Identification of Crocetin as a Dual Agonist of GPR40 and GPR120 Responsible for the Antidiabetic Effect of Saffron
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 in...
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MDPI AG
2023-11-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/22/4774 |
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| author | Xiaodi Zhao Dohee Ahn Gibeom Nam Jihee Kwon Songyi Song Min Ji Kang Hyejin Ahn Sang J. Chung |
| author_facet | Xiaodi Zhao Dohee Ahn Gibeom Nam Jihee Kwon Songyi Song Min Ji Kang Hyejin Ahn Sang J. Chung |
| author_sort | Xiaodi Zhao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T16:33:13Z |
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| id | doaj.art-51f6aeaaeb824cb59305f20d853204c6 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T16:33:13Z |
| publishDate | 2023-11-01 |
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| series | Nutrients |
| spelling | doaj.art-51f6aeaaeb824cb59305f20d853204c62023-11-24T14:59:16ZengMDPI AGNutrients2072-66432023-11-011522477410.3390/nu15224774Identification of Crocetin as a Dual Agonist of GPR40 and GPR120 Responsible for the Antidiabetic Effect of SaffronXiaodi Zhao0Dohee Ahn1Gibeom Nam2Jihee Kwon3Songyi Song4Min Ji Kang5Hyejin Ahn6Sang J. Chung7Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of KoreaDepartment of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of KoreaDepartment of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of KoreaDepartment of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of KoreaDepartment of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of KoreaDepartment of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of KoreaDepartment of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of KoreaCrocin, 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.https://www.mdpi.com/2072-6643/15/22/4774crocetinGPR40/120 dual agonistglucose-stimulated insulin secretion (GSIS)glucagon-like peptide (GLP)-1 |
| spellingShingle | Xiaodi Zhao Dohee Ahn Gibeom Nam Jihee Kwon Songyi Song Min Ji Kang Hyejin Ahn Sang J. Chung Identification of Crocetin as a Dual Agonist of GPR40 and GPR120 Responsible for the Antidiabetic Effect of Saffron Nutrients crocetin GPR40/120 dual agonist glucose-stimulated insulin secretion (GSIS) glucagon-like peptide (GLP)-1 |
| title | Identification of Crocetin as a Dual Agonist of GPR40 and GPR120 Responsible for the Antidiabetic Effect of Saffron |
| title_full | Identification of Crocetin as a Dual Agonist of GPR40 and GPR120 Responsible for the Antidiabetic Effect of Saffron |
| title_fullStr | Identification of Crocetin as a Dual Agonist of GPR40 and GPR120 Responsible for the Antidiabetic Effect of Saffron |
| title_full_unstemmed | Identification of Crocetin as a Dual Agonist of GPR40 and GPR120 Responsible for the Antidiabetic Effect of Saffron |
| title_short | Identification of Crocetin as a Dual Agonist of GPR40 and GPR120 Responsible for the Antidiabetic Effect of Saffron |
| title_sort | identification of crocetin as a dual agonist of gpr40 and gpr120 responsible for the antidiabetic effect of saffron |
| topic | crocetin GPR40/120 dual agonist glucose-stimulated insulin secretion (GSIS) glucagon-like peptide (GLP)-1 |
| url | https://www.mdpi.com/2072-6643/15/22/4774 |
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