Therapeutic Uses and Pharmacological Action of Trigonella foenum-Graecum Linn

 

Ajay Kr Meena1, Brijendra Singh2*, Uttam Singh2, Ajay Kr. Yadav2, Amit Nagariya2 and Kiran Sharma2

1National Institute of Ayurvedic Pharmaceutical Research, Patiala -147001, Punjab, (India).

2 School of Pharmaceutical Sciences, Shobhit University, Meerut, UP.

 

ABSTRACT

The medicinal plants are widely used by the traditional medical practitioners for curing various diseases in their day to day practice. Since ancient times, plants have been an exemplary source of medicine. Ayurveda and other Indian literature mention the use of plants in treatment of various human ailments. The leaves and seeds of Trigonella foenum-graecum Linn or fenugreek (known as Methi in Hindi), a small herb seen throughout India, have been recommended for the treatment of carminative, diuretics, small-pox, dysentery and also useful in the making of tonic. In folk medicine, Trigonella foenum-graecum has been used in the treatment of boils, cellulitis, and tuberculosis. The Trigonella foenum-graecum Linn. has also been suggested to possess Cholesterol-lowering effects, Glucose-lowering effects, Anti-inflammatory effects, Antioxidant effects and Antitumor  actions.

 

 

KEY WORDS: Medicinal plants, Trigonella foenum graecum Linn., Antioxidant, Ayurveda.

 

INTRODUCTION

Plants are one of the most important sources of medicines. Today the large number of drugs in use is derived from plants, like morphine from Papaver somniferum, aswagandhin from Withania somnifera, Ephedrine from Ephedra vulgaris, Atropine from Atropa belladonna, Reserpine from Roulphia serpentina etc. The medicinal plants are rich in secondary metabolites, which are potential sources of drugs and essential oils of therapeutic importance. The important advantages claimed for therapeutic uses of medicinal plants in various ailments are their safety besides being economical, effective and their easy availability1, 2. In traditional systems of medicine the Indian medicinal plants have been used in successful management of various disease conditions like bronchial asthma, chronic fever, cold, cough, malaria, dysentery, convulsions, diabetes, diarrhea, arthritis, emetic syndrome, skin diseases, insect bite etc. and in treatment of gastric, hepatic, cardiovascular and immunological disorders1,3-6.

 

Among the plants known for medicinal value, the plants of genus Trigonella foenum graecum Linn belonging to family fabaceae are very important for their therapeutic potentials. Trigonella foenum-graecum is commonly known as maithray (Bangla, Gujarati), methi or mithi (Hindi, Nepali, Marathi, Urdu and Sanskrit), menthyada soppu (Kannada), ventayam (Tamil), menthulu (Telugu), hilbeh (Arabic), ulluva (Malayalam) and shambalîleh (Persian)7. The species name "foenum graecum" means "Greek hay" indicating its use as a forage crop in the past Trigonella foenum-graecum is one of the oldest known medicinal plants in the recorded history8,9. Trigonella foenum-graecum grows as an erect annual with long, slender stems reaching 30 to 60 cm in height. The plant bears grey-green, tripartite, toothed leaves. White or pale yellow flowers appear in summer and develop into long, slender, sword-shaped seed pods with a curved, beak-like tip.


Each pod contains about 10 to 20 small, yellowish-brown, angular seeds. These are dried to form the commercial spice. The plant thrives in full sun on rich, well-drained soils and has a spicy odour that remains on the hands after contact.

 

Therapeutic uses of Trigonella foenum-graecum Linn:

Trigonella foenum-graecum leaves and seeds have been used extensively to prepare extracts and powders for medicinal uses10. In traditional medicines it is used as an aphrodisiac, astringent, demulcent, carminative, stomachic, diuretic, emmenagogue, emollient, expectorant, lactogogue, restorative, and tonic  Trigonella foenum-graecum is used for a variety of health conditions, including digestive problems, bronchitis, tuberculosis, fevers, sore throats, wounds, arthritis, abscesses, swollen glands, skin irritations, diabetes, loss of appetite, ulcers and menopausal symptoms, as well as in the treatment of cancer. An infusion of the leaves is used as a gargle for recurrent mouth ulcers. As an emollient it is used in poultices for boils, cysts and other complaints. It is used to reduce blood sugar level and to lower blood pressure. Fenugreek has been demonstrated to relieve congestion, reduce inflammation and fight infection. Trigonella foenum-graecum is used for treating sinus and lung congestion, and loosens and removes excess mucus and phlegm. The Chinese use the seed for abdominal pain, chilblains, cholecytosis, fever, hernia, impotence, hypogastrosis, nephrosis, and rheumatism7.

 

Phytochemical studies:

Trigonella foenum-graecum is known to contain alkaloids, flavonoids, salicylate and nicotinic acid. The concentrated methanolic extract from the stems of Trigonella foenum-greacum was fractionated by successive extraction with petroleum ether, ethyl acetate and n-BuOH. The n-BuOH extract was subjected to column chromatography (CC) on silica gel, followed by column chromatography on Sephadex LH-20 to yield compound 1. The aqueous fraction furnished compounds 2, 3 and 4 by combination of CC on silica gel and Diaion HP-20 and final purification by preparative HPLC. Complete acid hydrolysis of compounds 1, 2 and 3 afforded kaempferol, glucose and galactose (TLC for sugars and HPLC,UV for aglycones), respectively. Compound 1 was identified as kaempferol 3-O-b dglucosyl (1,2)-b-d-galactoside (lilyn) on the basis of acid hydrolysis, spectral data (UV, 1H NMR,13C NMR and FAB–MS), optical rotation value ([a]D) and comparison with published data . This is the second example of isolation of compound 1 from a natural source.

 

The appearance of three anomeric proton signals in the 1H NMR spectrum further confirmed that compound 2 is a kaempferol triglycoside. Compound 3 was also confirmed as a kaempferol triglycoside on the basis of its fragmentation behavior in the FAB-mass spectrum and the appearance of three anomeric proton signals in the 1H NMR spectrum. The 1H NMR (_ 1.65 ppm), 13C NMR (_ 20.4 and 169.3ppm) and IR (1730 cm_1) spectral data indicated the presence of an additional acetyl group in 3. Compound 4 released quercetin, glucose and galactose upon complete acid hydrolysis. The 1H and 13C NMR spectral data further confirmed the presence of the quercetin part in the structure. The 1H and 13C NMR spectral data of the sugar moieties of 4 resembled those of compound 2. Carbon shifts of the aglycone showed typical 3,7-disubstitution of quercetin. Thus, the structure of compound 4 was established as quercetin 3-O-b-d-glucosyl(1!2) - b-d-galactoside 7-O-b-d-glucoside,a new glycoside of quercetin. The  Figure .1 show the compound 1,2,3 & 4).

 

Figure 1. of compound 1, 2, 3 & 4

 

       R1                       R2                                        R3

1.       H                      glc(1-2)gal                          H

2.       Glc                   glc(1-2)gal                          H

3.       Glc                   glc(1-2)(6-Ac)gal               H

4.       Glc                   glc(1-2)gal                          OH

 

 

PHARMACOLOGICAL ACTIVITIES:

Cholesterol-lowering effects:

Fecal bile acid and cholesterol excretion are increased by Trigonella foenum-graecum administration11. This may be secondary to a reaction between the bile acids and Trigonella foenum-graecum-derived saponins causing the formation of micelles too large for the digestive tract to absorb. Another hypothesis attributes the cholesterol-lowering activities to the fiber-rich gum portion of the seed that reduces the rate of hepatic synthesis of cholesterol. It is likely that both mechanisms contribute to the overall effect. In a typical study, fractions of Trigonella foenum-graecum seeds were added to the diets of diabetic hypercholesterolemic and normal dogs. The defatted fraction, which contains about 54% fiber and about 5% steroidal saponins, lowered plasma cholesterol, blood glucose, and plasma glucagon levels from pre-treatment values in both groups of dogs12. The hypocholesterolemic effect has been reproduced in rats13-16. Administration of the fiber-rich fraction of Trigonella foenum-graecum to diabetic rats lowered total cholesterol, triglycerides, and low density lipoprotein (LDL) [17]. The level of high density lipoprotein (HDL) was increased.

 

Glucose-lowering effects:

The galactomannan-rich soluble fiber fraction of Trigonella foenum-graecum may be responsible for the anti-diabetic activity of the seeds [11]. Insulinotrophic and anti-diabetic properties also have been associated with the amino acid 4-hydroxyisoleucine that occurs in Trigonella foenum-graecum at a concentration of about 0.55%. In vitro studies have indicated that this amino acid causes direct pancreatic β-cell stimulation. Delayed gastric emptying and inhibition of glucose transport also have been postulated as possible mechanisms [18]. A typical study evaluated the hypoglycemic effects of the seeds in dogs. The defatted fraction of the seeds lowered blood glucose levels, plasma glucagons, and somatostatin levels; carbohydrate-induced hyperglycemia also was reduced19.

 

Antiradical and Antioxidant activities:

The antioxidant property of phenolics is mainly due to their redox properties. They act as reducing agents (free radical terminators), hydrogen donors, singlet oxygen quenchers and metal chelators20, An extract of Trigonella foenum-graecum seeds was isolated and evaluated for antioxidant activity using various in vitro assay systems. The seed extract exhibited scavenging of hydroxyl radicals (OH-) and inhibition of hydrogen peroxide-induced lipid per oxidation in rat liver mitochondria21.

 

Anti-cataract activity:

Alcoholic extract of Trigonella foenum-graecum Linn seeds (2 g kg−1 day−1) were given to alloxan (120 mg kg−1) diabetic rats until the development of cataract. Serum glucose and body weight were monitored at regular intervals while cataract was examined through naked eye as well as slit lamp at 75, 100 and 115 days after alloxan administration22.

 

Antinociceptive effects:

The extract of Trigonella foenum-graecum leaves produce antinociception in a dose dependent manner in both phases of formalin and tail-flick tests23.

 

Immunomodulatory effects:

Immunomodulatory activity of aqueous extract of Trigonella foenum graecum Linn., a widely used medicinal and dietary herb, was evaluated in male Swiss albino mice. Mice were treated with three doses of extract (50, 100 and 250 mg/kg body weight per os) for 10 days. Body weight, relative organ weight, cellularity of lymphoid organs, delayed type of hypersensitivity (DTH) response, plaque-forming cell (PFC) assay, haemagglutination titre (HT), quantitative haemolysis of SRBC (QHS) assay, phagocytosis, and lymphoproliferation were studied in various groups of animals24.

 

Anti-inflammatory:

Anti-inflammatory activity was measured using the formalin-induced edema in animal model25. Rats were injected with 0.05 ml of a 2.5% formaldehyde solution into the sub-plantar region of the left hind paw. The control group received DW and the positive control groups were treated with 100 and 300 mg:kg intraperitoneal (i.p.) doses of sodium salicylate. Experimental groups were treated with 500, 1000, and 2000 mg:kg i.p. and 1000 mg:kg p.o. doses of TFG extract. Single dose effects of Trigonella foenum-graecum extract and SS are shown as mean SEM. TFG reduced the edema in a dose dependent manner26, 27.

 

Antipyretic effects:

Rectal temperature was recorded with a multichannel electric thermometer, connected to a personal computer. Animals presenting an initial rectal temperature between 36 and 37°C were selected for the antipyretic tests. One and 2 h after injection, TFG (1000 mg:kg, i.p. and p.o.) and SS (300 mg:kg i.p.) significantly reduced this hyperthermia (PB0.001). Also, in 2 h after injection, Trigonella foenum-graecum was more potent than SS in reducing the hyperthermia (PB0.05)27.

 

Anticancer and antitumor effects:

A potential protective effect of Trigonella foenum-graecum seeds against 7,12 dimethy l benz(α) anthracene (DMBA) -induced breast cancer in rats. At 200 mg/kg b.wt., Trigonella foenum-graecum seeds' extract significantly inhibited the DMBA-induced mammary hyperplasia and decreased its incidence28,29.

 

Pregnancy/Lactation:

Trigonella foenum-graecum has documented uterine stimulant effects and has been used in traditional medicine to induce childbirth and hasten delivery by promoting uterine contractions. The seeds have been used in traditional medicine to augment milk supply in nursing women30.

 

Gastroprotective effect:

The aqueous extract and a gel fraction isolated from the seeds showed significant ulcer protective effects. The cytoprotective effect of the seeds seemed to be not only due to the anti-secretory action but also to the effects on mucosal glycoprotein’s. The Trigonella foenum-graecum seeds also prevented the rise in lipid peroxidation induced by ethanol presumably by enhancing antioxidant potential of the gastric mucosa thereby lowering mucosal injury31.

 

Spermicidal activity:

The seeds exhibit Spermicidal activity. The crude steroidal extract of the seeds exerts both Antifertility and androgenic activities in male alino rats. The extract when fed orally (100 mg/day) for 60 days significantly declined the sperm count32,33.

 

Antimicrobial activity:

The seeds of aqueous, ethanol and hexane extracts showed antibacterial activity34, 35.

 

Acetyl cholinesterase enzyme inhibitory activity:

Acetyl cholinesterase inhibitors (AChEI) give a symptomatic relief to some of the clinical manifestations of the disease The concentration of trigonelline was found to be 13 mg _1w/w in the hydro alcoholic extract of Trigonella foenum graecum. The  AChE inhibitory activity of crude Trigonella foenum-graecum  seed extracts, fractionsand trigonelline was evaluated using Elman’s method in 96-well micro plate’s assay and TLC bioassay detection36.

 

Antiplasmodium Activity:

In vitro anti-plasmodial assay of the extracted fractions of Trigonella foenum-graecum leaves was carried out using laboratory adapted chloroquine sensitive and resistant Plasmodium falciparum isolates. Schizont maturation inhibition assay was adopted to analyze the potential of the extracts. Ethanol extract (50%) seemed to possess profound anti-plasmodial activity with IC50 value of 8.75 ± 0.35 µg ml–1 and 10.25 ± 0.35 µg ml–1 against chloroquine sensitive and resistant P. falciparum isolates, respectively37.

 

ACKNOWLEDGEMENT:

The authors are very grateful to Director General, CCRAS, New Delhi and for providing encouragement and facilities for carrying out this work. Authors are thankful to Ms. Rekha her assistance for work of the paper.

 

REFERENCES:

1)      Atal CK, Kapoor BM. Cultivation and utilization of medicinal plants (Eds. PID CSIR), 1989.

2)      Siddiqui HH. Safety of herbal drugs-an overview. Drugs News & Views 1993; 1(2): 7–10.

3)      Chopra RN, Chopra IC, Handa KL, Kapoor LD. Indigenous drugs of India (Published by UN Dhar, Pvt. Ltd., Calcutta) 1993.

4)      Chopra RN, Nayar SI, Chopra IC. Glossary of Indian Medicinal Plants (Published by CSIR, New Delhi) 1956.

5)      Satyavati GV, Raina MK, Sharma M. Medicinal Plants of India (Published by ICMR, New Delhi), 1976.

6)      Nadkararni AK, Nadkarni KM. Indian Materia Medica (Published by Popular Prakashan Pvt. Ltd.,Bombay) 1976.

7)      Duke JA, Bogenschutz-Godwin MJ, deCellier J and Duke PK (2003). Trigonella foenum-graecum L. (Fabaceae) Trigonella foenum-graecum, Greek clover, Greek hay,in CRC Handbook of Medicinal Spices, CRC Press, Washington DC, p. 296.

8)      Petropoulos, G.A. Fenugreek - The genus Trigonella, Taylor and Francis, London and New York. 2002.

9)      Acharya S,.Srichamroen A, Basu S., Improvement in the nutraceutical properties of fenugreek (Trigonella foenum-graecum L.),2006,1-9

10)    Basch, E., Ulbricht, C., Kuo, G., Szapary, P. and Smith, M. 2003. Therapeutic applications of fenugreek. Alt. Med. Rev., 8: 20-27.

11)    Madar Z, Stark AH. New legume sources as therapeutic agents. Br J Nutr . 2002;88(suppl 3):S287-S292

12)    Valette G, Sauvaire Y, Baccou JC, Ribes G. Hypocholesterolaemic effect of fenugreek seeds in dogs. Atherosclerosis . 1984;50:105-111.

13)    Singhal PC, Gupta RK, Joshi LD. Hypocholesterolemic effect of Trigonella foenum-graecum (METHI). Curr Sci . 1982:51:136.

14)    Stark A, Madar Z. The effect of an ethanol extract derived from fenugreek ( Trigonella foenum traecum ) on bile acid absorption and cholesterol levels in rats. Br J Nutr . 1993:69:277-287.

15)    Sauvaire Y, Ribes G, Baccou JC, Loubatieeres-Mariani MM. Implication of steroid saponins and sapogenins in the hypocholesterolemic effect of fenugreek. Lipids . 1991;26:191-197.

16)    Yadav UC, Moorthy K, Baquer NZ. Effects of sodium-orthovanadate and Trigonella foenum-graecum seeds on hepatic and renal lipogenic enzymes and lipid profile during alloxan diabetes. J Biosci . 2004;29:81-91.

17)    Hannan JM, Rokeya B, Faruque O, et al. Effect of soluble dietary fiber fraction of Trigonella foenum graecum on glycemic, insulinemic, lipidemic and platelet aggregation status of Type 2 diabetic model rats. J Ethnopharmacol . 2003;88:73-77.

18)    Gupta A, Gupta R, Lal B. Effect of Trigonella foenum graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double-blind placebo controlled study. J Assoc Physicians India . 2001;49:1057-1061.

19)    Ribes G, Sauvaire Y, Baccou JC, et al. Effects of fenugreek seeds on endocrine pancreatic secretions in dogs. Ann Nutr Metab . 1984;28:37-43.

20)    Cook, N. C., & Samman, S. (1996). Flavonoids: Chemistry, metabolism, cardioprotective effects, and dietary sources. Nutritional. Biochemistry,7, 66–76.

21)    Anuradha C.V., Priyadarsini K.I., In vitro studies on antiradical and antioxidant activities of fenugreek (Trigonella foenum graecum) seeds, Food Chemistry 103 (2007) 31–37.

22)    Grover J.K., Vats V., Yadav S.P., Biswas N.R., Anti-cataract activity of Pterocarpus marsupium bark and Trigonella foenum-graecum seeds extract in alloxan diabetic rats, Journal of Ethnopharmacology 93 (2004) 289–294.

23)    M., Antinociceptive effects of Trigonella foenum-graecum leaves extract, Journal of Ethnopharmacology, 58 (1997) 125.

24)    Raisuddin S., Sayeed I., Bin-Hafeez B., Haque R., Parvez S,Pandey S.,Immunomodulatory effects of fenugreek (Trigonella foenum graecum L.) extract in mice, International Immunopharmacology 3 (2003) 257–265.

25)    Kumar, V.L., Basu, N., 1994. Anti-inflammatory activity of the latex of Calotropis procera. Journal of Ethnopharmacology 44, 123–125.

26)    Vane, J.R., Botling, R.M., 1995. New insights into the mode of action of anti-inflammatory drugs. Inflammation Research 44, 1–10 .Review.9

27)    Semnanian S. ,Javan M., Ahmadiani A.,. Kamalinejad, Anti-inflammatory and antipyretic effects of Trigonella foenum-graecum leaves extract in the rat, Journal of Ethnopharmacology 75 (2001) 283–286.

28)    Amr Amin, Aysha Alkaabi, Shamaa Al-Falasi, Sayel A. Daoud, Chemopreventive activities of Trigonella foenum graecum (Fenugreek) against breast cancer Cell Biology International, Volume 29, Issue 8, August 2005, Pages 687-694.

29)    Sur P, Das M, Gomes A, et al. Trigonella foenum graecum (fenugreek) seed extract as an antineoplastic agent. Phytother Res . 2001;15:257-259.

30)    Korman SH, Cohen E, Preminger A. Pseudo-maple syrup urine disease due to maternal prenatal ingestion of fenugreek. J Paediatr Child Health . 2001;37:403-404.

31)    Pandian RS, Anuradha CV, Viswanathan P. Gastroprotective effect of fenugreek seeds ( Trigonella foenum graecum ) on experimental gastric ulcer in rats. J Ethnopharmacol . 2002;81:393-397.

32)    Kamal et al, Phytother  Res , Fitoterapia, 1993, 7.

33)    Sethi et al ,Fitoterapia,1990,61,64.

34)    Sammour, R.H., El-Shanshoury, A.E.R.R., 1992. Antimicrobial activity of legume seed proteins. Botany Bulletin of Academia Sinica 33, 185–190.

35)    Bhatti, M.A., M.T.J. Khan, B. Ahmad, M. Jamshaid and W. Ahmad, Fitoterapia,1996, 67, 4, 372—374.

36)    Mukherjee  P .K, SatheeshKumar N., _,.Bhadra S, Saha B.P. Acetylcholinesterase enzyme inhibitory potential of standardized extract of Trigonella foenum graecum L and its constituents

37)    Palaniswamy M., Pradeep B. V., Sathya R. and Angayarkanni J., In vitro anti-plasmodial activity of Trigonella foenum–graecum L.,  oxford journal,2008

 

 

Received on 09.01.2010

Accepted on 10.03.2010     

© A&V Publication all right reserved

Research J. Pharmacology and Pharmacodynamics 2(2): March –April 2010: 172- 175