In-silico Inhibitory Potential of Triphala Constituents Against Cytochrome P450 2E1 for the Prevention of Thioacetamide-induced Hepatotoxicity

Abstract

Background: Triphala, which is a combination of fruits of Terminalia chebula, Terminalia bellerica and Embilica officinalis generally recommended as herbal drug formulation in the Indian traditional medicine system.
 Study Design: To study the in-silico inhibitory potential of Triphala constituents against cytochrome P450 2E1 (CYP2E1) for the prevention of Thioacetamide-induced Hepatotoxicity
 Place and Duration of Study: The work has been performed at MUP's College of Pharmacy (B Pharm), Degaon, Risod, Washim, Maharashtra, India in between February 2021 to May 2021.
 Methodology: We have studied the inhibitory potential of Triphala on CYP2E1 by applying molecular docking tools. The major chemical constituents of Triphala i.e. gallic acid, chebulic acid, ellagic acid, epicatechin, syringic acid, and ascorbic acid were docked on CYP2E1.
 Results: Docking results revealed the very good inhibitory potential of Triphala in terms of binding affinity towards CYP2E1. All the chemical constituents have formed at least 2 and at most 6 hydrogen bonds with the crystal structure of CYP2E1. The binding energies (kcal/mol) of gallic acid, chebulic acid, ellagic acid, epicatechin, syringic acid, and ascorbic acid are -6.1, -7.1, -9.1, -8.3, -6.3, and -5.7, respectively. Ellagic acid has formed strong hydrogen bonds with Thr-303 and Thr-304 with bond length of 1.98 A0 and 2.26 A0 which confirms the excellent inhibition of CYP2E1.
 Conclusion: These findings can be used to control the CYP2E1-facilitated biotransformation and drug interactions in the development of new chemical entities. In future, these phytoconstituents can be used as lead molecules to overcome the cancer associated with oxidative stress resulting from the hyperactivity of CYP2E1.