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Fenugreeks (Trigonella L. spp.), are well-known herbs belonging to the family Fabaceae, whose fresh and dried leaves have nutritional and medicinal value. In the present study, the content of phytochemical traits (essential oil, diosgenin, trigonelline, total phenol, total flavonoid, total saponins, and total tannins), bitterness value, pigments (chlorophyll, carotenoid, β-carotene, and anthocyanin), vitamins (group B vitamins and ascorbic acid), minerals, and antioxidant activity of thirty cultivated populations belonging to ten Trigonella species were evaluated. The species and populations were significantly different in all studied parameters. A significant positive and negative correlation (p < 0.05) was also observed between the studied parameters. In total, T. teheranica, T. elliptica, and T. foenum-graecum were distinguished as superior species. The results showed that fenugreeks leaves can be considered as a valuable source of food and phytochemical compounds. The obtained data can be help to expand the inventory of wild and cultivated Trigonella species for further exploitation of rich chemotypes in the new foods and specific applications., (© 2024. The Author(s).)

Sprouts are an attractive food product that contains high amounts of nutritional substances and has pro-health features. Sprout consumption has strongly increased despite its potential risk to health due to its microbial load. Both the safety and shelf life of sprouts may be negatively affected by a high microbial load. To reduce the microbial contamination in sprouts before consumption, the initial microbial load on the seeds needs to be controlled. Many herbal sprouts have been recommended for diabetes, and fenugreek is one of these sprouts. Thus, the current experiment aimed at disinfecting fenugreek seeds using microwave (5, 10, and 20 s) and hot water (30, 45, and 60 s) treatments for different durations. The best-disinfected sprouts with the highest nutritional properties were used to evaluate their influence on streptozocin-induced diabetic rats in comparison with fenugreek seed feeding. Microwave treatments showed the highest sprout length, fresh weight, total free amino acids, antioxidants, reducing sugars, and total phenols. Additionally, microwave seed treatments showed the lowest bacteria and mold counts on sprouts produced relative to hot water treatments, and the best seed treatment was a microwave for 20 s, which gave the best values in this respect. Feeding diabetic rats with different fenugreek seeds or sprout rates (0, 5, 7.5, and 10% w / w ) improved body weight, restricted the growth of glucose levels, lowered total cholesterol and triglycerides, and improved HDL compared with the positive control group, and fenugreek sprouts at higher rates showed the maximum improvements in blood glucose, total cholesterol, and triglycerides. Treating fenugreek seed with microwave radiation for 20 s to disinfect the seeds before sprouting is recommended for lowering the microbial load with optimum nutritional and antioxidant activity, and feeding diabetic rats with these sprouts at the rate of 7.5 and 10% had promising effects on hyperglycemia and associated disorders.

Six low molecular weight fenugreek polysaccharides (FP) were isolated and purified by ethanol stepwise precipitation (EFP-20, EFP-40, and EFP-60) and DEAE-52 cellulose column method (DFP-0, DFP-0.15, and DFP-0.3), respectively. The effects of different separation and purification techniques on the preliminary properties and biological activities of fenugreek polysaccharides were compared. The results showed that the DEAE-52 cellulose-eluted fractions had a higher total sugar content and displayed a looser structure. The molecular weights of all six fractions were in the range of 4-19 kDa, with significant changes in the ratio of galactose to mannose. All six fractions contained α-D-galactopyranose and β-D-mannopyranose structures. Activity tests showed that all six fractions possessed antioxidant, hypoglycemic and DNA-protective activities. Among them, the DFP-0 fraction showed the highest activity. Overall, different isolation and purification methods lead to changes in the properties and bioactivities of FP, which provides a theoretical basis for the development and application of FP in functional foods and drugs., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Trigonella, commonly known as Fenugreek, is among the most promising medicinal herbs consumed worldwide due its protein rich dietary contributions. This study involved induced mutagenesis on two Trigonella species (Trigonella foenum-graecum var. PEB and Trigonella corniculata var. Pusa kasuri) using caffeine and sodium azide as mutagens, resulting in the identification of nine high-yielding mutant lines in the M3 generation. Molecular characterization using SCoT markers revealed a high polymorphism of 28.3% and 46.7% in PEB and Pusa kasuri, respectively, facilitating the investigation of genetic divergence among the control and mutant lines. Similarity correlation analysis indicated a high similarity between mutant A and mutant C (0.97) and between mutant J and mutant O (0.88), while the lowest similarity was observed between mutant B and mutant F (0.74) and between control and mutant L (0.58). Mutant F and Mutant J displayed the highest seed yield and its attributing traits, and seed protein content in PEB and Pusa kasuri, respectively. Physiological parameters, including chlorophyll content (Mutants A and N) and carotenoids (mutant A and J), exhibited improvements. Assessment of stomatal and seed characteristics using scanning electron microscopy may lead to improved physiological processes and distinction at the interspecific level, respectively. Methanolic extracts of the control and the mutant lines of both species were subjected to GC-MS analysis, revealing 24 major phytocompounds known for their pharmacological activities (antioxidant, anti-inflammatory, anticancer, etc.). Statistical methods such as Pearson correlation heatmap and pairwise scatter plot matrix provided insights into the correlations and linear associations among parameters for both PEB and Pusa kasuri. The strong correlation between iron content and seeds per pod in the mutant lines suggests a promising avenue for further research. Continued research and breeding efforts using these mutants can lead to significant advancements in agriculture and medicine, benefiting farmers, consumers, and industries alike., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Naaz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Inflammatory bowel disease (IBD) incidence has increased in the last decades due to changes in dietary habits. IBDs are characterized by intestinal epithelial barrier disruption, increased inflammatory mediator production and excessive tissue injury. Since the current treatments are not sufficient to achieve and maintain remission, complementary and alternative medicine (CAM) becomes a primary practice as a co-adjuvant for the therapy. Thus, the intake of functional food enriched in vegetal extracts represents a promising nutritional strategy. This study evaluates the anti-inflammatory effects of artichoke, caihua and fenugreek vegetal extract original blend (ACFB) in an in vitro model of gut barrier mimicking the early acute phases of the disease. Caco2 cells cultured on transwell supports were treated with digested ACFB before exposure to pro-inflammatory cytokines. The pre-treatment counteracts the increase in barrier permeability induced by the inflammatory stimulus, as demonstrated by the evaluation of TEER and CLDN-2 parameters. In parallel, ACFB reduces p65NF-κB pro-inflammatory pathway activation that results in the decrement of COX-2 expression as PGE2 and IL-8 secretion. ACFB properties might be due to the synergistic effects of different flavonoids, indicating it as a valid candidate for new formulation in the prevention/mitigation of non-communicable diseases.

Background: Fenugreeks (Trigonella L. spp.), belonging to the legume family (Fabaceae), are well-known multipurpose crops that their materials are currently received much attention in the pharmaceutical and food industries for the production of healthy and functional foods all over the world. Iran is one of the main diversity origins of this valuable plant. Therefore, the aim of the present study was to explore vitamins, minerals, and fatty acids profile, proximate composition, content of diosgenin, trigonelline, phenolic acids, total carotenoids, saponins, phenols, flavonoids, and tannins, mucilage and bitterness value, and antioxidant activity of the seed of thirty populations belonging to the ten different Iranian Trigonella species., Results: We accordingly identified notable differences in the nutrient and bioactive compounds of each population. The highest content (mg/100 g DW) of ascorbic acid (18.67 ± 0.85‒22.48 ± 0.60) and α-tocopherol (31.61 ± 0.15‒38.78 ± 0.67) were found in the populations of T. filipes and T. coerulescens, respectively. Maximum content of catechin was found in the populations of T. teheranica (52.67 ± 0.05‒63.50 ± 0.72 mg/l). Linoleic acid (> 39.11% ± 0.61%) and linolenic acid (> 48.78 ± 0.39%) were the main polyunsaturated fatty acids, with the majority in the populations of T. stellata (54.81 ± 1.39‒63.46 ± 1.21%). The populations of T. stellata were also rich in trigonelline (4.95 ± 0.03‒7.66 ± 0.16 mg/g DW) and diosgenin (9.06 ± 0.06‒11.03 ± 0.17 mg/g DW)., Conclusions: The obtained data provides baseline information to expand the inventory of wild and cultivated Iranian Trigonella species for further exploitation of rich chemotypes in the new foods and specific applications., (© 2024. The Author(s).)

Diabetes causes elevated blood sugar levels, and it has been categorized as one of the most frequent causes of death worldwide. This work aimed to analyze and compare the nutraceutical and therapeutic efficacy of fenugreek seeds (FSs) (Trigonella foenum-graecum) and black cumin seeds (BCSs) (Nigella sativa) against streptozotocin-induced diabetes mellitus in albino rats. FS and BCSs were evaluated for proximate analysis, phytochemicals, and antioxidant activities. Male albino rats were used to evaluate the in vivo antidiabetic activities of these medicinal plants for 42 days. Blood samples were drawn at regular intervals of 1 week to analyze blood glucose, plasma insulin, and cholesterol levels and to determine the homeostatic model assessment of insulin resistance (HOMA IR) index. At the end of the trial, pancreas tissue was also collected for histological examination. Results of the proximate analysis showed the significant presence of moisture, ash, fat, protein, and fiber. Antioxidant parameters like 2,2-diphenyl-1-picrylhydrazyl, total phenolic content, and total flavonoid content were found to be significant. There was a significant (p < 0.05) decrease in blood glucose level, serum cholesterol level, and insulin resistance in treatment groups T3-T5. Insulin and body weight results of treatment groups were significant (p < 0.05) compared to streptozotocin-intoxicated animals. Histological examination revealed the nutraceutical impact of selected herbal plants due to enhancing impact on the size and the number of β-cells in the pancreas. Findings of current research work explore the antidiabetic capacity of selected nutraceutical and medicinal plants., (© 2024 Institute of Food Technologists.)

Green (Penicillium digitatum) mold can severely endanger the citrus fruits production and quality. Targeting the protection of lemon fruits from green mold infestations with nanobiotechnology approach, the fenugreek seed mucilage (FM) was extracted and exploited for biosynthesis of selenium (SeNPs) nanoparticles; their nanocomposites (NCs) with chitosan (CT) was constructed and employed as antifungal materials and edible coating (ECs) to protect lemon fruits against green mold. The nanoparticles formation and conjugations were verified by infrared (FTIR) analysis and electron microscopy. The FM-synthesized SeNPs had particles average of 8.35 nm, were the NCs of them with CT had size mean of 49.33 nm and charged with +22.8 mV. The CT/FM/SeNPs composite exhibited superior antifungal actions toward P. digitatum isolates, up to 32.2 mm inhibition diameter and 12.5 mg/mL inhibitory concentration, which exceeded the actions of imazilil. The microscopic screening of exposed P. digitatum to NCs clarified their mycelial destructive action within 30 h. The coating of infected lemons with fabricated NCs led to complete elimination of green mold development after 10 days of coating, without any infestation remarks. The innovative fabrication of NCs from CT/FM/SeNPs is strongly suggested to protect citrus crops from green mold and preserve fruits quality., Competing Interests: Declaration of competing interest The authors certify that the paper has neither been, nor will be sent elsewhere for publication. Moreover, the authors report no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The number of people diagnosed with type 2 diabetes is on the increase worldwide. Of growing concern, the prevalence of type 2 diabetes in children and youths is increasing rapidly and mirrors the increasing burden of childhood obesity. There are many risk factors associated with the condition; some are due to lifestyle, but many are beyond our control, such as genetics. There is an urgent need to develop better therapeutics for the prevention and management of this complex condition since current medications often cause unwanted side effects, and poorly managed diabetes can result in the onset of related comorbidities. Naturally derived compounds have gained momentum for preventing and managing several complex conditions, including type 2 diabetes. Here, we provide an update on the benefits and limitations of fenugreek and its components as a therapeutic for type 2 diabetes, including its bioavailability and interaction with the microbiome.

Trigonella foenum-graecum, known as fenugreek, belongs to the leguminous family of wild growth in Western Asia, Europe, the Mediterranean, and Asia; its ripe seeds contain a pool of bioactive substances with great potential in the food industry and medicine. In this study, fenugreek seed mucilage (FSM) was extracted and characterized in its structural properties by X-ray diffraction, nuclear magnetic resonance, and high-performance liquid chromatography. Then, the applicability of FSM as an antimicrobial agent was demonstrated via the development of novel, active, edible FSM-based biofilms containing carboxymethyl cellulose and rosemary essential oil (REO). Incorporating REO in the biofilms brought about specific changes in Fourier-transform infrared spectra, affecting thermal degradation behavior. Scanning electron microscopy and atomic force microscopy morphography showed an even distribution of REO and smoother surfaces in the loaded films. Besides, the solubility tests evidenced a reduction in water solubility with increasing REO concentration from 1 to 3 wt%. The biological assay evidenced the antimicrobial activity of REO-loaded biofilms against Staphylococcus aureus and Escherichia coli. Finally, whole apples were dip-coated with FSM-based solutions to showcase future edible systems. The REO-loaded biofilms extended the shelf life of apples to 30 days, demonstrating their potential for sustainable and active coatings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: This research explores sustainable applications for waste generated from fenugreek (Trigonella foenum-graecum), a plant with both nutritional and medicinal uses. The study specifically targets waste components as potential sources of nutrients and bioactive compounds., Objectives: The focus is to conduct detailed metabolic profiling of fenugreek waste, assess its anti-inflammatory properties by studying its cyclooxygenase (COX) inhibitory effect, and correlate this effect to the metabolite fingerprint., Materials and Methods: Ethanolic extracts of fenugreek fruit pericarp and a combination of leaves and stems were subjected to untargeted metabolic profiling using liquid chromatography-mass spectrometry integrated with online database searches and molecular networking as an effective dereplication strategy. The study also scrutinized the COX inhibitory capabilities of these extracts and saponin-rich fractions prepared therefrom. Molecular docking was employed to investigate the specific interactions between the identified saponins and COX enzymes., Results: The analysis led to the annotation of 81 metabolites, among which saponins were predominant. The saponin-rich fraction of the fruit pericarp extract displayed the strongest COX-II inhibitory activity in the in vitro inhibition assay (IC 50 value of 81.64 ± 3.98 μg/mL). The molecular docking study supported the selectivity of the identified saponins towards COX-II. The two major identified saponins, namely, proto-yamogenin 3-O-[deoxyhexosyl (1 → 2)] [hexosyl (1 → 4)] hexoside 26-O-hexoside and trigofenoside A, were predicted to have the highest affinity to the COX-II receptor site., Conclusion: In the present study, we focused on the identification of COX-II inhibitory saponins in fenugreek waste through an integrated approach. The findings offer valuable insights into potential anti-inflammatory and cancer chemoprotective applications of fenugreek waste., (© 2024 John Wiley & Sons Ltd.)

The golden spice turmeric with its main bioactive component curcumin is one of the most popular and extensively studied nutraceuticals. Despite numerous pre-clinical studies reporting positive pharmacodynamics of turmeric extracts and curcumin, the main issues in translating the pharmacological effects to clinical efficacy have been to overcome its poor pharmacokinetics and to deliver significant amounts of the biologically relevant forms of the actives to various tissues. This review is aimed at providing a first critical evaluation of the current published literature with the novel curcumagalactomannoside (CGM) formulation of curcumin using fenugreek galactomannan dietary fibre, specifically designed to address curcumin poor pharmacokinetics. We describe CGM and its technology as a food-grade formulation to deliver 'free' unconjugated curcuminoids with enhanced bioavailability and improved pharmacokinetic properties. The therapeutic relevance of improving bioavailability of 'free' curcuminoids and some of the technical challenges in the measurement of the 'free' form of curcuminoids in plasma and tissues are also discussed. A total of twenty-six manuscripts are reviewed here, including fourteen pre-clinical and twelve clinical studies that have investigated CGM pharmacokinetics, safety and efficacy in various animal models and human conditions. Overall current scientific evidence suggests CGM formulation has improved bioavailability and tissue distribution of the biologically relevant unconjugated forms of turmeric actives called 'free' curcuminoids that may be responsible for the superior clinical outcomes reported with CGM treatments in comparison with unformulated standard curcumin across multiple studies.

Background: A fracture is considered a medical emergency leading to considerable complications., Aim: This study aimed to describe the accelerating action of Ag-NPs-FG on fracture healing in rabbits., Methods: Silver NPs (AgNPs) were reduced with fenugreek (FG), loaded into a starch gel base, and investigated for their morphology, size, and charge. Four equal groups were randomly formed of 40 adult male rabbits. A 3.5 mm diameter bone defect was created at the proximal metaphysis of the right tibia in each rabbit. Groups 1-4 were injected with placebo saline, AgNPs-FG, plain gel, and FG-gel at the bone defect zone, respectively. The healing was assessed for 8 weeks postoperatively based on the radiographic, bone turnover markers, and histopathological examinations., Results: The AgNPs-FG was obtained as a faint reddish color, spherical in shape, with an absorbance of 423 nm, a size of 118.0 ± 1.7 nm, and a surface charge of -7.8 ± 0.518 mV. The prepared AgNPs-FG hydrogel was clear, translucent, and homogenous. The pH values were 6.55-6.5 ± 0.2, the viscosity of 4,000 and 1,875 cPs, and spreadability of 1.6 ± 0.14 and 2.0 ± 0.15 for both FG and AgNPs-FG hydrogel, respectively. The radiographic union scale was significantly ( p < 0.05) improved in group 2 with a significant ( p < 0.05) increase in bone turnover markers was found in comparison to other treated groups. Histopathological examination revealed the formation of mature bone on the 28th postoperative day in groups 2 and 4., Conclusion: Colloidal nano-formulation of AgNPs-FG loaded hydrogel could be a promising formulation to accelerate rabbits' tibial bone healing process., Competing Interests: The authors declare that there is no conflict of interest.

Metal-organic frameworks (MOFs) are a prominent class of materials due to their large surface area and customized structures. This gives them specificity and high adsorption capacity while they lack mechanical strength and reusability. Integrating MOFs with polysaccharide matrix may retain MOF characteristics along with imparting structural integrity. In the present study, zirconium MOF-based fenugreek composite (FG/Zr-AIPA) beads were synthesised by a single droplet method and utilised for removal of Cr(VI), Pb(II) and Fe(III) from aqueous solution. The structure, morphology and composition of beads were evaluated by FTIR, XRD, TGA, BET, FESEM, EDX, XPS and zeta potential analysis. Adsorption isotherm, kinetics and thermodynamics were studied for Cr(VI), Pb(II) and Fe(III) adsorption. Adsorption kinetics and isotherm study revealed that all the metal ions were adsorbed through a monolayer chemisorption process. The maximum adsorption capacity was 344.43, 270.02 and 223.21 mg g -1 for Cr(VI), Pb(II) and Fe(III), respectively, based on the Langmuir isotherm study. The thermodynamics study revealed that the interaction between the metal ions and the composite beads was spontaneous and endothermic. The FG/Zr-AIPA composite beads exhibited good reusability for the removal of Cr(VI), Pb(II) and Fe(III). The results open new possibilities for the preparation of polysaccharide MOF-based composite beads which exhibit substantial potential for water treatment applications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Phthorimaea absoluta is a global constraint to tomato production and can cause up to 100% yield loss. Farmers heavily rely on synthetic pesticides to manage this pest. However, these pesticides are detrimental to human, animal, and environmental health. Therefore, exploring eco-friendly, sustainable Integrated Pest Management approaches, including biopesticides as potential alternatives, is of paramount importance. In this context, the present study (i) evaluated the efficacy of 10 Bacillus thuringiensis isolates, neem, garlic, and fenugreek; (ii) assessed the interactions between the most potent plant extracts and B. thuringiensis isolates, and (iii) evaluated the gut microbial diversity due to the treatments for the development of novel formulations against P. absoluta. Neem recorded the highest mortality of 93.79 ± 3.12% with an LT 50 value of 1.21 ± 0.24 days, Bt HD263 induced 91.3 ± 3.68% mortality with LT 50 of 2.63 ± 0.11 days, compared to both Bt 43 and fenugreek that caused < 50% mortality. Larval mortality was further enhanced to 99 ± 1.04% when Bt HD263 and neem were combined. Furthermore, the microbiome analyses showed that Klebsiella, Escherichia and Enterobacter had the highest abundance in all treatments with Klebsiella being the most abundant. In addition, a shift in the abundance of the bacterial genera due to the treatments was observed. Our findings showed that neem, garlic, and Bt HD263 could effectively control P. absoluta and be integrated into IPM programs after validation by field efficacy trials., (© 2024. The Author(s).)

The aim of this study is to optimize the extraction process and characterize the proteins found in fenugreek seeds. The water and oil holding capacities, coagulated protein content, foaming and emulsification properties of the isolated proteins at all extraction conditions were investigated. Also, solubility, molecular weights, structural and thermal properties were determined. In the extraction processes carried out at different pHs (pH 6.0-12.0) and solid:solvent ratios (20-60 g/L), it was determined that the highest extraction yield (94.3±0.3%) was achieved when the pH was 11.47 and the solid-solvent ratio was 34.50 g/L. Three distinct bands (46, 59 and 80 kDa) in the range of 22-175 kDa were determined for the fenugreek seed protein isolate obtained at optimum extraction conditions. Protein secondary structures were achieved using Fourier Transform Infrared (FT-IR) spectra and it was determined that β-sheet structures were highly present. In addition, denaturation temperatures and denaturation enthalpy were calculated as ~119°C and 28 mJ/g, respectively.

Background: The determination of genome size is a fundamental step which provides a basis to initiate studies aimed at deciphering the genetic similarity of a species and to carry out other genomics based investigations. Fenugreek (Trigonella spp.) is an important spice crop which has numerous health promoting phytochemicals. Many species within this genus are known for their various health benefits owing to the presence of a wide diversity of important phytochemicals like diosgenin, trigonelline, fenugreekine, galactomannan, 4-hydroxy isoleucine, etc. It is a multipurpose crop being cultivated for food, animal feed and industrial purposes. Despite its importance, research on the genomics aspect of fenugreek remains scant. In the absence of sufficient genomic information, crop improvement in fenugreek is severely lagging., Methods and Results: Estimation of genome size of a species is the preliminary step for initiation of any genomic studies and therefore in the present study we have estimated the genome size for fenugreek. Here, we have determined the genome sizes of three different Trigonella spp. namely T. foenum-graecum, T. corniculata and T. caerulea through flow cytometry (FC). The 2 C DNA content values were found to be 6.05 pg (T. foenum-graecum), 1.83 pg (T. corniculata) and 1.96 pg (T. caerulea). The genome size of T. foenum-graecum is approximately three times the genome size of T. corniculata and T. caerulea. This variation in genome size of more than three-fold indicates the level of genetic divergence among the three species, though within the same genus., Conclusions: The differences observed in the genome sizes of the three species provide conclusive evidence of their genetic divergence. Additionally, the information about the genome size would provide an impetus to the structural and functional genomics-based research in this crop., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Despite long-standing uses in several food and medicine traditions, the full potential of the leguminous crop fenugreek (Trigonella foenum-graecum L.) remains to be realized in the modern diet. Not only its seeds, which are highly prized for their culinary and medicinal properties, but also its leaves and stems abound in phytochemicals with high nutritional and health promoting attributes. Fenugreek dual food-medicine applications and reported metabolic activities include hypoglycemic, antihyperlipidemic, antioxidative, anti-inflammatory, antiatherogenic, antihypertensive, anticarcinogenic, immunomodulatory, and antinociceptive effects, with potential organ-protective effects at the cardiovascular, digestive, hepatic, endocrine, and central nervous system levels. Effectiveness in alleviating certain inflammatory skin conditions and dysfunctions of the reproductive system was also suggested. As a food ingredient, fenugreek can enhance the sensory, nutritional, and nutraceutical qualities of a wide variety of foods. Its high nutritive density can assist with the design of dietary items that meet the demand for novelty, variety, and healthier foods. Its seeds provide essential protective nutrients and other bioactive compounds, notably galactomannans, flavonoids, coumarins, saponins, alkaloids, and essential oils, whose health benefits, alone or in conjunction with other bioactives, are only beginning to be tapped into in the food industries. This review summarizes the current state of evidence on fenugreek potential for functional food development, focusing on the nutrients and non-nutrient bioactive components of interest from a dietary perspective, and their applications for enhancing the functional and nutraceutical value of foods and beverages. New developments, safety, clinical evidence, presumed mechanisms of action, and future perspectives are discussed. HIGHLIGHTS: Fenugreek seeds and leaves have long-standing uses in the food-medicine continuum. Fenugreek phytochemicals exert broad-spectrum biological and pharmacological activities. They show high preventive and nutraceutical potential against common chronic diseases. Current evidence supports multiple mechanisms of action mediated by distinct bioactives. Opportunities for fenugreek-based functional foods and nutraceuticals are expanding., (© 2024 Institute of Food Technologists.)

Fenugreek (Trigonella foenum-graecum L) galactomannan play an important role in the food and pharmaceutical sectors due to its attractive physicochemical properties. In this study, the changes of structure, properties and biological activity of fenugreek galactomannan (FG) during germination are analyzed by the activity and mechanism of endogenous enzymes (α-D-galactosidase and β-D-mannanase). The enzymes generally increased during germination and synergistically altered the structure of GM by cutting down the main chains and removing partial side residues. The mannose to galactose ratio (M/G) increased from 1.11 to 1.59, which is accompanied by a drastic decrease in molecular weight from 3.606 × 10 6 to 0.832 × 10 6  g/mol, and the drop of viscosity from 0.27 to 0.06 Pa·s n . The degraded macromolecules are attributed to the increase in solubility (from 64.55 % to 88.62 %). In terms of antioxidation and antidiabetic ability, germinated fenugreek galactomannan has the ability to scavenge 67.17 % ABTS free radicals and inhibit 86.89 % α-glucosidase. This galactomannan with low molecular weight and excellent biological activity precisely satisfies the current demands of pharmaceutical reagents and food industry. Seeds germination holds promise as a means of industrial scale production of low molecular weight galactomannans., Competing Interests: Declaration of competing interest The authors declare that they have no known any financial and personal relationships with other people or organizations that could have appeared to influence the work reported in this study., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study employed network pharmacology-based analysis and reverse molecular docking to investigate the molecular targets and pathways associated with gynecological disorders, particularly those related to steroidal hormones and their receptors, and the potential therapeutic effects of fenugreek (Trigonella foenum-graecum L.) constituents. The STITCH 5.0 database was utilized to identify potential molecular targets, and a compound-target network was constructed. The main targets associated with gynecological disorders included estrogen receptor beta (ESR2), estrogen-related receptor gamma (GPER1), oxytocin receptor (OXTR), progesterone receptor (PGR), prolactin receptor (PRLR), and several enzymes involved in sex hormone biosynthesis. Additionally, network topological analysis revealed that specific compounds, such as quercetin, luteolin, genistein, and vitexin, had significant interactions with the identified targets. Reverse molecular docking analysis confirmed the interactions between the identified compounds and target proteins where quercetin, luteolin, genistein, 4'-methylgenistein, trigoneoside IIB, diosgenin, and vitexin possessed the highest combined docking scores, indicating their multi-target nature. The results highlighted the potential of steroidal saponins, isoflavones, and flavones as active constituents of fenugreek with implications for lactation, reproductive processes, and estrogenic activity. The chemical profiling of saponin-enriched and flavonoid-enriched fractions using UPLC/MS/MS further supported the presence of these bioactive compounds. In an animal model study, the steroidal saponins-enriched fraction of fenugreek seed exhibited a significant increase in the body weight of lactating female rats and serum prolactin levels while the flavonoids-enriched fraction showed an increase in serum estradiol levels and improved the histological structure of ovaries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Fenugreek (Trigonella foenum-graecum L.) is a multi-use annual forage legume crop that is widely used in food products such as syrup, bitter run, curries, stew, and flavoring. In the present study, morphological traits, proximate composition (moisture, crude fibre, protein, fat, carbohydrate, and energy value), total phenol and total flavonoid contents, and antioxidant properties of 31 Iranian agro-ecotypic populations of the plant was investigated. Among the leaf and seed samples studied, the seeds exhibited the high ash (3.94 ± 0.12%), fat (7.94 ± 0.78%), crude fibre (10.3 ± 0.25%), protein (35.41 ± 1.86%), and carbohydrate (50.5 ± 1.90%) content. In general, more energy value (kcal/100 g) was also obtained from the seed (318.88 ± 1.78-350.44 ± 1.27) than leaf samples (45.50 ± 1.32-89.28 ± 0.85). Antioxidant activity and power of leaf samples were ranged from 67.95 ± 0.05‒157.52 ± 0.20 μg/ml and from 45.17 ± 0.01‒361.92 ± 0.78 μmol Fe +2 per g dry weigh, respectively. Positive linear correlations between antioxidant activity and total phenolic compounds were observed. A significant correlation between proximate composition (dependent variable) and some morphological features (independent variable) was observed. Considerable variability in the studied traits among the plant samples can be interestingly used in further food and production systems., (© 2024. The Author(s).)

Introduction: Dysmenorrhea is the most common periodic pain, which affects more than 50% of women with regular menstruation. Fenugreek is one of the medicinal plants with analgesic properties. This study aimed to determine the effect of fenugreek application in the severity of dysmenorrhea and its side effects in women with dysmenorrhea. PICO: Population: women with dysmenorrhea; Intervention: fenugreek; Comparison: control groups; and Outcome: reduction in the severity of dysmenorrhea and its side effects., Methods: English database (PubMed, Cochrane Library, Scopus, and Web of Science) and Persian database [SID (Scientific Information Database) and Magiran] were used for research until February 11, 2023, using the keywords "Dysmenorrhea [Mesh]," "Foenum [Mesh]," "fenugreek [Mesh]," and "Trigonella [Mesh]." The reference list of the selected articles was also checked. The quality assessment was conducted through the Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0. The RevMan 5.3 software was used to analyze and report the data of the entered studies. Meta-analysis results were reported with the standardized mean difference (95% confidence interval). A subgroup analysis was performed based on the type of control groups. The quality of evidence was assessed using the GRADE approach., Results: After removing duplicates and ineligible cases, four articles were included in the systematic review out of the 1526 records obtained. The results showed that the pain intensity caused by primary dysmenorrhea decreased with fenugreek compared to placebo (pooled result SMD: -2.21; 95% CI: -3.26 to -1.17; Z: 4.17; p <0.001). There was no significant difference between fenugreek with mefenamic acid (SMD: 0.05; 95% CI: -0.57 to 0.67; Z: 0.17; p = 0.86) and fenugreek with Chandrasura churna (SMD: 0.06; 95% CI: -0.56 to 0.68; Z: 0.19; p = 0.85). Bias, in terms of incomplete outcome data and selective reporting, was low risk in all studies, and the available evidence was low quality according to the GRADE approach., Conclusion: The results showed that the effect of fenugreek on pain intensity in dysmenorrhea is highly uncertain. The true effect is likely to be substantially different from the estimate of effect. Regarding the importance of the health and quality of life of women of reproductive age and the low quality of evidence of the studies, clinical trials with stronger methodology are suggested in this field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Swertia chirayita, Trigonella foenum-gracum and Sesamum indicum are used as traditional medicines to treat diabetes mellitus. A collection of metabolic illnesses known as diabetes mellitus (DM) involves chronic hyperglycemia caused by flaws in insulin secretion, function, or both. Innate immunity and inflammation both play important roles in the etiology of diabetes- related microvascular problems., Objective: This study aims to examine the anti-diabetic effects and the acute toxicity of combined extract (1:1:1) of Swertia chirayita, Trigonella foenum-gracum and Sesamum indicum . To address the demand for higher effectiveness and safety, the current effort aims to construct anti-diabetic preparations containing methanolic extract from herbal medications., Methods: The OECD 423 method was used to investigate acute toxicity in rats. Rats were used as test subjects, and rats were given a 35 mg/kg BW injection of streptozotocin to develop diabetes. The diabetic control group was given Glibenclamide 0.25 mg/kg BW, while the experimental group's diabetic rats received 125 mg/kg BW and 250 mg/kg BW of a combined methanolic extract of all plants. Among the measurements looked at were acute oral toxicity, behavioral changes, body weight, serum glucose levels, lipid profiles, oxidative stress, renal function tests, and inflammatory mediators. All the rat groups' histopathologies of the kidney, liver, and stomach were compared. The data were evaluated using analysis of variance, and a post hoc test was then carried out., Results: The combined extracts' medium lethal doses (LD 50 ) were higher than 2000 mg/kg, indicating that they are not poisonous under the conditions that can be observed. Streptozotocin-induced diabetic rats' elevated blood glucose was found to be considerably lower (p 0.01) in the treated group of rats. In the treated group of rats, it was discovered that the damage and disarray in the cells typical of Streptozotocin-induced DM had been repaired. The treated group of rats returned to normal levels of the lipid profile, hyperglycemia, decreased serum protein and liver glycogen, increased liver function, and kidney function markers seen in the rats of the DM control group., Conclusion: The evaluated combined methanolic extract can be considered safe for use in rats. Combining methanolic extract from all selected medicinal plants ( Swertia chirayita, Trigonella foenum-gracum and Sesamum indicum ) has a potential anti-diabetic effect and can be safely developed as an alternative medicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Trigonella foenum-graecum L., commonly known as Ḥulba or Methi in Unani medicine, is an annual self-pollinating plant belonging to the Leguminosae family. It has been utilized for centuries to treat a wide range of diseases, and modern research has supported its traditional medicinal claims. In this study, the authors have conducted manual and online searches to gather and summarize the scientific literature on Ḥulba . This article seeks to underscore the potential of Ḥulba in addressing a variety of health conditions as identified by esteemed classical Unani scholars, as well as to investigate its phytochemistry and pharmacological properties in contemporary medicine. The authors have utilized electronic databases, such as PubMed, Science Direct, DOAJ, Google Scholar, and Ayush Research Portal to filter published material. According to the gathered literature, Unani physicians have consistently recommended Ḥulba seeds for a variety of ailments, such as indigestion, flatulence, colitis, arthritis, backache, paralysis, headaches, common cold, cough, bronchial asthma, diabetes mellitus, vitiligo, and pityriasis. Additionally, the seeds and green leaves of Ḥulba contain several chemical constituents, such as alkaloids, flavonoids, steroids, saponins, and amino acids. Furthermore, several pharmacological studies have demonstrated that Ḥulba possesses various properties, including antidiabetic, antispasmodic, hypolipidemic, immunological, antibacterial, anthelmintic, antiinflammatory, analgesic, and antioxidant activities. Based on the available evidence, it can be concluded that Ḥulba has been effectively used in Unani medicine for treating a wide range of diseases. Unani scholars have extensively documented its pharmacological properties, which have been supported by modern research studies. However, further research is necessary to validate some of the claims made in traditional medicine using scientific parameters., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Trigonella foenum-graecum L. is a Leguminosae plant, and the stems, leaves, and seeds of this plant are rich in chemical components that are of high research value. The chloroplast (cp) genome of T. foenum-graecum has been reported, but the mitochondrial (mt) genome remains unexplored., Results: In this study, we used second- and third-generation sequencing methods, which have the dual advantage of combining high accuracy and longer read length. The results showed that the mt genome of T. foenum-graecum was 345,604 bp in length and 45.28% in GC content. There were 59 genes, including: 33 protein-coding genes (PCGs), 21 tRNA genes, 4 rRNA genes and 1 pseudo gene. Among them, 11 genes contained introns. The mt genome codons of T. foenum-graecum had a significant A/T preference. A total of 202 dispersed repetitive sequences, 96 simple repetitive sequences (SSRs) and 19 tandem repetitive sequences were detected. Nucleotide diversity (Pi) analysis counted the variation in each gene, with atp6 being the most notable. Both synteny and phylogenetic analyses showed close genetic relationship among Trifolium pratense, Trifolium meduseum, Trifolium grandiflorum, Trifolium aureum, Medicago truncatula and T. foenum-graecum. Notably, in the phylogenetic tree, Medicago truncatula demonstrated the highest level of genetic relatedness to T. foenum-graecum, with a strong support value of 100%. The interspecies non-synonymous substitutions (Ka)/synonymous substitutions (Ks) results showed that 23 PCGs had Ka/Ks < 1, indicating that these genes would continue to evolve under purifying selection pressure. In addition, setting the similarity at 70%, 23 homologous sequences were found in the mt genome of T. foenum-graecum., Conclusions: This study explores the mt genome sequence information of T. foenum-graecum and complements our knowledge of the phylogenetic diversity of Leguminosae plants., (© 2023. The Author(s).)

Starch hydrolyzing α-amylase from germinated fenugreek (Trigonella foenum-graecum) has been purified 104-fold to apparent electrophoretic homogeneity with a final specific activity of 297.5 units/mg. SDS-PAGE of the final preparation revealed a single protein band of 47.5 kDa, supported by LC/MS analysis and size-exclusion chromatography on the Superdex 200 (ÄKTA-FPLC). α-Amylase exhibited maximum activity at pH 5.5. An activation energy (E a ) of 9.12 kcal/mol was found to exist in the temperature range of 20 to 90 °C. When substrate concentrations were evaluated between 0.5 and 10 mg/mL, the K m and V max values for starch were observed to be 1.12 mg/mL and 384.14 μmol/min/mg, respectively. The major substrate starch exhibited high specificity for fenugreek α-amylase. In the presence of EDTA (5 mM), the activity was lost, however, it could be largely reversed with the addition of calcium. Furthermore, an effort was made to assess the ability of fenugreek seed-derived partially purified (DEAE-cellulose enzyme) and purified α-amylase to disperse inside 48 h-old biofilms of Staphylococcus aureus MTCC740. The outcomes clearly demonstrated that the purified and partially purified α-amylase both exhibited strong biofilm dispersion activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Fenugreek ( Trigonella foenum-graecum ) has a great beneficial health effect; it has been used in traditional medicine by many cultures. Likewise, the α-amylase inhibitors are potential compounds in the development of drugs for the treatment of diabetes. The beneficial health effects of fenugreek lead us to explore the chemical composition of the seeds and their antioxidant and α-amylase inhibition activities. The flavonoid extraction from fenugreek seeds was achieved with methanol through a Soxhlet apparatus. Then, the flavonoid glycosides were characterized using HPLC-DAD-ESI-MS analysis. The antioxidant capacity of fenugreek seed was measured using DPPH, FRAP, ABTS, and CUPRAC assays. Finally, the α-amylase inhibition activity was carried out using in vitro and in silico methods. The methanolic extract was found to contain high amounts of total phenolics (154.68 ± 1.50 μg GAE/mg E), flavonoids (37.69 ± 0.73 μg QE/mg E). The highest radical-scavenging ability was recorded for the methanolic extract against DPPH (IC 50 = 556.6 ± 9.87 μg/mL), ABTS (IC 50 = 593.62 ± 9.35 μg/mL). The ME had the best reducing power according to the CUPRAC (A 0.5 = 451.90 ± 9.07 μg/mL). The results indicate that the methanolic extracts of fenugreek seed best α-amylase inhibition activities IC 50 = 653.52 ± 3.24 μg/mL. Twenty-seven flavonoids were detected, and all studied flavonoids selected have good affinity and stabilize very well in the pocket of α-amylase. The interactions between the studied flavonoids with α-amylase were investigated. The flavonoids from fenugreek seed present a good inhibitory effect against α-amylase, which is beneficial for the prevention of diabetes and its complications.

α-Amylase catalyses the hydrolysis of glucosidic bonds in polysaccharides such as starch, glycogen and their degradation products. In the present study, the three-dimensional structure of fenugreek ( Trigonella foenum-graecum ) α-amylase was determined using a homology modeling-based technique. The best predicted model was deposited in PMDB server with PMDB ID PM0084364. The phylogenetic tree was created using the UPGMA method with 8 homologous protein sequences, Trigonella foenum-graecum was utilized as the target protein. Alignment of the phylogenetic tree identified two primary functional groupings (A and B). α-Amylase from the target genome Trigonella foenum-graecum (Acc. No: GHNA01022531.1) was clustered with Medicago truncatula (Acc. No: XP003589186.1), Cicer arietinum (Acc. No: XP004499059.1), Cajanus cajan (Acc. No: XP020231823.1), Vigna angularis (Acc. No: NP001316768.1) and Vigna mungo (Acc. No: P17859.1), in group A cluster, while Hordeum vulgare (Acc. No: Q40015) and Oryza sativa (PDB ID: 3WN6) were in cluster B. The molecular dynamics simulations were performed to understand the molecular basis and mode of action of Trigonella foenum-graecum α-amylase. Additionally, a geometry-based molecular docking technique was used to evaluate potential binding interactions between the modeled structure of α-amylase and maltose. The results show that Trp 228 , Glu 226 , Arg 199 , His 308 , Tyr 165 , Asp 309 , Phe 202 and Asp 201 from Trigonella foenum-graecum α-amylase enzyme is involved in the binding to the substrate maltose. Our study provides a 3D model of Trigonella foenum-graecum α-amylase and aids in understanding the atomic level molecular underpinnings of the mechanism of α-amylase interaction with substrate maltose. Ca 2+ are essential for the stability of domain B since they are connected to it. Ca 2+ site ligands are Asp 139 , Glu 130 , Thr 133 , Asp 135 and Gly 131 residues. HIGHLIGHTSIn silico analysis, gene prediction of α-amylase was carried from Trigonella foenum-graecum .Analysis of the structure of α-amylase was carried out using homology modelling.Calcium binding sites and their interactions with α-amylase were visualised using BIOVIA DISCOVERY STUDIO 2019.The molecular interaction between Trigonella foenum-graecum α-amylase and maltose was studied in silico using a molecular docking-based method.To give the required simulation parameters, RMSD, RMSF, and Total Energy were calculated using BIOVIA DISCOVERY STUDIO 2019.[Figure: see text]Communicated by Ramaswamy H. Sarma.

This study reports the synthesis, characterization, and antibacterial activity of a novel Fe 3 O 4 nanocomposite coated with fenugreek seed gums and silver nanoparticles (AgNPs). To enhance the antibacterial properties of AgNPs and overcome the limitations of conventional methods for the production of three-component nanocomposites, a layer of natural polymer was used. Fenugreek seed gums (FSG) were used to coat Fe 3 O 4 NPs to prevent their decomposition and to facilitate the release of silver nanoparticles in aqueous media. The Fe 3 O 4 /FSG/Ag nanocomposites were characterized and then the antibacterial activity of the nanocomposites was evaluated against two gram-negative and two gram-positive bacteria and compared with Fe 3 O 4 , Fe 3 O 4 /FSG, FSG, and AgNO 3 . The results showed that the Fe 3 O 4 /FSG/Ag nanocomposites had higher antibacterial activity than the other samples and could be easily removed from treated water by a powerful magnet without causing pollution in the environment. Overall, these findings suggest that the Fe 3 O 4 /FSG/Ag nanocomposites have potential applications in water treatment for their improved antibacterial properties and ease of removal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Wild fenugreek (Trigonella monantha), a multi-purpose annual plant, has traditionally been used as a food, forage, and medicinal plant. However, the knowledge of the diversity of its chemical characteristics is limited. In this study, 40 wild fenugreek ecotypes collected from their natural habitats in Iran and grown together in field conditions, were analyzed for their seed chemical properties., Results: The ecotypes were cultivated in a randomized complete block design (RCBD) with three replications. The results of ANOVA revealed a significant difference among the ecotypes for all measured characters (P < 0.01). The results showed a high level of diversity among the ecotypes based on the measured characters, including antioxidant activity (48.19 to 86.85%), phenol (0.82 to 1.51 mg gallic acid per g dry weight), flavonoid (1.07 to 3.11 mg quercetin per g dry weight), trigonelline (0.02 to 0.08 mmol/l), 4-hydroxyisoleucine (0.197 to 0.906 mg/g), sucrose (0.13 to 3.77 mM), glucose (1.07 to 12.1 mM), and fructose (13.3 to 45.5 mM). The cluster analysis divided the ecotypes into four groups and the PCA analysis showed that the three first components explained 73% of the total variance among the ecotypes. Also, heat map correlation revealed that many positive and negative correlations were observed among the measured characters. The results did not show a relationship between the amounts of compounds and the place of sample collection., Conclusions: The present study suggests considerable diversity in the seed chemical compositions of the wild fenugreek ecotypes. Therefore, many ecotypes could be useful for medicinal purposes, as well as for human nutrition., (© 2023. The Author(s).)

The impact of household processes on fenugreek leaves and seeds has been analyzed for total phenolic (TP) and total flavonoid content (TF), and in-vitro biological activities such as antioxidant, antimicrobial, and anti-inflammatory properties. Processes included air-drying for leaves and germinating, soaking, and boiling for seeds. Air-dried fenugreek leaves (ADFL) had high TP (15.27 mg GAE g -1 D.W.) and TF (7.71 mg QE g -1 D.W.) (milligram quercetin equivalents per gram dry weight). The TP contents of unprocessed, germinated, soaked, and boiled seeds were 6.54, 5.60, 4.59, and 3.84 mg gallic acid equivalents per gram of dry weight (mg GAE g -1 D.W.), respectively. The TF contents in unprocessed fenugreek seeds, germinated fenugreek seeds, soaked fenugreek seeds, and boiled fenugreek seeds (BFS) were 4.23, 2.11, 2.10, and 2.33 mg QE g -1 D.W., respectively. Sixteen phenolic and nineteen flavonoid compounds has been identified using high-performance liquid chromatography. Antioxidant activity using 2,2-diphenyl-1-picrylhydrazil (DPPH · ), 2,2-azinobis (3-ethylbenothiazoline-6-sulfonic acid (ABTS +· ), and ferric reducing antioxidant power (FRAP · ) assays indicated that ADFL had the highest activity. Antimicrobial activity has been evaluated against each of the eight pathogenic bacterial and fungal strains. ADFL showed the strongest activity with minimum inhibitory concentrations values ranging from 0.03 to 1.06 and 0.04 to 1.18 mg ml ·1 against bacterial and fungal strains, respectively. Anti-inflammatory activity was evaluated in-vitro against RAW 264.7 macrophage cells using the nitric oxide (NO) assay. Results revealed that ADFL had the highest cytotoxicity and anti-inflammatory activity according to the NO assay. Household processes significantly reduced the in-vitro biological properties of processed seeds., (© 2023. The Author(s).)

The effect of intercropping of hyssop ( Hyssopus officinalis L.) from Lamiaceae with a medicinal legume, that is, fenugreek ( Trigonella foenum-graecum L.) on the hyssop essential oil was investigated. The highest herbage and essential oil yields of hyssop were produced from sole cropping and also intercropped hyssop with fenugreek (3:1 ratio); however, the highest antioxidant activity was obtained from the intercropped hyssop with fenugreek (1:3 ratio). The highest contents of the major constituents in the hyssop essential oil such as cis - and trans -pinocamphone and β-pinene were obtained from sole cropped of hyssop and the intercropping of hyssop with fenugreek (3:1 ratio). In conclusion, the intercropping of hyssop with fenugreek can increase biodiversity and efficiency of using resources. Therefore, this strategy could be considered in order to recommend in simultaneous production of secondary metabolites in the herbs like hyssop in an agricultural land.

The aqueous Trigonella foenum-graecum L. leaf extract belonging to variety HM 444 was used as reducing agent for silver nanoparticles (AgNPs) synthesis. UV-Visible spectroscopy, Particle size analyser (PSA), Field emission scanning electron microscopy coupled to energy dispersive X-ray spectroscopy (FESEM-EDX) and High-resolution transmission electron microscopy (HRTEM) were used to characterize AgNPs. Selected area electron diffraction (SAED) confirmed the formation of metallic Ag. Fourier Transform Infrared Spectroscopy (FTIR) was done to find out the possible phytochemicals responsible for stabilization and capping of the AgNPs. The produced AgNPs had an average particle size of 21 nm, were spherical in shape, and monodispersed. It showed catalytic degradation of Methylene blue (96.57%, 0.1665 ± 0.03 min -1 ), Methyl orange (71.45%, 0.1054 ± 0.002 min -1 ), and Rhodamine B (92.72%, 0.2004 ± 0.01 min -1 ). The produced AgNPs were excellent solid bio-based sensors because they were very sensitive to Hg 2+ and Fe 3+ metal ions with a detection limit of 11.17 µM and 195.24 µM, respectively. From the results obtained, it was suggested that aqueous leaf extract demonstrated a versatile and cost-effective method and should be utilized in future as green technology for the fabrication of nanoparticles.

Trigonella foenum-graecum (fenugreek) is a legume widely used as a food supplement in humans and less frequently in ruminants. Toxicity has been described sporadically in ruminants grazing mature fenugreek plants or stubble; however, the pathological features are unclear. This report describes a natural outbreak of intoxication in cattle fed fenugreek straw and the experimental reproduction using 8 sheep and 8 goats. Affected cattle presented clinical signs approximately 1 month after consuming the straw and 100 of 400 cattle (25%) were affected, of which 60 of 100 (60%) died or were euthanized. Clinical signs were characterized by proprioceptive positioning defects with abnormal postures and weakness of hindlimbs. Forelimbs were also affected in severely affected animals, and cattle became recumbent. Locomotion was characterized by trembling, and some cattle showed high-stepping movements of their forelimbs and knuckled over in their fetlocks. Experimental intoxication induced clinical signs only in sheep and were similar to cattle, although with signs starting in the forelegs. Gross and microscopic lesions were similar in spontaneous and experimental intoxications. Macroscopic changes corresponded with muscular hemorrhages and edema, mainly surrounding the peripheral nerves. Microscopic examination only demonstrated lesions in the distal peripheral nerves, which included edema, hemorrhages, and Wallerian degeneration. Neurofilament immunohistochemistry revealed altered axon labeling and S100 showed a decrease in myelin intensity and loss of its typical compact arrangement around axons. Biochemical and hematological abnormalities included elevated levels of muscle and liver enzymes and thrombocytopenia. These findings indicate that fenugreek straw induces peripheral neuropathy in cattle and sheep, but not in goats.

Background: An annual plant, Fenugreek (Trigonellafoenum-graecum L.) has well-known health care benefits in Ayurvedic and Chinese medicine. Its leaves and seeds have alkaloids, amino acids, caumarins, flavonoids, saponins, and other bioactive components. Various pharmacological properties such as antioxidants, hypoglycemic, and hypolipidemic have been attributed to fenugreek. Trigonelline, diosgenin, and 4- hydroxyisoleucine have shown neuroprotection against Alzheimer's disease, and the extract have also been reported to act as an anti-depressant, anti-anxiety, and also regulate cognitive functions. This review highlights various studies carried out on animals as well as on humans for the protective effect against Alzheimer's disease., Methods: The data presented in this review is taken from popular search engines, viz, Google Scholar, PubMed, and Scopus. This review highlights the studies and clinical trials performed to show the protective effect of Fenugreek on neurodegenerative diseases with special reference to AD from 2005 to 2023., Results: Fenugreek improves cognitive deficits by Nrf2-mediated antioxidative pathway and provides neuroprotection against amyloid-beta-induced mitochondria dysfunction. It enhances SOD and catalase activities and scavenges reactive oxygen species to protect the cellular organelle from oxidative stress. It normalizes the tubulin protein and improved axonal growth by regulating nerve growth factors. Fenugreek can also influence metabolism., Discussion: Fenugreek significantly improves the pathological symptoms of neurodegenerative disease, especially AD and can be used as a therapeutic agent to control disease conditions as evidenced by the review of the literature., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: In this study, the effects of seed weight (4, 8, and 12 g), extraction temperature (30, 60, and 90 °C), and pH (4, 7, and 10) on the yield of mucilage extraction from fenugreek seeds and its chemical properties were investigated using response-surface methodology., Results: The optimum condition for mucilage extraction was a seed weight of 8.30 g, a temperature of 86.10 °C, and pH 6.90. The results showed that the dry weight of extracted mucilage increased with increase and decrease of extraction temperature and pH respectively at high seed weight. Increasing temperature and pH increased the extraction yield, and the effect was more considerable at low seed weight. The maximum carbohydrate content of mucilage was achieved at average levels of variables. The protein, flavonoid, and total phenolic contents of extracted mucilage increased with increasing temperature. Both flavonoid and total phenolic contents were maximum at neutral pH, but they were maximum at moderate and low levels of seed weight respectively. Maximum antioxidant activity was obtained at the highest extraction temperature, seed weight of 8 g, and neutral pH. The study of rheological properties indicated that extracted mucilage solution showed mainly elastic and shear-thinning behavior., Conclusion: The Fourier transform infrared spectra of extracted mucilage exhibited the existence of polysaccharides and protein chains in fenugreek seeds mucilage. The X-ray diffraction corroborated the presence of crystals in the mucilage structure. The proton nuclear magnetic resonance spectra confirmed the polysaccharides and protein composition of extracted mucilage. The maximum mucilage mass loss was observed at 190-350 °C using thermogravimetric analysis. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Impacts of inhaling gasoline fumes on the lungs of adult male rats and the alleviating role of fenugreek seeds were evaluated. Twenty-four rats were divided into four groups, unexposed control and fenugreek groups, gasoline exposed groups for 6 h/6 day/week for 10 weeks with and without supplementation of fenugreek seed powder in food (5% w/w). Rats exposed to gasoline fumes showed significant elevation in lung tumor necrosis factor-α, as an inflammatory marker, and the proapoptotic marker Bax with a reduction in the antiapoptotic marker Bcl2. Moreover, remarkable elevations in transforming growth factor-β1, collagen and hydroxyproline were observed as fibrotic markers. Lung oxidative stress markers (hydrogen peroxides, malondialdehyde, and protein carbonyl) increased significantly along with marked decrease in total antioxidant capacity, superoxide dismutase, and catalase levels. Additionally, marked decreases in white and red blood cell counts, hemoglobin content, platelet count, accompanied by elevated red cell distribution width percentage were observed, supporting the inflammatory status. Histopathological changes represented by hematoxylin&eosin, immunohistochemistry staining for Bax&Bcl2, and transmission electron microscopy supported the negative impacts of gasoline fumes compared to the control group. Fenugreek seeds supplementation with gasoline exposure showed pronounced alleviation of lung biochemical and histopathological changes compared to the gasoline-exposed group., (© 2022. The Author(s).)

Nicotine is the most abundant ingredient in cigarette smoking and has serious side effects on the lung, heart, reproductive system, and many other human organs. Saponins extracted from many plants exhibit multiple biological actions such as anti-cancer effects. Therefore, the possible protective effect of fenugreek saponin (FS) and nanofenugreek saponin (NFS) against nicotine-induced toxicity in male rats was investigated in this study. Animals were divided into a control group and the nicotine (1.5 mg/kg/day), FS (25, 50, and 100 mg/kg/day), or/and NFS (20, 40, and 80 mg/kg/day) administered groups. Micronucleus assay, histopathological, and sperm abnormality examinations as well as measurement of the acetylcholinesterase (AChE) gene expression were conducted. Our findings revealed that nicotine treatment induced significant increases in the incidence of micronucleus, sperm abnormalities, and expression levels of AChE in addition to inducing histopathological changes in rat testis. On the other hand, administration of FS or NFS with nicotine significantly decreased the incidence of micronuclei and the percentage of sperm abnormalities as well as the expression levels of AChE gene. Moreover, nicotine-induced histological alterations were reduced by given FS or NFS with nicotine. In conclusion, nicotine-induced sperm abnormalities, chromosomal damage, and histological injuries were mitigated by administration of FS or NFS with nicotine, and thus, FS and NFS could be used as ameliorating agents against nicotine toxicity., (© 2022. The Author(s).)

Fenugreek is used as a spice and a traditional herbal medicine for a variety of purposes, given its antidiabetic and antioxidant effects. Self-emulsifying drug delivery systems (SEDDS) of herbal drugs are targets of extensive research aiming to increase bioavailability and stability. The study's objective was to formulate SEDDS containing Trigonella foenum-graecum extract to improve the stability of herbal extract and to increase their permeability through a Caco-2 monolayer. A characterized fenugreek dry extract was used for the formulations, while the SEDDS properties were examined by particle size analysis and zeta potential measurements. Permeability assays were carried out on Caco-2 cell monolayers, the integrity of which was monitored by follow-up trans-epithelial electric resistance measurements (TEER). Cytocompatibility was tested by the MTT method, and an indirect dissolution test was performed, using DPPH antioxidant reagent. Two different SEDDS compositions were formulated from a standardized fenugreek dry extract at either the micro- or the nanoemulsion scale with sufficient stability, enhanced bioavailability of the compounds, and sustained release from HPMC capsules. Based on our results, a modern, non-toxic, cytocompatible fenugreek SEDDS formulation with high antioxidant capacity was developed in order to improve the permeability and bioavailability of all components.

Results: When tested on the baseline of isolated tissues, Tfg.Cr was devoid of any activity (stimulant or relaxant) till 10 mg/ml. This is an interesting finding, keeping in mind that the fenugreek seeds are used to alleviate constipation and diarrhoea. When Tfg.Cr was tried for any potential AChE inhibitory activity, it did show an inhibitory effect in increasing concentrations (47-380  μ g/ml). This inhibitory effect was comparable to the effect produced by a standard AChE inhibitor physostigmine. One of the known fenugreek constituents, diosgenin, was also tested, and it also showed an AChE inhibitory effect in a concentration-dependent manner (11-190  μ g/ml). Interaction between diosgenin and AChE was further investigated by molecular docking and molecular dynamics simulations for 100 ns, which showed that diosgenin interacted with the active-site gorge of AChE through hydrophobic, pi-pi stacking, and hydrogen bonds with various amino acids of the AChE enzyme., Conclusion: The results show that the fenugreek extract does not possess any GI stimulant or relaxant activity even though it is used traditionally in GI motility disorders. The extract and diosgenin could inhibit the AChE enzyme pointing towards their benefit to enhance the memory., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Muhammad Nabeel Ghayur et al.)

Introduction: Fenugreek has been used in traditional remedies since ancient times. It has a long history of use against medical ailments as an antidiabetic, anticarcinogenic, hypocholesterolemic, antioxidant, antibacterial, hypoglycemic, gastric stimulant, and anti-anorexia agent. The major active constituents include alkaloids, fibres, saponins, proteins, and amino acids., Objectives: To provide a comprehensive overview of the application of chromatographic and spectroscopic methods, in addition to DNA-profiling methods to assess the quality of fenugreek. Also, to highlight the recent application of chemometrics combined with quality control methods during the last two decades., Methodology: A literature search conducted from January 2000 up to December 2020 using various scientific databases (e.g., Scopus, Medline, PubMed, EBSCO, JSTOR, ScienceDirect, Google Scholar, Web of Science and Egyptian Knowledge Bank, Academic Journals, and Springer Link); general web searches were also undertaken using Google applying some related search terms. Studies involving the application of quality control analyses were classified into three categories according to the conducted analysis method including chromatographic [high-performance liquid chromatography (HPLC), high-performance thin-layer chromatography (HPTLC), and gas chromatography (GC)], spectroscopic [ultraviolet (UV), infrared (IR), and nuclear magnetic resonance (NMR)], and DNA-based markers., Results: This review shed the light on relevant studies covering the past two decades, presenting the application of spectroscopic and chromatographic methods and DNA profiling in the quality control of fenugreek., Conclusion: The reviewed chromatographic and spectroscopic methods combined with chemometrics provide a powerful tool that could be applied widely for the quality control of fenugreek., (© 2021 John Wiley & Sons, Ltd.)

Trigonella foenum-graecum L. (fenugreek), a member of the legume family (Fabaceae), is a promising source of bioactive phytochemicals, which explains its traditional use for a variety of metabolic disorders including cancer. The current study aimed to evaluate extracts of fenugreek seeds and sprouts, and some of their constituents, to compare their cytotoxic and antiproliferative activities in MCF-7 breast cancer cells. The extracts were chemically characterised using high-resolution accurate mass liquid chromatography-mass spectrometry to reveal the detection of compounds assigned as flavone C -glycosides including those derived from apigenin and luteolin, in addition to isoflavones. Five different flavones or their glycosides (apigenin, vicenin-2, vitexin, luteolin and orientin) and two isoflavones (daidzein and formononetin) were quantified in the fenugreek extracts. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using MCF-7 cells treated with fenugreek methanolic extracts showed dose- and time-dependent effects on cell viability. The MCF-7 cancer cells treated with the fenugreek methanolic extracts also displayed increased relative mitochondrial DNA damage as well as suppressed metastasis and proliferation. This study demonstrates the potential anti-cancer effects of fenugreek seeds and sprouts and reveals fenugreek sprouts as an untapped resource for bioactive compounds.

Widely used in global households, fenugreek is well known for its culinary and medicinal uses. The various reported medicinal properties of fenugreek are by virtue of the different natural phytochemicals present in it. Regarded as a promising target, interleukin 2 receptor subunit alpha (IL2Rα) has been shown to influence immune responses. In the present research, using in silico techniques, we have demonstrated the potential IL2Rα binding properties of three polyphenol stilbenes (desoxyrhaponticin, rhaponticin, rhapontigenin) from fenugreek. As the first step, molecular docking was performed to assess the binding potential of the fenugreek phytochemicals with IL2Rα. All three phytochemicals demonstrated interactions with active site residues. To confirm the reliability of our molecular docking results, 100 ns molecular dynamics simulations studies were undertaken. As discerned by the RMSD and RMSF analyses, IL2Rα in complex with the desoxyrhaponticin, rhaponticin, and rhapontigenin indicated stability. The RMSD analysis of the phytochemicals alone also demonstrated no significant structural changes. Based on the stable molecular interactions and comparatively slightly better MM/PBSA binding free energy, rhaponticin seems promising. Additionally, ADMET analysis performed for the stilbenes indicated that all of them obey the ADMET rules. Our computational study thus supports further in vitro IL2Rα binding studies on these stilbenes, especially rhaponticin.

Trigonelline (TR), 4-hydroxyisoleucine (4-HI), and diosgenin (DG) are the main bioactives of the purified standardized extract of the popular plant Trigonella foenum-graecum L. (TFG), and it has been proven effective for the treatment of various diseases. However, to the best of our knowledge, no study has investigated the pharmacokinetic parameters of purified standardized T. foenum-graecum extract in normal and diabetic Wistar rats. The present study has developed and validated a rapid, reliable, and sensitive simultaneous ultra-performance liquid chromatography MS method to estimate these bioactives. The chromatographic separation was achieved using methanol, acetonitrile, and 0.1% formic acid with the ideal gradient flow system on a BEH Shield RP 18 column. A positive electrospray ionization mode was selected to estimate m/z values of TR (138.14 > 94.63), 4-HI (148.19 > 74.08), and DG (415.54 > 271.33). The method was robust and reproducible over the linearity range of 60-5000, 6-5000, and 15-5000 ng/mL for TR, 4-HI, and DG, respectively. Using this novel validated method, we investigated the pharmacokinetic parameters of bioactives using Phoenix WinNonlin version 8.0 (Certera) in normal and diabetic rats. The assay was successfully applied for the estimation of pharmacokinetic parameters using noncompartmental analysis. This investigation shows that the absorption rate increased, whereas distribution and elimination processes slowed down in diabetic rats compared with normal rats., (© 2021 John Wiley & Sons, Ltd.)

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia and insulin resistance. 4-hydroxyisoleucine (4-HIL) is a non-proteinogenic amino acid isolated from the fenugreek seeds and has enormous pharmacological activities. The present study was undertaken to investigate the antihyperglycemic effect of 4-HIL in streptozotocin (STZ)-induced diabetic rats. Moreover, its toxicity was evaluated in vitro and in vivo employing human embryonic kidney cells (HEK-293) and healthy rats, respectively. In experiment 1, STZ-induced diabetic male rats were subjected to an oral treatment of 4-HIL (100 mg/kg), while experiment 2 deals with the effects of 4-HIL on healthy male and female rats following oral administration. The treatment (experiment 1) declined the elevated blood glucose level, feed intake, and increased body weight(s). Additionally, blood glucose impairment was improved as observed by OGTT and IPGT tests. Pancreatic histopathology revealed mild changes in the 4-HIL group. Moreover, experiment 2 showed increased body weight, normal blood glucose levels (male-106.06 ± 7.49 mg/dl and female-100.06 ± 14.69 mg/dL), hematological parameters, and histopathological profiles in the treatment group. 4-HIL did not affect the viability of HEK-293 cells, and no signs of toxicity were observed in healthy rats. Therefore, the study concludes that 4-HIL has potential antihyperglycemic activity without any toxic effects.

Context: Trigonella foenum-graecum L. (Fabaceae) has many therapeutic properties and anticancer potential., Objective: The cytotoxic activities of standardized extracts and a fraction from fenugreek seeds and their compounds (sapogenins, flavone C-glycosides, alkaloid trigonelline) against human cancer SKOV-3, HeLa and MOLT-4 cells were evaluated., Materials and Methods: Fenugreek seeds were extracted with 70% methanol (A) or water (B). Furthermore, the seeds were purified with petroleum ether and chloroform and next extracted with methanol to obtain fraction (C). The quantitative analysis of saponins and flavonoids in the extracts was done with HPLC methods. The extracts (5-120 µg/mL) and compounds (1-50 µg/mL) were tested on the cells by MTT assay and RTCA system. The effect of a fraction on ROS production, mitochondrial membrane potential and caspase-3/7 activity in HeLa and SKOV-3 cells was also evaluated by flow cytometry., Results: The strongest cytotoxic activity on cancer cells showed the fraction C (IC 50 was 3.91 ± 0.03 for HeLa, 3.97 ± 0.07 for SKOV-3, and 7.75 ± 0.37 for MOLT-4) with the highest content of steroidal saponins (163.18 ± 11.03 μg/mg) and flavone C-glycosides (820.18 ± 0.05 μg/mg). The fraction significantly increased ROS production (up to four times higher than in keratinocytes as control) and caspases activity in the cells. The examined flavonoids did not exhibit the cytotoxic activity in contrast to yamogenin, tigogenin, and diosgenin., Conclusions: The obtained results complement the data on the cytotoxic activity of Foenugraeci Semen and synergistic effect of flavonoids and saponins complex contained in the plant.

Context: Garden cress (GC), fenugreek (FG), and black seed (BS) are traditional herbal medicine for managing hypertension., Objective: The effects of the three herbs on the pharmacodynamics of metoprolol tartrate (MT) in hypertensive rats were investigated., Materials and Methods: Wistar rats were divided in five groups ( n  = 6). Group I served as normal control group and Group II (hypertensive control group) had rats treated orally with N -nitro L-arginine methyl ester (L-NAME, 40 mg/kg/day) only. Groups III, IV, and V rats were orally treated with L-NAME (40 mg/kg/day) + GC (300 mg/kg, once daily), L-NAME (40 mg/kg/day) + FG (300 mg/kg, once daily) and L-NAME (40 mg/kg/day) + BS (300 mg/kg, once daily), respectively, for 2 weeks, and on the 14th day, blood pressure and heart rate were recorded using a tail-cuff blood pressure-measuring system. On the 16th day, a single dose of MT (10 mg/kg) was orally administered, and the rats' blood pressure and heart rate were recorded., Results: GC, FG, and BS decreased systolic blood pressure (SBP) by 8.7%, 8.5%, and 8.7%, respectively, in hypertensive rats. A greater decrease in SBP by 14.5%, 14.8%, and 16.1% was observed when hypertensive rats were treated with L-NAME + GC + MT, L-NAME + FG + MT, and L-NAME + BS + MT, respectively. Similarly, hypertensive rats treated with the combination of herbs and MT had significantly lower diastolic blood pressure (DBP) than those treated with herbs alone and those treated with L-NAME alone., Conclusions: The combination of investigated herbs and MT had a beneficial effect on hypertension. However, the concurrent administration of drugs, particularly those predominantly cleared through CYP450 2D6-catalyzed metabolism, with the three investigated herbs should be considered with caution.

A worldwide increase in the incidence of fungal infections, emergence of new fungal strains, and antifungal resistance to commercially available antibiotics indicate the need to investigate new treatment options for fungal diseases. Therefore, the interest in exploring the antifungal activity of medicinal plants has now been increased to discover phyto-therapeutics in replacement to conventional antifungal drugs. The study was conducted to explore and identify the mechanism of action of antifungal agents of edible plants, including Cinnamomum zeylanicum, Cinnamomum tamala, Amomum subulatum, Trigonella foenumgraecum, Mentha piperita, Coriandrum sativum, Lactuca sativa, and Brassica oleraceae var. italica . The antifungal potential was assessed via the disc diffusion method and, subsequently, the extracts were assessed for phytochemicals and total antioxidant activity. Potent polyphenols were detected using high-performance liquid chromatography (HPLC) and antifungal mechanism of action was evaluated in silico. Cinnamomum zeylanicum exhibited antifungal activity against all the tested strains while all plant extracts showed antifungal activity against Fusarium solani . Rutin, kaempferol, and quercetin were identified as common polyphenols. In silico studies showed that rutin displayed the greatest affinity with binding pocket of fungal 14-alpha demethylase and nucleoside diphosphokinase with the binding affinity (K d , -9.4 and -8.9, respectively), as compared to terbinafine. Results indicated that Cinnamomum zeylanicum and Cinnamomum tamala exert their antifungal effect possibly due to kaempferol and rutin, respectively, or possibly by inhibition of nucleoside diphosphokinase (NDK) and 14-alpha demethylase (CYP51), while Amomum subulatum and Trigonella foenum graecum might exhibit antifungal potential due to quercetin. Overall, the study demonstrates that plant-derived products have a high potential to control fungal infections.

Background: Fenugreek, also known as Trigonella foenum-graecum L, is a natural plant that belongs to the Fabaceae family and has been known as a promising source of bioactive compounds. It has been widely used as traditional medicine since it has shown to lower blood glucose, manage cholesterol levels and further aid in the prevention and treatment of cancer. Herein, we aim to evaluate the anticancer activity of methanolic fenugreek seed extract against several cancer cell lines., Methods: We sought to investigate the phytochemical classes present in multiple fenugreek seeds extracts using HPLC-DAD followed by LC/MS, predict and investigate anticancer activity using PASS online webserver, the CellTiter-Glo assay, evaluate ADME properties, and perform molecular docking for all bioactive compounds via Maestro software., Results: Multiple extracts exhibited distinct phytochemical classes that demonstrated different biological activities. Fenugreek methanolic extract contains flavonoid chemical class, which showed the highest anticancer activity against the HCT8 cell line of colorectal cancer (IC 50 of 8.83 μg/mL), followed by KAIMRC1 breast cancer cell line (IC 50 of 35.06 μg/mL), HL60 leukemia cell line (37.80 μg/mL), MDA-MB-231 breast cancer cell line (38.51 μg/mL), and lastly, HCT116 colorectal cancer cell line with IC 50 of 56.03 μg/mL. In contrast, the chloroform extract was inactive. The molecular docking study for all the bioactive compounds suggested that flavonoids F6 (-9.713 and -12.132), F7 (-10.166 and -12.411), and F11 (-10.084 and -13.516) possess the highest docking scores through SP and XP scores, respectively., Conclusion: The obtained results confirm that the bioactive compounds present in fenugreek seeds exhibit anticancer activity against several cancer cells that can mediate via tubulin polymerization inhibition. Although our study has evaluated the anticancer potential of Trigonella foenum-graecum as a promising natural source for new anticancer agents, fenugreek biological activity needs further research and investigations on their mechanism of action and toxicity profile., Competing Interests: The authors declare no conflicts of interest in this work., (© 2021 Alghamdi et al.)

Trigonelline is the main alkaloid with bioactivity presented in fenugreek, which was used in traditional medicine in Asian countries for centuries. It is reported that trigonelline has anti-inflammatory, anti-oxidant, and anti-pathogenic effects. We are wondering whether trigonelline have anti-aging effect. We found that 50  μ M of trigonelline had the best anti-aging activity and could prolong the lifespan of Caenorhabditis elegans ( C. elegans ) by about 17.9%. Trigonelline can enhance the oxidative, heat, and pathogenic stress resistance of C. elegans . Trigonelline could also delay the development of neurodegenerative diseases, such as AD, PD, and HD, in models of C. elegans . Trigonelline could not prolong the lifespan of long-lived worms with loss-of-function mutations in genes regulating energy and nutrition, such as clk-1 , isp-1 , eat-2 , and rsks-1 . Trigonelline requires daf-16 , hsf-1 , and aak-2 to extend the lifespan of C. elegans . Trigonelline can also up-regulate the expression of daf-16 and hsf-1 targeted downstream genes, such as sod-3 , gst-4 , hsp-16.1 , and hsp-12.6 . Our results can be the basis for developing trigonelline-rich products with health benefits, as well as for further research on the pharmacological usage of trigonelline., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2021 Wen-Yu Zeng et al.)