesalamine group and 30% in the Plantago ovata plus mesalamine group

UC: Ulcerative colitis; CD: Crohn’s disease; iNOS: Inducible nitric oxide synthase; Cox: Cyclooxygenase.

Table 4 Mechanisms of action of the plants used for the treatment of inflammatory bowel disease in traditional Iranian medicine

Plant	Activities
	Immunomodulatory1	Antioxidant2	Antibacterial	↓NF-κB	↓NO	↓Cox-2	↓LB4	Anti-inflammatory	Wound healing
Althaea spp.			*					*
Boswellia carterii and Boswellia serrata	*		*		*			*
Bunium persicum		*	*
Cassia fistula			*
Commiphora mukul	*	*	*	*	*	*
Cydonia oblonga		*	*
Foeniculm vulgare		*	*		*			*	*
Juglans regia		*
Lepidium sativum								*
Pistacia lentiscus	*				*	*			*
Plantago ovata	*	*			*		*	*	*
Solanum nigrum		*		*	*	*			*
Terminalia chebula			*		*				*

¹Modulating immune system by effects on factors of innate immunity including neutrophils, macrophages, dendritic cells, and natural killer cells are altered and defective mucosal helper T (Th) cell responses and greater expression of cytokines such as interleukin (IL)-1-β, IL-6, IL-12, tumor necrosis factor α (TNF-α) and interferon (IFN)-γ;

²Decreasing factors involved in oxidative stress and lipid peroxidation and/or increased factors enhanced antioxidant capacity. Asterisks indicate having that kind of effect under the column heading. LB4: Leukotriene B4; NO: Nitric oxide; Cox-2: Cyclooxygenase-2; NF-κB: Nuclear factor κB.