Alleviating effect of Nexrutine on mucosal inflammation in mice with ulcerative colitis: Involvement of the RELA suppression.
Immun Inflamm Dis
; 12(1): e1147, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-38270298
ABSTRACT
BACKGROUND:
Nexrutine 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.METHODS:
A 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.RESULTS:
The 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.CONCLUSION:
This study demonstrates that Nexrutine alleviates inflammatory mucosal barrier damage in UC by suppressing RELA transcription.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Extratos Vegetais
/
Colite Ulcerativa
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Immun Inflamm Dis
Ano de publicação:
2024
Tipo de documento:
Article