Alleviating effect of Nexrutine on mucosal inflammation in mice with ulcerative colitis: Involvement of the RELA suppression

Abstract

BackgroundNexrutine is an herbal extract derived from Phellodendron amurense, known for its anti‐inflammatory, antidiarrheal, and hemostatic properties. However, its effect on ulcerative colitis (UC) remains unclear.MethodsA mouse model of UC was induced by 3% dextran sulfate sodium, while human colonic epithelial cells NCM‐460 were exposed to lipopolysaccharide. Both models were treated with Nexrutine at 300 or 600 mg/kg, with Mesalazine applied as a positive control regimen. The disease activity index (DAI) of mice was calculated, and the pathological injury scores were assessed through hematoxylin and eosin staining. The viability of NCM‐460 cells was determined using the CCK‐8 method. Inflammatory cytokines were detected using ELISA kits. Expression of mucin 3 (MUC3), Claudin‐1, and tight junction protein (ZO‐1) was detected to analyze mucosal barrier integrity. Target genes of Nexrutine were predicted using bioinformatics tools. Expression of RELA proto‐oncogene (RELA) was analyzed using qPCR and western blot assays.ResultsThe Nexrutine treatments significantly alleviated DAI of mice, mitigated pathological changes in their colon tissues, decreased the production of pro‐inflammatory cytokines, enhanced the barrier integrity‐related proteins, and increased NCM‐460 cell viability in vitro. RELA, identified as a target gene of Nexrutine, showed elevated levels in UC models but was substantially suppressed by Nexrutine treatment. Adenovirus‐mediated RELA upregulation in mice or the overexpression plasmid of RELA in cells counteracted the effects of Nexrutine treatments, exacerbating UC‐related symptoms.ConclusionThis study demonstrates that Nexrutine alleviates inflammatory mucosal barrier damage in UC by suppressing RELA transcription.

Analysis and experimental validation of IL-17 pathway and key genes as central roles associated with inflammation in hepatic ischemia–reperfusion injury

“…The inflammatory cascade involved in RELA was demonstrated in recent studies, where STAT3 could promote IGF2BP1-RELA-mediated pro-inflammatory effects by binding to the insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) promoter 51 . Inhibition of RELA transcription attenuates liver and lung injury in septic mice 52 , 53 . In cardiomyocytes, activation of adenylate cyclase type 8 leads to cell-autonomous RELA-mediated NF-κB signaling, which induces a widespread and persistent inflammatory state 54 .…”