Cho, Yeon-Jin Choi, Sun-Hye Lee, Rami Hwang, Hongik Rhim, Hyewhon Cho, Ik-Hyun Kim, Hyoung-Chun Lee, Jeong-Ik Hwang, Sung-Hee Nah, Seung-Yeol 2024-01-19T18:02:18Z 2024-01-19T18:02:18Z 2021-09-05 2020-03 1420-3049 https://pubs.kist.re.kr/handle/201004/118888 Gintonin, a novel ginseng-derived glycolipoprotein complex, has an exogenous ligand for lysophosphatidic acid (LPA) receptors. However, recent lipid analysis of gintonin has shown that gintonin also contains other bioactive lipids besides LPAs, including linoleic acid and lysophosphatidylinositol (LPI). Linoleic acid, a free fatty acid, and LPI are known as ligands for the G-protein coupled receptors (GPCR), GPR40, and GPR55, respectively. We, herein, investigated whether gintonin could serve as a ligand for GPR40 and GPR55, using the insulin-secreting beta cell-derived cell line INS-1 and the human prostate cancer cell line PC-3, respectively. Gintonin dose-dependently enhanced insulin secretion from INS-1 cells. Gintonin-stimulated insulin secretion was partially inhibited by a GPR40 receptor antagonist but not an LPA1/3 receptor antagonist and was down-regulated by small interfering RNA (siRNA) against GPR40. Gintonin dose-dependently induced [Ca2+](i) transients and Ca2+-dependent cell migration in PC-3 cells. Gintonin actions in PC-3 cells were attenuated by pretreatment with a GPR55 antagonist and an LPA1/3 receptor antagonist or by down-regulating GPR55 with siRNA. Taken together, these results demonstrated that gintonin-mediated insulin secretion by INS-1 cells and PC-3 cell migration were regulated by the respective activation of GPR40 and GPR55 receptors. These findings indicated that gintonin could function as a ligand for both receptors. Finally, we demonstrated that gintonin contained two more GPCR ligands, in addition to that for LPA receptors. Gintonin, with its multiple GPCR ligands, might provide the molecular basis for the multiple pharmacological actions of ginseng. English Multidisciplinary Digital Publishing Institute (MDPI) Ginseng Gintonin Contains Ligands for GPR40 and GPR55 Article 10.3390/molecules25051102 1 Molecules, v.25, no.5 Molecules 25 5 Y scie scopus 000529219900085 2-s2.0-85080999209 Biochemistry & Molecular Biology Chemistry, Multidisciplinary Biochemistry & Molecular Biology Chemistry Article LYSOPHOSPHATIDIC ACID RECEPTORS CANNABINOID RECEPTOR INSULIN-SECRETION ENRICHED FRACTION CELL-MIGRATION TARGET ESTABLISHMENT INVOLVEMENT KINASE MICE ginseng gintonin GPR40 GPR55 insulin secretion cell migration