The Ameliorative Effect Of Stachydrine Hydrochloride On Rat Colitis

BackgroundInflammatory bowel disease(IBD)is an inflammatory disorders of gut characterized by increased intestinal epithelial permeability.There is no cure and effective drug in treating IBD in clinics currently.Stachydrine is an alkaloid purified from Chinese herb Leonurus heterophyllus and from the Citrus genus.Stachydrine is reported to have a variety of pharmacology activities,including antioxidative,anti-inflammatory,anti-cancer,and cardioprotective effects.However,the effect of stachydrine on inflammatory bowel disease(IBD)is rarely reported.In this study,we aimed to evaluate the therapeutic roles of stachydrine hydrochloride on ameliorating rat experimental colitis to suggest the value of its potential clinical uses.AimTo characterize the ameliorative effect of stachydrine on trinitrobenzene sulfonic acid(TNBS)-induced colitis and reveal the correlated mechanisms in both systemic and cell levels.Methods(1)After 24 hours of fasting,rat experimental colitis(REC)was established by intracolonic administration trinitrobenzene sulfonic acid(120 mg/kg).(2)The changes of body weight,food intake,and colonic pathological changes of REC after stachydrine treatment were observed.Intestinal IL-6,IL-1,TNF-α,and NO were determined using Elisa kit;Sirtl,NF-κB p65,MLCK,Claudin-2 and inducible nitric oxide synthase were measured using Western Blotting assay.mRNA changes of Sirtl were observed using real-time quantitative PCR.Investigate the effects of stachydrine on impaired barrier function and reveal the mechanism combining with cell transfection.ResultsStachydrine reversed the decreased body weight/food intake in REC and alleviated neutrophils infiltration,mucosal barrier damage,and decreased the activity of myeloperoxidase in REC.Stachydrine hydrochloride reversed the increased levels of intestinal IL-6,IL-1,TNF-α,NF-κB p65,MLCK,claudin-2,and inducible nitric oxide synthase in REC.Stachydrine hydrochloride enhanced the decreased expression of intestinal Sirtl in REC.The protective effect of stachydrine on intestinal barrier function was mediated through Sirtl-NF-κB-MLCK pathway.Conclusion(1)Stachydrine ameliorated REC through decreasing the cytokines and inflammation mediator levels.(2)Stachydrine ameliorated the increased intestinal epithelial permeability through up-regulation of Sirtl and down-regulation of NF-κB-MLCK pathway and restoration of barrier function.Novelty:It is the first time to reveal that stachydrine significantly alleviated REC induced by TNBS in rats through reducing inflammation and restored the barrier function,suggesting the potential value of multi-target anti-inflammation and restoration of barrier function.