Palmatine inhibits expression fat mass and obesity associated protein (FTO) and exhibits a curative effect in dextran sulfate sodium (DSS)-induced experimental colitis.
Int Immunopharmacol
; 132: 111968, 2024 May 10.
Article
em En
| MEDLINE
| ID: mdl-38579565
ABSTRACT
BACKGROUND:
Ulcerative colitis (UC) is an inflammatory disease whose pathogenesis and mechanisms have not been fully described. The m6A methylation modification is a general mRNA modification in mammalian cells and is closely associated with the onset and progression of inflammatory bowel disease (IBD). Palmatine (PAL) is a biologically active alkaloid with anti-inflammatory and protective effects in animal models of colitis. Accordingly, we examined the role of PAL on colitis by regulating N6-methyladenosine (m6A) methylation.METHODS:
A rat experimental colitis model was established by 5 % dextran sulfate sodium (DSS) in drinking water for seven days, then PAL treatment was administered for seven days. The colonic tissue pathology was assessed using hematoxylin-eosin (HE) and disease activity index (DAI). In in vitro studies, a human, spontaneously immortalized non-cancerous colon mucosal epithelial cell line (NCM460) was exposed to 2 % DSS and treated with PAL and cell viability was assayed using Cell Counting Kit-8 (CCK-8). The levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA) kits. The level of Zonula occludens-1 (ZO-1) was dectected by immunofluorescence. Transepithelial electrical resistance (TEER) of cells was also assessed. The methyltransferase-like 3 (METTL3), METTL14, AlkB homologate 5 (ALKBH5), and fat mass and obesity-associated protein (FTO) expression levels were assessed by western blotting. The localized expression of m6A was measured by immunofluorescence.RESULTS:
PAL significantly prevented bodyweight loss and shortening of the colon in experimental colitis rats, as well as decreasing the DAI and histological damage scores. Furthermore, PAL inhibited the levels of inflammatory factors (TNF-α, IL-6, IL-8, and IL-1ß) in both DSS treated rats and NCM460 cells. In addition, PAL enhanced the expression level of ZO-1, and increased the transepithelial electrical resistance to repaire intestinal barrier dysfunction. Colitis occurred due to decreased m6A levels, and the increased FTO expression led to a colitis phenotype. PAL markedly enhanced the METTL3 and METTL14 expression levels while decreasing ALKBH5 and FTO expression levels.CONCLUSIONS:
The findings demonstrated that PAL improved DSS-induced experimental colitis. This effect was associated with inhibiting FTO expression and regulating m6A methylation.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Alcaloides de Berberina
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Adenosina
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Citocinas
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Sulfato de Dextrana
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Ratos Sprague-Dawley
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Modelos Animais de Doenças
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Dioxigenase FTO Dependente de alfa-Cetoglutarato
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article