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Article Publish Status: FREE
Abstract Title:

A novel danshensu derivative ameliorates experimental colitis by modulating NADPH oxidase 4-dependent NLRP3 inflammasome activation.

Abstract Source:

J Cell Mol Med. 2020 11 ;24(22):12955-12969. Epub 2020 Sep 17. PMID: 32945118

Abstract Author(s):

Li-Long Pan, Zhengnan Ren, Yanyan Liu, Yalei Zhao, Hongli Li, Xiaohua Pan, Xin Fang, Wenjie Liang, Yang Wang, Jun Yang, Jia Sun

Article Affiliation:

Li-Long Pan

Abstract:

We have previously reported a novel compound [4-(2-acetoxy-3-((R)-3-(benzylthio)-1-methoxy-1-oxopropan-2-ylamino)-3-oxopropyl)-1,2-phenylene diacetate (DSC)], derived from danshensu, exhibits cytoprotective activities in vitro. Here, we investigated the effects and underlying mechanisms of DSC on dextran sodium sulphate (DSS)-induced experimental colitis. We found that DSC treatment afforded significant protection against the development of colitis, evidencing by suppressed inflammatory responses and enhanced barrier integrity. Intriguingly, DSC specifically down-regulated DSS-induced colonic NADPH oxidase 4 (Nox4) expression, accompanied by a balanced redox status, suppressed nuclear factor-κB (NF-κB) and NLRP3 inflammasome activation and up-regulated nuclear factor (erythroid-derived 2)-like 2 and haeme oxygenase-1 expression. In vitro study also demonstrated DSC also markedly decreased Nox4 expression and activityassociated with inhibiting reactive oxygen species generation, NF-κB activation and NLRP3 inflammasome activation in bone marrow-derived macrophages. Either lentiviral Nox4 shRNA-mediated Nox4 knockdown or Nox4-specific small-interfering RNA mimicked effects of DSC by suppressing NLPR3 inflammasomeactivation to alleviate experimental colitis or inflammatory macrophage response. Collectively, our results provide the first evidence that DSC ameliorates experimental colitis partly through modulating Nox4-mediated NLRP3 inflammasome activation.

Study Type : Animal Study

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