Ginsenoside Rd ameliorates colitis by inducing p62-driven mitophagy-mediated NLRP3 inflammasome inactivation in mice

Biochemical Pharmacology
Chao LiuQianming Du

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 fo...Continue Reading

Citations

Dec 17, 2019·Current Pharmaceutical Design·Fan CaoHai-Feng Pan
Oct 15, 2019·Acta Biochimica Et Biophysica Sinica·Zhenrui CaoGuiqiong He
Jan 10, 2020·Current Pharmaceutical Design·Mohamed Adil A AMohammad Waseem
Apr 1, 2020·Frontiers in Cell and Developmental Biology·Shanshan HuangPeng Zhang
Nov 2, 2019·Cells·Samantha N Devenport, Yatrik M Shah
Nov 28, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Shuangjiao DengHui Wu
Jul 8, 2020·International Journal of Molecular Sciences·Jae-Min YukEun-Kyeong Jo
Jan 20, 2021·Pharmacological Reports : PR·Zengping KangDuanyong Liu
May 7, 2020·Journal of Ginseng Research·Miyong Yun, Young-Su Yi
Mar 12, 2021·Journal of Ethnopharmacology·Xuanqing ChenShijia Liu
Aug 3, 2021·Frontiers in Pharmacology·Linshan DuanGuoyan Liu

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