The Effect And Molecular Mechanism Of Taraxacum Officinale And Its Monomer On Ulcerative Colitis

Objective To investigate the therapeutic effect and mechanisms of taraxacum officinale(TO)and taraxasterol on dextran sodium sulfate(DSS)-induced ulcerative colitis(UC)in mice.Methods Different concentrations of DSS(2.0%,3.0%,and 5.0%)were used to induce colitis.The symptoms of the mice induced by DSS were noted,the length and histological score of each colon were measured.Then,mice were treated with 3.0%DSS and two different concentrations of TO.The body weight,disease activity index(DAI),colon lengths,and histological score were assessed.Furthermore,a transcriptome sequencing was performed by using the colon tissues among the four groups,and the differentially expressed genes were conducted for KEGG and GSEA and were validated by q RT-PCR,western blotting,and immunohistochemistry(IHC)analysis.Besides,a 16 S r DNA sequencing was carried out to distinguish the differential gut microbiota by using the mouse fecal samples among the four groups.A network pharmacology approach was used to identify the candidate and collective targets of taraxasterol and colitis,and the UC model was established by oral administration of DSS in mice.Bodyweight,colon lengths,and the pathological score were assessed.The expression levels of target genes were further confirmed by q RT-PCR and IHC analysis in taraxasterol treated UC models.Results The mice with 2.0%,3.0%,and 5.0% DSS administration in a week could develop into UC models successfully.Especially oral administration of 3.0% DSS was a good inducer of UC models.TO attenuated the clinical symptoms,lowered the inflammatory scoring,and inhibited the secretion of pro-inflammatory factors in DSSinduced UC.KEGG and GSEA analysis demonstrated that fatty acid degradation,PPAR,and cytokine ? cytokine receptor signaling pathways were predominantly enriched in TO?treated colitis as compared with the DSS group.Also,TO induced the enrichment of S24-7 andadlercreutzia,but decreased the number of anaerostipes,enterococcus,enterobacteriaceae and peptostreptococcaceae.14 collective targets of taraxasterol and UC were identified by a network pharmacology analysis.Taraxasterol alleviated the unfavorable clinical symptoms and attenuated the intestinal inflammation response.q RT-PCR and IHC analysis revealed that taraxasterol decreased the expression of MMP3,increased PPARG expression level compared with the DSS group.Conclusions Oral administration of 3.0% DSS is a good inducer of UC models.TO ameliorated DSS-induced UC by regulating fatty acid degradation,PPAR,and cytokine-cytokine receptor signaling pathways.The protective effect of TO on DSSinduced UC may be related to the change of intestinal flora.Taraxasterol improved UC induced by DSS through regulating MMP3 and PPARG expression.