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Ginsenoside Rd Ameliorates Colitis by Inducing p62-driven Mitophagy-Mediated NLRP3 Inflammasome Inactivation in Mice

Ginsenoside Rd Ameliorates Colitis by Inducing p62-driven Mitophagy-Mediated NLRP3 Inflammasome Inactivation in Mice

Chao Liu, Jianing Wang, Yan Yang, Xiuting Liu, Yubing Zhu, Jianjun Zou, Sishi Peng, Thi Ha Le, Yu Chen, Shuli Zhao, Bangshun He, Qiongyu Mi, Xu Zhang, Qianming Du

Biochem Pharmacol. 2018 Sep;155:366-379.

PMID: 30012462

Abstract:

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-1β, 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-1β 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP52705938-A	Ginsenoside Rd		52705-93-8	Price

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