Abstract
BackgroundSalmonella typhimurium (ST) causes several intestinal diseases. Polyphenols including chlorogenic acid (CGA) inhibit pathogenesis.ObjectiveThis study aimed to investigate the mechanisms of CGA in ST infection.MethodsThe intestinal pathological changes and survival rate of ST-infected mice were measured to verify the protection of CGA on ST infection. The antibacterial effects of CGA in vitro on the invasion to intestinal epithelial cells and autophagy was evaluated. The relationships among GAS5, miR-23a, and PTEN were verified. Expression of inflammation- and autophagy-related proteins was detected.ResultsCGA treatment alleviated pathological damage, improved the secretion disturbance of intestinal cytokines caused by ST infection, and reduced the mortality of mice. Intestinal GAS5 was upregulated after CGA treatment. LncRNA GAS5 competitively bound to miR-23a to upregulate PTEN and inhibit the p38 MAPK pathway. CGA regulated the p38 MAPK pathway through lncRNA GAS5/miR-23a/PTEN axis to promote autophagy in ST infection. The functional rescue experiments of miR-23a and PTEN further identified these effects.ConclusionCGA promotes autophagy and inhibits ST infection through the GAS5/miR-23a/PTEN axis and the p38 MAPK pathway.
Highlights
To evaluate the effect of chlorogenic acid (CGA) on Salmonella typhimurium (ST) infection, we established a mouse enteritis model induced by ST and treated the mice with different concentrations of CGA by gavage
No Salmonella was detected in the organs of control mice, while a large amount of Salmonella was present in the organs of ST-infected mice
Increasing concentrations of CGA significantly reduced the bacterial loads in the spleen, liver and mesenteric lymph nodes of ST-infected mice (Figure 1E)
Summary
Typhimurium, ST) is a Gram-negative facultative intracellular pathogen in humans and animals (Viswanathan et al, 2009; Jiang et al, 2018). The ST invades intestinal phagocytic and epithelial cells to achieve its pathogenicity, intracellular replication, and dissemination to other tissues (Birhanu et al, 2018). The systemic dissemination of ST may cause acute intestinal inflammation, diarrhea and immunodeficiency disorders in people and result in an enormous economic loss in animal husbandry and food industry (Park et al, 2017; Yang et al, 2019). A comprehensive understanding of the mechanisms and new therapeutic agents will provide a novel insight to clarify ST infections and develop proper therapies to minimize economic loss. Salmonella typhimurium (ST) causes several intestinal diseases.
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