Study On Effect And Mechanism Of The Aqueous Extract From Siegesbeckia Pubescens On Ulcerative Colitis In Rats

Backgroud:Ulcerative colitis (UC) is one of inflammatory bowel disease (IBD), which has a long course and is difficult to be cured. UC has characteristic of recurrent episodes that seriously affect the patient’s quality of life as one of the modern intractable disease. 5-Aminosalicylates, immunomodulators and corticosteroids have been employed as therapeutic options for UC on clinic for decades. However, these drugs have disadvantages of severe adverse events, recurrent episodes after treatment and invalid effect for some refractory cases. Thus, there is a need to develop new therapeutic options with low toxicity and minimal side effects. The treatment of ulcerative colitis by traditional Chinese medicine (TCM) has received great interest in recent years. Herba Siegesbeckia is an anti-inflammatory traditional Chinese medicine for treating immune disease such as rheumatoid arthritis.OBJECTIVE:To evaluate the protective and therapeutic effect of the aqueous extract of Siegesbeckia pubescens (SPA) on UC in rats, and investigate the mechanism of action.Materials and methods:The effects of SPA were first evaluated on iodoacetamide (IA)-induced colitis in rats by disease activity index (DAI), colonic macroscopic changes and histopathology. Furthermore, mRNA levels of pro-inflammatory cytokines IL-1β, TNF-α and IL-6 in the colonic tissue were measured by Real-time PCR. Then, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats to investigate effects of SPA on disease activity index (DAI) and colonic macroscopic and microscopic injury. In addition, the protein and mRNA expression levels of pro-inflammatory cytokines were detected in the colonic tissues by enzyme-linked immunosorbent assay (Elisa) and Real-time PCR respectively. Western-blot was further adopted to analyze the changes of protein expression levels of PPAR-γ, IκB-α and NF-κB p65 in the colonic tissues.Results:1.The results of SPA in rats with IA-induced colitis revealed that SPA suppressed significantly body weight loss, diarrhea and fecal occult blood, and ameliorated hyperaemia and anabrosis of colonic tissue. SPA also suppressed significantly mRNA expressions of inflammatory cytokines TNF-α、 IL-6 and IL-1β.2. The results of SPA in rats with TNBS-induced colitis indicated that SPA ameliorated colonic macroscopic morphology and healing of colonic ulcers, and decreased inflammatory cells. Furthermore, SPA significantly inhibited production and mRNA expressions of inflammatory cytokines TNF-α, IL-6, IL-1β and IFN-y in rats with TNBS-induced colitis. SPA suppressed significantly TNBS-induced PPAR-y down regulation, IκcB-α phosphorylation degradation and NF-κB p65 nuclear translocation. Conclusions:SPA has therapeutic effects against ulcerative colitis possibly through activation of PPAR-y, inhibition of NF-κB pathway, and therefore suppression release of pro-inflammatory cytokines.