Journal
BIOCHEMICAL PHARMACOLOGY
Volume 155, Issue -, Pages 366-379Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2018.07.010
Keywords
Ulcerative colitis; Inflammation; Ginsenoside Rd; NLRP3 Inflammasome; P62
Categories
Funding
- Natural Science Foundation of China [81702833]
- Natural Science Foundation of Jiangsu Province [BK20170137, BK20170140]
- Sichuan Science and Technology Program [2018JY0204]
- Natural Science Foundation of Chengdu Medical College [CYZ17-13]
- Science and Technology Development Fund Project of Nanjing Medical University [2016NJMUZD041, 2016NJMUZD043]
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Previous studies reported that Ginsenoside Rd (Rd) had anti-inflammatory and anti-cancer effects. However, the molecular mechanism underlying the inhibition effect of Rd on colitis in mice hasn't been clarified clearly. Here, in our study, we detected the effects of Rd on dextran sulfate sodium (DSS)-induced murine colitis, and found that oral administration of Rd dose-dependently alleviated DSS-induced body weight loss, colon length shortening and colonic pathological damage with lower myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities and higher glutathione level. In addition, the production of pro-inflammatory cytokines (IL-1 beta, TNF-a and IL-6) in both serum and colonic tissues were significantly down-regulated by Rd administration. The activation of NLRP3 inflammasome was also suppressed in Rd-treated group, resulting in reduced caspase-1 production and IL-1 beta secretion. In vitro, Rd remarkably inhibited NLRP3 inflammasome activation which was mostly dependent on the mitochondrial translocation of p62 and mitophagy. Importantly, Rd-driven inhibition of the NLRP3 inflammasome was significantly blocked by various autophagy inhibitors. Furthermore, upregulation of AMPK/ULK1 signaling pathway accounted for Rd-induced autophagy, which was also seen in vivo. In conclusion, our results demonstrated the function of Rd on the inhibition NLRP3 inflammasome and its potential application for the treatment of NLRP3-associated diseases.
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