ginsenoside-rd and Colitis

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.

Topics: Animals; Colitis; Dextran Sulfate; Ginsenosides; Humans; Inflammasomes; Male; Mice; Mice, Inbred C57BL; Mitophagy; NLR Family, Pyrin Domain-Containing 3 Protein; RNA-Binding Proteins; THP-1 Cells

In this study, we investigated the effects and the protective mechanism of ginsenoside Rd (GRd) which has been identified as one of the effective compounds from ginseng on relapsing colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. After inducing relapsing colitis in experimental rats on two occasions by intracolonic injection of TNBS, GRd (10, 20 and 40 mg/kg) was administered to experimental colitis rats for 7 days. The inflammatory degree was assessed by macroscopic score, histology and myeloperoxidase (MPO) activity. The levels of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6 were determined by ELISA. Mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by western blotting method. The results showed that GRd markedly attenuates the inflammatory response to TNBS-induced relapsing colitis, as evidenced by improved signs, increased body weight, decreased colonic weight/length ratio, reduced colonic macroscopic and microscopic damage scores, inhibited the activity of MPO, lowered proinflammatory cytokine levels and suppressed phosphorylation of p38 and JNK. The possible mechanism of protection on experimental colitis after GRd administration was that it could reduce the accumulation of leukocytes and down-regulate multiple proinflammatory cytokines through modulation of JNK and p38 activation.

Topics: Animals; Body Weight; Colitis; Colon; Down-Regulation; Ginsenosides; Interleukin-1beta; Interleukin-6; Leukocytes; Male; MAP Kinase Kinase 4; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases; Peroxidase; Phosphorylation; Rats; Rats, Wistar; Trinitrobenzenesulfonic Acid; Tumor Necrosis Factor-alpha