Isolation of Positive Modulator of Glucagon-like Peptide-1 Signaling from Trigonella foenum-graecum (Fenugreek) Seed

King, Klim; Lin, Nai-Pin; Cheng, Yen Ju; Chen, Gao-Hui; Chein, Rong‐Jie

doi:10.1074/jbc.m115.672097

Cited by 36 publications

(25 citation statements)

References 48 publications

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“…In a screening program of edible plant extracts, King et al. found that ethanol extracts from fenugreek seeds enhance GLP‐1 signaling . An active compound (named N55, compound 3 ) with a novel γ‐lactone structure (Figure ) was purified and evaluated in receptor binding and endocytosis assays through insulin release from RINm5F cells.…”

Section: An Overview Of Nonpeptide Pams Of the Glp‐1rmentioning

confidence: 99%

“…An active compound (named N55, compound 3 ) with a novel γ‐lactone structure (Figure ) was purified and evaluated in receptor binding and endocytosis assays through insulin release from RINm5F cells. Compound 3 enhanced GLP‐1, but not exendin‐4‐induced cAMP production, with an EC 50 value of 3.70 μ m , and GLP‐1R endocytosis in a dose‐dependent and saturable manner . They also postulated that compound 3 bound to GLP‐1 peptide or the GLP‐1(7–36) amide binding site simultaneously with the natural ligand.…”

Section: An Overview Of Nonpeptide Pams Of the Glp‐1rmentioning

confidence: 99%

“…[26,27] In as creening program of edible plant extracts, King et al found that ethanol extracts from fenugreek seeds enhance GLP-1 signaling. [28] An active compound (namedN 55, compound 3)w ith an ovel g-lactone structure ( Figure 1) wasp urified and evaluated in receptor binding and endocytosis assays through insulin release from RINm5F cells. Compound 3 enhanced GLP-1, but not exendin-4-induced cAMP production, with an EC 50 value of 3.70 mm,a nd GLP-1R endocytosis in a dose-dependent and saturable manner.…”

Section: Pams Of the Glp-1r With Am Onocyclic Scaffoldmentioning

confidence: 99%

“…Compound 3 enhanced GLP-1, but not exendin-4-induced cAMP production, with an EC 50 value of 3.70 mm,a nd GLP-1R endocytosis in a dose-dependent and saturable manner. [28] They also postulated that compound 3 bound to GLP-1 peptide or the GLP-1(7-36) amide binding site simultaneously with the natural ligand. Thus, compound 3 is ar epresentative of an ew class of enhancers of GLP-1R signaling, that is, positive modulators of native ligand.…”

Section: Pams Of the Glp-1r With Am Onocyclic Scaffoldmentioning

confidence: 99%

“…The action of 25 was not inhibited by exendin-4(9-39), which confirmed an allosteric mode of binding. [26] Compound 25 induces cAMP signaling by activating GLP- (16)(17)(18)(19), hexahydroquinolone carboxylate (20,21), isoquinoline (22)derivatives, quercetin (23), and substituted quinoxaline (24)(25)(26)(27)(28)(29)(30)(31). ChemMedChem 2019, 14,514 -521 www.chemmedchem.org 1R [33,39,44] and increases the glucose-dependents ecretion of insulin in islets from wild type, but not from GLP-1Rk nockout, mice;t hus confirming its GLP-1R-mediated action.…”

Section: Pams Of the Glp-1r With Ab Icyclics Caffoldmentioning

confidence: 99%

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An Overview, Advantages and Therapeutic Potential of Nonpeptide Positive Allosteric Modulators of Glucagon‐Like Peptide‐1 Receptor

et al. 2019

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Due to uncomfortable injection regimens of peptidic agonists of glucagon‐like peptide‐1 receptor (GLP‐1R), orally available nonpeptide positive allosteric modulators (PAMs) of GLP‐1Rs are foreseen as the possible future mainstream therapy for type 2 diabetes. Herein, current GLP‐1R PAMs are reviewed. Based on the effectiveness and in silico predicted physicochemical properties, pharmacokinetics, and toxicity, possible candidates for further development as oral drugs were selected. The suggestion is that GLP‐1R PAMs might be used orally alone or in combination with dipeptidyl peptidase‐4 (DPP‐4) inhibitors, which could offer an optimal treatment option next to metformin monotherapy in type 2 diabetes mellitus, or in a wider spectrum of indications. Quercetin acts as a GLP‐1R PAM and DPP‐4 inhibitor, and therefore, might be considered as a pioneering agent with a dual mechanism of action, in terms of GLP‐1R positive allosteric modulation and DPP‐4 inhibition for potentiating GLP‐1 dependent effects.

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Section: An Overview Of Nonpeptide Pams Of the Glp‐1rmentioning

confidence: 99%

Section: An Overview Of Nonpeptide Pams Of the Glp‐1rmentioning

confidence: 99%

Section: Pams Of the Glp-1r With Am Onocyclic Scaffoldmentioning

confidence: 99%

Section: Pams Of the Glp-1r With Am Onocyclic Scaffoldmentioning

confidence: 99%

Section: Pams Of the Glp-1r With Ab Icyclics Caffoldmentioning

confidence: 99%

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An Overview, Advantages and Therapeutic Potential of Nonpeptide Positive Allosteric Modulators of Glucagon‐Like Peptide‐1 Receptor

et al. 2019

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Antidiabetic potential of fenugreek (Trigonella foenum‐graecum): A magic herb for diabetes mellitus

Sarker,

Ray,

Dutta

et al. 2024

Food Science & Nutrition

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Fenugreek (Trigonella foenum‐graecum) is a widely grown dietary herb in Asia, and its seeds are traditionally used for several diseases, including diabetes. The seeds and leaves possess a variety of compounds that play an important role in regulating their hypoglycemic effect. However, so far, no extensive systematic review exists on its antidiabetic effect, highlighting the molecular mechanisms and isolated compounds. The purpose of this review is to summarize the preclinical and clinical antidiabetic properties of fenugreek and its isolated compounds by focusing on underlying mechanisms. PubMed, Google Scholar, Science Direct, and Scopus databases were searched to retrieve articles until June, 2024. Preclinical studies demonstrated that the antidiabetic effect of fenugreek was mostly associated with enhanced glucose transporter type‐4 (GLUT4) translocation and hexokinase activity, decreased glucose‐6‐phosphatase and fructose‐1,6‐bisphosphatase activities, inhibited α‐amylase and maltase activities, protected β cells, and increased insulin release. Furthermore, few studies have reported its role as a glucagon‐like peptide‐1 (GLP‐1) modulator, 5′‐AMP‐activated kinase (AMPK) activator, and dipeptidyl peptidase‐IV (DPP‐IV) inhibitor. Further clinical trials showed that fenugreek seeds improved blood glucose levels, insulin resistance, insulin sensitivity, and lipid profiles. This study highlights significant evidence of the antidiabetic effect of fenugreek and its isolated compounds; therefore, it could be a potential therapy for diabetes.

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A small plant with big benefits: Fenugreek (Trigonella foenum‐graecum Linn.) for disease prevention and health promotion

Venkata

Swaroop²,

Bagchi

et al. 2017

Molecular Nutrition Food Res

174

102

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Plant-derived natural products have long-standing utility toward treating degenerative diseases. It is estimated that about two-thirds of world population depend on traditional medicine for primary medical needs. Fenugreek (Trigonella foenum-graecum Linn.), a short-living annual medicinal plant belonging to Fabaceae family, is used extensively in various parts of the world as herb, food, spice, and traditional medicine. Fenugreek is considered as one of the oldest medicinal plants and its health-promoting effects have been cited in Ayurveda and traditional Chinese medicine. The investigations into the chemical composition and pharmacological actions have seen a renaissance in recent years. Extensive preclinical and clinical research have outlined the pharmaceutical uses of fenugreek as antidiabetic, antihyperlipidemic, antiobesity, anticancer, anti-inflammatory, antioxidant, antifungal, antibacterial, galactogogue and for miscellaneous pharmacological effects, including improving women's health. The pharmacological actions of fenugreek are attributed to diverse array of phytoconstituents. The phytochemical analysis reveals the presence of steroids, alkaloids, saponins, polyphenols, flavonoids, lipids, carbohydrates, amino acids, and hydrocarbons. This review aims to summarize and critically analyze the current available literature to understand the potential of fenugreek for disease prevention and health improvement with special emphasis on cellular and molecular mechanisms. Current challenges and new directions of research on fenugreek are also discussed.

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Isolation of Positive Modulator of Glucagon-like Peptide-1 Signaling from Trigonella foenum-graecum (Fenugreek) Seed

Cited by 36 publications

References 48 publications

An Overview, Advantages and Therapeutic Potential of Nonpeptide Positive Allosteric Modulators of Glucagon‐Like Peptide‐1 Receptor

An Overview, Advantages and Therapeutic Potential of Nonpeptide Positive Allosteric Modulators of Glucagon‐Like Peptide‐1 Receptor

Antidiabetic potential of fenugreek (Trigonella foenum‐graecum): A magic herb for diabetes mellitus

A small plant with big benefits: Fenugreek (Trigonella foenum‐graecum Linn.) for disease prevention and health promotion

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