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Herbal medicines are commonly used as compound formulas in clinical practice to achieve optimal therapeutic effects. However, the combination mechanisms usually lack solid evidence. In this study, we report synergistic interactions through altering pharmacokinetics in Gegen-Qinlian Decoction (GQD), an anti-diabetic Chinese medicine formula. A multi-component pharmacokinetic study of GQD and the single herbs was conducted by simultaneously monitoring 42 major bioactive compounds (markers) in rats plasma using LC/MS/MS within 30 min. GQD could remarkably improve the plasma concentrations of berberine (BER) and other alkaloids in Huang-Lian by at least 30%, and glycyrrhizic acid (GLY) from Gan-Cao played a major role. A Caco-2 cell monolayer test indicated that GLY improved the permeability of BER by inhibiting P-glycoprotein. Although GLY alone did not show observable effects, the co-administration of GLY (ig, 50 or 80 mg/kg) could improve the anti-diabetic effects of berberine (ig, 50 mg/kg) in db/db mice in a dose-dependent manner. The blood glucose decreased by 46.9%, whereas the insulin level increased by 40.8% compared to the control group. This is one of the most systematic studies on the pharmacokinetics of Chinese medicine formulas, and the results demonstrate the significance of pharmacokinetic study in elucidating the combination mechanisms of compound formulas.

frontiers in pharmacology

A 42-Markers Pharmacokinetic Study Reveals Interactions of Berberine and Glycyrrhizic Acid in the Anti-diabetic Chinese Medicine Formula Gegen-Qinlian Decoction