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.
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页数:17
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