Li Jun, Yang Yang, Zhang Xinyu, Yang Ying, Wu Zhenlong
State Key Laboratory of Animal Nutrition, Department of Companion Animal Science, China Agricultural University, Beijing, 100193, P. R. China.
Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, 100193, China.
Eur J Nutr. 2025 Mar 19;64(3):128. doi: 10.1007/s00394-025-03602-3.
Salmonella typhimurium is a pathogen responsible for millions of cases of gastroenteritis in both humans and animals. This study aimed to evaluate the hypothesis that fisetin administration could mitigate colon damage and regulate the intestinal microbiota in mice treated with Salmonella typhimurium.
Six-week-old male mice were orally administered with or without 100 mg/kg fisetin and infected with Salmonella typhimurium.
Fisetin administration ameliorated Salmonella typhimurium-induced colitis as shown by the decreased body weight loss, lowered disease activity index score, reduced colon shortening, inflammatory infiltration, and apoptosis. Meanwhile, Salmonella typhimurium exposure upregulated colonic Tnf-α, Il-6, Il-1β, Ifn-β, Ccl2, Ccl8 relative expression and MDA and HO concentrations, whereas lowered Il-10, Nrf2, Nqo1, Coq10b, and Gss abundance, all of which were ameliorated by fisetin treatment. Moreover, fisetin recovered the occludin, zonula occludens-1, and zonula occludens-2 protein abundance in response to Salmonella typhimurium administration. Further investigation demonstrated that the protective role of fisetin was related to the inactivation of the TLR2/TLR4-NF-κB pathway, upregulation of Lactobacillus, and reduction of Salmonella abundance. Additionally, fisetin could limit the intracellular Salmonella typhimurium proliferation, which was likely to be attributed to the inhibition of focal adhesion kinase.
Together, our study elucidated the therapeutic potential of fisetin in ameliorating key aspects of colitis, including intestinal inflammation, oxidative stress, and barrier dysfunction, and these beneficial effects were mediated through the inactivation of the TLR2/TLR4-NF-κB pathway, the regulation of microbiota, and restricting the intracellular proliferation of Salmonella typhimurium by inhibiting focal adhesion kinase.
鼠伤寒沙门氏菌是导致人类和动物数百万例肠胃炎的病原体。本研究旨在评估下述假说：给予非瑟酮可减轻经鼠伤寒沙门氏菌处理的小鼠的结肠损伤并调节肠道微生物群。
对6周龄雄性小鼠口服给予或不给予100 mg/kg非瑟酮，然后感染鼠伤寒沙门氏菌。
给予非瑟酮改善了鼠伤寒沙门氏菌诱导的结肠炎，表现为体重减轻减少、疾病活动指数评分降低、结肠缩短减轻、炎症浸润和细胞凋亡减少。同时，暴露于鼠伤寒沙门氏菌会上调结肠Tnf-α、Il-6、Il-1β、Ifn-β、Ccl2、Ccl8的相对表达以及MDA和HO浓度，而降低Il-10、Nrf2、Nqo1、Coq10b和Gss丰度，所有这些均通过非瑟酮处理得到改善。此外，非瑟酮可恢复因给予鼠伤寒沙门氏菌而降低的闭合蛋白、闭合小环蛋白-1和闭合小环蛋白-2的蛋白丰度。进一步研究表明，非瑟酮的保护作用与TLR2/TLR4-NF-κB信号通路失活、乳酸杆菌上调以及沙门氏菌丰度降低有关。此外，非瑟酮可限制鼠伤寒沙门氏菌在细胞内的增殖，这可能归因于对粘着斑激酶的抑制。
总之，我们的研究阐明了非瑟酮在改善结肠炎关键方面（包括肠道炎症、氧化应激和屏障功能障碍）的治疗潜力，并且这些有益作用是通过TLR2/TLR4-NF-κB信号通路失活、微生物群调节以及通过抑制粘着斑激酶限制鼠伤寒沙门氏菌在细胞内的增殖来介导的。
