Ginsenoside Metabolite Compound K Promotes Recovery of Dextran Sulfate Sodium-Induced Colitis and Inhibits Inflammatory Responses by Suppressing NF-κB Activation

Juan Li,Weiwei Wang,Bing Zhang,Shaoping Hu,Gang Song,Tianhui Hu,Wei Zhong,Jiahui Yuan,Lucienne Chatenoud

doi:10.1371/journal.pone.0087810

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.

Highlights

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease, is associated with chronic, relapsing inflammation of the intestinal tract
To confirm the efficiency of anti-inflammatory effects of compound K (CK) and explore its functional mechanism, mice were treated with dextran sulfate sodium (DSS) for 4 days to induce mild colitis, and CK was administered via intraperitoneal injection for the following 3 days recovery (Fig. 1B, upper panel)
Mice were treated with DSS for 7 days, and CK was given to mice for the following 3 days recovery periods (Fig. 1B, lower panel)

Summary

Introduction

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease, is associated with chronic, relapsing inflammation of the intestinal tract. Acute intestinal inflammation is usually followed by physiologic healing of the damaged tissue and restoration of the normal structure and function of the intestine [6]. If the innate physiologic healing doesn’t work, acute inflammation can develop and character by continues events of injury, which associated with the innate immune system responses [7]. Unrestrained reaction may exaggerate inflammatory response and lead to intestinal damage [9]. Appropriate regulation of the innate immune reaction is very important to the severity of inflammation, so a clear understanding of the mechanism of the development and progression of IBD and colitis is crucial for researching new effective drugs on its therapy

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