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.

Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function

“…Inflammatory cytokine release and neutrophil infiltration play important roles in the process of inflammation [17][18][19] . The present study indicated that levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and myeloperoxidase (MPO) activity in the resected colon from TNBS-treated rats were significantly higher than in the vehicle control ( Figure 3A).…”

Ginsenosides Regulate PXR/NF-κB Signaling and Attenuate Dextran Sulfate Sodium–Induced Colitis

“…Although the anti-inflammatory effects of ginsenosides and its remedy effects against IBD have been well reported, the molecular mechanisms remain established (Yang et al, 2012a;Li et al, 2014;Ye et al, 2014). Here we hypothesized that ginsenosides may elicit its anti-inflammatory effects in IBD via restoring PXR/NF-kB signaling in the inflamed colon.…”

Dammarane-type triterpene ginsenoside-Rg18 inhibits human non-small cell lung cancer A549 cell proliferation via G1 phase arrest

“…Ginsenosides are responsible for the majority of functions of ginseng, including angiogenesis, vasorelaxation and antioxidation (8). These molecules also possess anti-inflammatory and anticancer properties (12)(13)(14). In a previous study, four dammarane-type triterpene saponins isolated from the Panax ginseng root exhibited effective hydroxyl radical scavenging ability, as well as antibacterial and cytotoxic activities (15).…”