Effect of a Benign Prostatic Hyperplasia (BPH) Xenobiotic - Croton membranaceus Müll.Arg. Root Extract on CYP1A2, CYP3A4, CYP2D6, and GSTM1 Drug Metabolizing Enzymes in Rat Model

Abstract Background Croton membranaceus Müll.Arg., root extract has been scientifically and clinically proven to be efficacious in the management of BPH. However, its effect on liver drug-metabolizing enzymes has not been established. This study aimed to determine the effect of the plant extract on phase I and phase II drug-metabolizing enzymes. Materials and methods Fifteen (15) castrated testosterone-induce BPH male Albino Wister rats weighing between 120–150 grams were randomly divided into 3 groups of 5 rats each (Groups II-IV). Five (5) uncastrated rats in Group I was used as a negative control, receiving only distilled water. Group II was administered 30 mg/kg b. wt extracts of C. membranaceus. Group III was the BPH-model group (administered distilled water) while Group IV was administered 0.5 mg/kg b. wt finasteride and was used as the positive control. BPH was induced in groups II-IV by administering testosterone propionate, 3 mg/kg b. wt for 28 days after a 7-day post castration rest period. Rats were euthanized and individual livers harvested for microsome preparation. The liver microsomes were assayed for, Phase I Drug Metabolizing Enzymes (DME); CYP1A2, CYP3A4, CYP2D6, and phase II; GST-M1 using Enzyme-Linked Immuno-Sorbent Assay (ELISA) techniques. Results Significant induction in phase I enzymes CYP1A2 was observed (p = 0.02), while CYP3A4 and CYP2D6 were inhibited (0.00, 0.01, respectively). Phase II enzymes, GSTM1, showed a significant induced (p = 0.01). C.membranaceus induced CYP1A2 strongly, GSTM1 modestly, and had an inhibitory effect on CYP3A4/CYP2D6. Conclusion Croton membranaceus induces and inhibits some phase I metabolizing enzymes while moderately inducing phase II metabolizing enzymes. Care should be taken in the use of phytotherapy in conjunction with other drugs.