Assessment of the Interaction Potential of (L.) Extracts on CYP2B6, 3A4, and Rifampicin Metabolism.

L. or basilicum is a common culinary herb, used as a traditional medicine for various medical conditions including HIV/AIDS and tuberculosis, in Africa. The objective of this study was to evaluate the effect of methanol, ethanol, aqueous and ethyl acetate extracts of the dried leaves and inflorescence of , on the activity of cytochrome P450 enzymes (CYPs) CYP2B6 and 3A4, as well as esterase-mediated metabolism of rifampicin to 25--desacetyl rifampicin (25ODESRIF). Human liver microsomes (HLM) were used to evaluate inhibition and CYP2B6/3A4 mRNA expression HepG2 assays were used to measure induction. Furthermore, the phytoconstituents likely involved in causing the observed effect were analyzed using biochemical tests and LC-MS. The aqueous and methanolic extracts showed reversible and time-dependent inhibition (TDI) of CYP2B6 with TDI-ICs 33.35 μg/ml (IC shift-fold >1.5) and 4.93 μg/ml (IC shift-fold >7) respectively, while the methanolic and ethanolic extracts inhibited 25ODESRIF formation (ICs 31 μg/ml, 8.94 μg/ml). In HepG2 assays, the methanolic and ethanolic extracts moderately induced CYP2B6, 3A4 mRNA with 38%-, 28%-fold shift, and 22%-, 44%-fold shift respectively. LC-MS full scans identified phenols rosmarinic acid [ 359 (M-H), approximately 2298 mg/L in aqueous extract] and caftaric acid along with flavones salvigenin [ 329 (M+H), approximately 1855 mg/L in ethanolic extract], eupatorin [ 345 (M+H), 668.772 mg/L in ethanolic extract], rutin [ 609 (M-H)] and isoquercetin [ 463 (M-H)] and other compounds-linalool [ 153 (M-H)], hydroxyjasmonic acid [ 225 (M-H)], eucommiol [ 187 (M-H)] and trihydroxy octadecenoic acid [ 329 (M-H), 530 mg/L in ethanolic extract]. The putative gastrointestinal tract (GIT) concentration for all extracts was calculated as 2,400 μg/ml and hepatic circulation concentrations were estimated at 805.68 μg/ml for the aqueous extract, and 226.56 μg/ml for methanolic extract. Based on the putative GIT concentration, estimated hepatic circulation concentration [I] and inhibition constant K, the predicted percentile of inhibition was highest for the aqueous extract on CYP2B6 (96.7%). The observations indicated that extracts may have the potential to cause clinically relevant herb-drug interactions (HDI) with CYP2B6 and rifampicin metabolism , if sufficient hepatic concentrations are reached in humans.