Mechanism of Modified Shengjiang Powder(升降散)in Treating Ulcerative Colitis by Regulating PKC Signaling Pathway Based on Metabolomics
Objective:To investigate the mechanism of modified Shengjiang Powder(升降散)in the treatment of rats with ulcerative colitis(UC).Methods:A total of 60 male rats were randomly divided into the model group,control group,Mesalazine enteric-coated tablet(0.5 g/kg)group,and modified Shengjiang Powder(3,1.5,and 0.75 g/kg)groups.Except for the control group,rats were induced by a dextran sulfate sodium salt(DSS)solution of 2.5％to establish the UC model.After 10 days of administration,the general conditions of rats in each group were observed.The disease activity index(DAI)was scored.Hematoxylin and eosin(HE)staining was used to observe the histopathological changes in the colon tissues.The serum contents of interleukin(IL)-6,IL-17,bioactive factor(SP),and tumor necrosis factor(TNF)-αwere determined by enzyme-linked immunosorbent assay(ELISA).Immunohistochemical(IHC)detection was used to assess the expression of mucoprotein 2(MUC2)in the colon tissue.Serum differential metabolites were analyzed by liquid chromatograph mass spectrometer(LC-MS),and then MetaboAnalyst website was used for metabolic pathway enrichment.Western blot was used to determine the protein expressions of CXCL5,CXCR4,Integrin-β3,and PKC-α.Results:Compared with the control group,the colon length of the model control group was short-ened(P＜0.05),and the DAI score was increased(P＜0.05).Colonic mucosal epithelial was defective,and lymphocyte infiltration was ex-tensively observed.Goblet cells were significantly reduced.The serum levels of IL6,IL17,SP,and TNF-α were significantly increased(P＜0.05).The expression of MUC2 in the colon tissue of rats was significantly decreased(P＜0.05),and the protein expression levels of CX-CL5,CXCR4,Integrin-β3,and PKC-α were significantly upregulated(P＜0.05).Compared with the model control group,the colon length of modified Shengjiang Powder groups was significantly increased(P＜0.05),and the DAI scores in the modified Shengjiang Powder(3 and 1.5 g/kg)groups and mesalazine enteric-coated tablet(0.5 g/kg)group were significantly decreased(P＜0.05).The structure and number of goblet cells and colonic mucosa of rats in modified Shengjiang Powder(3 and 1.5 g/kg)groups were repaired to varying degrees.The ser-um levels of IL6,IL17,SP,and TNF-α,as well as the protein expression levels of MUC2,CXCL5,CXCR4,Integrin-β3,and PKC-α in colon tissue were decreased in each group(P＜0.05).Metabolomics results showed that the metabolite levels of rats with UC were changed after administration of modified Shengjiang Powder,and 18 differential metabolites and one metabolic pathway related to inflammation were identi-fied.Conclusions:Modified Shengjiang Powder can ameliorate inflammation of rats with UC by inhibiting the PKC signaling pathway.
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