Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disease mainly associated with immune dysfunction and microbiota disturbance. Cinnamaldehyde (CIN) is an active ingredient of Cinnamomum cassia with immunomodulatory and anti‐inflammatory properties. However, the therapeutic effect and detailed mechanism of CIN on UC remains unclear, and warrant further dissection. In this study, network pharmacology and molecular docking analyses were introduced to predict the potential targets and mechanism of CIN against UC. The therapeutic effect and the predicted targets of CIN on UC were further validated by in vivo and in vitro experiments. Seven intersection targets shared by CIN and UC were obtained, and four hub targets, i. e., toll‐like receptor 4 (TLR4), transcription factor p65 (NF‐κB), NF‐kappa‐B inhibitor alpha (IκBα), prostaglandin G/H synthase 2 (COX2) were acquired, which were mainly involved in NF‐κB, tumor necrosis factor (TNF), Toll‐like receptor and NOD‐like receptor signaling pathways. CIN alleviated the symptoms of dextran sulfate sodium (DSS)‐induced colitis by decreasing the disease active index (DAI), restoring colon length, and relieving colonic pathology. CIN attenuated systemic inflammation by reducing serum myeloperoxidase (MPO), TNF‐α, interleukin‐6 (IL‐6), and interleukin‐1β (IL‐1β), down‐regulating TLR4, phosphorylated‐NF‐κB (p‐NF‐κB), phosphorylated‐IκBα (p‐IκBα), and COX2 expression in colonic tissues, and decreasing NOD‐like receptor protein 3 (NLRP3), Caspase‐1, and IL‐1β protein expression in lipopolysaccharide (LPS)‐stimulated RAW264.7 cells. These results indicate that CIN alleviates DSS‐induced colitis inflammation by modulating TLR4/NF‐κB signaling pathway and NLRP3 inflammasome activation.

Background Ulcerative colitis (UC) is a common type of inflammatory bowel disease. Due to the elusive pathogenesis, safe and effective treatment strategies are still lacking. Fraxini Cortex (FC) has been widely used as a medicinal herb to treat various diseases. However, the pharmacological mechanisms of FC for UC treatment are still unclear. Methods An integrated platform combining network pharmacology and experimental studies was introduced to decipher the mechanism of FC against UC. The active compounds, therapeutic targets, and the molecular mechanism of action were acquired by network pharmacology, and the interaction between the compounds and target proteins were verified by molecular docking. Dextran sulfate sodium (DSS)-induced colitis model was employed to assess the therapeutic effect of FC on UC, and validate the molecuar mechanisms of action predicted by network pharmacology. Results A total of 20 bioactive compounds were retrieved, and 115 targets were predicted by using the online databases. Ursolic acid, fraxetin, beta-sitosterol, and esculetin were identified as the main active compounds of FC against UC. PPI network analysis achieved 28 FC-UC hub genes which were mainly enriched in IL-17 signaling pathway, TNF signaling pathway and Pathways in cancer. Molecular docking confirmed that the active compounds had high binding affinities to the predictive target proteins. GEO dataset analysis showed that these target genes were highly expressed in the UC clinical samples compared with that in the healthy controls. Experimental studies shown that FC alleviated DSS-induced colitis symptoms, reduced inflammatory cytokines release, and suppressed the expression levels of IL1β, COX2, MMP3, IL-17 and RORγt in colon tissues. Conclusion FC exhibits anti-UC properties through regulating multi-targets and multi-pathways with multi-components. In vivo results demonstrated that FC alleviated DSS-induced colitis.

Background Ulcerative colitis (UC) is a common type of inflammatory bowel disease. Due to the elusive pathogenesis, safe and effective treatment strategies are still lacking. Fraxini Cortex (FC) has been widely used as a medicinal herb to treat some diseases. However, the pharmacological mechanisms of FC for UC treatment are still unclear. Methods An integrated platform combining network pharmacology and experimental studies was introduced to decipher the mechanism of FC against UC. The active compounds, therapeutic targets, and the molecular mechanism of action were acquired by network pharmacology, and the interaction between the compounds and target proteins were verified by molecular docking. Dextran sulfate sodium (DSS)-induced colitis model was employed to assess the therapeutic effect of FC on UC, and validate the molecular mechanisms of action predicted by network pharmacology. Results A total of 20 bioactive compounds were retrieved, and 115 targets were predicted by using the online databases. Ursolic acid, fraxetin, beta-sitosterol, and esculetin were identified as the main active compounds of FC against UC. PPI network analysis identified 28 FC-UC hub genes that were mainly enriched in the IL-17 signaling pathway, the TNF signaling pathway, and pathways in cancer. Molecular docking confirmed that the active compounds had high binding affinities to the predicted target proteins. GEO dataset analysis showed that these target genes were highly expressed in the UC clinical samples compared with that in the healthy controls. Experimental studies showed that FC alleviated DSS-induced colitis symptoms, reduced inflammatory cytokines release, and suppressed the expression levels of IL1β, COX2, MMP3, IL-17 and RORγt in colon tissues. Conclusion FC exhibits anti-UC properties through regulating multi-targets and multi-pathways with multi-components. In vivo results demonstrated that FC alleviated DSS-induced colitis.