ITRAQ-based pharmacoproteomics reveals potential targets of berberine, a promising therapy for ulcerative colitis

Abstract

Previous studies by us and others have indicated that berberine is a promising therapy for ulcerative colitis (UC). However, the mechanisms of UC and the therapeutic targets of berberine are poorly understood. iTRAQ-based proteomics was utilized to characterize the proteins and pathways associated with the development of colitis and its improvement after berberine treatment. By using a modified dextran sodium sulfate (DSS) colitis as the UC model, confirmed that berberine significantly attenuated clinical symptoms and colon shorting of the colitis mice. Proteomics identified 140 and 391 proteins that were differentially expressed in the colons of DSS- or DSS plus berberine-treated mice, respectively. Subsequent verification of 15 selected differentially expressed proteins (DEPs) by multiple reaction monitoring confirmed the reliability of the iTRAQ data. Further comparisons and bioinformatics analysis demonstrated that among the identified DEPs, 26, including Hist2h2be, Tubb3, and five immunoglobulins, were oppositely regulated by DSS and DSS plus berberine treatments. In addition, five commonly dysregulated pathways, including natural killer cell-mediated cytotoxicity and RRAR signaling were identified. Network analysis revealed that proteins involved in 7 and 11 pathways in DSS and DSS plus berberine treated mice, respectively, engaged in protein-protein interactions. Our study provides the first pharmacoproteomics profiling of colitis and its recovery after berberine treatment. The proteins, pathways and networks identified provide novel insights into the pathogenesis of colitis and the action mechanism of berberine, demonstrating their values for validation in human UC which could serve as targets for the development of novel therapies for UC.