An isopentenyl-substituted flavonoid norartocarpin activates Nrf2 signalling pathway and prevents oxidative insults in human lung epithelial cells. (4th March 2019)

• Record Type: Journal Article
• Authors: Yang, Wen-Jing; He, Ji-Xiang; Zhou, Ming-Xing; Huang, Min; Wang, Shu-Qi; Wang, Xiao-Ning; Lou, Hong-Xiang; Ren, Dong-Mei; Shen, Tao
• Is Part Of: Free radical research. Volume 53:Number 3(2019)
• Page Start: 348
• Page End: 358
• Publication Date: 2019-03-04
• Subjects: Beas-2B cells -- isopentenyl-substituted flavonoid -- Nrf2 -- oxidative stress; Free radicals (Chemistry) -- Periodicals; Antioxidants -- Periodicals; Vitamin C -- Periodicals; Vitamin E -- Periodicals; 541.224
• DOI: 10.1080/10715762.2019.1582769
• Languages: English
• ISSNs: 1071-5762

Abstract

Abstract: The nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in regulating the intracellular oxidative stress, and thus activation of Nrf2 by nature-derived molecules effectively alleviates the pathological process of oxidative stress-induced chronic diseases. The isopentenyl-substituted flavonoid norartocarpin (NOR) induced the activity of NAD(P)H: quinone reductase (QR), implying that it might be a potential Nrf2 activator. Further studies indicated that NOR upregulated the protein levels of Nrf2 and its downstream genes, NAD(P)H quinone oxidoreductase 1 (NQO1), and γ-glutamyl cysteine synthetase (GCLM) through facilitating the nuclear translocation of Nrf2 and enhancing Nrf2 protein stability. NOR-induced activation of Nrf2 pathway was associated with multiple upstream kinases, including mitogen-activated protein kinase (MAPK), phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K), protein kinase C (PKC), and protein kinase R-like endoplasmic reticulum kinase (PERK). Moreover, NOR protected human lung epithelial Beas-2B cells against sodium arsenite [As(III)]-induced cytotoxicity in an Nrf2-dependent manner. Collectively, NOR was firstly identified to be an Nrf2 activator, which demonstrated the capability of preventing oxidative insults in human lung epithelial cells.