title: Ginsenoside metabolite compound K promotes recovery of dextran sulfate sodium-induced colitis and inhibits inflammatory responses by suppressing NF-κB activation.
abstract: Phytogenic compounds with anti-oxidant and anti-inflammatory properties, such as ginsenoside metabolite compound K (CK) or berberine (BBR), are currently discussed as promising complementary agents in the prevention and treatment of cancer and inflammation. The latest study showed that ginsenoside Rb1 and its metabolites could inhibit TNBS-induced colitis injury. However, the functional mechanisms of anti-inflammation effects of ginsenoside, particularly its metabolite CK are still not clear. Here, using dextran sulfate sodium (DSS)-induced colitis in mice, clinical parameters, intestinal integrity, pro-inflammatory cytokines production, and signaling pathways in colonic tissues were determined. In mild and sever colitis mice, CK and BBR (as a positive agent) alleviated colitis histopathology injury, ameliorated myeloperoxidase (MPO) activity, reduced pro-inflammatory cytokines production, such as, IL-6, IL-1β, TNF-α, and increased anti-inflammatory cytokine IL-10 production in both mice colon tissues and blood. Nevertheless, the results revealed that CK and BBR inhibited NF-κB p65 nuclear translocation, downregulated p-IκBα and upregulated IκBα, indicating that CK, as well as BBR, suppressed the activation of the NF-κB pathway in the progression of colitis with immunofluorescence, immunohistochemical and western blotting analysis. Furthermore, CK inhibited pro-inflammatory cytokines production in LPS-activated macrophages via down-regulation of NF-κB signaling pathway. Taken together, our results not only reveal that CK promotes the recovery of the progression of colitis and inhibits the inflammatory responses by suppressing NF-κB activation, but also suggest that CK downregulates intestinal inflammation through regulating the activation of macrophages and pro-inflammatory cytokines production.
authors: Cancer Research Center, Medical College of Xiamen University, Xiamen, China.
authors: Juan
authors: J
authors: Li
authors: Cancer Research Center, Medical College of Xiamen University, Xiamen, China.
authors: Wei
authors: W
authors: Zhong
authors: Cancer Research Center, Medical College of Xiamen University, Xiamen, China.
authors: Weiwei
authors: W
authors: Wang
authors: Cancer Research Center, Medical College of Xiamen University, Xiamen, China.
authors: Shaoping
authors: S
authors: Hu
authors: Cancer Research Center, Medical College of Xiamen University, Xiamen, China.
authors: Jiahui
authors: J
authors: Yuan
authors: Department of Basic Medicine, Medical College of Xiamen University, Xiamen, China.
authors: Bing
authors: B
authors: Zhang
authors: Cancer Research Center, Medical College of Xiamen University, Xiamen, China.
authors: Tianhui
authors: T
authors: Hu
authors: Cancer Research Center, Medical College of Xiamen University, Xiamen, China.
authors: Gang
authors: G
authors: Song
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D001599:Berberine / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009195:Peroxidase / Q000097:blood / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D001599:Berberine; D016264:Dextran Sulfate; D009195:Peroxidase