Activation of Nrf2/HO-1 Pathway by Nardochinoid C Inhibits Inflammation and Oxidative Stress in Lipopolysaccharide-Stimulated Macrophages

作者：Jin-Fang Luo, Xiu‐Yu Shen, Chon Kit Lio, Yi Dai, Chunsong Cheng, Jian-Xin Liu, Yun-Da Yao, Yang Yu, Ying Xie, Pei Luo, Xin‐Sheng Yao, Zhongqiu Liu, Hua Zhou · 发表于：Frontiers in Pharmacology · 年份：2018 · DOI：10.3389/fphar.2018.00911 · 被引用次数：178 · 研究领域：Medicinal Plant Extracts Effects、Piperaceae Chemical and Biological Studies、Tryptophan and brain disorders

The roots and rhizomes of Nardostachys chinensis have neuroprotection and cardiovascular protection effects. However, the specific mechanism of N. chinensis is not yet clear. Dinardokanshone C is a new compound with new backbone isolated from N. chinensis and this study for the first time explored the anti-inflammatory and anti-oxidant effect of dinardokanshone C. The results showed that dinardokanshone C significantly reduced the release of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-activated RAW264.7 cells. The expression of pro-inflammatory proteins including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were also obviously inhibited by dinardokanshone C. Besides, the production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also remarkably inhibited by dinardokanshone C. Furthermore, dinardokanshone C inhibited the macrophage M1 phenotype and the production of reactive oxygen species (ROS). Mechanism studies showed that dinardokanshone C mainly activated nuclear factor-E2-related factor 2 (Nrf2) signaling pathway, increased the level of anti-oxidant protein heme oxygenase-1(HO-1) and thus produced the anti-inflammatory and anti-oxidant effects, which were abolished by Nrf2 siRNA and HO-1 inhibitor. These findings suggested that dinardokanshone C could be a new Nrf2 activator for the treatment and prevention of diseases related to inflammation and oxidative stress. Keywords: Nardostachys chinensis; dina...