Resveratrol ameliorates ulcerative colitis by upregulating Nrf2/HO‑1 pathway activity: Integrating animal experiments and network pharmacology

Yu,Xinya; Li,Xiaoxi; Xu,Yunchun; Li,Yuwei; Zhou,Ye; Zhang,Junhua; Guo,Le

doi:10.3892/mmr.2024.13201

Resveratrol ameliorates ulcerative colitis by upregulating Nrf2/HO‑1 pathway activity: Integrating animal experiments and network pharmacology

Authors:
- Xinya Yu
- Xiaoxi Li
- Yunchun Xu
- Yuwei Li
- Ye Zhou
- Junhua Zhang
- Le Guo
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Affiliations: Department of Medical Microbiology and Immunology, School of Basic Medical Sciences, Dali University, Dali, Yunnan 671000, P.R. China, Department of General Surgery, School of Clinical Medicine, Dali University, Dali, Yunnan 671000, P.R. China
Published online on: March 14, 2024 https://doi.org/10.3892/mmr.2024.13201
Article Number: 77
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 anti‑inflammatory and antioxidant properties. Nuclear factor erythroid‑2‑related factor 2/heme oxygenase 1 (Nrf2/HO‑1) pathway regulates occurrence and development of numerous types of diseases through anti‑inflammatory and antioxidant activity. However, it is not clear whether Nrf2/HO‑1 pathway is involved in the treatment of Res in UC. Therefore, the present study aimed to investigate whether Res modulates the Nrf2/HO‑1 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 (IL‑6, IL‑1β, TNF‑α and IL‑10) 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 pro‑inflammatory cytokines IL‑6, IL‑1β and TNF‑α and increased anti‑inflammatory factor IL‑10 expression. Res also restored the decreased protein expression of ZO‑1 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 anti‑inflammatory 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 HO‑1. In conclusion, Res treatment activated the Nrf2/HO‑1 pathway to decrease clinical symptoms, inflammatory responses, and intestinal mucosal barrier damage in experimental UC mice.

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