Synergistic Effect of Glibenclamide Combining With Vitexin on Type 2 Diabetes Mellitus Rats

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Background & objectives: The combination of drugs with herbs is a prevalent treatment for metabolic and chronic diseases. This study combined glibenclamide with vitexin and performed in vivo and in vitro investigations, aiming to evaluate their synergistic effect on type 2 diabetes mellitus (T2DM). Materials and methods: T2DM rat models were established by injecting streptozotocin, and the sham group was injected with a normal saline solution as the control. A single dosage was orally performed with 10 mg/kg glibenclamide, while the co-administrated was conducted by the pre-treatment of 20 mg/kg vitexin for 7 d to avoid potential chemical interactions. The pharmacokinetics of glibenclamide was evaluated in both sham and T2DM rats. The blood glucose of T2DM rats was detected in the presence of different administration strategies. The metabolic stability of glibenclamide was assessed in rat liver microsomes. Results: Glibenclamide showed a significant hypoglycemic effect on T2DM rats, which was enhanced by the co-administration of vitexin. Vitexin significantly affected the pharmacokinetics of glibenclamide in both sham and T2DM rats, where the AUC0-t, Cmax, and t1/2 of glibenclamide significantly increased, and the clearance rate decreased. Moreover, vitexin increased the in vitro half-life and decreased intrinsic clearance of glibenclamide in rat liver microsomes. The previously reported inhibitory effect of vitexin on CYP2C9 activity was hypothesized as the mechanism underlying the interaction. Conclusion: Co-administration of glibenclamide and vitexin would increase the systemic exposure and metabolic stability of glibenclamide and exert a synergistic effect on T2DM.