Resveratrol ameliorates ulcerative colitis by upregulating Nrf2/HO1 pathway activity: Integrating animal experiments and network pharmacology.
Mol Med Rep
; 29(5)2024 05.
Article
en En
| MEDLINE
| ID: mdl-38488031
ABSTRACT
Ulcerative colitis (UC) is a chronic idiopathic inflammatory condition affecting the rectum and colon. Inflammation and compromisation of the intestinal mucosal barrier are key in UC pathogenesis. Resveratrol (Res) is a naturally occurring polyphenol that exhibits antiinflammatory and antioxidant properties. Nuclear factor erythroid2related factor 2/heme oxygenase 1 (Nrf2/HO1) pathway regulates occurrence and development of numerous types of diseases through antiinflammatory and antioxidant activity. However, it is not clear whether Nrf2/HO1 pathway is involved in the treatment of Res in UC. Therefore, the present study aimed to investigate whether Res modulates the Nrf2/HO1 signaling pathway to attenuate UC in mice. Dextran sulfate sodium (DSS) was used to induce experimental UC in male C57BL/6J mice. Disease activity index (DAI) and hematoxylin eosin (H&E) staning was used to assessed the magnitude of colonic lesions in UC mice. ELISA) was utilized to quantify inflammatory cytokines (IL6, IL1ß, TNFα and IL10) in serum and colon tissues. Immunohistochemistry and Western blot were used to evaluate the expression levels of tight junction (TJ) proteins [zonula occludens (ZO)1 and Occludin] in colon tissues. Pharmacokinetic (PK) parameters of Res were derived from TCMSP database. Networkpharmacology was employed to identify the biological function and pharmacological mechanism of Res in the process of relieving UC, and the key target was screened. The binding ability of Res and key target was verified by molecular docking. Finally, the effectiveness of key target was substantiated by Western blot. Res decreased DAI, ameliorated histopathological changes such as crypt loss, disappeatance of the mucosal epithelium, and inflammatory infiltration in mice. Additionally, Res decreased expression of proinflammatory cytokines IL6, IL1ß and TNFα and increased antiinflammatory factor IL10 expression. Res also restored the decreased protein expression of ZO1 and occludin after DSS treatment, increasing the integrity of the intestinal mucosal barrier. The PK properties of Res suggested that Res possesses the therapeutic potential for oral administration. Network pharmacology revealed that Res alleviated UC through antiinflammatory and antioxidant pathways, and confirmed that Nrf2 has a high binding affinity with Res and is a key target of Res against UC. Western blotting demonstrated that Res treatment increased the protein levels of Nrf2 and HO1. In conclusion, Res treatment activated the Nrf2/HO1 pathway to decrease clinical symptoms, inflammatory responses, and intestinal mucosal barrier damage in experimental UC mice.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Colitis Ulcerosa
/
Colitis
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Experimentación Animal
Límite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Grecia