AUTHOR=Luo Jin-Fang , Shen Xiu-Yu , Lio Chon Kit , Dai Yi , Cheng Chun-Song , Liu Jian-Xin , Yao Yun-Da , Yu Yang , Xie Ying , Luo Pei , Yao Xin-Sheng , Liu Zhong-Qiu , Zhou Hua 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00911

DOI=10.3389/fphar.2018.00911

ISSN=1663-9812

ABSTRACT=Abstract 
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; dinardokanshone C; Nrf2; HO-1; ROS.