Inhibitory effect of Jatropha curcas aqueous and ethanol leaf extracts on cytochrome P450 enzyme activity in rat liver microsomes

Abstract Background Jatropha curcas is a well-known plant in Nigeria, frequently used to treat HIV infection and associated opportunistic infections. The potential herb-drug interactions (HDIs) mediated by drug metabolizing enzymes, which can arise from the popular use of this plant among HIV/AIDS patients who are on Highly Active Antiretroviral Therapy (HAART), remain unknown. Method This study aimed to investigate the effect of J. curcas extracts on cytochrome P450 (CYP) enzyme activity. The extracts were obtained by exhaustive mechanical extraction using water and ethanol as solvents. To investigate the effect of J. curcas on CYP1A2 and 3A4 activity, probe substrates of CYP enzymes were incubated in rat liver microsomes with and without J. curcas extracts, and IC 50 were calculated. Results The results showed that aqueous and ethanol extracts of J. curcas had inhibitory effects on the activity of CYP1A2 and CYP3A4 at concentrations lower than 1000 µg/mL. The two extracts showed moderate inhibition of CYP1A2 with IC 50 values of 90.24 ± 2.55 and 83.36 ± 2.06 µg/mL, respectively. The aqueous extract showed weak inhibition, and the ethanol extract showed moderate inhibition towards CYP3A4 activity with IC50 values of 194 ± 2.42 and 33.96 ± 3.72 µg/mL, respectively. Conclusion Based on these study results, J. curcas extracts can affect CYP1A2 and 3A4 activity. When used along with conventional drugs metabolized by these enzymes, the possible risk of herb-drug interactions should be considered.