Effects of combination treatment with metformin and berberine on hypoglycemic activity and gut microbiota modulation in db/db mice
Abstract
BACKGROUND: Gut microbiota alterations could influence the metabolism of administered drugs, leading to their altered pharmacokinetics and pharmacodynamics. Despite that metformin and berberine has individually demonstrated their impacts on hypoglycemic activities and gut microbiota alterations in diabetic mice, investigation regarding the impact of their combination treatment in diabetic treatment has never been conducted.
PURPOSE: Our current study was proposed aiming to investigate the effect of combination use of metformin with berberine on hypoglycemic activity and identify the possible intestinal bacteria involved in their microbiota-medicated drug-drug interactions in db/db mice.
STUDY DESIGN: Pharmacodynamics interactions between metformin and berberine were evaluated in six groups of db/db mice (db, M250, B250, B125, B250+M250, and B125+M250) with its wild type (WT) as control to receive 14 days treatment of vehicle, metformin at 250 mg/kg, berberine at 250/125 mg/kg, and metformin (250 mg/kg) 2 h after dosing berberine (250/125 mg/kg).
METHODS: On day 13, insulin tolerance test (ITT) was conducted. On day 15, fasting serum samples were obtained for insulin concentration determination followed by intraperitoneal glucose tolerance test (ipGTT), homeostatic model assessment for insulin resistance (HOMA-IR) calculation, and feces collection for microbial 16S rRNA sequencing analyses. In addition, metformin steady state plasma concentrations on day 15 were measured by…
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