Metabolic Study of Ginsenoside Rg3 and Glimepiride in Type 2 Diabetic Rats by Liquid Chromatography Coupled with Quadrupole-Orbitrap Mass Spectrometry.

RATIONALE Ginsenoside Rg3 and glimepiride have been applied to treat type 2 diabetes (T2DM) because of their good hypoglycemic effects. In this study, the effects of ginsenoside Rg3 acting synergistically with glimepiride were investigated in liver microsomes from rats with type 2 diabetes. METHODS An in vitro incubation system with normal rat liver microsomes (RLM) and type 2 diabetic rat liver microsomes (TRLM) was developed. The system also included two experimental groups consisting of RLM and TRLM pretreated with ginsenoside Rg3 and glimepiride (named the RLMR and TRLMR groups, respectively). The metabolism in different groups was analyzed by ultra-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry (UPLC-Q-Orbitrap MS). RESULTS The results showed that the concentration of glimepiride increased in RLM and TRLM after treatment with ginsenoside Rg3. Five metabolites (M1-M5) of glimepiride were found, and they were named 3N-hydroxy glimepiride, hydroxy glimepiride, 1,2-epoxy ether-3-hydroxy glimepiride, 1N-hydroxy glimepiride and 1N,2C,S,O,O-epoxy ether-3-hydroxy glimepiride. The metabolite of ginsenoside Rg3 was ginsenoside Rh2. CONCLUSION An in vitro incubation system with RLM and TRLM was developed. The system revealed pathways that produce glimepiride metabolites. Ginsenoside Rg3 may inhibit the activity of cytochrome P450 enzymes in vitro. The present study showed that ginsenoside Rg3 and glimepiride may be combined for the treatment of T2DM.