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Bioactive effects and safety profiles of fenugreek (Trigonella foenum-graecum L.) for pharmaceutical and medicinal applications

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  • International Institute of Veterinary Education and Research

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The leaves and seeds of fenugreek (Trigonella foenum-graecum L), an annual herb, are common condiments used in India, Mediterranean and North African regions. Fenugreek has a long history of its use in traditional medicine. It is one of the oldest medicinal plants used in traditional medicine that contains many natural chemical compounds like trigonellin, diosgenin, quercetin, 4-hydroxyisoleucine, galactomannan, and scopoletin. Several studies on identification of different chemical compounds present in fenugreek and their therapeutic effects have revealed its hypocholesterolemic, antidepressant, galactagogues, antidiabetic, immunomodulatory, and hepatoprotective properties suggesting their potential use in prevention and treatment of many diseases in human and animals. This article summarizes recent research findings regarding the therapeutic potential and safety profile of fenugreek.
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The Pharma Innovation Journal 2021; SP-10(12): 912-919
ISSN (E): 2277- 7695
ISSN (P): 2349-8242
NAAS Rating: 5.23
TPI 2021; SP-10(12): 912-919
© 2021 TPI
www.thepharmajournal.com
Received: 07-10-2021
Accepted: 09-11-2021
Naveen Kumar
Assistant Professor, College of
Veterinary and Animal Sciences,
G. B. Pant University of
Agriculture and Technology,
Pantnagar, U. S. Nagar,
Uttarakhand, India
Mahesh Kumar
College of Veterinary and Animal
Sciences, G. B. Pant University
of Agriculture and Technology,
Pantnagar, U. S. Nagar,
Uttarakhand, India
Manish Kumar Verma
College of Veterinary and Animal
Sciences, G. B. Pant University
of Agriculture and Technology,
Pantnagar, U. S. Nagar,
Uttarakhand, India
Sivaraman Ramanarayanan
College of Veterinary and Animal
Sciences, G. B. Pant University
of Agriculture and Technology,
Pantnagar, U. S. Nagar,
Uttarakhand, India
Amita Ranjan
College of Veterinary and Animal
Sciences, Rajasthan University
of Veterinary and Animal
Sciences, Bikaner, Rajasthan,
India
Rakesh Ranjan
ICAR-National Research Centre
on Camel, Jorbeer, Bikaner,
Rajasthan, India
Corresponding Author
Naveen Kumar
Assistant Professor, College of
Veterinary and Animal Sciences,
G. B. Pant University of
Agriculture and Technology,
Pantnagar, U. S. Nagar,
Uttarakhand, India
Bioactive effects and safety profiles of fenugreek
(Trigonella foenum-graecum L.) for pharmaceutical
and medicinal applications
Naveen Kumar, Mahesh Kumar, Manish Kumar Verma, Sivaraman
Ramanarayanan, Amita Ranjan and Rakesh Ranjan
Abstract
The leaves and seeds of fenugreek (Trigonella foenum-graecum L), an annual herb, are
common condiments used in India, Mediterranean and North African regions. Fenugreek has a long
history of its use in traditional medicine. It is one of the oldest medicinal plants used in traditional
medicine that contains many natural chemical compounds like trigonellin, diosgenin, quercetin, 4-
hydroxyisoleucine, galactomannan, and scopoletin. Several studies on identification of different chemical
compounds present in fenugreek and their therapeutic effects have revealed its hypocholesterolemic,
antidepressant, galactagogues, antidiabetic, immunomodulatory, and hepatoprotective properties
suggesting their potential use in prevention and treatment of many diseases in human and animals. This
article summarizes recent research findings regarding the therapeutic potential and safety profile of
fenugreek.
Keywords: fenugreek, safety, therapeutic properties, traditional-medicine, Trigonella
1. Introduction
Fenugreek (Trigonella foenum-graecum L.) is a leguminous herb belonging to the Fabaceae
family and is grown as a spice crop in several countries of Asia, Africa, and Mediterranean
Europe (Petropoulos, 2002; Srinivasan, 2006) [1, 2]. The plant grows 1-2 ft in height, seeds are
present in sickle-shaped pods and are yellowish when ripened. Fenugreek, declared as safe for
human consumption by United States Food and Drug Administration, have several medicinal
applications (Sureshkumar et al., 2018) [3]. For centuries, it is being used for therapeutic
purposes in Ayurvedic (Indian), Unani (Arabic) and Chinese traditional medicine (ElNour et
al., 2015) [4]. In traditional medicine, it is being used for treatment of common cold, cough,
bronchitis, sore throats, arthritis, menstrual pain and stimulate intestinal digestion (Herrera et
al., 2019; Younesy et al., 2014) [5, 6]. Fenugreek seeds contain a high level of total polyphenols
and flavonoids that provide beneficial physiological effects (Khlifi et al., 2016) [7]. Seeds have
been identified as a commercial source of diosgenin, a chemical compound used for the
production of steroids as drugs like sexual hormones, oral contraceptives and corticosteroids
(Bahmani et al., 2016) [8]. Recently, standardized extracts are also available as capsules or
tablets and are being used in the management of many diseases.
2. Chemical constituents and bioactive compounds
Major bioactive compounds present in fenugreek include alkaloids (pyridine, trigonellin),
polyphenols (choline, luteolin, quercetin), steroidal saponins (diosgenin, protodioscin,
yamogenin), coumarin, lipids, a non-proteinogenic amino acid (4-hydroxyisoleucine),
vitamins, galactomannans and minerals (Sureshkumar et al., 2018; Kiss et al., 2018) [3, 9]. The
fenugreek seeds contain 51.5% carbohydrates, 25.0% protein, and 6-8% lipids, while leaves
contain 20-30% protein, 22-30% starch, 12.5% neutral detergent fiber, 4.0% gum 10.6% ash,
and 4-6% lipids (Basu and Srichamroen, 2010) [10]. Trigonelline is the primary alkaloid present
in fenugreek that is degraded to nicotinic acid and pyridines during roasting and provide
typical flavor to the seeds (Ouzir et al., 2016) [11]. Fenugreek contains trigonelline that has high
therapeutic potential and low toxicity. About 80% of the total content of free amino acid
present in seeds is 4-hydroxyisoleucine (Fuller and Stephens, 2015) [12]. Fenugreek seeds also
constitute dietary fiber (both insoluble and soluble), mainly galactomannan (Srinivasan, 2019)
[13]. Presence of fourteen bioactive compounds was evident in fenugreek seeds in a
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Chromatography-Mass Spectrometry (GCMS) analysis
(Khalil et al., 2015) [14]. Fenugreek leaves contain highest
amount of phenolic compounds and flavonoids (Premanath et
al., 2011) [15]. The major active components responsible
forvarious pharmaceutical properties of fenugreek have been
described as diosgenin, trigonelline, galactomannan, 4-
hydroxyisoleucine quercetin and scopoletin. The chemical
structure of these components is mentioned in Figure 1
(Belaid-Nouira et al., 2012; Bairi et al., 2017) [16, 17].
3. Fenugreek on health promotion and disease prevention
Multiple biological effects have been reported in fenugreek
and its derivatives, on both health promotion and disease
prevention (Figure 2). The pre-clinical and clinical data
related to fenugreek bioactive effects is briefly discussed with
respective mode of action in following sections.
3.1 Anti-inflammatory activity
Nowadays, most anti-inflammatory treatments decrease the
levels of cytokines associated with inflammatory diseases.
Joints of rheumatoid arthritis patient contain more pro-
inflammatory cytokines such as interleukin (IL-6) and tumor
necrosis factor alpha (TNF-alpha) than the normal joints, and
are associated with the pathogenesis of rheumatoid arthritis
(Szollosi et al., 2018; Kawabata et al., 2011) [18, 19]. Both,
cytokines and myeloperoxidase are important pro-
inflammatory mediators for inflammatory reactions (Sindhu et
al., 2012) [20]. Blocking cytokines and myeloperoxidase could
produce a relief of symptoms in rheumatoid arthritis.
Fenugreek seeds extract inhibit the production of
inflammatory cytokines in cultured THP-1 cells (Sindhu et
al., 2018) [21]. Mucilage from fenugreek markedly decreases
the level of cytokines (TNF-alpha and IL-6) and
myeloperoxidase activity in experimentally induced arthritis
(Yacoubi et al., 2011; Suresh et al., 2012) [22, 23]. In another
study, ethanolic extract of fenugreek significantly decreased
the level of cytokines, TNF-alpha and IL-6 in arthritic albino
rats. These findings suggested anti-inflammatory activities of
fenugreek (Goto et al., 2004) [24].
3.2 Antinociceptive activity
Antinociceptive activity of fenugreek seed, leaves and stem
extracts were investigated by several workers. Fenugreek
extracts have proven antinociceptive and antipyretic effects in
animal model similar to that of non-steroidal anti-
inflammatory drugs (NSAIDs) (Ahmadiani et al., 2001;
Abbas et al., 2016) [25, 26]. Serotonergic system involves in the
antinociceptive action of NSAIDs (Miranda et al., 2003) [27].
The alkaloid content of fenugreek seeds might be responsible
for antinociceptive effect (Kaviarasan et al., 2008) [28]. In an
experimental study on rats, ethanolic extract of fenugreek
seeds showed antinociceptive effects, perhaps due to presence
of some endogenous opoids (Biswal et al., 2003) [29].
Methanolic extract of fenugreek leaves were found to have
greater inhibitory effect than paracetamol on writhing in rats
induced by acetic acid (Bhalke et al., 2009) [30]. Likewise, in a
double-blind placebo controlled clinical trial, transdermal
patch containing 10% ethanolic extracts of fenugreek seeds
were found to decrease pain score and demand for morphine
in postherniotomy patients (Ansari et al., 2019) [31].
3.3 Antimicrobial activity
Aqueous and ethanolic fenugreek seed extract was found to
have potent antibacterial activity (ElNour et al., 2015; Al-
Hussainy, 2015; Dharajiya et al., 2016) [4, 32, 33] against many
pathogenic bacterial strains including Staphylococcus aureus
and Pseudomonas aeruginosa (Al-Timimi et al., 2019) [34]. In
another study, ethanolic extract of fenugreek leaf was found
to have potent antibacterial activity against Staphylococcus
aureus and Pseudomonas aeruginosa (Premanath et al., 2011)
[15]. Likewise, methanolic extract of leaves of stem was found
to have good antibacterial activity against Staphylococcus
aureus and E. coli (Sharma et al., 2017) [35]. Aqueous extract
and essential oil derived from fenugreek seeds failed to inhibit
the growth of some common food borne pathogens including
Staphylococcus aureus, Pseudomonas aeruginosa, E. coli,
Bacillus cereus and Enterococcus feacalis (Bhatia and
Sharma, 2012) [36]. However, in other study, silver
nanoparticles (AgNPs) engineered fenugreek seed extract has
been found excellent antibacterial efficacy against Gram
positive, Gram negative, and even multidrug resistant bacteria
(Guardiola et al., 2018) [37].
3.4 Anticarcinogenic activity
Targeting the cell proliferation or inducing apoptosis is a
critical point in the cancer therapy. Apoptosis, the
programmed cell death, is characterized by the morphological
changes including DNA fragmentation (Kitai et al., 2017) [38].
Apoptotic pathways can be classified into extrinsic and
intrinsic that occurs inside the cell for the DNA
fragmentation. The activation of caspase-3 is common in
both, extrinsic and intrinsic pathways (Thakur and Ahirwar,
2019) [39]. Epithelial cells adaptation to persistent oxidative
stress is an important step in carcinogenesis. Activation of
Nrf2 (nuclear factor erythroid 2-related factor 2), through
proteasome, pathway results into carcinogenesis (Khan and
Khosla, 2018) [40]. Therefore, inhibiting Nrf2 is an important
target in anticancer therapy. Ethyl iso-allocholate, a steroidal
derivative from fenugreek seeds, is a potent anticancer agent
that produces apoptosis by activation of caspase signaling
pathway (Sebens et al., 2011) [41]. Alkaloid trigonelline
isolated from fenugreek also has potential use in cancer
therapy (Basu and Srichamroen, 2010) [10]. Trigonelline
promote programmed cell death in cancer cells by blocking
Nrf2-dependent proteasome activity (Cersosimo et al., 2018)
[42].
3.5 Antidiabetic effect
Diabetes may lead to multiple organ complications due to
long term progression before treatment. The pathogenesis of
type 2 diabetes mellitus (T2DM) involves aberrant alteration
in levels and function of many hormones including insulin
(Cersosimo et al., 2018) [42]. The glucose homeostasis in the
body is maintained by both insulin secretion and tissue
sensitivity to insulin. Cellular glucose uptake is dependent on
stimulation of insulin, which causes the translocation of
glucose transporter-4 (GLUT-4) to the plasma membrane.
Insulin resistance impairs glucose disposal by inhibiting
cellular glucose uptake in muscle and adipose tissue (Avalos-
Soriano et al., 2016) [43]. In T2DM patients, insulin stimulate
cellular glucose uptake by inducing GLUT-4 from an
intracellular compartment to the plasma membrane (Jaiswal et
al., 2012) [44]. Peroxisome proliferators activate receptor
(PPAR), a nuclear receptor that has supreme roles in lipid
metabolism, particularly PPARgamma is critical for
adipogenesis (Wafer et al., 2017) [45]. Variant in PPARgamma
reduce the adipocyte differentiation and is associated with a
substantial risk of T2DM. Fenugreek seeds contain large
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amounts of 4-hydroxyisoleucine that stimulates insulin
secretion and enhances the glucose uptake by translocation of
GLUT4 to the plasma membrane (Szabo et al., 2018) [46].
Polyphenol, stilbenes and rhaponticin present in fenugreek
seeds can increase insulin sensitivity (Li et al., 2018) [47].
PPAR is one of the major molecular targets in T2DM.
Diosgenin showed antihyperglycemic effect mediated
selectively by the PPARgamma (Sangeetha et al., 2013) [48].
Glycated hemoglobin is the most commonly used marker for
long term glycemic control (Sirsikar et al., 2016) [49].
Ingestion of fenugreek seeds significantly reduced fasting
blood glucose levels and glycosylated hemoglobin levels in
patients of T2DM (Khan and Khosla, 2018; Ranade and
Mudgalkar, 2017) [40, 50].
3.6 Antihypertensive effect
High blood pressure (i.e., hypertension) is one of the most
common preventable causes of death, worldwide.
Hypertension can be controlled using medicines like diuretics,
beta blockers, angiotensin converting enzyme (ACE)
inhibitors, angiotensin-II receptor blockers, calcium channel
blockers and aldosterone antagonist (Thomopoulos et al.,
2018) [51]. Chronic administration of a mineralocorticoid,
deoxycorticosterone acetate (DOCA) salt, induces
hypertension due to salt and water retention. It is assumed that
5-HT2B receptor is up-regulated by DOCA, resulting into
continued elevated blood pressure (Banes and Watts, 2003)
[52]. Administration of methanolic extract of fenugreek seeds
to rats showed antihypertensive action mediated through
serotonergic antagonistic property (via 5-HT2 receptor)
(Balaraman et al., 2006) [53]. Seeds of fenugreek are rich in
essential oil (i.e., terpenenes and omega-3 fatty acid), exhibit
antihypertensive effect by decreasing the activity of ACE
(Hamden et al., 2011) [54] in diabetic rats. In addition,
combination of dietary fenugreek seeds and onion
synergistically reduce the level of ACE in diabetic animals
(Pradeep and Srinivasan, 2017) [55]. The aqueous extract of
fenugreek showed diuretic activity, hence is helpful in
management of hypertension (Rohini et al., 2008) [56]. In
another study, fenugreek extracts increased excretion of
sodium and potassium ions with a hypocalciuric effect (Al-
Atwi, 2010) [57] like thiazide diuretic. Thiazide diuretics are
often used as the first choice drug in hypertension.
3.7 Immunomodulation
Natural immunomodulators produce strong activity with
negligible side effects. The natural immunostimulators
synthesis or/and secrete several cytokines including IL-1, IL-
2, IFN-gamma and TNF alpha (Vetvicka and Vetvickova,
2014) [58]. Bioactive compounds isolated from fenugreek can
inhibit the cytokines like IL-1, IL-6 and TNF-ɑ (Goyal et al.,
2018) [59]. Fenugreek is widely known for its
immunostimulatory properties (Guardiola et al., 2018) [37].
Dietary administration of seed stimulates the innate and
adaptive immune parameters in Sparus aurata L (gilthead
seabream). Different extracts of fenugreek showed
immunomodulatory effect on immune functions in rats
(Anarthe et al., 2014) [60], and Swiss albino mice (Bin-Hafeez
et al., 2003) [61] through stimulating specific and non-specific
immune mechanism.
3.8 Hypocholesterolemic activity
Excessively high plasma cholesterol level is a strong risk
factor for cardiovascular diseases, particularly for
development of peripheral vascular and coronary artery
diseases (Stapleton et al., 2010) [62]. 3-hydroxy-3-
methylglutaryl coenzyme-A reductase (HMG-CoA
reductase), the rate-limiting enzyme in cholesterol
biosynthesis is clinically used to treat cardiovascular disease
(Jiang et al., 2018) [63]. Galactomannan from fenugreek seeds
exerts hypolipidemic effect due to increased HMGA-CoA
reductase activity with additional bile acids and neutral sterols
excretion in faeces (Ramulu et al., 2011) [64]. Diosgenin, a
furostanol saponin, in fenugreek inhibits the absorption of
cholesterol and thereby lower hepatic cholesterol
concentration and increases biliary cholesterol excretion,
ultimately lowering the serum cholesterol concentration (Sfar
et al., 2018) [65]. Fenugreek seeds powder improve
atherogenic index (El-Masry et al., 2018) [66], a novel index
associated with triglycerides and high-density lipoprotein
cholesterol (Zhu et al., 2018) [67].
3.9 Neuroprotective effect
Several mechanisms are involved in different CNS disorders
including inflammation, oxidative stress, high cholesterol
level, and diabetes thus resulting into changes in brain
integrity and functions (Zameer et al., 2018) [68].
Neuroprotective effect of fenugreek has been observed due to
its efficacy in opposing 6-hydroxy dopamine (6-OHDA)
induced Parkinson's disease and restoration of neurons
(Mirzaie et al., 2016) [69]. Extract of fenugreek is reported to
inhibit the acetylcholinesterase enzyme (Satheeshkumar et al.,
2010) [70] which is crucial for the modulation of cognitive
functions in neurodegenerative disorders. Dementia is the
most common phenotype in Alzheimer's disease which is a
chronic neurodegenerative disorder (Fahanik-Babaei et al.,
2019) [71]. Fenugreek seeds attenuated the memory deficits,
amyloid and tau pathology against Alzheimer's disease in rats
(Prema et al., 2017) [72]. Methanolic extract of fenugreek
seeds, as an antiamnesic agent, improved learning and
memory processin mice (Assad et al., 2018) [73]. Fenugreek
extract also exhibited neuroprotective effect in persons
suffering from Parkinson's disease (Nathan et al., 2014) [74].
3.10 Antioxidant activity
Free radicals and other oxidants are derived from both
endogenous sources and exogenous sources. Free radicals
adversely affect the integrity of important biological
molecules including nucleic acids, proteins, and lipids,
thereby altering the normal redox status leading to several
disease conditions such as cancer, aging, neurodegenerative
diseases, cardiovascular diseases, diabetes mellitus, liver
damage, etc (Phaniendra et al., 2015) [75]. Antioxidants either
prevent excess generation of reactive oxygen species, or
speeds up their removal (Kunwar and Priyadarsini, 2011) [76]
so that damage to vital components of the cell can be
minimized. Fenugreek seeds exhibited a high antioxidant
potential (Kumar et al., 2021) [77] and restored the altered
activity of cellular antioxidant enzymes in tissue (Yashin et
al., 2017) [78]. The aqueous extract of fenugreek ameliorated
the oxidative stress in rats (Al-Sultan and El-Bahr, 2015) [79]
by activation of antioxidant enzymes and lowering hepatic
lipid peroxidation. Fenugreek seeds have also been reported
to provide protection to erythrocytes against oxidative
damage (Fatima et al., 2018) [80]. A functional assay indicated
that dietary fenugreek seed significantly restored the high-fat,
high-sugar diet-damaged arterial response to acetylcholine
(Szabo et al., 2018) [46], a classic vasodilatory signal
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molecule.
3.11 Effects on reproductive system
Women with dysmenorrhea suffer from increased painful
uterine contractions during menstruation. At menopause, there
is decrease in estrogen production leading to life altering
symptoms like cognitive instability, bone density reduction,
cardiovascular disease, etc (Harlow and Signorello, 2000) [81].
Fenugreek has been used for the treatment of dysmenorrhea
(Younesy et al., 2014; Yassin, 2018) [6, 82]. Fenugreek seeds
contain phytoestrogen compounds, exhibit estrogenic effects,
bind to estrogen receptors and induce expression of estrogen
responsive genes (El-Masry et al., 2018) [66]. The seed extract
ameliorated the symptoms of polycystic ovarian syndrome
associated with decrease in both size and number of ovarian
cysts, significant increase in LH and FSH level (Srinivasan
and Sharma, 2018) [83]. It is also reported that perineal wash
with seeds decoction significantly reduced vaginal discharge
and vulval itching (Thilagavathy, 2016) [84]. Fenugreek seed
has potential in balancing hormones to support libido in male
(Steels et al., 2011) [85]. Seeds extract improves the level of
total serum testosterone and sexual function in aging men (El-
Masry et al., 2018; Rao et al., 2016) [66, 86].
3.12. Gastroprotective effect
Various experimental trials have shown that fenugreek can
combat several pathologiccal conditions associated with
gastrointestinal disorders. Fenugreek seed extract significantly
decreased the volume of gastric juice, total acidity and gastric
ulcer index (Singaravelu et al., 2018) [87]. In rats, aqueous
extract of seeds exhibited ulcer protective effects by its
antisecretory action (Pandian et al., 2002) [88]. Dietary
fenugreek attenuates lithogenicity of bile thereby prevents
pathogenesis of gallstones formation (Reddy and Srinivasan,
2011) [89]. Authors also reported the gastroprotective effect of
fenugreek by increasing mucin secretion (Ghosal et al., 2016)
[90]. The H+/K+-ATPase pump is a crucial target for
gastroprotective effect. Fenugreek seeds produced
gastroprotective effect by antagonizing this pump (Figer et
al., 2017) [91].
3.13 Galactagogue activity
Galactagogues are a group of substances used to induce and
maintain milk production in female (Sim et al., 2015) [92].
Dopamine (D2 receptor) antagonists are conventional
galactagogues, commonly used in clinical practice. Dopamine
receptor antagonists increase milk production by increasing
the levels of prolactin (Sim et al., 2015) [92]. Fenugreek is a
safe and effective galactagogue (Forinash et al., 2012; Yadav
and Baquer, 2014) [93, 94]. The chemical compounds present in
fenugreek like diosgenin, luteolin and apigenin stimulate
anterior pituitary to enhance milk production (Bumrungpert et
al., 2018) [95]. Fenugreek increases breast milk volume and
prolactin levels in mother (Reeder et al., 2013) [96].
Stimulating sweat production may be another possible way by
which it increases milk production (Gabay, 2002) [97].
4. Safety and toxicity profile
Several in vitro and in vivo studies have established that
fenugreek seeds and other parts of the plant are quite safe in
animals and humans. Nevertheless, some reports have
highlighted certain deleterious side effects of fenugreek seeds
that are descried briefly in following sections.
4.1 Single dose effect
The acute oral median lethal dose (LD50) of fenugreek seed
extract was recorded to be greater than 2500 mg/kg body
weight/day in Wistar rats (Sureshkumar et al., 2018) [3]. In
another study, the oral LD50 of fenugreek seed powder was
found 2 and 5 g/kg or more in mice and rats, respectively
(Sharma et al., 1996) [98]. As per the guidelines of
Organization for Economic Corporation and Development
(OECD),value of LD50 < 2 gm/kg body weight is relatively
safe, hence fenugreek may be considered as non-toxic
(Sureshkumar et al., 2018) [3].
4.2 Repeated dose effect
In sub-chronic (90 days) toxicity study, debitterized fenugreek
seeds powder was found safe even at a dose of up to 20% in
the diet of weaning rats (Sharma et al., 1996) [98]. In a clinical
study in 60 diabetic patients, daily single intake of 25 gram
fenugreek seed powder for 24 weeks did not produce any sign
of adverse or toxic effect (Khalki et al., 2012) [99]. Saponin-
rich standardized seed extract is reported to be safe in rats
even after repeated intake for 90 days, with no observed-
adverse-effect level (NOAEL) of 1000 mg/kg body weight
per day (Sureshkumar et al., 2018) [3].
Alteration in neurobehavioral performance in mice was
recorded during the post-weaning period after prenatal
exposure to high dose of fenugreek seeds (Posadzki et al.,
2013) [100]. The consumption of fenugreek during pregnancy is
not recommended assaponincompound is reported to have
anti-fertility, anti-implantation and abortifacient activity
(Ouzir et al., 2016) [11]. In addition, fenugreek may increase
chances of morphological abnormalities and fetal death rate
(Khalki et al., 2010) [101].
Diosgenin
Galactomannan
4-hydroxyisoleucine
Trigonellin
Fig 1: Chemical structures of Fenugreek bioactive compounds
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Fig 2: Schematic illustration of fenugreek biological activities
5. Conclusion
Based on available scientific information, fenugreek appears
to have unique pharmacotherapeutic properties. Though it is a
part of our dietary constituents, it may also be recommended
as a therapeutic agent in several human and animal ailments.
However, the unusual high human equivalent dose to achieve
desired therapeutic effect is the major limiting factor in use of
fenugreek crude extracts in various human ailments. The
crude extract of any plant product is a complex mixture of
several compounds, hence pointing a specific action of a
particular component is often difficult. The process of drug
development from herbs or any plant product includes
multiple steps. Different active constituents extracted from
fenugreek can also be studied for their therapeutic potential
and subjected to drug designing and development. The
research for new drugs with minimal toxicity is of interest in
phytochemistry as occurrence of adverse drug effects is
frequently reported after prolonged use of several drugs.
6. Acknowledgments
This work was supported by University Grant Commission
(UGC), New Delhi, India in the form of Senior Research
Fellowship to the first author.
7. Conflicts of interest
All authors read and approved the final manuscript and
declare that they have no conflict of interests.
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... Fenugreek been an herb, grows only to about 1-2 ft heights and produces yellowish seeds in sickle-shaped pods. The herb though a spice has been utilized through several centuries for medicinal purposes across the Chinese, Arabic (Unani) and Indian (Ayurvedic) traditional medicines to treat cough, common cold, sore throats, bronchitis, cramps, arthritis [1]. Furthermore, fenugreek seeds are a commercial resource of diosgenin; a compound used for the manufacture of steroids like drugs such as oral contraceptives, sexual hormones and corticosteroids. ...
... Neutral lipids which make up 84% of the fenugreek seed lipid fraction consist of 6% diacylglycerols, 86% triacylglycerols and fewer quantities of phytosterols, monoacylglycerols and free fatty acids. Glycolipids and phospholipids constitute 5.5% and 10.5% of the crude lipids respectively [1]. A categorization of the fatty acid outline of nine fenugreek genotypes revealed that the lipids of fenugreek origin consisted mainly of diunsaturated and tri-unsaturated triacylglycerols. ...
... Their blood lipid profile was also reduced. Another investigated also reported a decline in the usual rise of postprandial hyperglycaemia after a meal of fenugreek-enriched whole wheat chapatti or boiled rice [1]. ...
Article
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Fenugreek; the extremely nutritional plant of the Fabaceae family ranks amongst the oldest therapeutic plants used in traditional medicine. The plant has a broad –spectrum of pharmacological and biological activities which are traceable to its bioactive compounds and protective nutrients contained such as; flavonoids, diosgenin, saponins, galactomannans, trigonellin, essential oils, coumarins, 4-hydroxyisoleucine and scopoletin. These bioactive compounds elicit nutraceutical, immunomodultory, antioxidant, anti-atherogenic, anti-oxidative, anti-hyperlipidemic, hypoglycaemic, anticarcinogenic, antinociceptive, anti-inflammatory and anti-hypertensive effects via various mechanisms against common chronic diseases. Moreover, the plant also has protective effects on the digestive, cardiovascular, endocrine, and reproductive systems. This article considers the role of fenugreek contained bioactives on human milk production and lactation. The other biological activities are also discussed.
... Among the herbal remedies is fenugreek (Trigonella foenum-graecum). It contains compounds like galactomannan and saponins (Rashid et al., 2019) that give it a variety of qualities, including anti-diabetic and antioxidant qualities (Kumar et al., 2021). Another study highlights that sage (Salvia officinalis L.) possesses diverse biological properties, such as hypoglycemic, antiinflammatory, and antioxidant effects (WHO, 2002). ...
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The study aimed to produce biscuit that fortified with three different concentrations of mixed antidiabetic medicinal plants including cinnamon, sage, moringa leaves, fenugreek, avarampoo, bitter gourd, panakilangu and ghritkumari for diabetic and evaluate the nutritional, antioxidant and antidiabetic characteristics of the biscuit. After preparation and baking of biscuit samples, a proximate composition, physical attributes, antioxidant and antidiabetic capacity such as phenol, flavonoid, ABTS scavenging capability, FRAP, α-amylase inhibition, α-glucosidase inhibition and glycemic index were measured. Our results demonstrated that the moisture, fat, carbohydrate content were found to significantly (p<0.05) decline as concentration of medicinal plant powder increased while the protein, fiber and ash content were found to significant (p<0.05) increase with increase the concentration of medicinal plant powder. According to the findings, the use of medicinal plants in high concentrations resulted in noticeably higher levels of phenol and flavonoid in addition to DPPH, ABTS radical scavenging activities and FRAP values. α-amylase and α-glucosidase enzymes are highly inhibited by the medicinal plant biscuit. Fortifying biscuits with medicinal plants may play an important role in controlling sugar levels where a high level of α-amylase enzyme inhibition and antioxidants may result in a lower blood glucose level. This could be a trend for diabetes control in the future. Therefore, it is anticipated that the antidiabetic, antioxidant-rich biscuits made in this study will offer consumers many important health advantages.
... Trigonella belongs to the family of Fabaceae which is considered for traditional medicinal herbs. Different portions of Trigonella species were used as food ingredients, as well as Ayurvedic medicine (Kumar et al., 2021). Further, Trigonella plants exhibit potential pharmacological effects such as antidiabetic, anti-inflammatory, antioxidant properties (Zameen et al., 2018). ...
... Verma MK et al., 2021 [13], discovered that fenugreek has a gastroprotective effect by reducing the volume of gastric juice and total acidity by antagonizing the H+/K+-ATPase pump. Proton Pump Inhibitors (PPIs), which act through a similar mechanism, have reported gastrointestinal disturbance during short-term administration, but they are generally well-tolerated by individuals. ...
Article
Full-text available
Fenugreek is a widely used herbal medicine as a complementary therapy for diabetes mellitus. Lots of clinical trials have proved its beneficial effect on glycemic control parameters and lipid profiles. Thus, we conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of fenugreek as a treatment for type 2 diabetes mellitus. We searched PubMed, Embase, Cochrane, China Knowledge Resource Integrated Database (CNKI), Korean studies Information Service System (KISS), Research Information Sharing Service (RISS), and ScienceON to select RCTs which used fenugreek targeting hyperglycemia with a control group. We used either a random effect model or a fixed model in a meta-analysis of Fasting blood glucose (FBG), 2 h plasma glucose during a 75 g oral glucose tolerance test (OGTT) (2-hPG), homeostatic model assessment for insulin resistance (HOMA-IR), glycosylated hemoglobin (HbA1c)/total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), body mass index (BMI). After screening, a total of 10 studies (706 participants) remained. Fenugreek significantly reduced FBG, 2-hPG, and HbA1c, but it did not significantly decrease HOMA-IR. Moreover, it significantly improved TC, TG, and HDL-C, while there were no significant differences in LDL-C and BMI. Hepatic or renal toxicity was not observed, and there were no severe adverse events associated with fenugreek despite mild gastrointestinal side effects in some studies. In conclusion, fenugreek improves overall glycemic control parameters and lipid profile safely.
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Aim: The study aimed to evaluate the impact of fenugreek seed powder supplementation on the growth performance of commercial broilers exposed to dexamethasone, a synthetic corticosteroid known to induce stress and suppress growth. Study Design: A total of 144 day-old broiler chicks (Vencobb) were randomly allocated to four treatment groups, each with three replicates of 12 birds, for a 42-days trial, receiving different dietary treatments, including a control diet, dexamethasone treatment and diets supplemented with fenugreek seed powder (FSP). Place and Duration of Study: The experiment was conducted for 42 days at the Instructional Poultry Farm of Govind Ballabh Pant University of Agriculture and Technology, located in Pantnagar, U.S. Nagar, Uttarakhand Methodology: The treatment groups included: T1 (Control) - standard diet; T2 - standard diet with dexamethasone (1 mg/kg body weight); T3 - standard diet with dexamethasone (1 mg/kg body weight) and FSP (1% of the diet); and T4 - standard diet with FSP (1% of the diet). Growth parameters such as body weight gain, feed intake and feed conversion ratio (FCR) were measured over a period of 42 days of all the four groups. Results: The results demonstrated that dexamethasone treatment in the T2 group led to a noticeable reduction in weight gain. On the other hand, broilers in the T3 and T4 groups, supplemented with 1% FSP, showed significant improvements in feed intake, weight gain and feed conversion efficiency compared to those without FSP or subjected to dexamethasone alone (P < 0.05). Conclusion: Dexamethasone exposure significantly reduced growth performance, while fenugreek seed powder supplementation mitigated these negative effects. Broilers receiving FSP demonstrated improved body weight gain and FCR compared to the dexamethasone-only and control groups. The findings suggest that incorporating FSP into broiler diets enhances growth performance and mitigates the adverse effects of dexamethasone-induced stress, making it a valuable dietary intervention under both normal and stressful conditions.Further research on optimal dosage and long-term effects is recommended.
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Fenugreek (Trigonella foenum-graecum) is a leguminous plant that is consumed as a spice to improve the flavor of food around the world. Fenugreek has been extensively cited to hold medicinal properties such as hypo-cholesterolemic, anti-carcinogenic, antidiabetic, immunological activity, and as carrier of potential antioxidants. Aside from its therapeutic uses as an alternate and complementary medicine, Fenugreek has been in use as a stabilizing, emulsifying, and binding ingredient in foodstuff and in manufacturing numerous processed foods. Fenugreek leaves and seeds are extremely valuable and featured with important phytochemicals such as amino acids, steroidal saponins, carbohydrates, alkaloids, and other organic and inorganic substances and minerals of human health significance. Fenugreek seeds and leaves can be consumed either fresh or cooked as a spice, culinary ingredient, flavoring agent, and or preservative. In this chapter, we will discuss the possible uses of fenugreek as a nutraceutical ingredient and as a functional food.
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Liver fibrosis is a leading cause of mortality and morbidity globally. For decades, plant secondary metabolites such as flavonoids and saponins have attained much consideration due to their safer therapeutic potential against chronic liver diseases. Trigonella foenum-graecum (Common name “Fenugreek”) is an annual herb used as a spice to increase the taste and aroma of food. Its fresh leaves are used as food and are rich in flavonoids. In the current study antifibrotic potential of Trigonella foenum-graecum flavonoid-rich leaf extract (TF) was evaluated in CCl4-induced hepatic fibrosis in mice. The ALT, AST, MDA, CAT, and GSH analysis illustrated that the treatment group significantly reverses CCl4-induced liver damage. The TF extract was found to be rich in quercetin and kaempferol derivatives analyzed through ESI-MS/MS. After four weeks of the TF treatment, hepatocyte architecture improved and collagen deposition in mice liver tissues reduced considerably. The expression of fibrotic markers, including COL-IA, α-SMA, PDGF, and TIMP1, was downregulated, and MMP3 was upregulated significantly at mRNA and protein levels. Interestingly, TF significantly downregulated NF-κB expression and TGF-β/Smad signaling pathway and upregulated miR-146a and miR-29b. Taking together, these results demonstrated that Trigonella foenum-graecum flavonoid-rich leaf extract ameliorated liver inflammatory and fibrogenic responses through miR-146a/miR-29b/TGF-β/Smad axis.
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Fenugreek seeds has a wide range of pharmacological activities like hypoglycemic, hypolipidemic , galactogogue and diuretic activities. Most of these effects have been well studied. However there is no separate study that evaluate the diuretic effect of fenugreek. Therefore, this study was designed to evaluate clinically the diuretic effect of this herb. Fenugreek extract has been compared with equal volume of distilled water each has been given to a group of five healthy adult male albino rabbits. Both serum and 24-hr urine samples then analyzed weekly for electrolytes level, osmolality and pH for four weeks. It has been found that fenugreek, caused a significant increases in sodium and potassium excretion with a significant reductions in osmolality with respect to the control group. It had a significant hypocalciuric effect, in respect to the control group.. Serum values of sodium, potassium, chloride, calcium, pH and osmolality did not reveal any significant change compared with the control values. It was concluded that fenugreek has a very powerful diuretic effect and this effect is thiazide-like regarding urine flow and urine composition of electrolytes.
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This work is about the utilization of fenugreek seed as an antibacterial and anticancer agents. The antibacterial activity of fenugreek seed extract on six pathological bacteria strains were specified through conventional biochemical tests using the Vitek2 automated system and diffusion agar method. The anticancer activities of fenugreek seed extract, on MCF-7 breast cancer cells, liver cancer HCAM cells and the non-cancerous Vero cell lines, were investigated using colorimetric MTT assay. Results showed that the highest activity of the extract of the seed was found on Staphylococcus aureus and Pseudomonas aeruginosa (22 mm and 17 mm diameter of inhibition zones respectively). The seed extract showed proliferative inhibition on MCF-7 cell line at a concentration of 400 µg/ml and 72 h of the incubation period. This was accompanied by insignificant apoptosis or necrosis. The seed extract showed no anticancer effect on liver and Vero cell lines. This work emphasizes that fenugreek seed extract is a potential source of antibacterial and anticancer agents. Keywords: Fenugreek seed- pathogenic bacteria- breast cancer- antibacterial effect
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Introduction: Fenugreek, scientifically known as Trigonella foenum-graecum, is one of the oldest cultivated medicinal plants which belong to the family Fabaceae. In fact, several beneficial effects on health, attributed to the consumption of fenugreek, have been demonstrated during tests in both animals and humans. The purpose of our work is to study its effect in a group of obese patients with type 2 diabetes.Methods: We followed a population of 56 obese type 2 diabetic women, after a daily consumption of 15g of fenugreek powder in the morning before breakfast during 4 weeks and following regular physical activity. We measured the anthropometric, biochemical and hormonal parameters (insulin and resistin) before and aftercare. Then, we evaluated the variations of these parameters and we studied the correlations between them.Results: Improvement of the various parameters monitoring after taking care of patients. Consumption of fenugreek powder show negatively correlated with BMI, waist circumference, HOMA-IR and resistin, whereas it shows positively correlated with HDL-cholesterol. Discussion: Fenugreek powder, by its constituents, promotes a better glucose and lipid profile by improving insulin sensitivity and increasing HDL-cholesterol levels. This leads to a regression of the resistin levels, decreasing its effects on insulin sensitivity and its pro-inflammatory role. In addition to its effect in predisposed patients to decrease the prevalence of diabetes.Conclusion: This study combined with the literature, allowed us to confirm the role of fenugreek consumption to improve glucose and lipid parameters of obese diabetic patients, thus controlling their complications and leading to a better prognosis.
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Statins are inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis, and have been clinically used to treat cardiovascular disease. However, a paradoxical increase of reductase protein following statin treatment may attenuate the effect and increase the side effects. Here we present a previously unexplored strategy to alleviate statin-induced reductase accumulation by inducing its degradation. Inspired by the observations that cholesterol intermediates trigger reductase degradation, we identify a potent degrader, namely Cmpd 81, through structure–activity relationship analysis of sterol analogs. Cmpd 81 stimulates ubiquitination and degradation of reductase in an Insig-dependent manner, thus dramatically reducing protein accumulation induced by various statins. Cmpd 81 can act alone or synergistically with statin to lower cholesterol and reduce atherosclerotic plaques in mice. Collectively, our work suggests that inducing reductase degradation by Cmpd 81 or similar chemicals alone or in combination with statin therapy can be a promising strategy for treating cardiovascular disease.
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Alzheimer’s disease (AD) is a chronic neurodegenerative disorder and the most common phenotype of dementia. Trigonelline is an alkaloid found in medicinal plants such as fenugreek seeds and coffee beans with neuroprotective potential and according to existing evidences, a favorable agent for treatment of neurodegenerative disorders. In this study, the possible protective effect of trigonelline against intracerebral Aβ(1–40) as a model of AD in the rat was investigated. For induction of AD, aggregated A(1–40) (10 μg/2 휇l for each side) was bilaterally microinjected into the hippocampal CA1 area. Trigonelline was administered p.o. at a dose of 100 mg/kg. The results showed that trigonelline pretreatment of Aβ-microinjected rats significantly improves spatial recognition memory in Y maze and performance in novel object recognition (NOR) task, mitigates hippocampal malondialdehyde (MDA), protein carbonyl, lactate dehydrogenase (LDH), and improves mitochondrial membrane potential (MMP), glutathione (GSH), and superoxide dismutase (SOD) with no significant change of catalase activity, nitrite level, caspase 3 activity, and DNA fragmentation. Additionally, trigonelline ameliorated hippocampal levels of glial fibrillary acidic protein (GFAP), S100b, cyclooxygenase 2 (Cox2), tumor necrosis factor α (TNFα), and interleukin 6 (IL-6) with no significant alteration of inducible nitric oxide synthase (iNOS). In addition, trigonelline pretreatment prevented loss of hippocampal CA1 neurons in Aβ-microinjected group. Therefore, our results suggest that trigonelline pretreatment in Aβ model of AD could improve cognition and is capable to alleviate neuronal loss through suppressing oxidative stress, astrocyte activity, and inflammation and also through preservation of mitochondrial integrity.
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Background: Exclusive breastfeeding is the best way to accomplish optimal growth and health in infants. Low milk volume is a major problem that leads to nonexclusive breastfeeding. Objective: This study aimed to examine the effects of mixed herbal supplementation, including fenugreek, ginger, and turmeric on human milk volume and nutrient content. Methods: The study design was a randomized double-blind controlled trial. Fifty exclusively breastfeeding mothers were randomly divided into two groups. The herbal group (n = 25) received mixed herbal supplementation containing fenugreek, ginger, and turmeric, three capsules three times daily for 4 weeks. The control group (n = 25) took a placebo. Anthropometric and dietary data, blood pressure, heart rate, and blood and milk samples were collected at baseline and 4 weeks after the intervention. Milk volume was measured using a manual breast pump and recorded for 2 days at baseline, week 2, and week 4. Results: Breastfeeding mothers receiving herbal supplementation had a 49% increase in milk volume at week 2 and a 103% increase at week 4. These increases were greater than mothers in the placebo group (p < 0.05). There was no difference in milk nutrient content for both groups. Moreover, there were no differences in adverse effects observed in the placebo and herbal groups. Conclusion: Mixed herbal supplementation that contained fenugreek, ginger, and turmeric can increase human milk volume without adverse effects.
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The present study investigated the safety of a saponin-rich standardized extract of fenugreek seeds (FenuSMART®; FHE), that has been clinically shown to be effective in ameliorating the postmenopausal discomforts and establishing hormonal balance. The safety was assessed by oral acute (2500 mg/kg b. wt. for 14 days) and subchronic (250, 500 and 1000 mg/kg b. wt. for 90 days) toxicity studies on Wistar rats and mutagenicity studies employing Salmonella typhimurium strains. Administration of FHE did not produce any toxicologically significant changes in clinical/behavioral observations, ophthalmic examinations, body weight, organ weight, feed consumption, urinalysis, hematology and clinical biochemistry parameters when compared to the untreated control group of animals. Highest dose recovery group (1000 mg/kg b. wt.) of animals also showed no mortality or adverse events; with hematological and biochemical parameters at par with those of controls. Terminal autopsy revealed no alterations in relative organ weight or any treatment-related histopathology changes. FHE also showed no mutagenicity upon Ames test employing TA-98, TA-100 and TA-102 Salmonella typhimurium strains with or without metabolic activation. Based on the results of the study, the no observed-adverse-effect level (NOAEL) of FHE was determined as 1000 mg/kg b. wt./day, the highest dose tested.
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Trigonella foenum graecum (Fenugreek) (Family: Leguminosae) is used as a traditional medicine in treating various diseases due to its antiinflammatory, antidiabetic and antilipidemic properties. In our study, aqueous extract of seeds were subjected for in vitro antioxidant activity by 1-diphenylpicryl-hydrazyl radical (DPPH), and ABTS radical cation assay. Total phenol and total flavonoid content were estimated. It was observed that free radicals were scavenged by the extract in a dose dependent manner. The content of total phenolics (expressed as mg of gallic acid equivalents/gm extract) and total flavonoids (expressed as mg of quercetin equivalent/gm extract) were determined along with antioxidant enzymes. The aqueous extract of fenugreek exhibited potent DPPH and ABTS radical scavenging activity with IC50 values of 62.67 μg/mL and 71.44 μg/mL, respectively. Based on the results it can be concluded that aqueous seed extract of fenugreek seeds may have potential antioxidant effects against several oxidants generated in the body.
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Background Fenugreek seeds have shown antinociceptive effect in animal studies. This double-blind placebo controlled trial was designed to study the effect of fenugreek transdermal patch 10% (FDP) for management of inguinal hernia (IH) post-operative pain. Methods Standardized extract of fenugreek seeds was used for FDP formulation. Ninety patients treated with 10% FDP, diclofenac dermal patch 1% (DP) and placebo twice daily after IH surgery. The pain intensity score was evaluated using a visual analogue score (VAS) up to 48 h after operation. Morphine consumption and diclofenac suppository demand were evaluated too. Results The pain score was significantly reduced in FDP group in comparison with the placebo group. This effect was also significantly different from DP up to 6 h after surgery (p<0.05). Morphine consumption and diclofenc suppository demand were significantly decreased in FDP group (p<0.05). Conclusion In all, results of the present study indicated that FDP decreases pain score and demand for morphine in post-surgery patients in comparison to diclofenac patch, and this preparation could be a suit option as a natural antinociceptive agent for pain management.
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Pain and inflammation can be eradicated by using various drugs. Herbal drugs can be opted to control pain, as they have few side effects. This study was done to compare anti-inflammatory, analgesic and antipyretic of aqueous extract of T. foenum-graecum sprouts (fenugreek) on albino mice with diclofenac sodium as a standard of reference. A microbial screening was conducted. Initially, seeds were collected, soaked in water, sprouts were formed then the active constituents was extracted with water. The analgesic activity of aqueous extract of T. foenum-graecum sprouts (fenugreek) on albino mice was found using hot plate method and acetic acid induced writhing method. Complete blood count (CBC) was also done. The animals were pretreated with diclofenac sodium (10mg/kg b.w.) i.p and T. foenum-graecum sprouts (200mg/kg b.w.) i.p for 4 days and latency time on hot plate without licking or jumping was checked at 30 minutes after the administration of last dose. T. foenum-graecum sprouts (200mg/kg b.w.)i.p differed significantly from the control (P<0.01) The latency time of fenugreek sprouts had decreased by 12.06% In the acetic acid writhing test maximum analgesic activity was observed in the mice treated with diclofenac sodium (10mg/kg b.w.) i.p. CBC was also done for all the animals. A further study was done to compare antipyretic activity of aqueous extract of T. foenum-graecum sprouts (fenugreek) on albino mice with diclofenac sodium. Temperature was measured by rectal route using digital thermometer. The animals were pretreated with diclofenac sodium (10mg/kg b.w.) i.p and T. foenum-graecum sprouts (200mg/kg b.w.) i.p for 4 days. Pyrexia was induced by subcutaneous administration of 20 % brewer's yeast suspension (10ml/kg). Twenty four hours after injection of yeast, body temperature was recorded. Maximum temperature reduction was observed in animals treated with fenugreek sprout extract. The acute anti-inflammatory activity of T. foenum-graecum sprouts (200mg/kg b.w.) i.p. was measured plethysmo graphically using carrageenan as inflammatory agent and comparing with diclofenac sodium (10mg/kg b.w.) i.p as reference standard. T. foenum-graecum sprouts (200mg/kg b.w.) has significant difference with control (P<0.05) at the 2 nd , 4th, 6th hour. Finally an antimicrobial screening was done. It was found that the sprouts had no antifungal activity and was having antibacterial effect on gram negative bacteria. It was concluded that T. foenum-graecum sprouts has mild analgesic effect, significant antipyretic effect, anti-inflammatory effect and antibacterial effect.