OBJECTIVE To exploring the effect and mechanism of Gardenia jasminoides Ellis exerting its hypoglycemic effect via bile acids-G protein-coupled bile acid receptor 5(TGR5)-glucagon-like peptide-1(GLP-1) signaling pathway.

METHODS The C57BL/6 diabetic model mice, mouse small intestinal endocrine cells(STC-1), and Caco-2 cells were employed as the subjects in this study. After being administered orally with Gardenia jasminoides Ellis aqueous extract to mice for 28 d, the levels of glucose(Glu), insulin(INS), glycosylated hemoglobin or glycated hemoglobin(GHbA1c), and GLP-1 in serum were evaluated, and then UPLC-MS/MS was used to analyze the concentration changes of 20 bile acids in colon tissue. Based on this, the potential effects of bile acids with characteristic changes in colon tissue on the TGR5-GLP-1 pathway were investigated in cell experiment.

RESULTS  Gardenia jasminoides Ellis could improve the levels of Glu, GHbA1c, INS, and GLP-1 in serum, and reversed those to normal levels, which suggested that Gardenia jasminoides Ellis exhibited apparent hypoglycemic and treatment effects; Gardenia jasminoides Ellis inhibited the apical sodium-dependent bile acid transporter(ASBT) at the apical membrane of the ileum to result in the amount of bile acids in colon tissue increased significantly, which was the embodiment of its choleretic effect; Gardenia jasminoides Ellis did not activate the TGR5-GLP-1 pathway, but the distribution of TGR5 agonist-like bile acids, including deoxycholic acid, taurine- conjugated deoxycholic acid, and hyodeoxycholic acid, in the colon tissue, increased significantly after administration with Gardenia jasminoides Ellis, which was the potential mechanism to promote the secretion of GLP-1 and exert hypoglycemic effect.

CONCLUSION  Gardenia jasminoides Ellis inhibite ileal ASBT to increase the distribution of TGR5 agonist-like bile acids in the colon, thereby promoting the secretion of GLP-1 and ultimately exerting hypoglycemic effects.