Nrf2 signaling pathway: Pivotal roles in inflammation.
Inflammation is the most common feature of many chronic diseases and complications, while playing critical roles in carcinogenesis. Several studies have demonstrated that Nrf2 contributes to the anti-inflammatory process by orchestrating the recruitment of inflammatory cells and regulating gene expression through the antioxidant response element (ARE). The Keap1 (Kelch-like ECH-associated protein)/Nrf2 (NF-E2 p45-related factor 2)/ARE signaling pathway mainly regulates anti-inflammatory gene expression and inhibits the progression of inflammation. Therefore, the identification of new Nrf2-dependent anti-inflammatory phytochemicals has become a key point in drug discovery. In this review, we discuss the members of the Keap1/Nrf2/ARE signal pathway and its downstream genes, the effects of this pathway on animal models of inflammatory diseases, and crosstalk with the NF-κB pathway. In addition we also discuss about the regulation of NLRP3 inflammasome by Nrf2. Besides this, we summarize the current scenario of the development of anti-inflammatory phytochemicals and others that mediate the Nrf2/ARE signaling pathway.
Department of Biochemistry, School of Medicine, Zhejiang University, Hangzhou 310058, PR China.
Syed Minhaj Uddin
SM
Ahmed
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, PR China; School of Pharmacy, Nantong University, Nantong 226001, PR China.
Lin
L
Luo
Department of Biochemistry, School of Medicine, Zhejiang University, Hangzhou 310058, PR China.
Akhileshwar
A
Namani
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, PR China.
Xiu Jun
XJ
Wang
Department of Biochemistry, School of Medicine, Zhejiang University, Hangzhou 310058, PR China. Electronic address: xiuwentang@zju.edu.cn.
Xiuwen
X
Tang
D000818:Animals; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D051267:NF-E2-Related Factor 2 / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000276:immunology; D015398:Signal Transduction
D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
ARE; Inflammation; Keap1; Nrf2; Oxidative stress; Phytochemical