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.
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http://dx.doi.org/10.3390/nu15224774 | DOI Listing |
Food Chem
February 2025
Department of Food Science and Biotechnology, Ewha Womans University, Seoul 03760, Republic of Korea. Electronic address:
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.
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Institute of Molecular and Industrial Biotechnology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego Street 2/22, Lodz 90-537, Poland.
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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.
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Research Unit of Biomedicine and Internal Medicine, Biocenter of Oulu, Medical Research Center, University of Oulu, Aapistie 5, 90220, Oulu, Finland.
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Research Laboratory of Translational Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, People's Republic of China.
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