Effects of Chaishen Jieyu Decoction on the Metabolic Profile of Fecal Bile Acids in Mice with Diarrhea Predominant Irritable Bowel Syndrome

  OBJECTIVE  To investigate therapeutic effect and potential mechanism of the Chaishen Jieyu Decoction on IBS-D mice model from regulating the fecal bile acid profile.

  METHODS  The C57BL/6 mice were randomly divided to 3 groups, normal mice, IBS-D mice and the Chaishen Jieyu Decoction intervention group. IBS-D mice were induced by the resisting immobilization stress and gavage of Folium senna. We studied the pathological changes of the mouse jejunum sections by HE, the protein expression of COX-2 and iNOS in jejunum, FITC-dextran and detected the relative mRNA expressions of main tight junctions proteins(ZO-1 & OCCLUDIN) in mice to determine the gastrointestinal permeability and analysis of fecal bile acid profile in mice using targeted metabolomics method.

  RESULTS  Compared with the control group, the fecal water content had an uptrend in the model group, showed a decreasing trend after treatment with Chaishen Jieyu Decoction. COX-2 and iNOS protein expression was upregulated in the jejunum of mice in the model group when compared to the control group, and Chaishen Jieyu Decoction could downregulate iNOS protein expression in jejunum (P < 0.01), and the mouse jejunum mRNA expression of ZO-1 and OCCLUDIN in model group were significantly decreased when compared with the control group(P < 0.01), while CSJY Decoction could increase these two proteins' mRNA expression(P < 0.05, P << 0.01);Also, compared with the control group, the pathological alterations such as incomplete jejunal structural organization, disorganized intestinal epithelial cell arrangement, crypt damage as well as intestinal epithelial integrity in the model group mice tended to be normalized after administration of CSJY Decoction. the composition and content of fecal bile acids in IBS-D mice were altered, after Chaishen Jieyu Decoction intervention, the disturbed fecal bile acid metabolism and disposition were significantly altered, especially for lithic cholic acid (LCA), deoxycholic acid (DCA) and deoxycholic acid (CDCA).

  CONCLUSION  Chaishen Jieyu Decoction has therapeutic effect on IBS-D mice and this effect may be partially contributed to regulating the bile acids metabolism.