1. (2S)-5,6,7,3′,4′-pentamethoxyflavanone, a citrus polymethoxyflavone ameliorates arsenic- and cigarette smoke extract-induced cytotoxicity via activating Nrf2-mediated defense system
- Author
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Ming-Xing Zhou, Guo-Hui Li, Xue-Yi Wu, Lin Sun, Yan-Ru Li, Wen-Jing Yang, Dong-Mei Ren, Xiao-Ning Wang, Lan Xiang, Hong-Xiang Lou, and Tao Shen
- Subjects
Flavonoid ,Nrf2 activator ,Oxidative insult ,Citrus polymethoxyflavone ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Exogenous toxicants (e.g. arsenic, cigarette smoke), trigger oxidative stress, and initiate the pathogenesis of many human diseases. Induction of nuclear factor E2-related factor 2 (Nrf2) counteracts exogenous toxicant-induced oxidative insults. Using a high-throughput screen, we firstly identified a citrus polymethoxyflavone, (2S)-5,6,7,3′,4′-pentamethoxyflavanone (PMF), to be an Nrf2 activator, and an investigation targeting Nrf2 pathway was performed. Our study indicated that: (i) PMF activated Nrf2 and its downstream genes, NQO1 and γ-GCS, and enhanced the stabilization of Nrf2 through inhibiting Nrf2 ubiquitination. (ii) Inhibition of PI3K, p38 MAPK, PKC and PERK by specific kinase inhibitors suppressed PMF-induced activation of Nrf2. (iii) PMF conferred Nrf2-dependent protection against sodium arsenite- and cigarette smoke extract- induced cytotoxicity in lung epithelial cells. Collectively, our data demonstrate that PMF is a novel Nrf2 activator with potential prevention against oxidative insults. The diverse pharmacological functions of citrus polymethoxyflavone might be related to their ability of activating Nrf2 pathway.
- Published
- 2019
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