Oncotarget

Research Papers:

7-deacetylgedunin suppresses inflammatory responses through activation of Keap1/Nrf2/HO-1 signaling

Jian-Yu Chen, Guo-Yuan Zhu, Xiao-Hui Su, Rui Wang, Juan Liu, Kangsheng Liao, Rutong Ren, Ting Li _ and Liang Liu

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:55051-55063. https://doi.org/10.18632/oncotarget.19017

Metrics: PDF 2105 views  |   HTML 2605 views  |   ?  


Abstract

Jian-Yu Chen1, Guo-Yuan Zhu1, Xiao-Hui Su1, Rui Wang1, Juan Liu1, Kangsheng Liao1, Rutong Ren1, Ting Li1 and Liang Liu1

1State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China

Correspondence to:

Ting Li, email: [email protected]

Liang Liu, email: [email protected]

Keywords: 7-deacetylgedunin, anti-inflammation, Keap1, Nrf2, HO-1

Received: April 12, 2017     Accepted: June 11, 2017     Published: July 05, 2017

ABSTRACT

Macrophages play a critical role in a variety of inflammatory diseases. Activation of Keap1/Nrf2/HO-1 signaling results in inactivation of macrophages and amelioration of inflammatory and autoimmune conditions. Hence, discovery for the activators of Keap1/Nrf2/HO-1 signaling has become a promising strategy for treatment inflammatory diseases. In the current study, the anti-inflammatory potential of 7-deacetylgedunin (7-DGD), a limonin chemical isolated from the fruits of Toona sinensis (A. Juss.) Roem, was intensively examined in vivo and in vitro for the first time. Results showed that 7-DGD alleviated mice mortality induced by LPS. Mechanistic study showed that 7-DGD suppressed macrophage proliferation via induction of cell arrest at the G0/G1 phase. Furthermore, 7-DGD inhibited iNOS expression, which is correlated with the increases of NQO1, HO-1 and UGT1A1 mRNA expression as well as HO-1 protein expression level in the cells. More importantly, 7-DGD markedly decreased Keap1 expression, promoted p62 expression, and facilitated Nrf2 translocation and localization in the nucleus of macrophages, and in turn up-regulates these anti-oxidant enzymes expression, eventually mediated anti-inflammatory effect. Collectively, 7-DGD suppresses inflammation in vivo and in vitro, indicating that the compound is valuable for further investigation as an anti-inflammatory agent in future.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 19017