REVIEW ARTICLE


Medicinal Properties of Fenugreek: A Review



Himanshi Varshney1, Yasir Hasan Siddique1, *
1 Department of Zoology, Drosophila Transgenic Laboratory, Section of Genetics, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India


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Creative Commons License
© 2023 Varshney and Siddique

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Zoology, Drosophila Transgenic Laboratory, Section of Genetics, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India; Tel: 0571-2700920-3447; E-mail:yasir_hasansiddique@rediffmail.com


Abstract

Background:

Due to its numerous health benefits, fenugreek (Trigonella foenum-graecum L.) is commonly used in Ayurvedic and Traditional Chinese medicine. Its leaves and seeds contain several compounds (e.g., alkaloids, amino acids, coumarins, flavonoids, saponins, polyphenols, carbohydrates, vitamins, and other bioactive compounds). Fenugreek is used for reproductive health problems, hepatoprotective properties, and improved digestion. Studies have shown that it has anti-cancerous, cardioprotective, anti-sterility, antimicrobial, antiparasitic, anti-helminthic, and neuroprotective properties. Various studies have been carried out on animals and humans to show the effectiveness of fenugreek against various diseases.

Methods:

This review focuses on studies and clinical trials to examine the effects of fenugreek on various diseases from 1990 to 2022, using popular databases, such as Google Scholar, PubMed, and Scopus.

Results:

By altering the activity of metabolic enzymes, fenugreek stimulates insulin secretion, reduces blood sugar, and controls cholesterol synthesis. It enhances SOD, glutathione peroxidase, glutathione-S-transferase, and catalase activity to protect cellular organelles from oxidative stress. Fenugreek improves the gastric mucosa lining and secretion, which improves gastric ulcers and digestion. Fenugreek ameliorates menstrual cramps and significantly increases sperm cell counts and testosterone levels in males.

Conclusion:

Studies and clinical trials have shown the beneficial effects of fenugreek. Therefore, it could be used as a therapeutic agent against various disorders.

Keywords: Fenugreek, Medicinal properties, Diseases, Therapeutic agent, Pharmacology, Disorders.



1. INTRODUCTION

Trigonella foenum graecum (fenugreek) belongs to the family Fabaceae. It is a medicinal herb used to treat various diseases, such as diabetes, inflammation, cancer, hypercholesteremia, reproductive dysfunction, and neurodegenerative disorders. For centuries, fenugreek seeds have been used as carminative, demulcent, expectorant, laxative, and stomachic agents [1]. It originated in Eastern Europe but is now grown all over the world. It has a variety of phytochemicals, such as flavonoids, alkaloids, coumarins, vitamins, carbohydrates (Galactomannan), saponins, trigonelline, diosgenin, and soluble fibers, which are responsible for the pharmacological effects. Numerous clinical and pre-clinical studies have revealed its anti-diabetic, anti-sterility, and anti-fertility effects. Moreover, it regulates the production of enzymes that control blood sugar levels and help in reducing cholesterol [2]. The hypoglycemic action of fenugreek corresponds to physiological requirements and is mediated by Glucogen-like peptide-1 levels [3]. Furthermore, it also regulates antioxidant and detoxifying enzymes to reduce oxidative stress. The flavonoids and saponins present in fenugreek prevent tumor formation by blocking carcinogen-DNA adduct formation [4]. Flavonoids and alkaloids are well known for their neuroprotective and antioxidative effects [5, 6]. The active components of fenugreek, i.e., 4-hydroxyisoleucine (4-OH-Ile) and galactomannan, have been reported to reduce blood glucose levels and improve lipid metabolism in vivo [7]. Trigonelline regulates ß cell regeneration, insulin secretion, enzymes involved in glucose metabolism, and neuron excitability [8]. Diosgenin suppresses tumor necrosis factor-induced invasion, suppresses proliferation, and enhances apoptosis. Fenugreek seeds are effective in boosting both total and free testosterone, sperm cells count, and sperm motility, thus promoting physical and sexual health [9]. Research studies have confirmed the traditional use of fenugreek in treating various health problems, such as diabetes, reno-protective properties in diabetic complications, and gastric ulcers. It is also recommended to be used as a protein supplement (about 20-30%) as it contains a high level of protein [10].

2. HISTORY OF FENUGREEK USAGE

Fenugreek can be grown in all seasons and has medicinal values known from ancient times. Its seeds, leaves, and stems have been used for various purposes. The seeds are popularly known as methi dana, which is commonly used as a spice in Indian curries and pickles and also as a flavoring agent in baking bread, cheese, syrups, etc. Its leaves and young plants are cooked as winter dishes. Earlier, Romans and Greeks used it for cattle food. In Egypt, it was used to ease labor and enhance milk flow. Many Egyptian women used it to reduce menstrual pain. Its medicinal properties are extensively documented in Ayurveda, Chinese, Arabic, Greek, and Latin pharmacopoeia [10].

3. MEDICINAL PROPERTIES OF FENUGREEK

Scientists have reported several therapeutic uses of fenugreek. It has shown anti-diabetic, hypoglycaemic, anti-hyperlipidemic, anti-fertility, anti-cancer, anti-microbial, anti-parasitic, lactation stimulant, galactagogue, hypocholesterolemic, immunomodulatory, anti-carcinogenic, anti-helminthic, anti-nociceptive, anti-oxidant, anti-microbial, anti-ulcer, gastroprotective, and hepatoprotective properties Table 1. Overnight-soaked seeds of fenugreek are used for hair and skin for a soft and smooth effect. It reduces the risk of myocardial damage and abnormal blood clotting linked with heart attacks and strokes [10.] It helps in reducing weight and heals inflammations. A number of studies have revealed that it also possess anti-carcinogenic property and neuroprotective effects. It is a rich source of iron, calcium, sulphur, chlorine, and vitamins A and C. Earlier, fenugreek has been used as a tonic for the treatment of weakness and edema of the legs. It is commonly used to treat menstrual cramps and acts as a lactation stimulant [11]. Its pharmacological properties against diseases have been identified by experimental evidence and clinical studies [12, 13]. The active constituents of fenugreek have been reported to have protective effects against diseases, such as diabetes, neurodegenerative disorders, various heart complications, cancer, hypolipidemic, gastroprotective effects, arthritis, etc. (Fig. 1).

Fig. (1). Pharmacological effects of bioactive components of fenugreek

4. PHARMACOLOGICAL PROPERTIES OF FENUGREEK

4.1. Anti-diabetic Effects

The bioactive components of fenugreek, like galactomannan, saponins, trigonella, diosgenin, and 4-hydroxyisoleucine, have been reported to exert positive effects on diabetes. Several components have been isolated, and various studies have revealed their action on blood sugar [14]. Fenugreek controls diabetes via multi-physiological pathways, such as restoring pancreatic β-cell function and inhibiting sucrase as well as alpha-amylase activities. 4-Hydroxyisoleucine directly induces insulin secretion from pancreatic β-cells. Fenugreek saponin extract has shown anti-diabetic, hepatoprotective, and hypolipidemic effects [2, 15-17]. Fenugreek saponins regulate glycogen enzyme activities in the intestine and liver of rats, enhance hepatic glycogen content, lower blood glucose levels, and improve oral glucose tolerance [18]. In a study, 15 diabetic patients were given fenugreek seed powder for 10 days, which resulted in a significant reduction of fasting glucose level, LDL, and VLDL cholesterol and improved glucose tolerance. This also led to a 64% reduction in 24 hr urinary glucose excretion [19]. Galactomannan, one of the components of fenugreek, exhibits protection against diabetes. A group of 32 patients (type-2 diabetic) were given galactomannan and compared with the control (32 patients placebo). The study revealed a notable decrease in fasting blood glucose, HbA1c, total cholesterol, triglycerides, and low-density lipoprotein. Overall, galactomannan could be a good candidate for hyperglycemia and hypolipidemia. Diosgenin, a glycan in fenugreek, boosted glucose metabolism by stimulating adipocytes, inhibiting inflammation in adipose tissue, and lowering triglycerides in the plasma of obese diabetic mice. In research, it was observed that 10 gm/40 ml of liquid fenugreek extract could reduce the glucose level of blood. It was found that its liquid dosage is better than crushed and powdery forms [2].

Table 1. Therapeutic uses of fenugreek.
Non-communicable Diseases Model Conclusion References
- Anti-diabetic Effect - - -
1. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Human Fenugreek diet notably decreased fasting blood sugar and improve glucose tolerance test. [71]
2. Effect of fenugreek seeds on non-insulin dependent diabetic subjects Human Fenugreek lowers fasting blood glucose levels and enhance glucose tolerance test. [72]
3. Effect of fenugreek and lupine seeds on the development of experimental diabetes Rat Diabetic animals supplement with fenugreek showed reduction in hyperglycemia, free fatty acids, and cholesterol and triglycerides levels. [73]
4. Effects of a fenugreek seed extract on feeding behaviour Rat Administration of fenugreek seed extract displayed hyperinsulinemia as well as hypercholesterolemia effect. [74]
5. Effect of steroid saponins from fenugreek seeds on feeding behaviour and plasma cholesterol Rat Saponins lower down plasma cholesterol levels in rats. [75]
6. Effect of fenugreek seeds on blood lipid peroxidation and antioxidants levels Rat Fenugreek seed supplementation in the diet showed regulation in the free radical metabolism in diabetic animals [76]
7. Effect of Trigonella foenum graecum (fenugreek) seed powder on glucose homeostasis Rat Trigonellaseed powder treatment altered glucose and lipid metabolising enzyme activities to normal values [77]
8. Effect of fenugreek seed aqueous extract of on alloxan diabetic males Rat Fenugreek seed aqueous extract display antioxidant property which decrease the biochemical and histopathological alteration caused by alloxan. [78]
9. Effects of fenugreek seed powder on type 2 diabetic patients Human Fenugreek seeds powder notably reduce serum lipid profile in type 2 diabetic patients. [12]
10. Effects of fenugreek alkaloid extract on streptozotocin induced hyperglycemia Rat Fenugreek suppressed lipid profile and oxidative stress via converting liver and kidney pathology caused by diabetes to normal level. [79]
11. Effect of Trigonella foenum-graecum (fenugreek) extract on streptozotocin-induced diabetes Rat Trigonella foenum-graecum extract decrease blood glucose, blood lipid levels and enhance hemorheological properties [80]
12. Effect of fenugreek on Type 2 diabetic Patients Human Fenugreek seeds notably control pathology of diabetic patients if used as an adjuvant in type 2 diabetes mellitus. [14]
13. Effect of fenugreek saponins on Diabetes Rat Fenugreek saponins reduce the absorption of LDL-cholesterol and increase the HDL-cholesterol level. [18]
14. Effect of fenugreek galactomannan on digestive enzymes Rat Fenugreek galactomannan hamper diabetes-induced kidney injury and creatinine content in plasma. [19]
15. Effect of fenugreek oil on alloxan-induced diabetes Rat Fenugreek oil maintained hematological status, and renal toxicity by acting on immunomodulatory activity and stimulate insulin action. [81]
16. Effect of Omega-3 fattyacid and fenugreek essential oil on diabetes Rat Fenugreek oil regulates starch and glucose oral tolerance and drops down triglycerides and total cholesterol level [82]
17. Effect of Trigonella foenum graecum (fenugreek) on alloxan induced diabetes Rat Fenugreek aqueous seed extract and ethanol extract combination remarkably reduced the increased level of blood glucose and increased the levels of serum insulin. [83]
18. Effect of fenugreek on STZ-induced diabetic nephropathy Rat Diabetic rats significantly reduced the renal dysfunction, pathological alteration, and oxidative stress by fenugreek treatment. [84]
19. Effect of cinnamon, fenugreek and their combination on patients with type 2 diabetes Human Daily supplementation of cinnamon, fenugreek or their combination to patients effectively lowering HbA1C and 2 h PPG (postprandial glucose) in type 2 diabetic patients [16]
20. Effect of fenugreek (Trigonella foenum-graecumL.) intake on glycemia: a meta-analysis of clinical trials Human Fenugreek treatment lower down the glucose levels in treated patients. [13]
21. Effect of fenugreek (Trigonella foenum-graecum) on experimentally induced diabetes mellitus Rabbit Total lipids and serum sugar level is notably attenuated by fenugreek in experimentally induced diabetes mellitus in rabbit. [85]
22. Effect of fenugreek seeds on Type 2 diabetes Type-2 diabetic Patients Fenugreek seeds regulate glucose metabolism, serum lipid profile and adiponectin levels in studied patients. [86]
23. Effect of Trigonella foenum-graecum(Fenugreek) seed on glucose homeostasis U2OS cell line Fenugreek bioactive component bind with GLP-1 and stimulate GLP-1 signalling and show hypoglycaemic effect. [15]
24. Effect of Fenugreek on type 2 diabetes mellitus in prediabetes Human It results reduction in fasting plasma glucose (FPG), postprandial plasma glucose (PPPG) and low density lipoprotein cholesterol (LDLc) and increament in blood insulin by fenugreek. [87]
25. Effect of fenugreek in Type2 diabetes Humans Fenugreek liquid dosage form of 10gm/40ml notably reduced blood sugar level in diabetic patients. [88]
26. Effect of Trigonella foenum graecum (fenugreek) on diabetes Rat TFG seed extractshowed more antiperoxidative activity than leaves extract of it. [89]
27. Effect fenugreek seed (Trigonella foenum-graecum) extract (FenfuroTM) in patients with type 2 diabetes Human Fenugreek supplement leads to reduction in both fasting plasma and post-prandial blood sugar levels. [90]
28. Effect of fenugreek-based bio-nanocomposite on renal dysfunction Rat Fenugreek-based bio-nanocomposite enhance kidney function marker contents in the blood and improve renal dysfunction [91]
29. Effect of fenugreek compound (N55) in treating type-2 diabetes Mice N55 decreases plasma glucose by enhancing the response of physiological levels of GLP-1 and affect glucose tolerance. [3]
30. Effect of fenugreek seeds powder (Trigonella foenum-graecumL.) on experimental induced hyperlipidemia Rabbit Fenugreek seeds powder had a significant hypolipidemic effect in experimentally-induced hyperlipidemic rabbits. [92]
31. Effect of fenugreek (Trigonella foenum-graecumL.) seeds on insulin sensitivity and mitochondrial functions 3T3-L1 cells Polyphenol stilbenes from the fenugreek kill scavenge reactive oxygen species (ROS). [93]
32. Effect of flavonoid glycosides from fenugreek seeds on 3T3-L1 adipocytes in vitro 3T3-L1 cells It lowers glucose and insulin-resistance-improving agent for the treatment of diabetes [17]
33. Effect of fenugreek seed extract on type 2 diabetes mellitus Human Type 2 diabetes patients display lower level of HbA1c and require lower dose of insulin per day due to the uptake of fenugreek. [94]
34. Effects of fenugreek on high fat fed dyslipidemia Rat Fenugreek seems to be an effective hypolipidemic agent to control the increasing risk of dyslipidemia. [95]
35. Effect of fenugreek polysaccharides on type-2 diabetes Human Galactomannan notably reduce fasting blood glucose, HbA1c,total cholesterol,triglycerideand low-density lipoprotein. [2]
36. Effect of Trigonellafoenum graecum on streptozotocin induced diabetic complications Rat Fenugreek improved the biochemicall and histological parameters of diabetic complications [96]
37. Effect of fenugreek (Trigonella foenum graecum) seed aqueous extract in streptozotocin-induced diabetes Rat Fenugreek treatment control blood glucose, lipid profile, liver, and kidney function [97]
38. Effect of fenugreek seed powder solution (Trigonella foenum-graecum L.) on hyperlipidemia in Diabetes Human Trigonella foenum-graecumseed powder solution ameliorates lipid metabolism of type II diabetic patients. [98]
39. Effect of fenugreek seeds in alloxan-induced diabetes Rat Fenugreek seeds showed hypoglycemic and hypolipidemic properties. [99]
40. Effects of fenugreek alkaliod extract on alloxan induced hyperglycemia Rat Treatment with alkaloid extract of fenugreek dried seeds displayed reduction of blood glucose and increase in serum insulin [100]
41. Effect of Fenugreek and Buckthorn as antioxidant and antidiabetic agent Rat Aqueous extract of fenugreek and buckthorn seed was more effective than leaves extract. [101]
Anti-cancerous effect
42. Trigonella foenum seed extract as an anti-neoplastic agent Mice Trigonella foenum graecum show anti-inflammatory and anti-neoplastic property. [102]
43. Effect of fenugreek on 1,2- dimethylhydrazine-induced hepatic oxidative stress during colon carcinogenesis Rat Fenugreek reduced circulatory lipidperoxidation and increased antioxidant levels. [103]
44. Effect of diosgenin, a steroid saponin of Trigonella foenum graecum on azoxymethane-induced aberrant crypt foci formation. Rat and HT-29 Human Colon Cancer Cells Fenugreek seed and diosgenin are helpful in preventing colon cancer. Diosgenin stops cell proliferation and initiate apoptosis in HT-29 human colon cancer cell lines. [104]
Effects of Trigonella foenum graecum (fenugreek) seed on colon cancer Rat and HT-29 human colon cancer cell lines It significantly induced apoptosis in HT-cells cells.
45. Effect of diosgenin on adenocarcinoma cells HCT-116 cells Diosgenin significantly decrease the expressions of β-catenin, peroxisome proliferator-activated receptor (PPAR) –γ and inhibit adenocarcinoma cells by targeting different cholesterol biosynthetic pathways [105]
46. Effect of diosgenin, a steroidal saponin constituent of fenugreek as chemoprotectant Rat Diosgenin significantly repressed both invasive and non-invasive colon tumor incidence upto 60%. [106]
47. Effect of diosgenin on 3-hydroxy-3-methylglutaryl CoA reductase expression HCT-116 cells Diosgenin suppressed growth and induced apoptosis in human colon carcinoma cells [107]
48. Effect of fenugreek seeds on 1,2- dimethylhydrazine-induced hepatic oxidative stress during colon carcinogenesis. Rat Fenugreek modulate DMH- induced oxidative stress [4]
49. Effect of traditional medicines thymoquinone and diosgenin as antineoplastic and apoptotic agent Human SCC A431, Hep2 and RPMI 2650 cells Thymoquinone and diosgenin suppress cell division and cytotoxicity in A431 and Hep2 cells. [30]
50. Effect of Trigonella Foenum-Graecum on cytotoxic anti-cancer properties T-cell lymphoma (TCP), B-cell lymphomas, Thyroid Papillary carcinoma (FRO) and breast cancer (MCF7 Fenugreek has selective cytotoxic effects against cancer cellsand cell lines induce apoptosis. [32]
51. Effect of diosgenin on Akt-mediated prosurvival signalling MCF-7 (ER1), MDA 231 (ER2) and MCF-10A cells In vivo tumour studies shows diosgenin remarkably inhibits tumour growth in both MCF-7 and MDA231 xenografts in nude mice. [31]
52. Effect of Trigonella foenum(Fenugreek) on hepatocellular carcinoma Hep G2 cells FCE act as a promising non-toxic herbal drug induce apoptosis and upregulates caspase-3 dependent pathway. [108]
53. Effects of Trigonella foenum graecum methanol and ethyl acetate extracts, against cancer cell lines Mice There are significant anticancer and neuroprotective properties of both amurensin and cosmosiin derived from T. foenum extracts. [109]
Hepatoprotective effect
54. Effect of fenugreek steroid saponins and sapogenins on hypocholesterolemia condition Dog Saponins present in the seed, reduced hypercholesterolemia and hypertriglyceridemia of alloxan-diabetic dogs. [110]
55. Hypolipidaemic effect of fenugreek seeds Human Fenugreek powder resulted in a significant reduction in the serum total cholesterol, LDL and VLDL cholesterol and triglyceride levels. [111]
56. Effect of fenugreek seeds on non-insulin dependent diabetic patients Human Fenugreek seed powder resulted in a significant reduction of total cholesterol, LDL and VLDL cholesterol and triglyceride levels [23]
57. Effect of fenugreek oil on the efficiency of ovarian and liver tissues Rat Administration with fenugreek oil at 0.1 and 0.15 ml/mouse increased the totalnumber of cumulus-oocyte complexes as well as improved their quality. [21]
58. Effect of fenugreek seed (Trigonella foenum graecum) on ethanol-induced collagen and lipid accumulation Rat Administration of FPEt to alcohol-fed rats significantly improved lipid profile and reduced collagen content [112]
59. Effect of fenugreek (Trigonella foenum graecum) seed polyphenols on alchohol toxicity Rat Increased hepatocyte viability and reduced apoptotic nuclei were observed in FPEt-treated rats. [20]
60. Effect of fenugreek (Trigonella foenum graecum) seed polyphenols on alcohol-induced protein and lipid damage Rat FPEt ameliorates the pathological liver changes induced by chronic ethanol feeding [113]
61. Effect of dietary fenugreek seeds (Trigonella foenum-graecum) as antilithogenic herb Mice Fenugreek increased antioxidant enzyme activity and reduced hepatic lipid peroxidises. [114]
62. Effect of fenugreek seeds on fat accumulation and upregulation of LDL receptor Mice Hypolipidemic effect of TEFS is due to inhibition of fat accumulation and upregulation of LDLR [115]
63. Effect of fenugreek on diet-induced metabolic disorders Rat Fenugreek dose-dependently reduced the hepatic triglyceride and total cholesterol levels. [116]
64. Effect of fenugreek seeds extract against carbon tetrachloride induced liver toxicity Rat Fenugreek seeds extract as a good
candidate to be used against drug induced hepatotoxicity
[117]
65. Effect of fenugreek against metabolic disorders Rat FRB (1.2 ~ 4.8%) prevents diet-induced metabolic disorders such as insulin resistance, dyslipidemia and fatty liver. [7]
66. Effect of Trigonella foenum-graecum L. (Fenugreek) on liver enzymes in Ischemia-Reperfusion injury Rat Trigonella foenum-graecum L. (Fenugreek) treatment protects the rat liver against hepatic ischemia-reperfusion injury [22]
67. Effect of fenugreek seeds on adipogenesis and lipolysis Rat Fenugreek seed inhibits formation of new differentiated adipocytes from precursor cells through an anti-proliferative effect on preadipocytes [118]
68. Effects of fenugreek,Nigella and termis seeds on non-alcoholic fatty liver in obese diabetic albino rats Rat Considerable improvement in the liver of experimental animals was observed. [119]
69. Effect of combined extracts of red yeast rice and fenugreek on lipotoxicity HepG2 hepatocytes Combined extracts of red yeast rice and fenugreek, as low as 10–3 μg/ml, suppressed lipid content and apoptosis [120]
70. Effect of fenugreek in acetaminophen induced hepatotoxicity Rat FEN has a protective role against acetaminophen -induced hepatotoxicity by enabling hepatocyte regeneration and supressing inflammatory activity [121]
71. Effect of fenugreek (Trigonella foenum graecum Linn) in cirrhotic ascitic patients Human First human trial of fenugreek is safe and tolerable, no side-effects were observed. [122]
72. Effect of fenugreek seed supplementation on patients with type 2 diabetes mellitus Human Fenugreek seed has beneficial effects on fasting plasma glucose, systolic blood pressure, and liver and kidney function. [123]
73. Effect of fenugreek seeds extract supplementation on thioacetamide induced liver damage Rat Fenugreek seeds extract supplementation significantly increased plasma glucose and HDL level and remarkably decreased triglyceride, cholesterol, LDL, VLDL [124]
74. Effect of fenugreek (Trigonella foenum-graecumL.) seeds on liver antioxidant defense systems Mice The dietary supplementation of fenugreek seed showed a positive effect on the activities of the hepatic antioxidant defence enzymes in the aged mice. [125]
75. Effect of phytochemicals present in fenugreek on metabolic inflammation Mice Fenugreek seed suppressed metabolic inflammation via the mediation of gut microbiota. [126]
Cardioprotective effect
76. Effect of fenugreek on isoproterenol-induced myocardial infarction in rats Rat Fenugreek displays cardioprotective effect on lipid peroxidation and antioxidant defense system during isoproterenol-induced myocardial infarction in rats. [24]
77. Effect of trigonelline from fenugreek seed on isoproterenol-induced myocardial injury Rat Its administration increases serum level of cardiac markers for cardiac dysfunctioning [127]
78. Effect of dietary fenugreek (Trigonella foenum-graecum) seeds and garlic (Allium sativum) on experimental myocardial infarction Rat Together fenugreek seeds with garlic offered significant changes in lipid profiling of cardiac tissue [128]
79. Dietary effect of fenugreek (Trigonella foenum-graecum) seeds and garlic (Allium sativum) in experimental myocardial infarction Rat Combine dietary effect of garlic and fenugreek seeds reflect higher cardioprotective properties. [129]
80. Effect of fenugreek (Trigonella foenum-graceum) seed extract on streptozotocin induced diabetic rats as cardioprotectant agent Rat It lowers the metabolic abnormalities, oxidative stress and regulates apoptosis. [25]
Gastroprotective effect
81. Effect of fenugreek seeds (Trigonella foenum graecum) on experimental gastric ulcer Rat Fenugreek seed decrease the mucosal injury by increasing antioxidant potential of thegastric mucosa. [27]
82. Effect of honey in combination with fenugreek seed extract on experimental gastric ulcer Rat Honey combination with fenugreek seed extract proved to be protective against lesion formation. [26]
83. Effect of aqueous Trigonella feonum-gracum and Linum ussitatissimum seed extracts as gastroprotective agents Mice T. foenum-gracum and L. usitatissimum posses anti-ulcer effect and reduce oxidative damage [29]
84. Effect of fenugreek seeds (Trigonella foenum graecum) on experimental gastric ulcer Rat Fenugreek seed prevent gastric ulcers and lesion formation. [28]
85. Effect of aqueous extracts of barley and Fenugreek on ulcer induction Rat Showed gastroprotective effect by lowering stomach lesion and GSH enzyme concentration. [130]
86. Effect of fenugreek, ginger, peppermint oil on experimentally induced gastric ulcer
Rat Fenugreek oil notably reduced the gastric ulcer and possess gastroprotective property. [131]
87. Effect of fenugreek against indomethacin induced ulcer Wistar rat Sugaheal provide protection against oxidative damage and posses gastroprotecion property. [8]
88. Effect of fenugreek seed extract on gastric ulcers AGS cells and Rat Phytoconstituents like flavonoids and saponins, exhibit antioxidant and gastroprotective activity in the extract [132]
89. Effect of fenugreek seed extract in experimentally induced gastric ulcer Wistar rats Group fed with fenugreek showed a notable reduction in ulcer index, volume of gastric juice and acidity. [133]
Anti-sterility and anti-fertility effect
90. Effect of fenugreek oil on the efficiency of ovarian and liver tissues Mice 0.10-0.15ml/mouse dose displayed notable changes in number and quality of cumulus-oocyte complexes. [21]
91. Effect of fenugreek seeds in male and female on fertility Rabbit Treated animal showed proliferative changes of endometrial glands and histopathology changes of testis tissue [134]
92. Effects of aspirin and fenugreek seed on the testes Mice Fenugreek seed reversed the structural changes occurred in the testis of mice caused by aspirin [135]
93. Effect of hydro-alcoholic extract of fenugreek seeds on female reproductive hormones Mice Fenugreek significantly increases the progesterone level and reduction in folliculogenesis. [136]
94. Effect of fenugreek seed extract on carbendazim-inhibited spermatogenesis Rat Fenugreek significantly reduced testicular toxicity of carbendazim. [137]
95. Effect of fenugreek seeds extracton cyclophosphamide-induced changes in testes
Mice Fenugreek seed extract decreased testis damage induced by cyclophosphamide. [138]
96. Effect of steroidal extract of fenugreek on reproductive functions Mice Fenugreek notably improve reproductive parameters in male mice [139]
97. Effect of fenugreek seed extract on cytotoxicity and testicular alterations Rat Activity of catalase (CAT) and superoxide dismutase (SOD) increased in the testis of treated animals [140]
98. Effect of fenugreek on menstrual disorders Human Fenugreek helped in managing menstrual disorders by relieving pelvic congestion, breast tenderness and improve reproductive health. [11]
99. Effect of fenugreek on reproductive, cytological and biochemical toxicity Mice Total sperm count and sperm motility increased in fenugreek treated mice. [141],
100. Effect of combination of fenugreek with insulin and Glimepiride on male reproductive system Rat Fenugreek in combination with insulin and glimepiride showed improvement in reproductive parameters of diabetic rats. [142]
101. Effect of novel extract of fenugreek husk (FenuSMART™): A Randomized, Double-Blind, Placebo-Controlled study on postmenopausal symptoms and hormonal balance Human FHE supplementation was also found to have a beneficial effect in the management of healthy serum calcium levels [143]
102. Efficacy of FurosapTM, a novelTrigonella foenum-graecumseed extract on testosterone level and sperm profile Human

It improved the sex hormone level in volunteers and modulate sperm morphology positively. [9]
103. Effect of fenugreek extract with docosahexaenoic acid in attenuating learning and memory deficits in ovariectomized rats Rat Fenugreek with acid supplementation could be used to improve menopause induce memory and learning impairment. [144]
104. Effect of diosgenin on testicular damage Rat Diosgenin improved testosterone level and prevent testicular apoptosis. [145]
105. Effect of fenugreek seeds aqueous extract on ovarian hyperstimulation syndrome Rat Fenugreek seed extract decrease serum estradiol level in rat. [34]
106. Effects of the fenugreek seeds' powder and its aqueous and oil extracts on male reproductive system Rat Fenugreek seed showed significant changes in sperm viability and sperm count in rat. [35]
107. Effect of Trigonella foenum-graecumseed extract in male volunteers Human Sperm motility, reflex erection score, mood and mental alertness incresead in the male volunteers. [146]
108. Effect of fenugreek on menopause induced memory loss, BDNF and dendritic arborization in ovariectomized rats Rat

Combination of fenugreek with choline-docosahexaenoic acid could be helpful in improving memory deficit. [147]
109. Effect of fenugreek on reproductive health Human Fenugreek improved reproductive health of women [148]
Antibacterial property
110. Effect of fenugreek seed oil Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium and Aspergillus niger The highest antimicrobial activity was recorded against E.coli as compared to others [36]
111. Antibacterial effect of fenugreek seed extract Bacillus subtilis, Staphylococcus aureus, and Escherichia coli Fenugreek extract from germinating seeds recorded highest antimicrobial property compared to ethanolic and methanolic extract [149]
112. Antibacterial effect of fenugreek extracts Escherichia coli, Pseudomonas aeruginosa , and Serratia marcescens, and Bacillus cereus T. foenum-graecum leaves extracts showed notable antibacterial effect with maximum activity against Serratia marcescens [42]
113. Effect of fenugreek seed gum based nanocomposites Listeria monocytogenes, Escherichia coli, Staphylococcus aureus and Bacillus cereus Fenugreek seed gum based clay nanocomposite films showed strong antimicrobial property against foodborne payhogens [150]
114. Effect of fenugreek seed extract showing antibacterial property Escherichia coli, Pseudomonas aeruginosa, Salmonella Typhi, Streptococcus pyogenes and Staphylococcus aureus Fenugreek seed extract might show antibacterial property at the concentration of 50-100 mg/ml [151]
115. Effect of fenugreek seeds and shoots extract Staphylococcus aureus and Pseudomonas aeruginosa Fenugreek shoots extract have strong antimicrobial property compared to its seeds extract [152]
116. Effect of fenugreek seed extract as antibacterial agent Staphylococcus aureus, Pseudomonas aeruginosa, Proteus mirabilis, Salmonella typhi, Escherichia coli, and Vibrio parahaemolyticus. Highest antibacterial activity was recorded with Staphylococcus aureus and Pseudomonas aeruginosa (22 mm and 17 mm diameter of inhibition zones respectively) [37]
117. Effect of fenugreek seeds’ phytoconstituents S. aureus, E. coli, Citrobacter freundii, and Pseudomonas aeruginosa Extract showed an activity index of 1 to 1.25 with Gram-positive bacterial strains and 1 to 1.21 activity index with Gram-negative bacterial strains [40]
118. Effect of si;ver nano particle synthesized using fenugreek leaves extract S. aureus, E. coli, P. aeruginosa and V. cholera Highest inhibitory activity was found againstP.aeruginosacompared to other bacteria. [39]
119. Effect of fenugreek oil nanoemulsion Escherichia coli,Bacillus subtilis,Staphylococcus aureus, and Pseudomonas aeruginosa Nanoemulsion recorded antimicrobial effect against Gram positive and Gram negative bacterial strains used in the study [153]
Antifungal property
120. Effect of fenugreek as antifungal agent Candida species (C. albicans, C. glabrata, C. parapsilosis). Fenugreek extract found to have antifungal activity against human pathogenic fungal strains [43]
121. Effect of seed and callus extract of fenugreek Aspergillus niger and Candida albicans Petroleum ether extract of T.foenum- graecum seeds have higher antimicrobial activity than methanoilc extract. [41]
122. Effect of novel defensin-like antifungal peptide from fenugreek Fusarium oxysporum,Fusarium solani, andRhizoctonia solani. Defensin-like antifungal peptide (Tf-AFP)isolated from fenugreek seed possess antifungal property. [45]
123. Effect of silver nano particle by using fenugreek seed extract as antifungal agent Candida Albicans Silver nanoparticle synthesized using fenugreek showed antifungal property against Candida species [46]
Immunological property
124. Effect of fenugreek extract as immunomodulator Mice Fenugreek stimulates the immune function by up-regulating immune related genes [47]
125. Effect of aqueous extract of fenugreek (Trigonella foenum-graecumL.) on immune response Hen Fenugreek extract dose of 15 ml/l added to the drinking water improved inmmune responses of treated model [51]
126. Effect of fenugreek combined with prebiotics on immune system of treated model Sparus aurata Fenugreek combined with prebiotic strains enhance humoral immunity [50]
127. Effect of fenugreek on immune status of gilthead seabream Sparus aurata Inclusion of fenugreek seeds in the diet at 5% or 10% enhanced humoral and cellular immune activities [48]
128. Effect of fenugreek on immune functions Sparus aurata Fenugreek supplemented diet at higher inclusion dose upregulate skin mucosal immunity responses [49]
129. Effect of fenugreek on hematological parameters Rat Fenugreek enhanced Hb, RBC and WBC count at a dose of 400 mg/kg body weight. [53]
130. Effect of fenugreek on immune system Humans Diet combined with fenugreek impoved haematological status of treated obese women [52]

4.2. Hepatoprotective Effects

Impairments of the liver can be favorably cured or controlled by the supplementation of antioxidants. Components like diosgenin, saponins, flavonoids, and polyphenol possess antioxidant, hypolipidemic, and hypocholesterolemic properties. In one study, fenugreek improved lipid profile and collagen content in the hepatotoxic Wistar rats at a dose of 200 mg/kg per day [20]. In another study, fenugreek reduced lipid aggregation in the liver by increasing lipid excretion in feces. Serum total cholesterol, low-density lipoproteins, very low-density lipoproteins, cholesterol, and triglycerides were also significantly reduced. However, the high-density lipoprotein and cholesterol fraction remained unchanged [21]. Active components of fenugreek, such as 4-hydroxyisoleucine and galactomannan, lowered blood glucose levels and improved lipid metabolism. Metabolic and hepatic damage that occurred after ischemia-reperfusion could be prevented by fenugreek. Fenugreek was found to be effective in reducing damage caused by ischemia-reperfusion. It has been shown that polyphenols and flavonoids are helpful in treating hepatic ischemia. The exposure of fenugreek extract to rats showed that the levels of plasma serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were significantly reduced, thus showing the hepatoprotective effects [22].

4.3. Cardioprotective Effects

Studies have revealed that fenugreek seeds are effective in lowering cholesterol levels and thus may also act as a cardioprotective agent [23]. The constituents of fenugreek, such as saponins, diosgenin, galactomannan, coumarin, fenugreekine, nicotinic acid, sapogenins, phytic acid, scopoletin, and trigonelline, have pharmacological properties. The effect of fenugreek was studied on isoproterenol-induced myocardial infarction in rats. The study revealed the cardioprotective effect of fenugreek in rats by increasing the activities of both enzymatic and non-enzymatic antioxidants (SOD, CAT, GPx, and GSH) [24]. Fenugreek strongly regulates blood lipid levels; hence, it is effective against atherosclerosis by lowering cholesterol, triglycerides, and LDL levels and raising HDL levels [12]. Fenugreek, a good anti-oxidant, protects the myocardial tissue from oxidative stress and improves metabolic abnormalities. One of the studies demonstrated the protective effect of the hydro-alcoholic extract of fenugreek seeds in STZ-induced diabetic rats. The results showed that fenugreek seed extract has the potential to treat diabetic cardiomyopathy by altering the expression of genes involved in apoptosis. It was reported that the expression of pro-apoptotic Bax gene and intercellular adhesion molecule was downregulated, and the anti-apoptotic gene BCl2 was upregulated, indicating the anti-oxidant and anti-apoptotic property of fenugreek [25].

4.4. Gastroprotective Effects

Lifestyle and unhealthy diet style result in abdominal discomfort, loss of appetite, nausea, vomiting, gastric ulcer, and peptic ulcer. There are several studies reporting the beneficial role of fenugreek against gastrointestinal diseases. It possesses anti-ulcer, anti-inflammatory, gastroprotective, antioxidant as well as anti-secretory properties. The study on Albino rats revealed that when fenugreek seeds were orally given to rats, the severity of ulcers reduced significantly compared to the untreated group of rats [26]. Mucosal damage, hyperaemia, submucosal oedema, and severe congestion of vessels marked by HCl-ethanol induced in rats were significantly lowered in pre-treated rats with fenugreek seeds [27]. The fenugreek seed gel fractions of 700 mg/rat given orally proved anti-ulcerogenic. Gel fraction showed significantly less lesion formation, altered gastric secretion, reduced lipid peroxidation, and increased antioxidant capacity of the gastric mucosa [28]. Sugaheal®, the 4-hydroxyisoleucine and trigonelline enriched fraction (TF4H 28%), a well-known anti-diabetic drug possesses good antioxidant properties. In a study, sugaheal given to Wistar rats showed the beneficial property against gastric ulcers. Microscopic analysis of the stomach wall revealed a reduction in ulcer spots. A 100 mg/kg body weight (BW) dose of sugaheal displayed maximum protection against ROS damage mediated by a 48 mg/kg BW dose of indomethacin in a rat's stomach [8]. The polyphenols present in fenugreek are responsible for treating gastric and acute gastric injuries induced by chemicals [29]. Fenugreek seeds improve appetite and gastric discomfort, and their oral administration enhances salivary flow as well as lactase activity [26].

4.5. Anti-cancerous Effects

Fenugreek contains a bioactive compound, ‘diosgenin,’ which is an anti-cancer agent [30]. Several studies have shown the benefit of fenugreek against cancerous cells by inducing apoptosis. Diosgenin arrests the G1 phase of the cell cycle (in both MCF-7 and MDA-231 cells) by downregulation of cyclin D1 and cdk-2. Treatment with diosgenin showed upregulation of p21 without involving p53 in the treated cells. It was also found to be involved in the up- and down-regulation of the protein involved in the apoptosis of cells (in vivo as well as in vitro) [31]. Levels of Bcl2 decreased in the breast cancer (BCa) cells, and the activity of caspase 3 increased in the treated cells compared to control cells. The results showed that diosgenin influences the apoptotic pathway in cancerous cells. Akt-mediated signaling, crucial for the progression of breast cancer cells, was downregulated by the treatment of diosgenin [31]. Thymoquinone and diosgenin possess anti-neoplastic property as they increase the expression of apoptotic genes and caspase activity, inhibit Akt and JNK phosphorylations, and thus prevents cell division. These two bioactive components possess synergistic effects and anti-proliferative properties [30]. A study showed that intraperitoneal administration of the fenugreek seed extract caused 70% inhibition of tumor cell growth compared to control and modulated 1,2-dimethylhydrazine-induced hepatic oxidative stress during colon carcinogenesis by increasing catalase, superoxide dismutase, glutathione-s-transferase activities in the liver of treated animal [4]. Fenugreek possesses a cytotoxic property, which has shown to be useful in the prevention and treatment of cancer [32]. According to a study, treatment with 10-15 ug/ml of FE for 72 hr showed inhibition of tumor growth in breast, pancreatic, and prostate cancer cell lines (PCa) [33].

4.6. Anti-sterility and Anti-fertility Effects

Reproductive health benefits of fenugreek include regulation of sex hormones, sperm viability, sperm count, and other sexual dysfunction in both genders. Bioactive components of fenugreek, such as steroidal saponins (Diosgenin and yamogenin), possess anti-sterility and anti-androgenic effects. According to some studies, saponin binds to estradiol receptors and modulates the activity of E2 in the rat model of Ovarian Hyperstimulation Syndrome [34]. Diosgenin regulates sexual activity by stimulating growth hormones from the pituitary [35]. Diosgenin is a precursor used for the majority of commercially available cortisone, pregnenolone, progesterone, and other steroids. Rats exposed to fenugreek powder, oil extract, and aqueous extract altered sex hormone levels, sperm count, and sperm viability [35].

4.7. Anti-Bacterial Property

The antimicrobial property of fenugreek has become popular among various herbal extracts. The effectiveness of fenugreek against many bacteria has been studied. Sulieman et al. [36] studied the antimicrobial property of fenugreek against Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and Aspergillus niger. They reported that the 100% concentrated fenugreek oil showed maximum inhibition against Escherichia coli rather than Salmonella typhimurium and Staphylococcus aureus. Ethanolic extract of fenugreek seed was also tested on 6 bacterial strains, including Staphylococcus aureus, Pseudomonas aeruginosa, Proteus mirabilis, Salmonella typhi, Escherichia coli, and Vibrio parahaemolyticus, with low to moderate activity except on Staphylococcus aureus and E. coli [37]. Phytochemical analysis showed the antibacterial properties of fenugreek seed extracts due to the presence of alkaloids, flavonoids, tannins, saponins, terpenoids, and steroids [38]. The antibacterial activity of AgNPs synthesized using fenugreek leaves extract was tested against S. aureus, E. coli, P. aeruginosa and V. cholera, with an inhibition zone of 6, 12, 11, and 6 mm, respectively. Fenugreek leaves contain bioactive components, such as flavonoids, including quercetin, vitexin, and kaempferol and glycosides, phenolic compounds, and ascorbic acid, which act as a bioactive source or reducing agent for the synthesis of silver nanoparticles [39]. Phytoconstituents, particularly polyphenols, showed low to strong effects on most tested strains, with a strong antibacterial effect of fenugreek compared to aqueous extracts [40]. An in vitro study on methanolic and petroleum ether extracts of seeds and callus extracted from hypocotyls and cotyledons explants of fenugreek against standard microorganisms, Bacillus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger, and Candida albicans reported antimicrobial activity of petroleum ether extract with inhibition zones of 17±0.33mm and 15±0.57mm against Escherichia coli and Staphylococcus aureus, respectively, which were higher than methanolic extract [41]. The minimum inhibitory concentration (MIC) recorded was 6.25 to 25 mg/ml of Trigonella foenum-graecum leaf extract, showing significant antibacterial properties that could be therapeutic for a wide range of drug-resistance microorganisms with minimal or no side effects [42].

4.8. Antifungal Property

Multi-drug resistant strains of pathogenic fungi have led to the utilization of medicinal plants and compounds isolated from them for their antifungal property. Extract of fenugreek was proved to be effective against pathogenic fungi strains of Candida species [43]. A study on ethanolic extract of fenugreek showed the highest zone of inhibition of 16.510+ 0.85 mm and 38.395% of mycelial inhibition using 100 µl of concentration against Microsporum gypseum. Such antifungal property of fenugreek is due to the presence of secondary metabolites, such as flavonoids, saponins, alkaloids, steroids, and tannins [44]. Maximum zone of inhibition, i.e., 20±0.88 mm against Aspergillus niger by concentration 250 mg/ml and 17±0.57mm of inhibition zone against Candida albicans by concentration 250 mg/ml have been recorded by petroleum ether extract of fenugreek seeds [41]. A novel defensin-like antifungal peptide (Tf AFP) of molecular mass 10.3 kDa has been isolated from Trigonella foenum graecum (fenugreek) and demonstrated antifungal properties against Fusarium oxysporum, Fusarium solani, and Rhizoctonia solan fungal species [45]. Elsidding et al. [46] synthesized silver nanoparticles using fenugreek extract as an antifungal agent against Candida albicans. Three different concentrations of silver nitrate were mixed with fenugreek extract, which served as a reducing agent and generated silver nanoparticles.

Fig. (2). Medicinal properties of fenugreek.

4.9. Immunological Property

Several studies reported the immunomodulatory activity of fenugreek on immune functions, including humoral immunity, leucocytic count, phagocytic index, serum globulins, and related genes. Mice treated with three different doses of aqueous extract of fenugreek showed increased activity of humoral immunity at 100 mg and delayed hypersensitivity. The phagocytic index and phagocytic capacity of macrophages were significantly elevated in the treated mouse model [47]. The dietary supplement action of fenugreek (Trigonella foenum graecum) with gilt-head seabream (Sparus aurata L.) was found to stimulate the immune system by up-regulating immune-related genes along with significant improvement in the hematological parameters [48] and enhance skin mucosal immunity response by increasing some enzymatic activities [49]. Fenugreek combined with prebiotic strains showed a significant rise in the expression of immune-related genes (igm, tcr-β, csfr1, and bd) and the growth performance of the species [50]. In addition, fenugreek extract refined the immune system of egg-laying hens and production performance [51]. Ebrahimi et al. [52] reported remarkable improvement in the levels of immunoglobulins (IgG), lymphocytes, and leukocytes in obese women after 6 weeks of regular, intense training and fenugreek supplementation. Hematological parameters analysis revealed that the extract notably (p<0.05) enhanced Hb, RBC, and WBC count at a dose of 400 mg/kg body weight in the rodent model [53]. Therefore, the efficacy of fenugreek on hematological parameters could be used to strengthen the immune system.

CONCLUSION

For ages, the plant extract and its products have been proven to be successful in treating various ailments associated with diseases or drugs in humans and available experimental models [54-70]. Fenugreek has been used for centuries to treat various diseases due to a wide range of properties, including anti-diabetic, hepatoprotective, cardioprotective, anti-cancerous, anti-androgenic effects, and anti-sterility effects. Results obtained from in vivo and in vitro studies on fenugreek have shown beneficial effects not only on diabetes, reproductive issues, and hypolipidemic conditions but also on immune functions. It has several properties, including anticancer properties, antimicrobial, gastroprotective, cardioprotective, antioxidative, antinociceptive, antimicrobial properties, anthelmintic, anti-arthritic, and vascular protective effects (Fig. 2). However, more studies are required on its interaction with other drugs. Furthermore, its diverse chemical composition attributes for future application as therapeutic agents. The consumption of fenugreek is safe and proved to be a necessary ingredient of our daily diet to drive health benefits. A comprehensive investigation based on clinical trials is required to investigate the role of fenugreek in the treatment of numerous ailments.

CONSENT FOR PUBLICATION

Not applicable.

AVAILABILITY OF DATA AND MATERIALS

The author that confirmed all the sources for the data search are mentioned in the manuscript.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

Declared none.

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