Molecular Docking of Volatile Oily Constituents of Chinese Herbal Medicine Asari Radix et Rhizoma and CYP1A2 Enzyme / 中国实验方剂学杂志

ABSTRACT

Objective:To study the mechanisms of action of four volatile oil components (safrole, myristicin, methyleugenol and asarone) and the reactive metabolites of safrole and myristicin with CYP1A2. Method:The inhibitory effects of the volatile oil components of Asari Radix et Rhizoma on the human liver microsomal enzymes CYP1A2, CYP2D6, CYP2E1, CYP3A4 and CYP2C19 were screened by the " Cocktail" probe substrate method. The ability of the volatile oil components and intermediates in binding to CYP1A2 enzyme was studied by means of semi-flexible molecular docking. Result:The screening results showed that the components had a strong inhibitory effect on CYP1A2.Molecular docking scores were 3.048 7 kcal·mol-1 (safrole), 6.016 4 kcal·mol-1 (myristicin), 16.969 2 kcal·mol-1 (methyleugenol), 16.013 8 kcal·mol-1 (asarone), 23.923 3 kcal·mol-1 (safrole reactive metabolites) and 25.594 3 kcal·mol-1 (myristicin reactive metabolites). Conclusion:Molecular docking results indicate that safrole metabolic intermediate and myristicin metabolic intermediate have the strongest ability in binding to CYP1A2 enzyme. This study further confirms that safrole and myristicin are the mechanism-based inhibitors of CYP1A2 enzyme, which is consistent with the results of previous IC50-shift and glutathione capture experiments.