Inhibitory effects of herbal medicines with claimed anticancer indications on cytochrome P450—An evaluation of drug-herb interactions risk

Abstract

Herbs have the potential to interact with conventional medicines or each other upon concurrent administration. This can be at the level of absorption, distribution, metabolism and excretion (ADME). With an estimation that 80% of the population in poor regions of the world utilise herbal medicines for primary healthcare, there is a likelihood that some people will take both herbal and conventional medicines. This could present a risk for herb-drug interactions (HDI) at the various levels of the ADME process. Most common HDI have been observed at metabolism level involving inhibition or induction of the major drug metabolising liver enzymes called cytochrome P450s. In this study, we investigated the inhibitory effects of Parinari curatellifolia (MC), Fluggea virosa (ST), Garcinia livingstonei (MT), Pterocarpus angolensis (M), Tapinanthus quequensis (MF) and Cussonia arborea (GM) on recombinant CYP1A2, CYP2D6, CYP2C9 and CYP2C19. Plate based fluorescent assays were used to follow enzyme activity. Inhibition was determined at 5 mg/ml and 100 mg/ ml of herbal extract, with IC50 determined for herbs that showed potent inhibition. A total of 10 out of 13 extracts showed significant inhibitory effects. Pterocarpus angolensis(bark), Fluggea virossa (leaf), Cussonia arborea(bark), Parinari curatellifollia (root) had very potent effects on CYP1A2 as indicated by an IC50 of <9.9 μg/ml. Based on the worst-case-scenario of complete absorption and exposure, these herbs are predicted to result in HDI if co-administered with medicines which depend on the affected CYPs for metabolism and elimination. Significance of the main findings: There is a potential threat of drug toxicities due to drug-herb interactions for patients undergoing chemotherapy or taking other medications where comorbidities exist during chemotherapy. Drugs that are substrates of CYP1A2 should be administered with caution for patients who are taking the herbs which have been studied in this research as risk for drug toxicities may be high. The findings act as a guide to medical doctors and patients in evaluating potential for herb-drug interactions during prescribing medications which are substrates for the studied CYPs.