{"title":"Rosmarinic Acid Attenuates <i>Salmonella enteritidis</i>-Induced Inflammation via Regulating TLR9/NF-κB Signaling Pathway and Intestinal Microbiota.","authors":"Dandan Yi, Menghui Wang, Xia Liu, Lanqian Qin, Yu Liu, Linyi Zhao, Ying Peng, Zhengmin Liang, Jiakang He","doi":"10.3390/antiox13101265","DOIUrl":null,"url":null,"abstract":"<p><p><i>Salmonella enteritidis</i> (<i>SE</i>) infection disrupts the homeostasis of the intestinal microbiota, causing an intestinal inflammatory response and posing a great threat to human and animal health. The unreasonable use of antibiotics has led to an increase in the prevalence of drug-resistant <i>SE</i>, increasing the difficulty of controlling <i>SE</i>. Therefore, new drug strategies and research are urgently needed to control <i>SE</i>. Rosmarinic acid (RA) is a natural phenolic acid with various pharmacological activities, including antioxidant, anti-inflammatory and antibacterial properties. However, the protective effects and mechanism of RA on intestinal inflammation and the gut microbial disorders caused by <i>SE</i> have not been fully elucidated. In this study, RAW264.7 cells, MCECs and BALB/c mice were challenged with <i>SE</i> to assess the protective effects and mechanisms of RA. The results showed that RA enhanced the phagocytic ability of RAW264.7 cells, reduced the invasion and adhesion ability of <i>SE</i> in MCECs, and inhibited <i>SE</i>-induced inflammation in cells. Moreover, RA inhibited the activation of the NF-κB signaling pathway by upregulating TLR9 expression. Importantly, we found that RA provided protection against <i>SE</i> and increased the diversity and abundance of the intestinal microbiota in mice. Compared with infection control, RA significantly increased the abundance of <i>Firmicutes</i> and <i>Acidibacteria</i> and decreased the abundance of <i>Proteobacteria</i>, <i>Epsilonbacteraeota</i> and <i>Bacteroidota</i>. However, RA failed to alleviate <i>SE</i>-induced inflammation and lost its regulatory effects on the TLR9/NF-κB signaling pathway after destroying the gut microbiota with broad-spectrum antibiotics. These results indicated that RA attenuated <i>SE</i>-induced inflammation by regulating the TLR9/NF-κB signaling pathway and maintaining the homeostasis of the gut microbiota. Our study provides a new strategy for preventing <i>SE</i>-induced intestinal inflammation.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":null,"pages":null},"PeriodicalIF":6.0000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504439/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antioxidants","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/antiox13101265","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Salmonella enteritidis (SE) infection disrupts the homeostasis of the intestinal microbiota, causing an intestinal inflammatory response and posing a great threat to human and animal health. The unreasonable use of antibiotics has led to an increase in the prevalence of drug-resistant SE, increasing the difficulty of controlling SE. Therefore, new drug strategies and research are urgently needed to control SE. Rosmarinic acid (RA) is a natural phenolic acid with various pharmacological activities, including antioxidant, anti-inflammatory and antibacterial properties. However, the protective effects and mechanism of RA on intestinal inflammation and the gut microbial disorders caused by SE have not been fully elucidated. In this study, RAW264.7 cells, MCECs and BALB/c mice were challenged with SE to assess the protective effects and mechanisms of RA. The results showed that RA enhanced the phagocytic ability of RAW264.7 cells, reduced the invasion and adhesion ability of SE in MCECs, and inhibited SE-induced inflammation in cells. Moreover, RA inhibited the activation of the NF-κB signaling pathway by upregulating TLR9 expression. Importantly, we found that RA provided protection against SE and increased the diversity and abundance of the intestinal microbiota in mice. Compared with infection control, RA significantly increased the abundance of Firmicutes and Acidibacteria and decreased the abundance of Proteobacteria, Epsilonbacteraeota and Bacteroidota. However, RA failed to alleviate SE-induced inflammation and lost its regulatory effects on the TLR9/NF-κB signaling pathway after destroying the gut microbiota with broad-spectrum antibiotics. These results indicated that RA attenuated SE-induced inflammation by regulating the TLR9/NF-κB signaling pathway and maintaining the homeostasis of the gut microbiota. Our study provides a new strategy for preventing SE-induced intestinal inflammation.
肠炎沙门氏菌(SE)感染会破坏肠道微生物群的平衡,引起肠道炎症反应,对人类和动物的健康构成巨大威胁。抗生素的不合理使用导致耐药 SE 的流行率上升,增加了控制 SE 的难度。因此,迫切需要新的药物策略和研究来控制 SE。迷迭香酸(RA)是一种天然酚酸,具有多种药理活性,包括抗氧化、抗炎和抗菌特性。然而,RA 对 SE 引起的肠道炎症和肠道微生物紊乱的保护作用和机制尚未完全阐明。在本研究中,RAW264.7 细胞、MCECs 和 BALB/c 小鼠受到 SE 的挑战,以评估 RA 的保护作用和机制。结果显示,RA能增强RAW264.7细胞的吞噬能力,降低SE对MCECs的侵袭和粘附能力,抑制SE诱导的细胞炎症。此外,RA 还能通过上调 TLR9 的表达来抑制 NF-κB 信号通路的激活。重要的是,我们发现 RA 能保护小鼠免受 SE 的感染,并能增加小鼠肠道微生物群的多样性和丰度。与感染对照组相比,RA能明显增加固缩菌和酸性杆菌的丰度,降低蛋白杆菌、epsilonbacteraeota和类杆菌的丰度。然而,在使用广谱抗生素破坏肠道微生物群后,RA 未能缓解 SE 诱导的炎症,也失去了对 TLR9/NF-κB 信号通路的调节作用。这些结果表明,RA通过调节TLR9/NF-κB信号通路和维持肠道微生物群的平衡来减轻SE诱导的炎症。我们的研究为预防SE诱导的肠道炎症提供了一种新策略。
AntioxidantsBiochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍:
Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.