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OPEN ACCESS JOUR OF SOCIAL ISSUES N AND HUMANITIES AL Therapeutic Uses of Fenugreek ( foenum-graecum L.) Jasim Naeem Al-Asadi College of Medicine, Basrah University, Basrah, ; [email protected]

Abstract are used medicinally in different countries by around 80 % of people around the world, mostly in the developing countries. They are a source of many potent and powerful drugs, principally due to the common belief that they are without any side effects along with being economical and locally accessible. Fenugreek (Trigonella foenum-graecum L.) is an that grows anywhere around the world. Fenugreek is one of the oldest medicinal , originating in India and Northern Africa. Its dried seeds have a wide application as a flavoring additive and are good source of , , crude fiber, minerals and . In addition It has a broad spectrum of therapeutic properties. It has been used for numerous indications, including labor induction, aiding digestion, and as a general tonic to improve metabolism and health. Human and animal trials suggest possible hypoglycemic and antihyperlipidemic properties of oral fenugreek seed powder. Mucilaginous fiber present in fenugreek seeds may bind bile acids to reduce cholesterol and fat absorption. The protein in fenugreek might exert a lipid lowering effect. Steroidal , and 4-hydroxy-isoleucine may promote glucose metabolism and inhibit absorption of cholesterol. Furthermore some chemical constituents of fenugreek may directly stimulate insulin secretion from B-cells resulting in blood sugar reduction. Its cardioprotective effects are attributed to its modulating effect on blood lipid levels and anti- oxidant properties. In a number of studies, of fenugreek seeds and some of their constituents have shown anticarcinogenic potency. In addition, fenugreek was reported to have gastroprotective effect, antimicrobial activities, anticancer effect, used in treatment of arthritis, reducing weight, increasing milk production and may regulate hyperthyroidism. The aim of this chapter is to review the literatures that investigate the various therapeutic uses of fenugreek. Keywords: Fenugreek, Trigonella foenum-graecum L., therapeutic uses, pharmacological, hypoglycemic,

Abbreviations: AlCl3: Aluminum Chloride; CRP: C- Reactive Protein; DMBA: 7,12- Dimethylbenz [a] Anthracene; DNA: Deoxyribonucleic Acid; EAC: Ehrlich Ascites Carcinoma; ER: Estrogen Receptor; ERK: Extracellular Signal Regulating Kinase; ESR: Erythrocyte Sedimentation Rate; HDL: High Density Lipoprotein; HL: Human Leukemia; JNK: c-Jun N- terminal Kinase; L-Dopa: L-3,4-dihydroxyphenylalanine; LDL-C: Low Density Lipoprotein Cholesterol; NSAIDs: Non-Steroidal Anti-Inflammatory Drugs; PD: Protodioscin; SH: Sulfhydryl; TG: Triglycerides; Th: T-helper; WBC: White Blood Cells

AJSIH | ISSN: 2276 – 6928 Fenugreek Special Issue Mar/Apr 2014 | Editors: S. K. Basu & G. Agoramoorthy | 21 AMERICAN

OPEN ACCESS JOUR OF SOCIAL ISSUES N AND HUMANITIES AL

INTRODUCTION Active constituents Herbs have been used in all parts of the Fenugreek seed contains 45-60 % world not only as food but also as potent , mainly mucilaginous fiber drugs for thousands of years. They do not (galactomannans); 20-30 % high in work like chemical drugs and they are not lysine and tryptophan; 5-10 % fixed oils substitute of them [1, 2]. (lipids); pyridine-type alkaloids, mainly are used by 80 % of the world population trigonelline (0.2-0.3 6%), choline (0.5 %), especially in developing countries to cure gentianine, and carpaine; the and improve the general health, principally apigenin, luteolin, orientin, quercetin, due to the common belief that plant-derived vitexin, and isovitexin; free amino acids, drugs are without any side effects along with such as 4-hydroxyisoleucine (0.09 %); being economical and locally accessible [3]. arginine, histidine, and lysine; and Fenugreek, Trigonella foenum-groecum L., ; saponins (0.6-1.7 %); glycosides is an annual herb grown in various countries yielding steroidal sapogenins on hydrolysis around the world. It was thought to be (diosgenin, yamogenin, tigogenin, indigenous to the countries bordering on the neotigogenin); cholesterol and sitosterol; eastern shores of the Mediterranean [4], but vitamins A, B1,C, and nicotinic acid; and now is widely cultivated in India, China, 0.015 % volatile oils (n-alkanes and northern and eastern Africa, and parts of sesquiterpenes), which are thought to Europe and Argentina [5]. The health- account for many of its presumed promoting property of fenugreek has been therapeutic effects [10-12]. long documented when it is taken as vegetables, food supplements or medicinal Pharmacological effects and mechanisms remedies. It has been used in many different of action cultures, but especially in Asia and the Fenugreek is known to have several Mediterranean region [6]. pharmacological effects such as: hypoglycemic [13], and antilipidemic or Historical uses of fenugreek hypocholestrolemic [14]. However, the Fenugreek has a long history as both a exact mechanism of action is still unclear. culinary and medicinal herb in the ancient The antidiabetic effect of Fenugreek was world. Applications of fenugreek were thought to be due to formation of a documented in ancient Egypt, where it was colloidal-type suspension in the stomach and used in incense and to embalm mummies intestines when the mucilagenous fiber of [7]. The Greeks and Romans used it for the seeds is hydrated, therefore affecting cattle fodder (hence the Latin foenum gastrointestinal transit, slowing glucose graecum meaning Greek hay). In ancient absorption. The antilipidemic effects of Rome, fenugreek was purportedly used to Fenugreek was thought to be due to aid labor and delivery. In traditional Chinese inhibition of intestinal cholesterol absorption medicine, fenugreek seeds are used as a due to -cholesterol complex tonic, as well as a treatment for weakness formation, increased loss of bile through and edema of the legs [8]. In India, fecal excretion due to saponin-bile fenugreek is commonly consumed as a complexes, thus increasing conversion of and used medicinally as a cholesterol to bile by the liver, and effects of lactation stimulant [9]. amino acid pattern of fenugreek on serum

cholesterol [15]. Furthermore, this plant has an antioxidant action [16], gastroprotective

AJSIH | ISSN: 2276 – 6928 Fenugreek Special Issue Mar/Apr 2014 | Editors: S. K. Basu & G. Agoramoorthy | 22 AMERICAN

OPEN ACCESS JOUR OF SOCIAL ISSUES N AND HUMANITIES AL activity [17], appetite stimulation [18], and the effects of fenugreek seeds on glycemic antirheumatism [19] Histopathological control [32]. Twenty five newly diagnosed examination of liver and brain has revealed patients with type 2 diabetes (fasting glucose that, aqueous of fenugreek seeds < 200 mg/dl) were randomly divided into offer a significant protection against ethanol two groups. Group I (n = 12) received 1 toxicity [20]. gm/day hydroalcoholic extract of fenugreek seeds and Group II (n = 13) received usual THERAPEUTIC USES OF care (dietary control, exercise) and placebo FENUGREEK capsules for two months. There were no significant differences between groups in Diabetes mellitus mean glucose tolerance test values at the Diabetes mellitus is a chronic metabolic study’s end, but there was an increase in disorder characterized by derangements in percent insulin sensitivity. The authors the metabolism of , protein and concluded that adjunct use of fenugreek lipids caused by complete or relative seeds improves glycemic control and insufficiency of insulin secretion or/and decreases insulin resistance in mild type-2 action [21]. Diabetes is a major health diabetic patients. In a study done in Iran, concern and its burden is increasing on 24 Type 2 diabetics showed 10 g a day of globally. medicine plays an fenugreek for 8 weeks decreased fasting important role in treatment of diabetes [22, blood glucose from 182 mg/dl to 136 mg/dl, 23]. Fenugreek seeds, leaves and extracts but did not change the HbA1C [33]. A study had been used as an anti-diabetic in many on 166 type 2 diabetics in Jordan showed a model systems [24-26]. In Arab countries, in dose dependent improvement in 2 hour post Saudi Arabia [27] and Iraq [28], fenugreek prandial sugars in the group receiving 5 g was found to be among the most common fenugreek compared to those on 2.5 g herbs used among people with diabetes. fenugreek and the control group [24]. In Animal studies suggest hypoglycemic another study on healthy subjects, Shakib et effects of fenugreek [29, 30]. Human al found those who consumed bread with studies also showed possible hypoglycemic fenugreek had an improvement in the properties of fenugreek. Sharma et al (1990) postprandial glucose response compared to [31] conducted a randomized, controlled, those who ate bread without fenugreek crossover trial in 10 patients with type1 [34].Apart from biochemical improvements, diabetes. Over a 10-day period, the subjects fenugreek seeds have been reported to were served meals that contained 100 g markedly suppress the clinical symptoms of fenugreek seed powder in two divided doses diabetes such as polyuria, polydypsia, each day (lunch and dinner) or meals weakness and weight losses [35]. The without fenugreek. At the study’s end, hypoglycaemic effect of fenugreek is significant improvement was noted in the thought to be largely due to its high content fenugreek group in several parameters, of soluble fiber which acts to decrease the including a 54 % reduction in 24-hour urine rate of gastric emptying, thereby delaying glucose levels and mean reductions in absorption of glucose from the small glucose tolerance test values and fasting intestine [36]. 4-hydroxyleucine, a novel serum-glucose levels (from 15.1 ± 2.4 amino acid from fenugreek seeds increased mMol/L to 10.9 ± 2.75 mMol/L; P < 0.01). glucose stimulated insulin release by islet

cells in both rats and humans [37]. Owing to Gupta et al reported the results of a double its particular insulinotropic action, 4- blind placebo controlled study to evaluate

AJSIH | ISSN: 2276 – 6928 Fenugreek Special Issue Mar/Apr 2014 | Editors: S. K. Basu & G. Agoramoorthy | 23 AMERICAN

OPEN ACCESS JOUR OF SOCIAL ISSUES N AND HUMANITIES AL hydroxyisoleucine might be considered as a al conducted a study on 100 diabetic novel secretagogue with potential role in patients. Those patients were randomly treatment of diabetes [38]. Saponin divided into two groups. Fifty patients as a compounds diosgenin, alkaloids and control group were maintained on routine trigonelline were shown to be associated dose of Glibenclamide, while the other 50 with inhibition of intestinal glucose uptake patients as an intervention group were given in vitro [39]. Fenugreek has been shown to capsules containing equal amount of increase erythrocyte insulin receptors and combined powder of N-sativa and T. improve peripheral glucose utilization, thus foenum-graecum seeds, in addition to their showing potential pancreatic as well as routine dose of Glibenclamide. Serum extrapancreatic effects [40]. triglyceride, and HDL levels were measured for every patient at the start and after 3 Effect of fenugreek on serum lipids months of therapy. Comparison of the mean There is some evidence from randomized values of parameters measured in both clinical trials that fenugreek reduces serum groups showed that serum HDL levels were cholesterol. In a single-blind study of 20 significantly (P < 0.05) raised in healthy male volunteers, Abdel-Barry et al intervention group as against the control, found a non significant decrease of 9.2 % in whereas the levels for serum triglycerides total serum cholesterol after a single dose of was comparable in both the groups [44]. The an aqueous extract made from fenugreek fiber constituents of fenugreek delay the leaves (40 mg/kg) compared with a digestion and absorption of carbohydrates reduction of 2.8 % after dilute coffee extract [45]. The soluble fiber from fenugreek (placebo)[26]. Sharma et al investigated 15 appears to decrease reabsorption of bile non-obese, asymptomatic, hyperlipidemic acids in the small intestine increasing the adults. After ingestion of 100 gm defatted excretion of cholesterol and bile acids into fenugreek powder per day for three weeks, the feces. Consequently, the need of the subjects showed a decrease in their cholesterol for bile acid biosynthesis is triglyceride (TG) and low density enhanced and blood cholesterol lipoprotein cholesterol (LDL-C) levels as concentrations are reduced [46]. compared with baseline values. Slight decreases in high density lipoprotein (HDL) Diosgenin, the primary furostanol saponin in levels were also noted [41].The triglyceride fenugreek has been proven to have various lowering effect may be due to the pectin effects on cholesterol metabolism, the most component that absorbs bile acids [42]. important being its capacity to lower plasma Sowmya and Rajyalakshmi observed cholesterol concentration. This significant reductions in total cholesterol hypocholesterolemic effect appears to be and low density lipoprotein cholesterol dependent upon the capacity of diosgenin to (LDL-C) levels in 20 adults with inhibit cholesterol absorption, to decrease hypercholesterolemia who received 12.5- liver cholesterol concentration and to 18.0 gm powdered, germinated fenugreek increase biliary cholesterol secretion and the seeds for one month [43]. To evaluate the fecal excretion of neutral sterols. The lipid- effect of combination of L. lowering effect of fenugreek might also be and Trigonella foenum-graecum L. seeds attributed to its estrogenic constituent, with Glibenclamide on serum triglyceride, indirectly increasing thyroid hormone [47]. and high density lipoprotein (HDL) levels in The quality and quantity of protein in the type-2 diabetes mellitus patients, Memon et diets have a direct effect on the levels of

AJSIH | ISSN: 2276 – 6928 Fenugreek Special Issue Mar/Apr 2014 | Editors: S. K. Basu & G. Agoramoorthy | 24 AMERICAN

OPEN ACCESS JOUR OF SOCIAL ISSUES N AND HUMANITIES AL cholesterol. Generally plant protein appears presumably by enhancing antioxidant to lower cholesterol level [48]. potential of the gastric mucosa thereby lowering mucosal injury [51]. In another Cardioprotective effects study done on rats also, aqueous extracts of An animal study revealed that barley grains (Hordeum vulgare L.) and administration of fenugreek proved to be fenugreek seeds (Trigonella foenum - effective in reducing the extent of graecum L.) were administered to a group of myocardial damage and significantly Albino rats previously subjected to aspirin at counteracted the oxidative stress during 400mg/kg b.w., for gastric ulcer induction. isoproterenol-induced myocardial infarction The results revealed that rats treated with in rats [49]. Fenugreek has a strong barley and fenugreek aqueous extracts modulating effect on blood lipid levels. It showed significant decline in ulceration has demonstrated a remarkable ability to severity as determined by ulcer index as lower cholesterol, triglycerides and LDL well as curative ratios. Also, there was a levels while raising HDL levels [50], so can significant increase in gastric mucus substantially reduce the risk of (carbohydrate/ protein ratio in mucosa). The atherosclerosis. Another property of anti-ulcer effect was further confirmed fenugreek is the reduction of platelet histopathologically [52]. Another study aggregation due to its and other investigated the effect of fenugreek seeds on constituents which, in turn, dramatically Aspegic induced gastric mucosal ulcer in reduces the risk of abnormal blood clotting rats. The results showed that fenugreek associated with heart attacks and strokes seeds possess antiulcer potential [53]. The [15]. Fenugreek also contains many antiulcer activity of fenugreek may be important antioxidants and has the added attributed to its flavanoids contents since benefit of protecting other dietary and they were reported to protect the mucosa by internally produced antioxidants from free- preventing the formation of ulcerative radical damage. This has important lesions by various necrotic agents [54, 55].It cardioprotective benefits, as well as helping was reported that the polysaccharide fraction to fortify the body against a range of other of fenugreek seeds forms a mucin like gel chronic conditions [49]. layer of galactomannan on the surface of the mucosa, or forms a protecting complexes Gastroprotective effect between gel and mucus as a barrier against One of the historical uses of fenugreek is the agents introduced into the stomach or treatment of gastric ulcer. The ulcer against endogenously formed acid and protective effect of fenugreek seeds pepsin in the stomach [56]. Increase in compared to omeprazole was studied on gastric mucosa content of sulfhydryl may ethanol-induced gastric ulcer in rats. The contribute to the anti-ulcer activity of the aqueous extract and a gel fraction derived fenugreek seeds. Gastric mucosal sulfhydryl from the seeds showed significant ulcer compounds (SHs) act as antioxidants and are protective effects compared to those on important for maintenance of mucosal omeprazole. The researchers found that the integrity in the stomach [57, 58]. cytoprotective effect of the seeds seemed to be due to the anti-secretory action and to the Anticancer effect effects on mucosal glycoproteins. The In a number of studies, extracts of fenugreek fenugreek seeds also prevented the rise in seeds and some of their constituents have lipid peroxidation induced by ethanol shown anticarcinogenic potency.

AJSIH | ISSN: 2276 – 6928 Fenugreek Special Issue Mar/Apr 2014 | Editors: S. K. Basu & G. Agoramoorthy | 25 AMERICAN

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Consumption of fenugreek was PD displayed strong growth inhibitory effect accompanied with decreased polyamines against HL-60 cells, but weak growth (spermine, spermidine, putrescine) content inhibitory effect on KATO III cells. The in tumor tissue [59]. Srinivasan et al [60] fragmentation by PD of DNA to investigated the effect of diosgenin, a oligonucleosomal-sized fragments, that is a biologically active constituent of fenugreek characteristic of apoptosis, was observed to seeds on breast cancer cell lines. Diosgenin be both concentration and time-dependent in caused G1 cell cycle arrest by down the HL-60 cells. These findings suggest that regulating cyclin D1, cdk-2 and cdk-4 growth inhibition by PD of HL-60 cells expression in both estrogen receptor positive results from the induction of apoptosis by ER (+) and estrogen receptor negative ER (- this compound in HL-60 cells [64]. In 1,2- ) breast cancer cells resulting in the dimethylhydrazine (DMH) [which is a colon inhibition of cell proliferation and induction carcinogen] treated rats, inclusion of of apoptosis. Furthermore, diosgenin was fenugreek seed powder in their DMH treated found to inhibit migration and invasion of diet reduced the colon tumor incidence to prostate cancer PC-3 cells by reducing 16.6 % through modulation of DMH- matrix metalloproteinases expression. It also induced oxidative stress [65]. Chatterjee et inhibited extracellular signal regulating al reported a chemopreventive activity of the kinase (ERK), c-Jun N-terminal kinase methanolic extract of fenugreek seeds on (JNK) and phosphatidylinositide-3 kinase 7,12-dimethylbenz [a] anthracene (DMBA) (PI3K/Akt) signaling pathways as well as induced skin papilloma genesis in Swiss nuclear factor kappa B (NF-Κb) activity albino mice. They supposed that the [61]. Das et al also showed that diosgenin inhibition of tumorigenesis by the seed alone or in combination with Thymoquinone extract might have been executed either by obtained from black (Nigella sativa preventing the formation of active L.) inhibit cell proliferation and induce carcinogens from their precursors or by apoptosis in squamous cell carcinoma [62]. augmenting detoxification process, The antineoplastic effect of Trigonella preventing promotional events in the mouse foenum graecum seed extract has been also skin through free radical scavenging evaluated in the Ehrlich ascites carcinoma mechanism. The chemopreventive activity (EAC) model in Balb-C mice. Intra- of the methanolic extract of fenugreek seeds peritoneal administration of the alcohol may be due to the rich chemical constituents extract of the seed both before and after (such as, saponins, flavonoids, alkaloids, inoculation of EAC cell in mice produced galactomannans) that are present in the seed more than 70 % inhibition of tumour cell working synergistically at various stages of growth with respect to the control. angiogenesis [66]. Fenugreek tea was Treatment with the extract was found to reported to have an ability to inhibit further enhance both the peritoneal exudate cell and growth of cancer cells without harming the macrophage cell counts. The extract also healthy cells of the body. Shabbeer et al produced a significant anti-inflammatory demonstrated that fenugreek extract were effect [63]. cytotoxic in vitro to a panel of cancers but not normal cells. Treatment with 10-15 The effects of Protodioscin (PD) which was µug/mL of fenugreek extract for 72h was purified from fenugreek on cell viability in growth inhibitory to breast, pancreatic and human leukemia HL-60 and human stomach prostate cancer cell lines [67]. cancer KATO III cells were investigated.

AJSIH | ISSN: 2276 – 6928 Fenugreek Special Issue Mar/Apr 2014 | Editors: S. K. Basu & G. Agoramoorthy | 26 AMERICAN

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Use of fenugreek in arthritis additives [73, 74]. The antimicrobial Rheumatoid arthritis is an autoimmune activities of plant extracts may reside in a disease and estrogen-like compounds have variety of different components, including been known to inhibit inflammation of tissue aldehyde and phenolic compounds. Many by activating pathways that counteract the studies had reported the antibacterial activity effects of autoimmunity disorders through of fenugreek. Omolosa and Vagi reported binding of estrogen metabolites to DNA strong activity of T. foenum-graecum against [68]. Fenugreek has been shown to stall 26 bacterial pathogens [75]. Randhir et al auto-immune disorders by acting as a mimic observed a high antimicrobial activity of estrogen. Sreeja et al found that fenugreek against peptic ulcer-linked Helicobacter bound to estrogen receptors and acted as pylori in the fenugreek sprout extract. They estrogen by influencing genetic activities hypothesized that in fenugreek sprouts, and inducing the expression of estrogen- simple free phenolics that are less responsive proteins [69]. In another study, polymerized have more antimicrobial Ethanol extract of fenugreek was tested function [76]. Phenolic-type antimicrobial against Freund's complete adjuvant-induced agents have long been used for their arthritis in rats. It was found that the antiseptic, disinfectant, or preservative activities of cyclooxygenase-2 and properties [77]. Methanol extract of myeloperoxidase and concentration of fenugreek (Trigonella foenum-graecum L.) thiobarbituric acid reactive substance were and (Coriandrum sativum L.) decreased and the activities of antioxidant revealed an elevated antimicrobial activity enzymes, vitamins C and reduced against Pseudomonas spp., , glutathione level were increased on Shigella dysentiriae and Salmonella typhi treatment with fenugreek . The [78]. Also it was reported that fatty oil of increment in erythrosedmintation rate (ESR) fenugreek seeds showed very significant and total white blood cells (WBC), antimycotic activity against Aspergillus reduction in red blood cells (RBC) count niger and A. fumigates [79]. and hemoglobin and aberrant changes to the C-reactive protein (CRP) levels observed in Effect of fenugreek on body weight the arthritic animals were also found to be Fenugreek seeds have long been used as a significantly restored in fenugreek mucilage for treating metabolic and treated rats. Histo-pathological examination nutritive dysfunctions. Some studies also revealed decreased edema formation indicated that fenugreek seed extract and cellular infiltration on supplementation supplementation may reduce the body and with fenugreek mucilage [70]. Vyas et al adipose tissue weight [80, 81]. A 6-week reported that combination of fenugreek, double-blind randomized placebo-controlled Boswellia and Acacia shows restoration of parallel trial of a fixed dose of a fenugreek vascular and endothelial dysfunction caused seed extract on 39 healthy overweight male by chronic arthritis in rats [71]. It was volunteers revealed that repeated hypothesized that the anti-inflammatory and administration of a fenugreek seed extract antioxidant activities of T. foenum graecum slightly but significantly decreased dietary L. may be the possible reason behind the fat consumption in those healthy overweight observed anti-arthritic activity [72]. subjects [82]. The probable mechanism of fenugreek decreasing the total body and Antimicrobial effects of fenugreek adipose tissue weight may be that fenugreek Herbal extracts are fast becoming popular as flushes out the carbohydrates from the body natural antimicrobial preservatives or

AJSIH | ISSN: 2276 – 6928 Fenugreek Special Issue Mar/Apr 2014 | Editors: S. K. Basu & G. Agoramoorthy | 27 AMERICAN

OPEN ACCESS JOUR OF SOCIAL ISSUES N AND HUMANITIES AL before they enter the blood stream resulting formulation [90]. Fenugreek was also in weight loss. Also, fenugreek seeds reported to be a useful adjuvant treatment contain a high proportion (40 %) of soluble with L-Dopa in management of Parkinson's fiber. This fiber forms a gelatinous structure disease patients [91]. Reduction in cataract (similar to gaur gum) which may have incidence has been demonstrated in diabetic effects on slowing the digestion and rats receiving an extract of fenugreek seeds absorption of food from the intestine and and leaves [92]. Another study showed a creates a sense of fullness in the abdomen, significant delay in the onset and thus suppresses appetite and promotes progression of galactose-induced cataracts in weight loss [81]. The 4-hydroxyisoleucine rats fed on 2.5 % fenugreek diet [93]. component of fenugreek extract may also Fenugreek leaves extract can exert analgesic decrease plasma triglyceride gain effects. Trigonella foenum-graecum extract consequently leading to prevent the obesity may have analgesic activity similar to non- induced by a high-fat diet [80]. steroidal anti-inflammatory drugs (NSAIDs) [94]. Analgesic effects of fenugreek seed Other uses of fenugreek extract were shown in other studies, perhaps Both leaves and seeds of fenugreek were by decreasing inflammation[95], or the advised because of their haematinic value. It blocking of spinal purinoceptors may was reported that the seeds contain high contribute to the analgesic effect of amounts of iron and germination of the Trigonella foenum-graecum leaves extract fenugreek improves its vitamins A, B and C [96]. Wound healing properties of fenugreek content. They are rich in proteins with seeds have also been demonstrated in essential amino acids, Ascorbate and Folate excision, incision and dead-space wound content, have restorative and nutritive models in rats [97]. properties and were found to raise blood haemoglobin [83]. T. foenum-graecum Adverse effects extract indicated a stimulatory influence on Although fenugreek has traditionally been immune functions in mice through considered safe and well tolerated, some increasing the phagocytic index and side effects have been associated with its phagocytic capacity of macrophages [84]. use. Caution in using fenugreek is warranted Fenugreek may correlate with increased in patients known to be allergic to it or who milk production [85]. Fenugreek has also are allergic to chickpeas because of possible been used to protect liver from ethanol- cross-reactivity [9]. Hypersensitivity induced hepatotoxicity [86], aluminum reactions that have been reported including chloride (AlCl3) induced hepatotoxicity rhinorrhea, wheezing and fainting after [87], and regulate hyperthyroidism [88]. It inhalation of the fenugreek- seed powder was found to be useful therapeutic agent in [98] and facial angioedema after application allergic inflammatory diseases. In animal of a topical fenugreek paste for dandruff [9]. study, fenugreek extract cures T-helper 2 is an expected effect; (Th2)-induced allergic skin inflammation by therefore, monitoring of blood glucose enhancing T-helper 1 (Th1) differentiation levels should be taken once starting [89]. An emulsion containing fenugreek supplementation [31]. Fenugreek may seeds extract using liquid paraffin oil was increase the risk of bleeding due to its applied to the cheeks of human volunteers coumarin content [99]. The effects of for six weeks. A significant decrease in skin fenugreek on haematopoietic stem cell of melanin and erythma was produced by that bone marrow were reported. Fenugreek in

AJSIH | ISSN: 2276 – 6928 Fenugreek Special Issue Mar/Apr 2014 | Editors: S. K. Basu & G. Agoramoorthy | 28 AMERICAN

OPEN ACCESS JOUR OF SOCIAL ISSUES N AND HUMANITIES AL teratogenic dosages can decrease the attention in medicine due to the rising severity of bone marrow cell proliferation popular concern about their safety. and increase fetal mortality rate [100]. A However, the long-term safety for use as potential antifertility activity of fenugreek herbal medicinal products has not been had been reported in rabbits fed diets established; fenugreek an herb that may hold containing 30 % fenugreek [101]. Dyspepsia promise in this regard. Depending on human and mild abdominal distention have been and animal studies, fenugreek had been reported in studies using large doses of the considered by many researchers as a seeds [32]. Mild central nervous stimulation, potential medicinal herb particularly as an rapid respiration and tremors were observed anti-diabetic, hypolipidemic and an anti- following high doses of the aqueous extract oxidant agent. It has an influence on of fenugreek [102, 103]. immune functions, anticancer properties, antimicrobial, gastro and cardioprotective Interactions with other drugs effects, anti-arthritic and vascular protective Caution in using fenugreek with some drugs effect. However, many of its effects are should be warranted. Because of its subjected to lack of clinical trials coumarin constituents, it may potentially confirmation. Furthermore, fenugreek can enhance the effect of drugs cause undesired effects and it is also [104]. Also, due to its high content of fiber reported to interact with many drugs. which is mucilaginous and has high Therefore, detailed clinical studies are viscosity in the gut, fenugreek may decrease needed to strengthen these findings and to or delay absorption of concomitant oral evaluate the pharmacological properties and medications [105]. Since fenugreek was effects of fenugreek. reported to reduce potassium level in some healthy subjects [26], it may precipitate REFERENCES hypokalemia when used with some diuretics, 1. Horne SH. Natural remedies for laxatives or other hypokalemic agents. common health conditions: A guide to Because of its hypoglycemic effects, herbs and supplement for specific fenugreek may have additive hypoglycemic heath problems. Available online at: activity when used with other anti-diabetic www.treelite.com/downloads/Natural- medication [106]. Although, some herbalists Remedies.pdf advocate its use during prolonged labor, use (Accessed February 10, 2013) of fenugreek during pregnancy should be 2. Vuorelaa M, Leinonenb M, Saikkuc P, avoided because it has documented uterine Tammelaa P, Rauhad JP, Wennberge T stimulant effects. In addition, and Vuorela H. Natural products in the urine disease, a disorder of branched-chain process of finding new drug amino acid catabolism that results in candidates. Curr Med Chem 2004; abnormal accumulations of the amino acids 11(11): 1375-1389. and their metabolites, was suspected in a 3. Gupta LM and Raina R. Side effects healthy infant born to a mother who ingested of some medicinal plants. Curr Sci a paste prepared from fenugreek seeds early 1998;75: 897-900. in labo [107]. 4. Fenugreek seeds. Available from: http://chestofbooks.com/health/materia CONCLUSION -medica-drugs/Textbook-Materia- Natural products have been a major source Medica/Fenugreek-Seeds-Semina- of new drugs. Herbs have gained more

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Foeni-Graeci.html. (Accessed 12. Yoshikawa M, Murakami T, Komatsu February 15, 2013) H, Murakami N, Yamahara J and 5. Basu S, Acharya S, Bandara M and Matsuda H. Medicinal Foodstuffs: IV. Thomas J. Agronomic and genetic Fenugreek seeds (1): structures of approaches for improving seed quality trigoneosides Ia, Ib, IIb, IIIa and IIIb and yield of fenugreek (Trignella new furostanol saponins from the foenum-graceum L.) in western seeds of Indian Trigonella foenum- Canada. In: Proc. Science of Changing graecum L. Chem Pharmacol Bull Climates-Impact on Agri., Forest. 1997; 45: 81-87. Wetlands, Univ. of Alberta, 13. Sharma RD, Raghuram TC and Rao Edmonton, AB, Canada, 2004, pp. 38. NS. Effects of fenugreek seeds on 6. Passano P. The Many Uses of Methi. blood glucose and serum lipid in type I No. 91(November-December 1995) diabetes. Eur J clin nutr 1990; 44: MANUSHI. Available online at: 301-306 www.manushi- 14. Ajabnoor MA and Tilmisany AK. india.org/.../nutrition_methi.pdf. Effect of Trigonella foenum-graecum (Accessed March 18, 2013). on blood glucose levels in normal and 7. Morcos SR, Elhawary Z and Gabrial alloxan-diabetic mice. J GN. Proteinrich food mixtures for Ethnopharmacol 1998; 22: 45-49. feeding the young in Egypt. 1. 15. Natural Medicines Comprehensive Formulation. Z Ernahrungswiss 1981; Database. Available online at: 20:275-282. http://www.naturaldatabase.com/mono 8. Yoshikawa M, Murakami T, Komatsu graph.asp?mono_id=733&hilite=1(Ac H, Murakami N, Yamahara J and cessed May 26. 2013). Matsuda H. Medicinal foodstuffs. IV. 16. Belguith-Hadriche O, Bouaziz M, Fenugreek seed. (1): structures of Jamoussi K, El Feki A, Sayadi S and trigoneosides Ia, Ib, IIa, IIb, IIIa, and Makni-Ayedi F. Lipid-lowering and IIIb, new furostanol saponins from the antioxidant effects of an ethyl acetate seeds of Indian Trigonella foenum- extract of fenugreek seeds in high- graecum L. Chem Pharm Bull cholesterol-fed rats. J Agric Food Che. 1997;45(1):81-87. 2010; 58(4):2116-2122. 9. Patil SP, Niphadkar PV and Bapat 17. Pandian RS, Anuradha CV and MM. Allergy to fenugreek (Trigonella Viswanathan P. Gastroprotective effect foenum graecum). Ann Allergy Asthma of fenugreek seeds (Trigonella foenum Immunol 1997; 78:297-300. graecum) on experimental gastric ulcer 10. Granick B, Neubauer D and in rats. J Ethnopharmacol 2002; 81: DerMarderosian A (Eds). The 393-397. Lawrence review of natural products. 18. Max B. This and That: The essential St. Louis: Facts and Comparisons; pharmacology of herbs and 1996, Pp: 1-3. Trends. Pharma Sci 1992; 13: 15-20. 11. Snehlata HS and Payal DR. 19. Suresh P, Kavitha ChN, Babu SM, Fenugreek (Trigonella foenum- Reddy VP and Latha AK. Effect of graecum L.): An Overview. IJCPR ethanol extract of Trigonella foenum November 2011-January 2012; 2(4); graecum (Fenugreek) seeds on 169-187. Freund's adjuvant-induced arthritis in

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albino rats. Inflammation 2012; of Family Medicine 2012;10(10):38- 35(4):1314-1321. 44. 20. Thirunavukkarasu V, Anuradha CV, 29. Broca C, Gross R, Petit P, Sauvaire Y, and Viswanathan P. Protective effect Manteghetti M, Tournier M, et al. 4- of fenugreek (Trigonella foenum Hydroxyisoleucine: experimental graecum) seeds in experimental evidence of its insulinotropic and ethanol toxicity. Phytother Res 2003; antidiabetic properties. Am J Physiol 17: 737-743. Endocrinol Metab 2004; 287(3): 21. American Diabetes Association. E463–471. Diagnosis and classification of 30. Al-Khateeb E, Hamadi SA, Al- diabetes mellitus. Diabetes Care 2009; Hakeemi AAN, and Abu-Taha M, Al- 32: S62-267. Rawi N. Hypoglycemic effect of 22. Bailey CJ and Day C. Traditional trigonelline isolated from Iraqi plant medicines as treatments for Fenugugreek seeds in normal and diabetes. Diabetes Care 1989; 12:553- Alloxan-diabetic rabbits. European 564. Scientific Journal 2012; 8(3). [Online] 23. Jarald E, Joshi SB and Jain D. 31. Sharma RD and Raghuram TC. Diabetes and Herbal Medicines. Hypoglycaemic effect of fenugreek Iranian Journal of Pharmacology and seeds in non-insulin dependent Therapeutics 2008; 7(1): 97-106. diabetic subjects. Nutr Res 1990; 10: 24. Bawadi HA, Maghaydah SN, Tayyem 731-739. RF and Tayyem RF. The Postprandial 32. Gupta A, Gupta R and Lal B. Effect of Hypoglycemic Activity of Fenugreek Trigonella foenum-graecum Seed and Seeds' Extract in Type 2 (fenugreek) seeds on glycaemic Diabetics: A Pilot Study. control and insulin resistance in type 2 Pharmacognosy Magazine 2009; diabetes mellitus: a double blind 5(18): 134–138. placebo controlled study. J Assoc 25. Srinivasan K. Fenugreek (Trigonella Physicians India 2001; 49:1057-1061. foenum-graceum): A review of health 33. Kassaian N, Azadbakht L, Forghani B beneficial physiological effects. Food and Amini M. Effect of fenugreek Rev Int 2006;22: 203-224. seeds on blood glucose and lipid 26. Abdel-Barry JA, Abdel-Hassan IA profiles in type 2 diabetic patients. Int and Al-Hakiem MHH. J Vitam Nutr Res 2009; 79(1): 34–39. Hypoglycaemic effect of aqueous 34. Shakib MC and Gabrial SGN. Post- extract of the leaves of Trigonella prandial responses to different bread foenum-graecum in healthy volunteers. products based on wheat, barley and Eastern Mediterranean Health Journal fenugreek or or both in healthy 2000; 6(1): 83-88. volunteers and their effect on the 27. Al- Rowais NA. Herbal medicine in glycemic index of such products. J Am the treatment of diabetes mellitus. Sci 2010; 6(10): 89–96. Saudi Medical Journal 2002; 23:1327- 35. Sharma RD. Effect of fenugreek seeds 1331. and leaves on blood glucose and serum 28. Al-Asadi JN and Salih N. Herbal insulin responses in human subjects. remedies use among diabetic patients Nutr. Res. 1986; 6:1353–1364. in Nassyria, Iraq. Middle East Journal 36. Yin W, Yuan Z, Tsutsumi K, Xie Y, Zhang Q, Wang Z, Fu G and Long G,

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Yang Y. A lipoprotein lipase- 44. Memon AR, Shah SS, Memon AR promoting agent, NO-1886, improves and Naqvi SHR. Effect of glucose and lipid metabolism in high combination of Nigella sativa and fat, high sucrose-fed New Zealand Trigonella foenum-graecum with white rabbits. Int J Exp Diabesity Res. Glibenclamide on serum triglycerides, 2003;4(1):27-34. HDL, and Creatinine levels in type 2 37. Sauvaire Y, Petit P, Broca C, diabetes mellitus patients. Pakist. J Mantehgetti AK, Baissac Y, Pharmac 2012;29(1): 1-6. Fernandez-Alvarez J, et al. 4- 45. Basch E, Ulbricht C, Kuo G, Szapary hydroxyleucine: a novel amino acid P and Smith M. Therapeutic potentiator of insulin secretion. applications of fenugreek. Alternative Diabetes 1998; 47: 206-210. Medicine Review 2003; 8(1): 20-27. 38. Baquer NZ, Kumar P, Taha A, Kale 46. Muraki E, Hayashi Y, Chiba H, RK, Cowsik SM and Mclean P. Tsunoda N and Kasono K. Dose- Metabolic and molecular action of dependent effects, safety and Trigonella foenum-graecum tolerability of fenugreek in diet- (fenugreek) and trace metals in induced metabolic disorders in rats. experimental diabetes tissues. J Biosci Lipids Health Dis. 2011;10:240. 2011; 36: 383-396. 47. Sauvaire Y, Ribes G, Baccou JC and 39. Al-Habori M, Raman A, Lawrence Loubatieères-Mariani MM. MJ and Skett P. In vitro effect of Implication of steroid saponins and fenugreek extracts on intestinal sapogenins in the hypocholesterolemic sodium-dependent glucose uptake and effect of fenugreek. Lipids hepatic glycogen phosphorylase A. Int 1991;26:191-197. J Exp Diabetes Res 2001;2: 91–99. 48. James H. Atrovastatin reduces 40. Raghuram TC, Sharma RD, remnant lipoproteins and small, dense Sivakumar and Sahay BK. Effect of low-density lipoprteins regardless of fenugreek seeds on intravenous the baseline lipid pattern. Prev glucose disposition in non-insulin Cardiol 2004; 7: 154-60. dependent diabetic patients. Phytother 49. Murugesan M, Revathi R and Manju Res 1994;8:83–86. V. Cardioprotective effect of 41. Sharma RD, Raghuram TC and fenugreek on isoproterenol-induced Dayasagar Rao V. Hypolipidaemic myocardial infarction in rats. Indian J effect of fenugreek seeds: A clinical Pharmacol. 2011; 43(5): 516–519. study. Phytother Res 1991;3:145-147. 50. Moosa ASM, Rashid MU, Asadi 42. Mitra A and Bhattacharya D. Dose- AZS, Ara N, Uddin MM, and Ferdaus dependent effects of Fenugreek A. Hypolipidemic effects of fenugreek composite in Diabetes with seed powder. Bangladesh J dislipidaemia. Internet Journal of Pharmacol 2006; 1: 64-67. Food Safety 2006;8:49-55. 51. Pandian RS, Anuradha CV and 43. Sowmya P and Rajyalakshmi P. Viswanathan P. Gastroprotective effect Hypocholesterolemic effect of of fenugreek seeds (Trigonella germinated fenugreek seeds in human foenum- graecum) on experimental subjects. Plant Foods Hum Nutr gastric ulcer in rats. J 1999;53:359-365. Ethnopharmacol. 2002;81(3):393-397.

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52. Al-dalain S, El-kutry M and Ibrahim Damodaran C. Diosgenin targets Akt- HS. Inhibitory Effect of Aqueous mediated prosurvival signaling in Extracts of Barley and Fenugreek on human breast cancer cells. Int J Ulcer Induction in Rats. World Applied Cancer 2009;125(4):961-967. Sciences Journal 2008;5(3): 332-339. 61. Chen PS, Shih YW, Huang HC and 53. Helmy HM. Study the Effect of Cheng HW. Diosgenin, a Steroidal Fenugreek Seeds on Gastric Ulcer in Saponin, Inhibits Migration and Experimental Rats. World Journal of Invasion of Human Prostate Cancer Dairy & Food Sciences 2011;6(2): PC-3 Cells by Reducing Matrix 152-158. Metalloproteinases Expression. PLoS 54. Gálvez J, De Medina FS, Jiménez J One 2011; 6(5): e20164. and Zarzuelo A. Effects of flavonoids 62. Das S, Dey KK, Dey G, Pal I, on gastrointestinal disorders. Studies in Majumder A, MaitiChoudhury S, natural products chemistry 2001; 25: kundu SC and Mandal M. 607-649. Antineoplastic and apoptotic potential 55. Choi SM, Shin JH, Kang KK, Ahn of traditional medicines thymoquinone BO and Yoo M. Gastroprotective and diosgenin in squamous cell effects of DA-6034, a new carcinoma. PLoS One derivative, in various gastric mucosal 2012;7(10):e46641 damage models. Dig Dis Sci. 63. Sur P, Das M, Gomes A, 2007;52(11):3075-3080. Vedasiromoni JR, Sahu NP, Banerjee 56. Madar Z and Shomer I. S, Sharma RM and Ganguly DK. Polysaccharide composition of a gel Trigonella foenum- graecum fraction derived from fenugreek and its (fenugreek) seed extract as an effect on starch digestion and bile acid antineoplastic agent. Phytother Res. absorption in rats. J. Agricultural Food 2001;15(3):257-259. Chemistry 1990; 38: 1535-1539. 64. Hibasami H, Moteki H, Ishikawa K, 57. Szabo S, Nagy L and Plebani M. Katsuzaki H, Imai K, Yoshioka K, Glutathione, protein sulfhydryls and Ishii Y and Komiya T. Protodioscin cysteine proteases in gastric mucosal isolated from fenugreek (Trigonella injury and protection. Clinica chimica foenum-graecum L.) induces cell death acta; international journal of clinical and morphological change indicative chemistry 1992;206(1-2): 95-105. of apoptosis in leukemic cell line H- 58. López A, Motilva V, Alarcón de la 60, but not in gastric cancer cell line Lastra C, Martín MJ and La Casa C. KATO III. Int J Mol Med. The role of gastric mucosal 2003;11(1):23-26. sulphydryls in the ulcer-protecting 65. Devasena T and Venugopal MP. effects of cisapride. The Journal of Fenugreek seeds modulate 1,2- pharmacy and pharmacology 1996; dimethylhydrazine-induced hepatic 48(1): 37-40. oxidative stress during colon 59. Zhilenko VV, Zalietok SP and Klenov carcinogenesis. Ital J Biochem. OO. Effect of fenugreek on the growth 2007;56(1):28-34. of different genesis tumors. Lik 66. Chatterjee S, Kumar M, and Kumar Sprava. 2012;(5):133-139. A. Chemomodulatory Effect of 60. Srinivasan S, Koduru S, Kumar R, Trigonella foenum graecum (L.) Seed Venguswamy G, Kyprianou N and Extract on Two Stage Mouse Skin

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Carcinogenesis. Toxicol Int. 2012; edible Irish seaweeds. International 19(3): 287–294. Food Research Journal 2010;17: 205- 67. Shabbeer S, Sobolewski M, Anchoori 220 RK, Kachhap S, Hidalgo M, Jimeno A, 75. Omolosa AD and Vagi JK. Broad- et al. Fenugreek: a naturally occurring spectrum antibacterial activity of edible as an anticancer agent. Trigonella foenum-graecum. Nat. Cancer Biol Ther. 2009;8(3):272-278. Prod. Sci. 2001;7(1): 13-16. 68. Khan WA, Moinuddin and Assiri AS. 76. Randhir R, Lin YT and Shetty K. Immunochemical studies on catechol- Phenolics, their antioxidant and estrogen modified plasmid: possible antimicrobial activity in dark role in rheumatoid arthritis. J Clin germinated fenugreek sprouts in Immunol. 2011;31(1):22-29. response to peptide and phytochemical 69. Sreeja S, Anju VS and Sreeja S. In elicitors. Asia Pac J Clin Nutr 2004;13 vitro estrogenic activities of fenugreek (3):295-307. Trigonella foenum graecum seeds. 77. Hugo WB and Bloomfield SF. Studies Indian J Med Res 2010;13:814-819. on the mode of action of the phenolic 70. Sindhu G, Ratheesh M, Shyni GL, antibacterial agent Fentichlor against Nambisan B, and Helen A. Anti- Staphylococcus aureus and inflammatory and antioxidative effects Escherichia coli. III. J Appl Bacteriol of mucilage of Trigonella foenum 1971; 34 : 579-591. graecum (Fenugreek) on adjuvant 78. Dash BK, Sultana S and Sultana N. induced arthritic rats. Int Antibacterial Activities of Methanol Immunopharmacol. 2012;12(1):205- and Acetone Extracts of Fenugreek 211. (Trigonella foenum) and Coriander 71. Vyas AS, Patel NG, Panchal AH, (Coriandrum sativum). Life Sci Med Patel RK and Patel MM. Anti-Arthtitic Res 2011, 27:1-8. and vascular protective effects of 79. Wagh P, Rai M, Deshmukh SK and Fenugreek. Boswellia and Catechu Durate MCT. Bio-activity of oils of alone and in combinations. Pharma Trigonella foenum-graecum and Science Monitor 2010;1(2): 95-111. Pongamia pinnata. African Journal of 72. Suresh P, Kavitha ChN, Babu SM, Biotechnology 2007; 6 (13):1592- Reddy VP and Latha AK. Effect of 1596. ethanol extract of Trigonella foenum 80. Handa T, Yamaguchi K, Sono Y and graecum (Fenugreek) seeds on Yazawa K. Effects of fenugreek seed Freund's adjuvant-induced arthritis in extract in obese mice fed a high-fat albino rats. Inflammation diet. Biosci.Biotechbol.Biochem 2005; 2012;35(4):1314-1321. 69(6):1186-1188. 73. Pazos M, Alonso A. Sanchez I and 81. Geetha M, Suneel KR, Krupanidhi Medina I. Hydroxytyrosol prevents AM, Muralikrishna K S, Avin A P and oxidative deterioration in foodstuffs Prashanth P. Effect of Fenugreek on rich in fish lipids. Journal of Total Body and Organ Weights: A Agricultural Food Chemistry Study on Mice. Pharmacologyonline 2008;56(9): 3334-3340. 2011;3:747-752. 74. Cox S, Abu-Ghannam N and Gupta S. 82. Chevassus H, Gaillard JB, Farret A, An assessment of the antioxidant and Costa F, Gabillaud I, Mas E, et al. A antimicrobial activity of six species of fenugreek seed extract selectively

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reduces spontaneous fat intake in cream containing extract of fenugreek overweight subjects. Eur J Clin seeds. Acta Pol Pharm. Pharmacol. 2010;66(5):449-455. 2010;67(2):173-178. 83. Doshi M, Mirza A, Umarji B, and 91. Nathan J, Panjwani S, Mohan V, Joshi Karambelkar R. Effect of Trigonella V and Thakurdesai PA. Efficacy and foenum-graecum (Fenugreek/ Methi) Safety of Standardized Extract of on Hemoglobin Levels in Females of Trigonella foenum-graecum L Seeds Child Bearing Age. Biomedical as an Adjuvant to L-Dopa in the Research 2012; 23 (1): 47-50. Management of Patients with 84. Bin-Hafeez, B, Haque R, Parvez S, Parkinson's Disease. Phytother Res. Pandey S, Sayeed I and Raisuddin S. 2013 Mar 20. doi: 10.1002/ptr.4969. Immunomodulatory effects of 92. Vats V, Yadav SP, Biswas NR and fenugreek (Trigonella foenum graecum Grover JK. Anti-cataract activity of L.) extract in mice. Int. Pterocarpus marsupium bark and Immunopharmacol 2003;3: 257-265. Trigonella Foenum-graecum seeds 85. Zapantis A, Steinberg JG and Schilit extract in alloxan diabetic rats. J L. Use of as galactagogues. J Ethnopharmacol 2004;93:289-294. Pharm Pract 2012;25(2):222-231. 93. Kumar GS, Kalaiselvan V, Srivastava 86. Kaviarasan S and Anuradha CV. S, Saxena R and Sunder Agrawal S. Fenugreek (Trigonella foenum Inhibitory Effect of Trigonella graecum) seed polyphenols protect Foenum-Graecum on Galactose liver alcohol toxicity: A role on Induced Cataracts in a Rat Model; in hepatic detoxification system and vitro and in vivo Studies. J Ophthalmic apoptosis. Pharmazi 2007; 62: 299- Vis Res. 2009;4(4):213-219. 304. 94. Parvizpur A, Ahmadiani A, and 87. Belaïd-Nouira Y, Bakhta H, Haouas Kamalinejad M. Spinal serotonergic Z, Flehi-Slim I, Neffati F, Najjar MF system is partially involved in and Cheikh HB. Fenugreek seeds, a antinociception induced by Trigonella hepatoprotector forage crop against foenum-graecum (TFG) leaf extract. J chronic AlCl(3) toxicity. BMC Vet Ethnopharmacol. 2004;95(1):13-17. Res. 2013;9:22. 95. Vyas S, Agrawal RP, Solanki P, 88. Tahiliani P and Kar A. The combined Trivedi P. Analgesic and anti- effects of Trigonella and Allium inflammatory activities of Trigonella extracts in the regulation of foenum-graecum (seed) extract. Acta hyperthyroidism in rats. Pol Pharm. 2008;65(4):473-476. Phytomedicine 2003;10: 665-668. 96. Parvizpur A, Ahmadiani A, 89. Bae MJ, Shin HS, Choi DW and Shon Kamalinejad M. Probable role of DH. Antiallergic effect of Trigonella spinal purinoceptors in the analgesic foenum-graecum L. extracts on allergic effect of Trigonella foenum (TFG) skin inflammation induced by leaves extract. J Ethnopharmacol. trimellitic anhydride in BALB/c mice. 2006;104(1-2):108-112. J Ethnopharmacol 2012;144(3):514- 97. Taranalli AD and Kuppast IJ. Study of 522. wound healing activity of seeds of 90. Waqas MK, Akhtar N, Ahmad M, Trigonella foenum graecum in rats. Murtaza G, Khan HM, Iqbal M, et al. Ind. J. Pharm. Sci. 1996;58(3):117– Formulation and characterization of a 119.

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98. Ohnuma N, Yamaguchi E and 103. Javan M. Ahmadiani A, Semanaian S Kawakami Y. Anaphylaxis to and Kamalinejad M. Antinoceptive powder. Allergy 1998;53:452-454. effects of T. foenum-graceum leaves 99. Lambert JP and Cormier A. Potential extract. J Ethnopharmacol interaction between warfarin and 1997;58:125-129. -fenugreek. Pharmacotherapy 104. Heck AM, DeWitt BA and Lukes AL. 2001;21(4):509-512. Potential interactions between 100. Araee M, Norouzi M, Habibi G and alternative therapies and warfarin. Am Sheikhvatan M. Toxicity of Trigonella J Health Syst Pharm. Foenum Graceum (Fenugreek) in bone 2000;57(13):1221-1227. marrow cell proliferation in rat. Pak J 105. Basch E, Ulbricht C, Kuo G, Szapary Pharm Sci 2009;22(2):126-130. P and Smith M. Therapeutic 101. Kassem A, Al-Aghbari A, AL-Habori Applications of Fenugreek. Altern Med M and Al-Mamary M. Evaluation of Rev 2003;8(1):20-27. the potential antifertility effect of 106. Vijayakumar MV and Bhat MK. fenugreek seeds in male and female Hypoglycemic effect of a novel rabbits. Contraception. dialysed fenugreek seeds extract is 2006;73(3):301-306. sustainable and is mediated, in part, by 102. Abdel-Barry JA, Abdel-Hassan IA and the activation of hepatic enzymes. Al-Hakiem, MHH. Hypoglycaemic Phytother Res 2008;22(4):500-505. and anti-hyperglycaemic effects of 107. Korman SH, Cohen E and Preminger Trigonella foenum-graecum leaf in A. Pseudo-maple syrup urine disease normal and alloxan induced diabetic due to maternal prenatal ingestion of rats. J Ethnopharmacol 1997;58, 149– fenugreek. J Paediatr Child Health 155. 2001;37:403-404

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