In silico targeting of lipoxygenase, CYP2C9, and NAD(P)H oxidase by major green tea polyphenols to subvert oxidative stress

Abstract

Oxidative stress (OS) is a phenomenon caused by an imbalance between free-radical production and antioxidant activity within the body. Status of endogenous antioxidants is not always sufficient to mitigate the oxidative damage. In this case, exogenous antioxidants could help to minimize free-radical production and subsequent OS. Green tea is rich in several phenolic compounds that have strong antioxidant properties. However, their mechanism of action is still unclear. Hence, the present study aims to investigate binding affinities of six green tea polyphenols such as catechin, epicatechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, and gallocatechin for common ROS producers such as Lipoxygenase (LOX), CYP2C9, and NAD(P)H oxidase (NOX). Results indicated that polyphenols interacted with binding pockets of these enzymes through hydrogen bonds and other stable interactions such as van der waals, Pi-Pi, Pi-alkyl, and alkyl. All polyphenols showed varied binding affinities. Among them, epigallocatechin gallate and epigallocatechin showed the highest binding affinities for the ROS producers. Findings of the present study suggest that, apart from free radical scavenging activity, green tea polyphenols may directly interact with binding pockets of LOX, CYP2C9, and NOX to dampen ROS production and OS. However, studies involving animal models are required for additional validation of results.