In Silico Analysis of Antioxidant Phytochemicals with Potential NADPH Oxidase Inhibitory Effect

Abstract

Objective: NADPH oxidase (NOX) is known to produce reactive oxygen species (ROS) at physiological concentrations. However, it can be over-activated with some disease conditions and produces excess ROS. Several molecules have shown an ability to suppress the enzyme’s over-activity, although some weaknesses have been found. Hence, the attempt to screen phytochemicals, with the aim of finding the most specific and effective NOX inhibitor. Material and Methods: The study was carried-out via an in-silico approach. First, phytochemicals with antioxidant activity, according to the literature review, were selected and downloaded from the PubChem database in SDF files. NOX with PDB: 2CDU was downloaded from the protein databank. Drug-likeness properties and biological activities were predicted using ADMETMESH and the Predict Activity Spectra of Substances (PASS) software. Phytochemical-NOX interactions were performed via molecular docking, whereas, docked conformations and bond residue amino acids were analyzed using Protein-plus software. Results: The result of this study predicted 13 phytochemicals with drug-likeness properties, out of which 9 showed NOX-inhibitory activity. Docking results predicted all of the 9 phytochemicals were capable of interacting with NOX, by binding to at least one amino acid. The reference inhibitor (Apocynin, -8.3 kcal/mol) and some phytochemicals (caffeic, eriodictyol, hesperetin, and morin with ΔG -6.1 to -7.7 kcal/mol) were predicted to have bonded to Ser115, via hydrogen bonding. On the other hand, epicatechin gallate and quercetin with ΔG −8.7 and −8.1 kcal/mol did not bind to Ser115, but rather through other amino acids. Conclusion: This study has led to the prediction of phytochemicals with NOX-inhibitory effects, which could be considered for further study.

In vitro and in silico evaluation of bioactivities and chemical composition of the aerial parts of Anchusa officinalis L. methanol extract

“…67 Most of the phytochemical compounds were unspecific in their inhibitory function, and certain phytochemicals showed binding specificity to enzymes such as NOX, which decreased the generation of ROS. 68 Apoptosis, the programmed cell death, is an essential component of several processes, including normal cell turnover, immune system development and function, hormone-dependent atrophy, embryonic development, and chemical-induced cell death. There are two primary apoptotic routes in mammalian cells: the extrinsic or death receptor pathway and the intrinsic or mitochondrial system.…”

“…The phytochemicals can also regulate the expression pathways of receptor tyrosine kinases, mitogen‐activated protein kinases, and estrogenic receptors 67 . Most of the phytochemical compounds were unspecific in their inhibitory function, and certain phytochemicals showed binding specificity to enzymes such as NOX, which decreased the generation of ROS 68 . Apoptosis, the programmed cell death, is an essential component of several processes, including normal cell turnover, immune system development and function, hormone‐dependent atrophy, embryonic development, and chemical‐induced cell death.…”

Investigation of NADPH-Oxidase’s Binding Subunit(s) for Catechin Compounds Induce Inhibition

“…Catechin compounds were among many phytochemicals reported to possess the capacity to bind NADPH oxisdase (NOX) and induce an effect [14], [20], [22]. According to a literature reviewed, catechins binds to NADPH-oxidase and cause conformational changes leading to the retardation of the enzyme's activity [7], [22]. However, the exact subunit(s) by which the catechin compounds binds on the enzyme to induce effect is not clear.…”

Tapping into Nature’s Arsenal: Harnessing the Potential of Natural Antioxidants for Human Health and Disease Prevention

“…One key area is molecular docking and dynamic simulations, which predict the binding affinity and interaction of antioxidants with specific target proteins, such as enzymes involved in oxidative stress pathways [188]. For instance, studies have investigated phytochemicals and natural compounds with antioxidant activity interacting with enzymes like NADPH oxidase and superoxide dismutase [189][190][191].…”