Andrographolide protects against the intestinal barrier dysfunction and inflammatory response through modulating ETEC virulence factors in a mouse model of diarrhea

IF 3.8 2区农林科学 Q2 FOOD SCIENCE & TECHNOLOGY

Journal of Functional Foods Pub Date : 2024-11-17 DOI:10.1016/j.jff.2024.106568

Peng Wang , Aoshuang Fan , Jinduo Zhao , Yangming liu , Lin Feng , Fangyu Xia , Yuting Tian , Liping Gan , Hanzhen Qiao , Erzhen Duan , Jin Huang , Sen lin , Jinrong Wang

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Abstract

Infectious diarrhea is a common disease that endanger both human and livestock animals. However, there are limited safety strategy for preventing Enterotoxigenic Escherichia coli (ETEC) induced diarrhea. A mouse diarrhea model was established by orally administering ETEC following andrographolide pretreatment. Pretreatment with andrographolide improved the body weight losses, diarrhea, intestinal barrier dysfunction and inflammation of ETEC infected mice. Andrographolide pretreatment protected against the ETEC-induced downregulation of intestinal Na⁺/H⁺ exchange protein 3 (Nhe3) and upregulation of cystic fibrosis transmembrane conductance regulator (Cftr) mRNA expression. Andrographolide pretreatment also reduced coliform colonization in the jejunum but did not affect fecal coliform levels in infected mice. By using an in vitro model, it was shown that andrographolide downregulated the expression of virulence factors involved in ETEC k88 colonization, as well as heat-labile and heat-stable enterotoxins. These results unveil a novel finding that andrographolide protect against ETEC infection by regulating its virulence factors.

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穿心莲内酯在腹泻小鼠模型中通过调节 ETEC 毒力因子防止肠屏障功能紊乱和炎症反应

感染性腹泻是一种危害人类和牲畜的常见疾病。然而，预防肠毒性大肠杆菌（ETEC）诱发腹泻的安全策略有限。通过口服 ETEC 并进行穿心莲内酯预处理，建立了小鼠腹泻模型。穿心莲内酯预处理可改善 ETEC 感染小鼠的体重减轻、腹泻、肠屏障功能障碍和炎症。穿心莲内酯预处理可防止 ETEC 诱导的肠道 Na+/H+ 交换蛋白 3（Nhe3）下调和囊性纤维化跨膜传导调节因子（Cftr）mRNA 表达上调。穿心莲内酯预处理还可减少空肠中的大肠菌群定植，但不会影响感染小鼠粪便中的大肠菌群水平。通过使用体外模型，研究表明穿心莲内酯下调了参与 ETEC k88 定殖的毒力因子以及热敏性和热稳定性肠毒素的表达。这些结果揭示了穿心莲内酯通过调节 ETEC 的毒力因子来防止其感染的新发现。

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来源期刊

Journal of Functional Foods FOOD SCIENCE & TECHNOLOGY-

CiteScore

9.60

自引率

1.80%

发文量

428

审稿时长

76 days

期刊介绍： Journal of Functional Foods continues with the same aims and scope, editorial team, submission system and rigorous peer review. We give authors the possibility to publish their top-quality papers in a well-established leading journal in the food and nutrition fields. The Journal will keep its rigorous criteria to screen high impact research addressing relevant scientific topics and performed by sound methodologies. The Journal of Functional Foods aims to bring together the results of fundamental and applied research into healthy foods and biologically active food ingredients. The Journal is centered in the specific area at the boundaries among food technology, nutrition and health welcoming papers having a good interdisciplinary approach. The Journal will cover the fields of plant bioactives; dietary fibre, probiotics; functional lipids; bioactive peptides; vitamins, minerals and botanicals and other dietary supplements. Nutritional and technological aspects related to the development of functional foods and beverages are of core interest to the journal. Experimental works dealing with food digestion, bioavailability of food bioactives and on the mechanisms by which foods and their components are able to modulate physiological parameters connected with disease prevention are of particular interest as well as those dealing with personalized nutrition and nutritional needs in pathological subjects.