Abstract

L. Gwaza, A. R. Wolfe, L. Z. Benet, B. J. Guglielmo, T. E. Chagwedera, C. C. Maponga and C. M. Masimirembwa*

Herbal medicines have been shown to cause clinically significant interactions with conventional medicines. Herbal medicines can alter the activity of drug- metabolizing enzymes and transporters, potentially resulting in herb -drug interactions. However, such information is generally not yet available for herbal medicines used only in developing nations. The inhibitory effects of crude extracts of Hypoxis obtusa and Dicoma anomala on cytochrome P450 (CYP) isoforms 1A2, 2C9, 2C19, 2D6 and 3A4 were evaluated in vitro using human liver microsomes. Herbal extracts at concentrations of 50 and 250 g/ml were tested for inhibition of P-glycoprotein (Pgp) transport across Caco-2 cell monolayers using 4.3 nM [3H]-digoxin as the substrate. Extracts of Hypoxis inhibited CYPs strongly, while extracts of Dicoma were moderate CYP inhibitors. The IC50 values for methanol and water extracts on CYP3A4 were 0.20 and 1.0 mg/ml for Hypoxis and 1.2 and 2.4 mg/ml for Dicoma. In the Pgp inhibition experiments, the (basolateral to apical) / (apical to basolateral) digoxin efflux ratios did not change significantly in the presence of the herbal extracts. Whilst, the extrapolation of the data to in vivo is rather speculative, there is need for assessment of the clinical significance of Hypoxis - drug interactions.