Jatrorrhizine alleviates ulcerative colitis via regulating gut microbiota and NOS2 expression

Background The natural protoberberine jatrorrhizine (JA) is reported to have several medicinal properties and a significant effect on the gut microbiota of mice. The regulation of gut microbiota is generally known to play an important role in the intestinal mucosal immune response to ulcerative colitis (UC). However, whether JA can be used in the treatment of UC is still unclear. Our study aimed to investigate the underlying therapeutic effects and mechanisms of JA in treating colitis. Results Compared with the DSS-induced colitis model group, the JA + DSS treated group had more significant improvements in weight loss, disease activity index score, colon length shortening, and pathological inflammation. 16s rRNA sequencing analysis showed that JA treatment protected colitis mice against DSS-induced disturbance of gut microbiota. At the phylum level, reductions in Deferribacteres and Proteobacteria were observed in the JA-treated group; At the genus level, the JA-treated group showed an increased relative abundance of Akkermansia and decreased abundance of Escherichia-Shigella, Desulfovibrio, Mucispirillum, etc. Network pharmacology was then used to screen out five drug-disease target genes (NOS2, ESR1, CALM1, CALM2, CALM3). Transcriptomics analysis further validated that the NOS2 expression was significantly reduced in colon tissue of JA-administered mice compared with DSS control mice. Additionally, analysis of correlation suggested that NOS2 expression was negatively correlated with the relative abundance of AKKermansia and positively correlated with Desulfovibrio, Rikenella. Conclusion JA alleviates ulcerative colitis via regulating gut microbiota and NOS2 expression. Keywords: Jatrorrhizine, Colitis, Gut microbiota, 16s rRNA, Network pharmacology, Transcriptome sequencing