In vitro studies of berberine metabolism and its effect of enzyme induction on HepG2 cells

Abstract

Ethnopharmacological relevance: Berberine (BER) and BER-original herbal medicines have a variety of pharmacological functions and have been widely used in clinical. However, its effect of enzyme induction on cytochrome P450 (CYP) in human hepatocytes is unknown.

Material and method: Metabolism of berberine and its effect on main metabolic enzymes in HepG2 cell in vitro was investigated. Cocktail probe drugs, mRNA expression and protein expression were used to evaluate the metabolism potency. Meanwhile, an UPLC-MS/MS method was validated for the analysis of BER and four probe drugs in HepG2 cell.

Result: BER significantly increased the metabolism of midazolam, phenacetin and tolbutamide by inducing the CYP1A2 and 3A4 enzyme in a dose-dependent manner, the mRNA and protein expression of CYP1A2 and 3A4 were increased by berberine at 1000ng·mL(-1). The activity of CYP1A2 and 3A4 could be induced by BER more than 500ng·mL(-1) in HepG2 cell, which was confirmed by the increase of its mRNA and protein expression.

Conclusion: BER increases the metabolism of cocktail drugs such as midazolam, phenacetin and tolbutamide by increasing the mRNA and protein expression of CYP1A2 and 3A4.

Keywords: Berberine; CYP enzyme; Drug metabolism; Drug–drug interaction; HepG2 cell; Metabolic enzyme induction.