Berberine hydrochloride ameliorates DSS-induced ulcerative colitis in rat by inhibiting pyroptosis mediated by NLRP3
Objective:Berberine hydrochloride(BBR)is commonly used for the treatment of ulcerative colitis(UC),but its molecular mechanism,especially the mechanism of rescue of inflammatory-induced pyroptosis,needs to be further analyzed.Meth-ods:SD male rats were randomly divided into four groups:control group(Ctrl),DSS model group,BBR treatment group(DSS+BBR)and BBR+NLRP3 agonist group(DSS+BBR+BMS-986299).The UC rat model was established by the dextran sulfate sodium method(DSS).At the same time,BBR was intragastrically administered to BBR treatment group and BBR+NLRP3 agonist group twice per-day for 7 consecutive days.BMS-986299 was intraperitoneally injected to BBR+NLRP3 group twice a day.During the experiment,the body weights were weighed,the general condition was observed,and the disease activity index(DAI)was evaluated every day.After the experiment,the gross morphology and length of colon were observed and evaluated.HE staining was used to observe the pathologi-cal changes of colon tissue and evaluate the tissue injury index(TDI).ELISA was employed for detecting the contents of TNF-α and IL-1β in colon tissue,and Western blot was employed for detecting NLRP3,ASC,GSDMD-N,Cleaved-caspase 1 and IL-1β expres-sions.Results:BBR could effectively improve the UC-induced weight loss,colon tissue integrity and cell pyroptosis,reduce the expression levels of inflammatory factors such as TNF-ɑ and IL-1β,the proportion of pyroptosis,and the levels of proteins NLRP3,IL-1β,GSDMD-N,and Cleaved-caspase 1 which play crucial roles in pyroptosis pathway.The therapeutic effect and the regulated pro-tein expression through BBR were reversed by NLRP3 activation.Conclusion:BBR exerts a therapeutic effect by reducing the proteins levels of mature NLRP3,IL-1β,GSDMD-N,Cleaved-caspase 1,which are responsible for pyroptosis pathway.This result provides a molecular basis for BBR in treatment of UC.
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