{"id":54179,"date":"2023-12-31T11:58:16","date_gmt":"2023-12-31T11:58:16","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=54179"},"modified":"2024-01-05T05:48:40","modified_gmt":"2024-01-05T05:48:40","slug":"medicinal-value-of-phytoestrogens-in-trigonella-foenum-graecum-l-fenugreek-review","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol16no4\/medicinal-value-of-phytoestrogens-in-trigonella-foenum-graecum-l-fenugreek-review\/","title":{"rendered":"Medicinal value of Phytoestrogens in Trigonella foenum-graecum L (Fenugreek) &#8211; Review"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\"><strong>Introduction<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\nfenugreek (<em>Trigonella foenum-graecum L.<\/em>)\nbelongs to the family <em>Fabaceae<\/em>. It is\none of the most significant commercial spice crops. Its fresh leaves, shoots\n(tender), and seeds are widely used in food, medicine, and cosmetics<sup>1<\/sup>.\nFenugreek showed many pharmacological effects, such as hypoglycemic effect<sup>2<\/sup>,\nhypocholesterolemic effect<sup>3<\/sup>, antioxidant action<sup>4<\/sup>,\ngastroprotective activity<sup>5<\/sup>, stimulator of appetite<sup>6<\/sup>, antirheumatic\neffect<sup>7<\/sup>, for reducing the adipose tissue weight in the body<sup>8<\/sup>.\nIt has also been shown that flavonoids in fenugreek act as an estrogen-mimicking\nagent. &nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Phytochemical\nanalysis shows that the Fenugreek seed contains carbohydrates (45-60%), including\nmucilaginous fiber; proteins (20-30%), mostly tryptophan and lysine; lipids\n(5-10%); and pyridine-type alkaloids, mostly choline, trigonelline (0.5%),\ncarpaine and gentianine. The flavonoids such as orientin, apigenin, vitexin,\nand quercetin are also found in them. Amino acids (4-hydroxy isoleucine\n(0.09%); arginine (Arg), histidine (His), and lysine (Lys)) are also detected\nin seeds. Saponins (0.6-1.7%); glycosides generating sapogenins on hydrolysis (cholesterol\nand vitamins A, B<sub>1<\/sub>, C), and 0.015% volatile oils (sesquiterpenes) similarly\nidentified in fenugreek seeds<sup>9<\/sup>. Fenugreek is also found to contain\nyamogenin, gitogenin, tigogenin, and trigoneoside, choline, saponin, and nicotinamide<sup>10<\/sup>. It\nhas been found that unhydrolyzed fenugreek seeds contain phytoestrogens such as\nisoflavones (daidzein, genistein), lignans (secoisolariceresinol), and\ncoumestrol in hydrolyzed fenugreek seeds<sup>11<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Fenugreek\nseeds contain diosgenin<sup>12<\/sup>, which is recognized to be a significant\nprecursor for the production of testosterone and estrogens<sup>13<\/sup>. Even the highest dose of 1000\nmg\/kg body weight, fenugreek seeds (FenuSMART\u00ae; FHE) administered to animals in\na toxicological evaluation did not cause appreciable toxicological changes in feed\nconsumption, body weight, biochemical parameters, behavioral observations,\nophthalmic examinations, and urinalysis compared to normal animals.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Materials and Methods<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\nliterature search was conducted in Scopus, PubMed, ScienceDirect, and Google\nScholar to identify all published articles on <em>Trigonella foenum graceum<\/em> (Fenugreek) between June 2021 and\nSeptember 2022. The search criteria was based on the phytoestrogen role of\nfenugreek in postmenopause, pregnancy, offspring, sexual functions, bone and\nskin health, milk production, ovary, vagina, cardiovascular system, eye, tumor\ncells, pancreas, and kidney. Studies with full text in the English language were\nincluded in this review. Non-English studies were excluded from the search. In\neach manuscript, the search outcomes were reviewed by all the authors.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Phytoestrogen<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Phytoestrogens are one of the constituents of fenugreek, and these are nonsteroidal compounds that resemble the structure of 17\u03b2 -estradiol and can bind to the ER\u03b1 and ER\u03b2 estrogen receptors. It acts as an estrogen receptor modulator and produces antiestrogenic and\/or estrogenic effects depending on the blood estrogen levels<sup>14<\/sup>. Several health benefits are due to phytoestrogens, such as lowering the hot flashes and risk of cardiovascular disease (CVD), metabolic syndrome, brain function disorders, osteoporosis, and other malignancies (breast, prostate, and bowel). On the contrary, it has also been shown that phytoestrogens may act as anti-estrogenic agents and adversely disrupt endocrine functions<sup>15<\/sup>. The main functions of phytoestrogens are depicted in Figure 1.<\/p>\n\n\n<table style=\"width: 70%;\" border=\"1\" cellpadding=\"5\">\n<tbody>\n<tr>\n<td><img decoding=\"async\" class=\"alignnone size-thumbnail wp-image-54193\" src=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2023\/12\/Vol16No4_Med_Anj_Fig1-150x150.jpg\" alt=\"\" width=\"150\" height=\"150\" srcset=\"https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/12\/Vol16No4_Med_Anj_Fig1-150x150.jpg 150w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/12\/Vol16No4_Med_Anj_Fig1-256x256.jpg 256w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/12\/Vol16No4_Med_Anj_Fig1.jpg 595w\" sizes=\"(max-width: 150px) 100vw, 150px\" \/><\/td>\n<td>\n<p><strong>Figure 1: <\/strong><strong>Effect of Phytoestrogen components present in fenugreek.<\/strong><\/p>\n<p><\/p>\n<p><a href=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2023\/12\/Vol16No4_Med_Anj_Fig1.jpg\" target=\"_blank\" rel=\"noopener noreferrer\">Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n<p class=\"wp-block-paragraph\">In\naddition to phytoestrogen activity via estrogen receptors and their downstream\ngene activity, they also can act by altering the specific gene epigenetics, by the\ninitiation of AMP-activated protein kinase pathway, by kinase inhibition\nactivity, by activating the PPAR (NRC1C) family, or by the initiation of antioxidant\nor electrophile response element (EpRE)-mediated gene expression by stimulation\nof nuclear factor erythroid 2-related factor 2-Keap1 signaling<sup>16<\/sup>. Furthermore,\nSirotkin and Abdel have extensively explored the potential issues with\nunderstanding and using phytoestrogens since they have many targets and various\nestrogen receptor-dependent and -independent modes of action<sup>17<\/sup>. Because\npS2 gene expression is used to test the estrogenicity of multiple drugs,\nfenugreek seeds were shown to promote pS2 transcription, which might impact the\ntranscription of estrogen-sensitive genes, resulting in estrogenic effects<sup>18<\/sup>. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Use of Phytoestrogens of Fenugreek in Typical Menopausal Symptoms<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Menopausal\nchanges are known to be initiated by the decrease in estrogen level, which\ninduces signs like osteoporosis, depression, hot flashes, anxiety, and dementia.\nAs life expectancy increases with advances in medical sciences, women live 1\/3\nof their lives with disorders related to menopause. The current treatment for\nthese complications is estrogen replacement therapy (ERT). However, prolonged\nERT increases the frequency of uterine, ovarian, and breast cancer, limiting\nERT in clinical use. Instead, phytoestrogen-rich plant products such as fenugreek\nare considered the alternative strategy to treat menopause-related ailments\nwithout many adverse side effects.&nbsp; <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">At\na dosage of 1000 mg per day, fenugreek (<em>Trigonella\nfoenum-graecum<\/em>) standardized extract (FenuSMARTTM) has been demonstrated to\nenhance plasma estradiol, decrease the frequency of hot flashes, and play a significant\nrole in managing the lipid profile in menopausal women<sup>19<\/sup>. When\ntreated with fenugreek seed extract, postmenopausal women were reported to show\nimprovements in somatic, psychological, and urogenital issues (reduction in hot\nflashes, pain in leg muscles and joints, night sweats, less irritability, and\nvaginal dryness). In these women, a significant rise in estradiol and\nprogesterone and a decline in follicular stimulating and luteinizing hormone\nlevels were observed, indicating the achievement of hormonal balance<sup>20<\/sup>.\nPhytoestrogen-rich food such as fenugreek has effectively reduced the severity\nof premenopausal\/menopausal symptoms such as forgetfulness, swelling, and\nweight fluctuation<sup>21<\/sup>.&nbsp; <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Menopause and the associated loss of estrogen-related\nhormones cause inflammation, which results in the expression of circulating\ncytokines and other inflammatory responses. Menopause is\nassociated with an increase in triglycerides (T.G.), low-density lipoproteins (LDL),\nincreased tunica intima and&nbsp;media thickness, and an increased risk of\ncardiovascular diseases (CVD). Inflammation in\nmenopause with dyslipidaemia is a source of TNF- \u03b1 (increases the expression of leptin and metabolic\nsyndrome), a contributing factor in the etiopathogenesis of atherosclerosis<sup>22<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Menopausal\nobesity is associated with decreased PPAR-\u03b3 and adiponectin expression. Few studies\nsupport fenugreek&#8217;s phytoestrogen action in postmenopausal women<sup>23,24<\/sup>.\nAccording to a meta-analysis, the cardiometabolic risk is decreased by fenugreek\nin humans<sup>25<\/sup>. The advantages of fenugreek in reducing cholesterol and\nmetabolic disorders are discussed in another systematic review. This effect may\nbe due to the existence of phytoestrogens<sup>26<\/sup>. Fenugreek therapy for\n12 weeks lowered total cholesterol (TC), TG, AST, and ALT while increasing mRNA\nexpression of PPAR and adiponectin. TNF-\u03b1 and leptin levels returned to normal\nfollowing supplementation with fenugreek seed extract. Furthermore, fenugreek\nseed extracts reduced renal glomerular hypertrophy, micro-steatosis in the\nliver, and thickness of tunica intima (T.I.) and media (T.M.) of the common\ncarotid artery (CCA). The phytoestrogen components of fenugreek are responsible\nfor the protective effect<sup>24, 27<\/sup>. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Menopausal cognitive impairment with estrogen insufficiency\nresults in lower levels of brain-derived neurotrophic factor (BDNF). Declined BDNF levels influence the growth\nof neurons, dendritic spine density, and arborization in postmenopause. Ovariectomized\nrat menopausal model supplemented with fenugreek seed extract and choline-DHA suggestively\nelevated BDNF, dendritic branching points, and intersections, thus modulating\nthe learning and memory problems caused by menopause through phytoestrogen properties<sup>28<\/sup>.\nSimilarly, it was shown that ovariectomized rats displayed poor memory and\nlearning abilities and neuronal atrophy and death in the hippocampal CA1 and\nCA3 regions. Fenugreek seed extract dramatically improved memory and\nlearning while protecting hippocampus neuronal architecture and survival in\nthese ovariectomized rats. These changes could be due to the phytoestrogen\ncomponents in fenugreek, and they may be useful in addressing\nmenopausal-induced cognition deficits<sup>29<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Use of Phytoestrogen in Fenugreek in Sexual Functions<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Phytoestrogens\npresent in the fenugreek are shown to have several effects on sexual function.\nSignificant improvement in sexual interest was observed after supplementation\nwith the fenugreek husk<sup>19<\/sup>. Crude fenugreek seed\noil significantly affected spermatogenesis in young male patients with\ncomplaints of infertility due to natural oligospermia<sup>30, 31<\/sup>. An\nincrease in sexual function, fertility, free testosterone levels, and sperm\nprofile has been recorded in male individuals treated with the fenugreek\nextract<sup>32,33<\/sup>. Kassemet et al. stated that <em>Trigonella foenum-graecum (TFG) <\/em>administration has reduced plasma\nandrogen levels and significantly decreased sperm count<sup>31<\/sup>. This\neffect could be due to saponins in fenugreek seeds, which can act like\nestrogen. The reduction in sperm count and plasma testosterone level may also be\nattributed to the fact that <em>TFG <\/em>can\nincrease prolactin, and its high levels are known to obstruct the production of\ngonadotropin-releasing hormone (GnRH). This intern leads to a decline in FSH\nand LH and thus decreases spermatogenesis<sup>34<\/sup>. It has been shown that phytoestrogens\non long-term exposure (or high-dose exposure) severely affect sperm count by reducing\nmale reproductive function<sup>35<\/sup> and increasing apoptosis of developing germ\ncells<sup>36<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Similarly,\nSreeja and Anuj found that when fenugreek seeds are included in the diet of\nrabbits, the testis weight is reduced, seminiferous tubules and interstitial\ntestis tissue sections are damaged, which is followed by a drop-in androgen\nhormone and sperm concentrations<sup>18<\/sup>. Several studies show that\nfenugreek induces a significant decrease in sperm motility and count, a rise in\nspermatozoa morphology and chromosomal abnormalities<sup>35<\/sup>, and a decreased\nconcentration of testosterone and sperm mass and motility<sup>36<\/sup>. Male\ninfertility and antiandrogenic activities of fenugreek are attributed to a decrease\nin cholesterol level, which is the primary precursor of the sex hormone<sup>2<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Effect\non Pregnancy and Offspring <\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In a study of prenatal exposure to\nfenugreek seeds (aqueous extract), the progeny of exposed mice in the\npost-weaning period showed growth retardation, such as reduced body weight and\nreduced brain weight at birth. These pups (both male and female) also showed a significant\ndecrease in neurobehavioral performances, such as locomotor activity, motor\ncoordination, and a substantial decrease in successful impulsive alternations\nin the T-maze test. These changes may be attributed to phytoestrogens such as\nform ononetin in fenugreek<sup>37<\/sup>.\nContrary to that, if consumed in moderation, fenugreek is only safe for\npregnant women. Excessive intake may result in premature uterine contractions<sup>38<\/sup>.\nConsuming an excess of fenugreek in late pregnancy causes miscarriage and\npremature labor<sup>39<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Phytoestrogens in Fenugreek on Bone Health <\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A\nstudy showed that estrogen deficiency worsens the increases in bone turnover\nindicators, bone mineralization and mechanical properties of tibial metaphysis. Trigonelline (alkaloid), found in TFG\nseeds and coffee, has demonstrated phytoestrogen action and did not affect the\nbones of non-ovariectomized (with an average level of estrogen) rats, while in\novariectomized (with low estrogen level) rats phytoestrogens significantly lower\nthe mineralization and mechanical characteristics of cancellous bone.\nTrigonelline&#8217;s detrimental effects on the skeletal system depend on estrogen,\nand it only affects cancellous bone in ovariectomized rats<sup>4<\/sup>. However, supplementation of TFG seed extract significantly\nincreased the maximum flexor load, tibia dry weight, and preserved the\ntrabecular and cortical bone thickness suggestively compared to ovariectomized\nrats<sup>41<\/sup>. The protective action of fenugreek on osteoporosis by\nenhancing bone mineral density and restoring bone physiology is via the estrogenic\nactivity of trigonelline in them<sup>42<\/sup>. Fenugreek mucilage in arthritic rats\nsignificantly decreased the activity of inflammatory enzymes myeloperoxidase\nand lipoxygenase<sup>43<\/sup>. Diosgenin, another\nconstituent in fenugreek seed, is also shown to increase the protein synthesis\nof bone matrix and Runx2 transcription in an osteoblastic cell line MC3T3-E1<sup>44<\/sup>.\nDiosgenin is also known to inhibit osteoclastogenesis, invasion, and\nproliferation of osteoclast cells by downregulating the Akt, IkB kinase\nactivator, and NFkB-regulated gene expressions<sup>45<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Skin Health <\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Oral or topical estradiol\ntreatment in postmenopausal women is known to enhance skin thickness and\ncollagen synthesis, and inhibition of the ER\u03b1\nand ER\u03b2 (estrogen receptors) by the antagonist decreases the secretion of these\nproteins. Because\nof the risks of breast and endometrial cancer associated with estradiol,\ntopical use of phytoestrogens is an alternate therapy for age-related skin\nalterations in postmenopausal women. Research has been conducted to demonstrate\nthe advantages of phytoestrogens as a substitute for HRT to improve or decrease\nthe detrimental influence of menopause-induced aging of the skin<sup>46<\/sup>. Fenugreek\nsupplementation enhances the secretion of COL1A1 (collagen type 1 alpha 1) and\nCOL3A1 (and type 3 alpha 1) through estrogen receptor \u03b1, and estrogen receptor \u03b2,\nand is primarily arbitrated by ER\u03b2 in fibroblasts of menopausal women. Thus, the\nphytoestrogen constituent of the fenugreek may act as a ligand to ER\u03b1 and ER\u03b2<sup>47<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Breast Size and Milk Production<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Nursing women also use dietary supplementation\nof fenugreek as a galactagogue to enhance insufficient breast milk production\nand improve the indications of breast milk sufficiency in newborns<sup>48-54<\/sup>.\nSimilarly, breastfeeding women fed with fenugreek tea three times a day showed\nincreased breast milk volume and an increase in prolactin levels in the early\ndays of breastfeeding. However, such influence of fenugreek was found in the latter\ndays of breastfeeding<sup>55<\/sup>. Further, it has also been shown that the consumption\nof fenugreek increases\nbreast size in women <sup>56<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Earlier\nstudies explain the possible mechanisms by which the phytoestrogens act as\ngalactagogues agents. They may act via binding to receptors in the mammary\ngland and induce the proliferation of alveolar cells. They may also bind to the\nER\u03b2 through the pituitary membrane isoform (associated estrogen) and promote the\nexpression of prolactin. These phytoestrogens act as agonists to dopamine receptor-activated\npathways and increase prolactin secretion<sup>57<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Egg Production<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Dietary supplementation of phytoestrogen\nplant products such as fenugreek seeds improved the egg mass and production, egg\nweight, albumen, and yolk content in aged laying hens. An increase in the crude\nfat and calcium in the yolk and a decrease in cholesterol in the egg yolk were\nobserved in these hens. The supplementation of fenugreek seeds with flax seeds\nalso positively affected plasma hormones (LH &amp; FSH)<sup>58<\/sup>. Adding turmeric\nand fenugreek in the hen\u2019s diet increases production, quality of eggs and\nimproves the financial efficiency of hen foods (Sinai local) at the late phase\nof productive age (59 \u2013 74 weeks)<sup>59<\/sup>. Another study showed that supplementing the mandarah hen diets with\nfenugreek delayed sexual maturity but increased ovarian weight, egg mass with\nincreased egg yolk albumin, and reduced cholesterol level<sup>60<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Effect on Ovary <\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Fenugreek also influences the structure and\nfunctions of the ovary. Treating the mice with fenugreek seed extract significantly\ndecreases the number of primaries, secondary, and griffin\nfollicles<sup>61<\/sup>. It was also found that fenugreek directly affects\novarian growth factors or decreases the pituitary gonadotropin hormones (FSH\nand LH)<sup>62<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Swaroop\net al. investigated the effectiveness of TFG seed extract on PCOS in women aged\n18 to 45 years. Reduced levels of LH were observed after\nthe first month of administration and reverted to baseline after two months in\nthe individuals who received fenugreek seed extract. After three months of\ntreatment, the LH levels have significantly increased. Similarly, FSH\nlevels gradually increased. Further, the irregular cycle rate remained\nunaffected in women after one month. At two months, 33.33% of patients stated a\nregular cycle, but at three months (the conclusion of the trial period), 71.43%\nof patients reported a normal cycle<sup>63<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Estradiol\n2 has a significant role in the pathophysiology of ovarian hyper-stimulation\nsyndrome (OHSS) through VEGF. Prevention of OHSS requires a reduction in E2\nlevels. A\nrecent study found that fenugreek extract effectively reduces blood Estradiol 2\n(E2) levels in ovarian hypersensitivity syndrome animal models<sup>64<\/sup>. Fenugreek\nextract may also act through inhibition of aromatase, leading to reduced\ntestosterone breakdown to estrogen<sup>65,<\/sup> which may be the reason for the\nreduction in serum E2 levels in these animals. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>On\nthe Uterus and Vagina<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Research\nby Hilles et al. stated that fenugreek seeds, which contain phytoestrogens with\nestrogenic activity, increased uterine weight and proliferation of epithelial\ncells, which increased the uterine layers. The use of fenugreek seeds is also\nconsidered a safe contraceptive method<sup>66<\/sup>. Vaginal atrophy is one of\nthe most prevalent postmenopausal complications. Consuming estrogen hormone to progress\nthese symptoms is inevitable. Alternatively, Fenugreek vaginal cream,\ncontaining phytoestrogens, effectively reduced postmenopausal vaginal atrophy\nand endorsed using this cream instead of estrogen (synthetic) to decrease the\ncomplications<sup>67<\/sup>. However, it was also found that symptoms of\natrophic vaginitis are diminished with fenugreek vaginal cream, although it is\nnot as efficient as ultra-low-dose estrogen<sup>68<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>&nbsp;Cardiovascular System <\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In various animal and clinical studies, fenugreek\nis claimed to be hypocholesterolemic<sup>69<\/sup> owing to the presence of\nsaponin (diosgenin) and other sapogenins<sup>70<\/sup>. In the digestive tract,\nthe saponins are hydrolyzed partly into sapogenins. Numerous studies described\nthe hypocholesterolemic effect of saponins and diosgenin<sup>71, 72<\/sup> in\nfenugreek.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The hypocholesterolemic role of fenugreek was\nshown by increased fecal excretion of bile acids, sterols and reduced cholesterol\nin the liver<sup>73<\/sup>. Dietary fiber (galactomannans or beta-glucans)\nhelps in the management of hypercholesterolemia. Fenugreek-derived\ngalactomannans have abundant efficacy in decreasing plasma cholesterol.\nAdditionally, soluble fiber elements lower LDL and increase HDL<sup>74<\/sup>. These\nbeneficial changes in the lipid profile by dietary fenugreek protect against\ncoronary heart disease and atherosclerosis. In a study of rats supplemented\nwith 400 mg\/kg\/day of the fenugreek seed\nextract, HDL levels improved significantly, and total cholesterol, TG, and LDL\ndecreased significantly. This effect might be attributed to the saponins found\nin fenugreek extract, which slow down cholesterol absorption and hepatic\ncholesterol formation by lowering the activity of the regulatory enzyme of\ncholesterol synthesis<sup>24, 27<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Diosgenin-derived phytoestrogen from\nfenugreek has been shown to decline plasma and hepatic TG levels<sup>75<\/sup>. Experimental studies\nhave established the lipid-lowering potential of diosgenin. Diosgenin reduced the\nelevated cholesterol and increased HDL fractions in rats fed with cholesterol.\nBesides, diosgenin prevented cholesterol absorption and inhibited its uptake\nand accumulation in the liver<sup>76<\/sup>. Diosgenin-mediated modulation of cholesterol-metabolizing enzymes\nreduced hepatosteatosis and hypercholesterolemia<sup>77<\/sup>. Diosgenin also\nprevented angiotensin II-induced remodeling of cardiac fibroblasts in rats by\nsuppressing the signaling growth factor \u03b21 \/ Smad3 pathway. Subsequently,\ndiosgenin could have therapeutic potential to treat cardiac fibrosis<sup>78<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>&nbsp;Eye<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A\nstudy confirmed that steroid hormones significantly influence ocular surface\nequilibrium and functions, and a reduction in these steroid hormones in\nconditions such as menopause can affect the eye&#8217;s surface. However, in\npostmenopausal women, phytoestrogen treatment significantly alleviated the\nsigns and symptoms of dry eye syndrome<sup>79<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It has been reported that tear osmolality and levels of sex\nhormones are negatively correlated, and these sex hormones have a role in the\npathogenesis of postmenopausal dysfunctional tear syndrome. Daily consumption\nof 200 mb of fenugreek seeds significantly improved signs and symptoms of postmenopausal\nwomen with severe evaporative dysfunctional tear syndrome without any\nsignificant side effects attributed to the phytoestrogens in fenugreek<sup>80<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Tumor Cells <\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Phytoestrogens from different sources are known to act by\nvarious mechanisms, providing several health benefits and protect\/treat\ndifferent cancers (oral, breast, colon, liver, lung, prostate) and many other\ncarcinomas<sup>81<\/sup>. In MCF-7 breast cancer cell lines, fenugreek seeds (ethanol\nextract) lowered cell feasibility and triggered (early) apoptotic alterations,\nsuch as reversing phosphatidylserine activity and reducing the potential of the\nmitochondrial membrane. Furthermore, DNA fragmentation and cell cycle arrest\nduring the G2\/M phase have been described<sup>82<\/sup>. In vitro, experiments have\nshown that the fenugreek constituent diosgenin, steroidal saponins which can\nact as phytoestrogen by preventing bcl-2 and increasing the expression of caspase-3\nprotein, promotes apoptosis and decreasing cell proliferation in the cell line\nof HT-29 human colon cancer. Diosgenin, in the fenugreek, is shown to have antitumor\nactivity in azoxymethane-induced colon cancer model of rats and cell lines of HT-29\nhuman colon cancer by inhibiting the aberrant crypt foci formation and\ninhibition of proliferation of cancer cell line along with apoptosis induction<sup>83<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The diet containing fenugreek seeds inhibited colon cancer\nby significantly decreasing \u03b2-glucuronidase activity, thus preventing the\nhydrolysis of the carcinogen-glucuronide conjugate, which may release a carcinogenic\nsubstance that affects the colonocytes. It also declined the action of mucinous,\nthus reducing the hydrolysis of protective mucin in the colon and protecting\nthe colonial lumen. These alterations are due to phytoestrogen saponins and\nother constituents of the fenugreek seeds<sup>84<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Pancreas <\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Fenugreek controls blood\nsugar levels mainly by the presence of saponins (phytoestrogen components)\ninhibiting digestion and absorption of carbohydrates and enhancing the insulin\nperipheral activity<sup>85<\/sup>. In a trial with streptozotocin-induced\ndiabetic rats, 45 days of oral diosgenin (15, 30, and 60 mg\/kg) administration\nat elevated doses have resulted in the restoration of blood glucose and enzymes\ninvolved in the carbohydrate metabolism, indicating the antidiabetic potential<sup>86<\/sup>.\nSaponin and an amino acid called\n4-hydroxyleucine in fenugreek were attributed to increasing the insulin level\nin hyperglycemic rats and humans and showing antidiabetic effects<sup>87<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Kidney<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">TFG seed extract restored kidney function in diabetic rats by ameliorating ultra-morphologic abnormalities, such as irregular thickening of the base membrane of the glomerulus. These results indicate that TFG extract offered a defense against functional and morphological kidney injury<sup>88<\/sup>. Sayed et al. stated that renal histology of diabetic rats showed a mild diffuse mesangial expansion compared with normal glomeruli. In contrast, rats supplemented with 5% fenugreek seed powder mixed with a rat pellet diet showed a reduced score of mesangial development<sup>89<\/sup>.<em>The renal damage caused by AlCl<sub>3 <\/sub>was confirmed by elevated plasma nephrotoxicity markers and altered histological features of the renal tissue<\/em><strong>. <\/strong>Aqueous fenugreek seed extract restored the function of diabetic rat kidneys through its phytoestrogenic antioxidant activity. On the other hand, flavonoids in the TFG seed powder have a beneficial effect on collagenous structure (filtration membrane and basement membrane)<sup>90<\/sup>. The male albino rats treated with 2.5% TFG showed preserved architecture, normal glomeruli, and tubules with normal cortical blood vessels. The medulla showed normal tubules and blood vessels of interstitial tissue<sup>91<\/sup>. Thebeneficial effects of <em>Trigonella foenum-graecum <\/em>on different organs were presented in Table 1.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Table 1: Beneficial effects of <em>Trigonella foenum-graecum<\/em><\/strong><\/p>\n\n\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td width=\"71\">\n<p style=\"text-align: center;\"><strong>S. No<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"154\">\n<p><strong>Different organs<\/strong><\/p>\n<\/td>\n<td width=\"425\">\n<p style=\"text-align: center;\"><strong>Beneficial effect<\/strong><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"71\">\n<p style=\"text-align: center;\">1.<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"154\">\n<p>Bone<\/p>\n<\/td>\n<td width=\"425\">\n<p style=\"text-align: center;\">Lowers the mineralization and mechanical characteristics of cancellous bone<sup>4<\/sup> and also increases the maximum flexor load, dry weight, preserves the trabecular and cortical bone thickness.<sup>41&nbsp; <\/sup><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"71\">\n<p style=\"text-align: center;\">2<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"154\">\n<p>Skin<\/p>\n<\/td>\n<td width=\"425\">\n<p style=\"text-align: center;\">Improves the secretion of COL1A1 and COL3A1through ER\u03b1, and ER\u03b247.<sup>47<\/sup><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"71\">\n<p style=\"text-align: center;\">3<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"154\">\n<p>Ovary<\/p>\n<\/td>\n<td width=\"425\">\n<p style=\"text-align: center;\">Affects ovarian growth factors or decreases the pituitary gonadotropin hormones.<sup>64<\/sup><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"71\">\n<p style=\"text-align: center;\">4<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"154\">\n<p>Uterus and vagina<\/p>\n<\/td>\n<td width=\"425\">\n<p style=\"text-align: center;\">Increases uterine weight and proliferation of epithelial cells<sup>66<\/sup>, effectively reduces postmenopausal vaginal atrophy.<sup>67<\/sup><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"71\">\n<p style=\"text-align: center;\">5<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"154\">\n<p>Cardiovascular system<\/p>\n<p>&nbsp;<\/p>\n<\/td>\n<td width=\"425\">\n<p style=\"text-align: center;\">The hypocholesterolemic role is shown by increased faecal excretion of bile acids, sterols and reduced cholesterol.<sup>73<\/sup><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"71\">\n<p style=\"text-align: center;\">6<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"154\">\n<p>Eye<\/p>\n<\/td>\n<td width=\"425\">\n<p style=\"text-align: center;\">Improves signs and symptoms of postmenopausal women with severe evaporative dysfunctional tear syndrome.<sup>80<\/sup><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"71\">\n<p style=\"text-align: center;\">7<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"154\">\n<p>Tumor cells<\/p>\n<\/td>\n<td width=\"425\">\n<p style=\"text-align: center;\">In MCF-7 breast cancer cell lines- lowered cell feasibility and triggered early apoptotic alterations such as reversing phosphatidylserine activity and lowering the potential of mitochondrial membrane.<sup>82<\/sup><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"71\">\n<p style=\"text-align: center;\">8<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"154\">\n<p>Pancreas<\/p>\n<\/td>\n<td width=\"425\">\n<p style=\"text-align: center;\">Increasing the insulin level in hyperglycemic rats and humans and showing antidiabetic effects.<sup>87<\/sup><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"71\">\n<p style=\"text-align: center;\">9<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"154\">\n<p>Kidney<\/p>\n<\/td>\n<td width=\"425\">\n<p style=\"text-align: center;\">Preserved architecture, normal glomeruli, and tubules with normal cortical blood vessels.<sup>91<\/sup><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>&nbsp;<\/p>\n\n\n<p class=\"wp-block-paragraph\"><strong>Conclusion<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Several components present in the fenugreek\nact like estrogen-mimicking agents. Several health\nbenefits are attributed to phytoestrogens, such as lowering the menopausal\nadverse symptoms like hot flushes, inflammation, menopausal obesity, lowering\nthe risks of CVD, type 2 diabetes, menopausal cognitive impairment, sexual\nfunctions, osteoporosis, breast cancer, and prostate cancer. Other purposes\ninclude maintaining skin health, enhancing breast milk and egg production, increasing\nuterine weight, and maintaining ocular surface equilibrium. Based on the\nnumerous health benefits highlighted in this study and several previously\nreported scientific findings, fenugreek may be advised and used as part of our\nregular diet. This natural herb is safe to consume in limited amounts and can\nprovide a variety of health advantages. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Conflict of Interest<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The authors declare no conflict of interest.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Founding Source<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">No external funding for this study.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>References<\/strong><\/p>\n\n\n\n<ol class=\"wp-block-list\"><li>Malhotra SK. &#8220;Fenugreek (Trigonella foenumgraecum L.). In book: Genetic Resources, Chromosome Engineering and Crop Improvement. I<sup>st <\/sup>Edition Chapter 4.&#8221;&nbsp; <em>CRC Press<\/em>. 2011; 801-46. <\/li><li>&nbsp;Banarase NB, Khadabadi SS, Farooqui IA, Aswar PB, Bhopale NM. A novel effervescent tablet of fenugreek extract. <em>Research J. Pharm. and Tech<\/em>. 2008; 1(3):252-54.<\/li><li>Ajabnoor MA, Tilmisany AK. 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Middle East J Appl Sci. 2017; 7(4):967-73.<\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"<p>Introduction The fenugreek (Trigonella foenum-graecum L.) belongs to the family  [&#8230;]<\/p>\n","protected":false},"author":15,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[111],"tags":[],"class_list":["post-54179","post","type-post","status-publish","format-standard","hentry","category-vol16no4"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/54179","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/15"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=54179"}],"version-history":[{"count":5,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/54179\/revisions"}],"predecessor-version":[{"id":55027,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/54179\/revisions\/55027"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=54179"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=54179"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=54179"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}