Abstract
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.
Highlights
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) production are essential for maintaining the body homeostasis and play a key role as regulatory mediators necessary for cell–cell communication or triggering certain signaling pathways
Among 19 natural compounds extracted from the Ginkgo biloba extracts (GBE), rutin and procyanidin B2 were reported to suppress t-butyl hydroperoxide (t-BHP)-induced oxidative stress in retinal pigment epithelial cells by stimulating Nrf2 expression together with activating Erk1/2 signaling in injured retinal epithelial cells, suggesting that rutin can act as a protective agent in inhibiting oxidative stress-mediated retinal diseases [102]
It was reported that rutin increased the phosphorylation of PI3K, p-AKT, and p-glycogen synthase kinase (GSK)-3β and upregulated Nrf2 expression, and it was suggested that the PI3K/AKT/GSK3β/NRF-2 pathway is involved in the neuroprotective effect of rutin against acrylamide and g-radiation (5Gy)-induced brain damage [103]
Summary
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) production are essential for maintaining the body homeostasis and play a key role as regulatory mediators necessary for cell–cell communication or triggering certain signaling pathways. Studies using MCF-7 and SK-BR breast carcinoma cells showed that NRF2 significantly increased the proliferation activity and progression activity of both carcinoma cells and suggested that NRF2 acts as a prognostic factor in breast cancer patients [7]. Phytochemicals such as polyphenols, flavonoids, steroids, organosulfur compounds, and vitamins are plant metabolites that are widely distributed in various parts of plants and essential for plant growth and development. Phytochemicals are reported to directly scavenge ROS and enhance the expression of cellular antioxidant enzymes, protecting against oxidative stress-mediated cellular injury [9]. We will explain the latest update in the research progress on dietary phytochemicals that could effectively target NRF2/ARE signaling under various pathological conditions
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