Effects of extracts of <i>Sutherlandia frutescens</i>on drug transport and drug metabolising enzymes

Abstract

Drug-drug and drug-herb interactions must be considered in both pre-clinical studies and clinical use. This study set out to investigate the possible interactions caused by extracts of Sutherlandia frutescens (Sutherlandia) at drug transporter (P-gp) level and at hepatic metabolic enzyme level (CYP 450).

MDCK-MDR1 cells were treated with aqueous Sutherlandia extract (6.8 mg/ml to 1.7 μg/ml) in the presence of amprenavir, a protease inhibitor used to treat HIV infection. For CYP inhibition the P450-Glo™ assay kit was used and aqueous and organic extracts of Sutherlandia tested. Higher doses of Sutherlandia extract from 850 µg/ml upwards adversely affected tight junctions (TJ) as shown by the reduced transepithelial electric resistance (TEER) readings. At lower concentrations, Sutherlandia caused increased amprenavir permeability in a dose-dependent manner, suggesting that the extract inhibited P-gp and reduced amprenavir efflux. In the CYP inhibition assays, Sutherlandia extracts showed IC₅₀ values above 10 µg/ml for all enzyme isoforms, hence CYP enzyme inhibitory interactions at this level are not expected to be clinically significant.