Ginsenosides Rd monomer inhibits proinflammatory cytokines production and alleviates DSS-colitis by NF-κB and P38MAPK pathways in mice

Abstract

Background Ulcerative colitis (UC) is dramatically increasing worldwide, cannot be thoroughly cured, and reduces patients’ quality of life. Excessive activation of macrophages and over-production of cytokines play an important role in the pathogenesis of UC. Therefore, for its treatment, inhibiting macrophages' hyperactivation would be effective to develop new treatment approaches. Ginsenosides, extracted from ginseng, show an anti-inflammatory effect on the immunologic process. Our study used ginsenosides Rd monomer (GRd) to intervene in DSS-induced colitis mouse models and tested the immunological effect of macrophages. Method We observed body weights, weights of colons, colonic lengths, and inflammatory scores, as well as histological changes of DSS/DSS-GRd mice. We also isolated intestinal and peritoneal macrophages, performed qRT-PCR and ELISA to detect cytokines production by macrophages, and screened possible involved pathways by Western blotting. Results Administering 20 mg/Kg GRd to DSS mice for 7–14 days reduced colonic inflammation. Moreover, both in vivo and in vitro, levels of TNF-α, IFN-γ, IL-6, IL-12/23p40, and IL-17A were all inhibited by GRd at 14 days in intestinal macrophages, and 20 μmol/L GRd at 12 h in peritoneal macrophages, respectively, but longer time made no more benefit. Western blotting showed GRd could decrease expression of pJNK, p-p38, pIκBα, and P65 in nuclear. Conclusions Our data indicate that GRd could down-regulate cytokines production in macrophages and alleviate DSS-colitis in mice, which may be related to NF-κB and P38MAPK pathways. These results suggest that GRd has an anti-inflammatory effect on experimental colitis and may have potential efficacy in the treatment of UC alone or in combination.