Ginsenoside Rd Inhibits The Activation Of NF-κB Signal Transduction Pathways In Colonic Tissues Of Rats With Ulcerative Colitis In The Acute Phase

Aims:To investigate the therapeutic effect of ginsenoside Rd on ulcerative colitis (UC). To explore regulating mechanisms of ginsenoside Rd on activation of NF-κB signal transduction pathway in colonic tissues of rats with TNBS-induced colitis.Methods: Colitis was induced by intracolonic injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS,100 mg/kg) dissolved in 50% ethanol. Ginsenoside Rd (10,20 and 40 mg/kg) was intragastrically administered into male Wistar rats with colitis once per day for 7 days. Sulfasalazine (SASP) at 500 mg/kg was used as a positive control drug. Macroscopic and microscopic damage scores and changes in weight/length ratio (mg/mm) of colon segments were analyzed. The malonyldialdehyde (MDA) level, myeloperoxidase (MPO), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities in the colon tissues and serum were measured by biochemical methods. The levels of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), protein kinase C (PKC), inhibitor kappa B kinase (IKK), phospho-I kappa-B (pIκBα) and nuclear factor-kappa B (NF-κB) in the colon tissues were all measured by enzyme-linked immunosorbent assay (ELISA) methods. The levels of PKC, IKK and pIκBαin the colon tissues were detected with Western blot technique.Results:The colonic weight/length ratio was increased significantly in the control group as compared with that of normal group, and was decreased sharply in the Rd groups as compared with that of the control group. The colonic macroscopic and microscopic damage scores were also notably reduced in Rd treated groups. Compared with the TNBS control group, the levels of MPO and MDA in the colon tissues and serum were decreased significantly in Rd groups. The GSH-Px and SOD activities were significantly higher in rats treated with Rd than those in TNBS control group in colon tissues and serum. Compared with the TNBS control group, Rd also reduced the expression of IL-1βTNF-α, PKC, IKK, pIκBαand NF-κB in the colon tissues.Conclusions: Rd exerts a beneficial antiinflammatory effect in the acute phase of TNBS-induced colitis in rats by downregulating some of the mediators involved in the intestinal inflammatory response, inhibiting inflammatory cell infiltration and antioxidation damage, promoting damaged tissue repair, and decreasing production of proinflammatory cytokines IL-1βand TNF-a. The molecular mechanisms of the therapeutic effects of Rd are that Rd ameliorates intestinal inflammation by inhibiting the activation of NF-κB signal transduction pathways.