Esculetin Combats Multidrug-Resistant Salmonella Infection and Ameliorates Intestinal Dysfunction via the Nrf2 Pathway

被引:1
|
作者
Xu, Wenjiao [1 ,2 ]
Ding, Wenjun [2 ]
Jia, Liyan [3 ]
Zhu, Kui [3 ]
Luo, Qingfeng [1 ]
机构
[1] Chinese Acad Med Sci, Beijing Hosp, Natl Ctr Gerontol, Dept Gastroenterol,Inst Geriatr Med, Beijing 100730, Peoples R China
[2] Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China
[3] China Agr Univ, Coll Vet Med, Natl Key Lab Vet Publ Hlth & Safety, Beijing 100193, Peoples R China
基金
中国国家自然科学基金;
关键词
coumarin; esculetin; intestinal barrier; multidrug-resistant (MDR); Nrf2; <italic>S</italic>. Tm; INFLAMMATION;
D O I
10.3390/antiox13101170
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The increasing incidence of multidrug-resistant (MDR) Salmonella enterica serovar Typhimurium (S. Tm), known for causing invasive enteric infections, presents a significant public health challenge. Given the diminishing efficacy of existing antibiotics, it is imperative to explore novel alternatives for the treatment of MDR S. Tm infections. Here, we identified esculetin (EST), a natural coumarin abundant in dietary foods and herbs, as a compound exhibiting broad-spectrum antibacterial properties against a range of MDR bacteria. Our findings demonstrate that EST effectively inhibited the proliferation and expansion of MDR S. Tm in both in vitro experiments and animal models. Specifically, EST significantly downregulated the type 3 secretion system-1 (T3SS-1) virulence expression of MDR S. Tm, thereby preventing its invasion into intestinal epithelial cells. In S. Tm-infected mice, we observed cecal injury characterized by the upregulation of inflammatory cytokines, a reduction in goblet cell numbers, a decreased expression of tight junction proteins, and microbial dysbiosis. Conversely, EST treatment ameliorated these pathological changes induced by S. Tm infection and reduced oxidative stress by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, thereby improving intestinal barrier function. These results suggest that dietary coumarins or a targeted plant-based diet may offer a promising strategy to counteract MDR bacteria-induced enteric diseases.
引用
收藏
页数:17
相关论文
共 50 条
  • [41] Astaxanthin Ameliorates the Lipopolysaccharides-Induced Subfertility in Mouse via Nrf2/HO-1 Antioxidant Pathway
    Wang, Lei
    Zhuang, Lili
    DOSE-RESPONSE, 2019, 17 (03):
  • [42] Ketamine ameliorates oxidative stress-induced apoptosis in experimental traumatic brain injury via the Nrf2 pathway
    Liang, Jinwei
    Wu, Shanhu
    Xie, Wenxi
    He, Hefan
    DRUG DESIGN DEVELOPMENT AND THERAPY, 2018, 12 : 845 - 853
  • [43] Itaconate ameliorates methicillin-resistant Staphylococcus aureus-induced acute lung injury through the Nrf2/ARE pathway
    Liu, Gang
    Wu, Yaxian
    Jin, Sihao
    Sun, Jiaojiao
    Wan, Bin-Bin
    Zhang, Jiru
    Wang, Yingying
    Gao, Zhi-Qi
    Chen, Dan
    Li, Shengpeng
    Pang, Qingfeng
    Wang, Zhiqiang
    ANNALS OF TRANSLATIONAL MEDICINE, 2021, 9 (08)
  • [44] Atorvastatin induces mitochondrial dysfunction and cell apoptosis in HepG2 cells via inhibition of the Nrf2 pathway
    Li, Li-Zhong
    Zhao, Zeng-Ming
    Zhang, Li
    He, Jun
    Zhang, Ting-Fen
    Guo, Jia-Bin
    Yu, Lin
    Zhao, Jun
    Yuan, Xiao-Yan
    Peng, Shuang-Qing
    JOURNAL OF APPLIED TOXICOLOGY, 2019, 39 (10) : 1394 - 1404
  • [45] Naringenin reduces oxidative stress and improves mitochondrial dysfunction via activation of the Nrf2/ARE signaling pathway in neurons
    Wang, Kaihua
    Chen, Zhenzhen
    Huang, Longjian
    Meng, Bing
    Zhou, Xinmei
    Wen, Xiaodong
    Ren, Ding
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2017, 40 (05) : 1582 - 1590
  • [46] Edaravone alleviates sepsis-induced diaphragmatic dysfunction via Sirt1/ Nrf2 pathway
    Zhang, Youping
    Dai, Hongkai
    Lv, Man
    Wang, Yurou
    Zheng, Yingfang
    Luo, Jinlong
    Li, Shusheng
    INTERNATIONAL IMMUNOPHARMACOLOGY, 2025, 153
  • [47] Angiotensin-(1-7) ameliorates intestinal barrier dysfunction by activating the Keap1/Nrf2/HO-1 signaling pathway in acute pancreatitis
    Gu, Ruru
    Cui, Tianyu
    Guo, Yinan
    Luan, Yingyi
    Wang, Xueran
    Liu, Ruixia
    Yin, Chenghong
    MOLECULAR BIOLOGY REPORTS, 2023, 50 (07) : 5991 - 6003
  • [48] MOTILIPERM Ameliorates Immobilization Stress-Induced Testicular Dysfunction via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway in SD Rats
    Karna, Keshab Kumar
    Soni, Kiran Kumar
    You, Jae Hyung
    Choi, Na Young
    Kim, Hye Kyung
    Kim, Chul Young
    Lee, Sung Won
    Shin, Yu Seob
    Park, Jong Kwan
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (13) : 1 - 17
  • [49] Keratinocyte Growth Factor 2 Ameliorates UVB-Induced Skin Damage via Activating the AhR/Nrf2 Signaling Pathway
    Gao, Shuang
    Guo, Keke
    Chen, Yu
    Zhao, Jungang
    Jing, Rongrong
    Wang, Lusheng
    Li, Xuenan
    Hu, Zhenlin
    Xu, Nuo
    Li, Xiaokun
    FRONTIERS IN PHARMACOLOGY, 2021, 12
  • [50] Isoliquiritigenin Protects Against Pancreatic Injury and Intestinal Dysfunction After Severe Acute Pancreatitis via Nrf2 Signaling
    Zhang, Man
    Wu, Yan-Qing
    Xie, Ling
    Wu, Jiang
    Xu, Ke
    Xiao, Jian
    Chen, Da-Qing
    FRONTIERS IN PHARMACOLOGY, 2018, 9