Modulation of biotransformation and elimination systems by BM-21, an aqueous ethanolic extract from Thalassia testudinum, and thalassiolin B on human hepatocytes

Abstract

BM-21 is an extract obtained from Thalassia testudinum marine plant with pharmacological properties. The effects of BM-21 and thalassiolin B (TB), its main component, on enzyme and transport proteins involved in drug metabolism and excretion in human cultured hepatocytes were evaluated. Cells were exposed for 48 h to sub-cytotoxic concentrations of BM-21 or TB. Effects on P450 isoforms revealed significant reductions of CYP1A2, 3A4 and 2D6 activities (up to 56%, 66% and 44% inhibition, respectively) after exposition to BM-21, no changes on CYP2A6 and 2C9 activities. TB produced a concentration-dependent reduction of all P450 activities. In addition, a decrease in total UGT and UGT2B7 activities was found at 250 μg/mL BM-21, while UGT1A1 and 1A9 were significantly reduced (50 μg/mL). TB only inhibited significantly UGT1A9 activity. Both products were able to reduce P-gp activity in treated hepatocytes. Quantification of specific mRNAs revealed a reduction in CYP3A4 and 3A5 mRNAs content and an increase in CYP1A1 and 1A2 mRNAs. No appreciable effects in the levels of CYP2A6, 2B6, 2C9, 2C19, 2D6, 2E1, UGT1A1, UGT1A9 and ABCB1 (P-gp) were found. BM-21 inhibited P450, UGTs and P-gp activities in human hepatocytes; therefore, it should be examined for potential pharmacokinetic drug interactions in vivo.

Keywords

• Thalassia testudinum
• Thalassiolin B
• Polyphenols
• Cytochrome P450
• UDP-glucuronosyltransferases
• P-glycoprotein