Bioactive Compounds in Oxidative Stress-Mediated Diseases: Targeting the NRF2/ARE Signaling Pathway and Epigenetic Regulation
Muthu Thiruvengadam,
Baskar Venkidasamy,
Umadevi Subramanian,
Ramkumar Samynathan,
Mohammad Ali Shariati,
Maksim Rebezov,
Shabari Girish,
Sivakumar Thangavel,
Anand Raj Dhanapal,
Natalya Fedoseeva,
Joohyun Lee,
Ill-Min Chung
Affiliations
Muthu Thiruvengadam
Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Seoul 05029, Korea
Baskar Venkidasamy
Department of Biotechnology, Sri Shakthi Institute of Engineering and Technology, Coimbatore 641062, Tamil Nadu, India
Umadevi Subramanian
Translational Research Platform for Veterinary Biologicals, Tamil Nadu Veterinary and Animal Sciences University, Madhavaram Milk Colony, Chennai 600051, Tamil Nadu, India
Ramkumar Samynathan
R&D Division Alchem Diagnostics, New No. 1/1, Old No. 78, Gokhale Street, Ramnagar, Coimbatore 641009, Tamil Nadu, India
Mohammad Ali Shariati
Research Department, K.G. Razumovsky Moscow State University of Technologies and Management, 73 Zemlyanoy Val, 109004 Moscow, Russia
Maksim Rebezov
School of Agricultural Sciences, Liaocheng University, 34 Wenhua Road, Liaocheng 252000, China
Shabari Girish
School of Life Sciences, St. Joseph College (Autonomous), Bengaluru 560027, Karnataka, India
Sivakumar Thangavel
Post Graduate Department of Microbiology, Ayya Nadar Janaki Ammal College, Sivakasi 626124, Tamil Nadu, India
Anand Raj Dhanapal
Department of Biotechnology, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India
Natalya Fedoseeva
Department of Zootechnii, Production and Processing of Livestock Products, Russian State Agrarian Correspondence University, 50 Shosse Entuziastov, 143907 Balashikha, Russia
Joohyun Lee
Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Seoul 05029, Korea
Ill-Min Chung
Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Seoul 05029, Korea
Oxidative stress is a pathological condition occurring due to an imbalance between the oxidants and antioxidant defense systems in the body. Nuclear factor E2-related factor 2 (NRF2), encoded by the gene NFE2L2, is the master regulator of phase II antioxidant enzymes that protect against oxidative stress and inflammation. NRF2/ARE signaling has been considered as a promising target against oxidative stress-mediated diseases like diabetes, fibrosis, neurotoxicity, and cancer. The consumption of dietary phytochemicals acts as an effective modulator of NRF2/ARE in various acute and chronic diseases. In the present review, we discussed the role of NRF2 in diabetes, Alzheimer’s disease (AD), Parkinson’s disease (PD), cancer, and atherosclerosis. Additionally, we discussed the phytochemicals like curcumin, quercetin, resveratrol, epigallocatechin gallate, apigenin, sulforaphane, and ursolic acid that have effectively modified NRF2 signaling and prevented various diseases in both in vitro and in vivo models. Based on the literature, it is clear that dietary phytochemicals can prevent diseases by (1) blocking oxidative stress-inhibiting inflammatory mediators through inhibiting Keap1 or activating Nrf2 expression and its downstream targets in the nucleus, including HO-1, SOD, and CAT; (2) regulating NRF2 signaling by various kinases like GSK3beta, PI3/AKT, and MAPK; and (3) modifying epigenetic modulation, such as methylation, at the NRF2 promoter region; however, further investigation into other upstream signaling molecules like NRF2 and the effect of phytochemicals on them still need to be investigated in the near future.
