Formononetin ameliorates dextran sulfate sodium-induced colitis via enhancing antioxidant capacity, promoting tight junction protein expression and reshaping M1/M2 macrophage polarization balance.

Autor: Xiao Q; College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China., Huang J; Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China., Zhu X; Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China., Shi M; College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China., Chen L; Laboratory Animal Research Center for Science and Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China., Chen L; Institute of Cancer Research, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China., Liu X; Laboratory Animal Research Center for Science and Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China., Liu R; College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China. Electronic address: rhliu@163.com., Zhong Y; Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China. Electronic address: zhong-youbao@foxmail.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 05; Vol. 142 (Pt B), pp. 113174. Date of Electronic Publication: 2024 Sep 16.
DOI: 10.1016/j.intimp.2024.113174
Abstrakt: Ulcerative colitis (UC) is a complex, refractory inflammatory bowel disease characterized impared intestinal mucosal barrier and imbalanced M1/M2 macrophage polarization mediating its progression. Formononetin (FN), a bioactive isoflavone with established anti-inflammatory and immunomodulatory properties, shows promise in mitigating UC, yet its therapeutic and underlying mechanisms remain unclear. In this study, colitis was induced in mice by administering 2.5% (w/v) dextran sulfate sodium (DSS) solution for 7 days. Oral (25, 50, and 100 mg/kg) FN for 10 days significantly ameliorated colitis symptoms in a dose-dependent manner, by mitigating body weight loss, reducing disease activity index (DAI), colonic weight, and colonic weight index, while enhancing survival rates and colonic length. Histological analysis revealed FN remarkably suppressed inflammatory damage in colonic tissues. Furthermore, FN modulated the expression of pro- and anti-inflammatory cytokines and enhanced antioxidant capacity. Notably, FN treatment significantly enhanced the expression of tight junction (TJ) proteins (claudin-1, ZO-1, occludin) at both protein and mRNA levels in the colon tissues, suggesting improved intestinal barrier function. Crucially, FN inhibited macrophage infiltration in colonic tissues and rebalanced M1/M2 macrophage polarization. While, macrophage depletion largely abrogated FN's protective effects against colitis, indicating a crucial role for macrophages in mediating FN's therapeutic response. Overall, FN effectively alleviated colitis primarily via modulating inflammatory cytokine expression, enhancing antioxidant capacity, upregulating TJs proteins expression, and remodeling M1/M2 macrophage polarization equilibrium. These findings suggest that FN could be the next candidate to unlocking UC's treatment challenge.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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