Phytochemical profiling and in silico prediction of interactions between Artemisia afra Jacq. ex-Wild, Catharanthus roseus (L.) G. Don and CYP2B6 enzyme

Abstract

Understanding herb-drug interactions is important due to the increasing use of herbal medicines alongside conventional drugs. These interactions can alter the pharmacokinetic properties of drugs, potentially causing subtherapeutic effects or adverse reactions. Artemisia afra and Catharanthus roseus, two traditional African plants used separately to treat malaria, are rich in phytochemicals and may be co-administered with the antimalarial drug artemether. This study aimed to identify the phytochemical compounds present in the aqueous extracts of A. afra and C. roseus, and to use in silico methods to predict the potential of these phytochemicals to inhibit CYP2B6, the enzyme that metabolises artemether. Analysis of the aqueous extracts using UHPLC-QTOF-MS identified a diverse array of phytochemicals in both plants. Potential CYP2B6 inhibitors were identified by docking the phytochemicals into the enzyme’s active site using Discovery Studio software. This in silico method was validated against three metrics: root mean square deviation, enrichment factor, and receiver operating characteristic. Three docking algorithms (LibDock, LigandFit, and CDOCKER) with native scoring functions and ten additional scoring functions were assessed. The LibDock/Ludi 3 combination most effectively distinguished active inhibitors. Multiple compounds, including acacetin, isoscopoletin, and scopoletin, found in A. afra demonstrated strong binding affinities to the active site of CYP2B6, suggesting that phytochemicals from A. afra could inhibit CYP2B6-mediated metabolism, potentially affecting the pharmacokinetic profiles of co-administered substrate drugs. Such inhibition could lead to increased drug plasma concentrations, increased levels of toxicity, or reduced therapeutic efficacy, underscoring a clinically relevant risk for herb-drug interactions in populations using these herbal remedies.

HIGHLIGHTS • Prominent phytochemicals in extracts of Artemisia afra and Catharanthus roseus identified by UHPLC-QTOF-MS. • A structure-based in silico method was validated and used for molecular docking of phytochemicals identified. • Artemisia afra and Catharanthus roseus are rich in bioactive compounds; however, only A. afra phytochemicals successfully interacted with the target ligand, CYP2B6