Morin alleviates sepsis-associated encephalopathy through inhibiting ferroptosis via SIRT1.

Abstract

PURPOSE: Sepsis-associated encephalopathy (SAE) is a diffuse central nervous system dysfunction that occurs during sepsis. Morin has anti-inflammatory and antioxidative effects. The role of morin in SAE is unclear. METHODS: For in vivo experiments, a SAE mouse model was constructed by cecal ligation and perforation (CLP). The mice were treated using morin and erastin (ferroptosis agonist). The Morris water maze was chosen to examine cognitive function. The mouse hippocampus was collected for HE staining, ELISA, RT-qPCR, western blot, and transmission electron microscopy. For in vitro experiments, HT22 cells received LPS to construct a SAE cell model. The cells were treated with morin, erastin and EX527 (SIRT1 inhibitor) and collected for CCK8 assay, ELISA, western blot and immunofluorescence analysis. RESULTS: In vivo experiments showed that morin ameliorated cognitive dysfunction, hippocampal pathological damage, peripheral inflammation and neuroinflammation in SAE mice. Morin raised the level of SLC7A11, GPX4, FTH1 and GSH, while decreased the level of ACSL4, MDA and iron in SAE mice. Morin also alleviated CLP-induced mitochondrial damage. Erastin diminished the protective effects of morin on SAE mice. In vitro experiments demonstrated that morin alleviated LPS-induced HT22 cell damage and inflammation. Erastin and EX527 reversed the effects of morin on HT22 cells. EX527 additionally reversed inhibitory effect of morin on ferroptosis in HT22 cells. CONCLUSION: Morin alleviates SAE by inhibiting ferroptosis via SIRT1.