Mogroside V ameliorates astrocyte inflammation induced by cerebral ischemia through suppressing TLR4/TRADD pathway.

Inflammation and oxidative stress are pivotal factors in the onset and progression of secondary injury following cerebral ischemia-reperfusion (I/R). Mogroside V (MV), a primary active compound of Siraitia grosvenorii, exhibits significant anti-inflammatory and antioxidant properties. However, its specific effects in cerebral ischemia remain unclear. In this study, we evaluated the neuroprotective effects of MV in a model of focal cerebral ischemia. Male C57BL/6J mice were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) as an in vivo model of cerebral ischemia-reperfusion injury (CIRI), while U87 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate CIRI in vitro. MV administration was found to reduce mortality, infarct volume, cerebral edema, and alleviate neurological deficits in these I/R mice. Furthermore, MV mitigated cerebral I/R injury by decreasing oxidative stress markers, such as reactive oxygen species (ROS) and malondialdehyde (MDA), while enhancing superoxide dismutase (SOD) levels. Gene Set Enrichment Analysis (GSEA) of the KEGG pathway revealed that most differentially expressed genes (DEGs) were involved in the Toll-like receptor/NF-κB/TNF/apoptosis signaling pathway. These findings were confirmed by real-time PCR, western blotting, immunohistochemistry, and immunofluorescence co-localization which demonstrated that MV reduced astrocyte inflammatory responses by inhibiting cytokine secretion associated with the TLR4/TRADD pathway. Additionally, MV protected neurons from apoptosis, as supported by TUNEL, Nissl, and HE staining. In conclusion, MV attenuates astrocyte inflammation and exerts neuroprotective effects following cerebral I/R injury, likely through suppression of the TLR4/TRADD signaling pathway.