Hypoglycemic Effect of Ginsenoside Compound K Mediated by N-Acetylserotonin Derived From Gut Microbiota.

Abstract

Ginsenoside compound K (GCK) has been proved to have great hypoglycemic effect pertinent to gut microbiota. However, the improvement of high-fat-diet (HFD)-induced type 2 diabetes (T2D) as well as the mechanism of GCK mediated by gut microbiota is not well-known. This study aimed to investigate the hypoglycemic effects and mechanism of GCK on a HFD-induced diabetic mouse model. HFD-induced pseudo-germ free (GF) T2D mice model and fecal microbiota transplantation (FMT) experiments were performed to clarify the role of gut microbiota in the hypoglycemic effect of GCK. Differential metabolites were screened by untargeted metabolomics analysis and their functions were verified by suppling to T2D mice. The level of glucagon-like peptide-1 (GLP-1) in plasma was detected by ELISA analysis to explore the potential hypoglycemic mechanism of GCK. The results showed GCK alleviated metabolic disorders and altered gut microbiota in HFD-induced diabetic mice, which was transmitted to pseudo-GF diabetic mice via FMT experiment to reproduce the hypoglycemic effect. Non-targeted metabolites analysis on cecal content samples indicated that N-acetylserotonin (NAS) was markedly increased after GCK treatment. Moreover, gavage with NAS improved insulin sensitivity and increased the secretion of GLP-1 in HFD mice. Our study showed that GCK had hypoglycemic effect through modifying gut microbiota profiling.