Abstract | Aim: Intestinal ischemia/reperfusion (I/R) injury is a challenging pathological phenomenon accountable for significant mortality in clinical scenarios. Substantial evidence has supported the protective role of esculetin in myocardial I/R injury. This study is designed to reveal the specific impacts of esculetin on intestinal I/R injury and disclose the underlying mechanism. Methods: First, intestinal I/R injury model and intestinal epithelial cell line hypoxia/reoxygenation (H/R) model were established. Pathologic damages to intestinal tissues were observed through H&E staining. Serum diamine oxidase (DAO) levels were examined. RT-qPCR and Western blot examined the expression of inflammatory mediators. Commercial kits were used for detecting the levels of oxidative stress markers. TUNEL assay and caspase 3 activity assay measured cell apoptosis. Immunofluorescence (IF) staining measured autophagy levels. Western blot analyzed the expression of apoptosis-, Sirtuin 3 ( SIRT3)/ AMP activated protein kinase (AMPK)/ mammalian target of rapamycin (mTOR) signaling- and autophagy-related proteins. Molecular docking verified the interaction of esculetin with SIRT3. Cell viability was explored via CCK-8 assay. Results: The experimental results revealed that esculetin treatment mitigated pathological damage of intestinal tissues, reduced serum DAO level, ameliorated inflammation, oxidative stress and apoptosis and promoted autophagy in intestinal I/R rats. Moreover, esculetin bond to SIRT3 and activated SIRT3/AMPK/mTOR signaling both in vitro and in vivo. Furthermore, esculetin treatment enhanced cell viability and SIRT3 silencing reversed the impacts of esculetin on autophagy, inflammation, oxidative stress and apoptosis in H/R cell model. Conclusion: In a word, esculetin activated SIRT3/AMPK/mTOR signaling and autophagy to protect against inflammation, oxidative stress and apoptosis in intestinal I/R injury.
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Authors | Xin Shen, Hai Shi, Xinli Chen, Junwei Han, Haiwang Liu, Jie Yang, Yuan Shi, Jiajia Ma |
Journal | Journal of inflammation research
(J Inflamm Res)
Vol. 16
Pg. 3655-3667
( 2023)
ISSN: 1178-7031 [Print] New Zealand |
PMID | 37641705
(Publication Type: Journal Article)
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Copyright | © 2023 Shen et al. |