Simultaneous Interaction of Aqueous Extract of Annona Muricata (Sa-001ae) and Croton Membranaceus (Ct 0163ae) On Phase I and Phase Ii Drug Metabolizing Enzymes Using Bph Experimental Rat Models

Abstract

Aqueous extracts of Croton membranaceus (CT 0163AE) and Annona muricata (SA-001AE) are known to have anti-Benign prostate hyperplasia (BPH) properties. Even though they are considered safe and natural, they may be antagonistic or synergistic, when used simultaneously due to possible interactions between the active compounds in the individual extracts that are able to induce or inhibit Cytochrome P450 enzymes (CYP450). The study strived to determine the interactive outcome of A. muricata and C. membranaceus on some Phase I and Phase II hepatic drug metabolizing enzymes. Twenty-eight (24) castrated -testosterone BPH induced and four (4) uncastrated male Albino Wister rats were used in this experimental laboratory study. The animals were organized into 7 groups consisting 4 rats each: Group I was uncastrated and used as a negative control the group was only administered distilled water. Group II was treated with 30 mg/kg b. wt extracts of C. membranaceus. Group III was treated with 30 mg/kg b. wt. extracts of A. muricata while group IV was treated with 30 mg/kg b. wt. mixed extract of both A. muricata and C. membranaceus (A60:C40), group V was treated with 30 mg/kg b. wt of both A. muricata and C. membranaceus (A40:C60), group VI was the model group while Group VII was treated with 0.5 mg/kg b. wt finasteride and it was used as the positive control. BPH was induced by administering testosterone propionate, 3mg/kg b. wt for 28 days pre-treatment. The respective extracts were administered daily for 30 days through oral gavage. The animals were euthanized and individual liver harvested and frozen before isolating the microsomes by homogenization and differential centrifugation. The liver microsomes were assayed for, Phase I Drug Metabolizing Enzymes (DME); CYP1A2, CYP3A4, CYP2D6, CYP2C9, and phase II; Arylsulfatase G, GST-P1, and GST-M1 using Enzyme Linked Immuno-Sorbent Assay (ELISA) techniques. ANOVA Bonferroni post hoc test showed statistical significance in phase I enzymes; University of Ghana http://ugspace.ug.edu.gh III CYP1A2, CYP3A4, CYP2D6, (p=0.02, 0.00, 0.01) respectively. Phase II enzymes GSTM1, GSTP1 and ARSG showed a statistical significance (p=0.01, 0.00, 0.00) respectively. CYP2C9 showed no statistical significance. Both A. muricata and C. membranaceus had an inhibitory effect on CYP3A4, CYP2D6, GSTM1, GSTP1 ARSG and induced CYP1A2, CYP2C9 and GSTM1. The combined extract (A60:C40) inhibited CYP3A4, CYP2D6, GSTP1 and ARSG but induced CYP1A2, CYP2C9 and GSTM1.The combined extract (A40:C60) inhibited CYP3A4, CYP2D6, CYP2C9, GSTP1 and ARSG but induced CYP1A2 and GSTM1 enzymes.