Aim Ulcerative colitis （UC） is an increasingly common condition particularly in developed countries. The lack of satisfactory treatment fuels the search for alternative therapeutic strategies. In the present study, ...Aim Ulcerative colitis （UC） is an increasingly common condition particularly in developed countries. The lack of satisfactory treatment fuels the search for alternative therapeutic strategies. In the present study, we as- sessed the preclinical activity of berberine for the treatment of dextran sodium sulphate （DSS）-induced chronic re- lapsing colitis in C57BL/6 mice. Methods Colitis of mice was induced by three cycles of 2.0% DSS. From day13 onward, colitis mice were orally administered with 20 mg/kg berberine for 30 days. The disease severity was de- termined by daily monitoring the body weight, stool consistency, and stool bleeding of mice. At the end of treat- ment, colons were collected and subjected to histological, RT-qPCR, Western blot, and LC-MS analyses. Lympho- eytes were isolated from spleens and cultured for assessment of eytokine secretion. Results Berberine significantly ameliorated disease severity, colon shortening, histological injuries of colitis mice. Further, berberine treatment consistently and notably regulated DSS-assoeiated increase in mRNAs levels of Thl7-related eytokines （inhibition of IL-17 and ROR-γt） in the colon out of all tested eytokines. Moreover, the increases of TNF-α, IL-6 and IL-23 mRNA, and the phosphorylated STAT3 in colons of DSS - treated mice were significantly reversed by berberine. In addition, berberine directly inhibited TNF-α and IL-17 secretion from cultured lymphoeytes upon PMA/ionomyein -1 re-stimulation. In the meanwhile, a six-time amount of berberine in colon tissue （4.26 ± 2.62 ng · g^-1 colon） was measured when compared that in serum （0.76 ± 0.23 ng · m1^-1） and no detected histological changes was found in major organs of colitis mice. Conclusion We demonstrate for the first time that berberine exerts immuno- modulatory effect in alleviating DSS-indueed chronic relapsing colitis via inhibition of the JAK/STAT signalling acti- vation in the inflamed colon. The demonstration of activity in this model supports the possibility of clinical efficacy of berberine in treating chronic UC.展开更多
文摘Aim Ulcerative colitis （UC） is an increasingly common condition particularly in developed countries. The lack of satisfactory treatment fuels the search for alternative therapeutic strategies. In the present study, we as- sessed the preclinical activity of berberine for the treatment of dextran sodium sulphate （DSS）-induced chronic re- lapsing colitis in C57BL/6 mice. Methods Colitis of mice was induced by three cycles of 2.0% DSS. From day13 onward, colitis mice were orally administered with 20 mg/kg berberine for 30 days. The disease severity was de- termined by daily monitoring the body weight, stool consistency, and stool bleeding of mice. At the end of treat- ment, colons were collected and subjected to histological, RT-qPCR, Western blot, and LC-MS analyses. Lympho- eytes were isolated from spleens and cultured for assessment of eytokine secretion. Results Berberine significantly ameliorated disease severity, colon shortening, histological injuries of colitis mice. Further, berberine treatment consistently and notably regulated DSS-assoeiated increase in mRNAs levels of Thl7-related eytokines （inhibition of IL-17 and ROR-γt） in the colon out of all tested eytokines. Moreover, the increases of TNF-α, IL-6 and IL-23 mRNA, and the phosphorylated STAT3 in colons of DSS - treated mice were significantly reversed by berberine. In addition, berberine directly inhibited TNF-α and IL-17 secretion from cultured lymphoeytes upon PMA/ionomyein -1 re-stimulation. In the meanwhile, a six-time amount of berberine in colon tissue （4.26 ± 2.62 ng · g^-1 colon） was measured when compared that in serum （0.76 ± 0.23 ng · m1^-1） and no detected histological changes was found in major organs of colitis mice. Conclusion We demonstrate for the first time that berberine exerts immuno- modulatory effect in alleviating DSS-indueed chronic relapsing colitis via inhibition of the JAK/STAT signalling acti- vation in the inflamed colon. The demonstration of activity in this model supports the possibility of clinical efficacy of berberine in treating chronic UC.
