Affiliation:
1. Department of Pharmacology, College of Pharmacy Dalian Medical University Dalian China
2. Affiliated Zhongshan Hospital of Dalian University Dalian China
3. Key Laboratory for Basic and Applied Research on Pharmacodynamic Substances of Traditional Chinese Medicine of Liaoning Province Dalian Medical University Dalian China
Abstract
AbstractEffective amelioration of ischemia/reperfusion (I/R)‐induced intestinal injury and revealing its mechanisms remain the challenges in both preclinic and clinic. Potential mechanisms of naringin in ameliorating I/R‐induced intestinal injury remain unknown. Based on pre‐experiments, I/R‐injured rat intestine in vivo and hypoxia–reoxygenation (H/R)‐injured IEC‐6 cells in vitro were used to verify that naringin‐alleviated I/R‐induced intestinal injury was mediated via deactivating cGAS‐STING signaling pathway. Naringin improved intestinal damage using hematoxylin and eosin staining and decreased alanine aminotransferase and aspartate aminotransferase contents in plasma. Naringin decreased inflammation characterized by reducing IL‐6, IL‐1β, TNF‐α, and IFN‐β contents in both plasma and IEC‐6 cells. Naringin mitigated oxidative stress via recovering superoxide dismutase, glutathione, and malondialdehyde levels in the I/R‐injured intestine. Naringin reduced the expression of apoptotic proteins, including Bax, caspase‐3, and Bcl‐2, and reduced terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick‐end labeling‐positive cells both in vivo and in vitro, and decreased Hoechst 33342 signals in vitro. cGAS, STING, p‐TBK1, p‐IRF3, and NF‐κB expressions were up‐regulated both in vivo and in vitro respectively and the up‐regulated indexes were reversed by naringin. Transfection of cGAS‐siRNA and cGAS‐cDNA significantly down‐regulated and up‐regulated cGAS‐STING signaling‐related protein expressions, respectively, and partially weakened naringin‐induced amelioration on these indexes, suggesting that deactivation of cGAS‐STING signaling is the crucial target for naringin‐induced amelioration on I/R‐injured intestine.
Funder
Natural Science Foundation of Liaoning Province
Cited by
2 articles.
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