Crocin, a glycoside of crocetin, has been known as the principal component responsible for saffron's antidiabetic, anticancer, and anti-inflammatory effects. Crocetin, originating from the hydrolytic cleavage of crocin in biological systems, was subjected to ligand-based virtual screening in this investigation. Subsequent biochemical analysis unveiled crocetin, not crocin, as a novel dual GPR40 and GPR120 agonist, demonstrating a marked preference for GPR40 and GPR120 over peroxisome proliferator-activated receptors (PPAR)γ. This compound notably enhanced insulin and GLP-1 secretion from pancreatic β-cells and intestinal neuroendocrine cells, respectively, presenting a dual mechanism of action in glucose-lowering effects. Docking simulations showed that crocetin emulates the binding characteristics of natural ligands through hydrogen bonds and hydrophobic interactions, whereas crocin's hindered fit within the binding pocket is attributed to steric constraints. Collectively, for the first time, this study unveils crocetin as the true active component of saffron, functioning as a GPR40/120 agonist with potential implications in antidiabetic interventions.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10675071PMC
http://dx.doi.org/10.3390/nu15224774DOI Listing

Publication Analysis

Top Keywords

gpr40 gpr120
12
crocetin
5
identification crocetin
4
crocetin dual
4
dual agonist
4
agonist gpr40
4
gpr120 responsible
4
responsible antidiabetic
4
antidiabetic saffron
4
saffron crocin
4

Similar Publications

The physiological functions of various fatty acid-originating metabolites from foods and fermented products remained mostly untouched. Thereby, this study examined the biological activities of hydroxy fatty acids as agonists of G protein-coupled receptors (i.e.

View Article and Find Full Text PDF

N-acyl glycines produced by commensal bacteria potentiate GLP-1 secretion as GPCR ligands.

Biomed Pharmacother

November 2024

Institute of Molecular and Industrial Biotechnology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego Street 2/22, Lodz 90-537, Poland.

Commensal microbiota is crucial for nutrient digestion and production of biologically active molecules, many of which mimic endogenous ligands of human GPCRs. Bacteroides spp. are among the most abundant bacteria residing in the human gut and their absence has been positively correlated with metabolic disorders.

View Article and Find Full Text PDF

GPR40/GPR120 Agonist GW9508 Improves Metabolic Syndrome-Exacerbated Periodontitis in Mice.

Int J Mol Sci

September 2024

Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.

G protein-coupled receptor (GPR)40 and GPR120 are receptors for medium- and long-chain free fatty acids. It has been well documented that GPR40 and GPR120 activation improves metabolic syndrome (MetS) and exerts anti-inflammatory effects. Since chronic periodontitis is a common oral inflammatory disease initiated by periodontal pathogens and exacerbated by MetS, we determined if GPR40 and GPR120 activation with agonists improves MetS-associated periodontitis in animal models in this study.

View Article and Find Full Text PDF

Effect of hypoxia on GLP-1 secretion - an in vitro study using enteroendocrine STC-1 -cells as a model.

Pflugers Arch

October 2024

Research Unit of Biomedicine and Internal Medicine, Biocenter of Oulu, Medical Research Center, University of Oulu, Aapistie 5, 90220, Oulu, Finland.

Glucagon-like peptide (GLP)-1 is a hormone released by enteroendocrine L-cells after food ingestion. L-cells express various receptors for nutrient sensing including G protein-coupled receptors (GPRs). Intestinal epithelial cells near the lumen have a lower O tension than at the base of the crypts, which leads to hypoxia in L-cells.

View Article and Find Full Text PDF

Pathophysiological relevance and therapeutic outlook of GPR43 in atherosclerosis.

Biochem Cell Biol

December 2024

Research Laboratory of Translational Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, People's Republic of China.

Atherosclerosis (AS) is an inflammatory arterial disorder that occurs due to the deposition of the excessive lipoprotein under the artery intima, mainly including low-density lipoprotein and other apolipoprotein B-containing lipoproteins. G protein-coupled receptors (GPCRs) play a crucial role in transmitting signals in physiological and pathophysiological conditions. GPCRs recognize inflammatory mediators, thereby serving as important players during chronic inflammatory processes.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!