The effect of gentiopicroside on brain tissue repair in mice during the acute phase of middle cerebral artery occlusion.

BACKGROUND

Gentiopicroside (GPS) has reported anti-inflammatory and neuroprotective effects. This research aimed to explore the reparative impacts and molecular mechanisms of GPS on brain injury in acute phase of middle cerebral artery occlusion (MCAO).

METHODS

Potential GPS targets were identified via network pharmacology. Then biological processes and pathways were elucidated. Differentially expressed genes (DEGs) related to cerebral ischemia reperfusion injury (CIRI) were identified based on GSE236381 dataset, and a disease target interaction network was constructed. The diagnostic value of core genes was validated using external dataset (GSE241280 and GSE131193). An MCAO mouse model was established, and the neuroprotective effects of GPS (GPS-L (100 mg/kg/day), GPS-M (200 mg/kg/day), and GPS-H (400 mg/kg/day)) were evaluated through neurological scores, and TTC and HE staining. Serum inflammatory factors, pyroptosis-related indicators, and the levels of NF-κB in nuclear or cytoplasm were detected by ELISA and Western blot, respectively.

RESULTS

125 potential GPS targets were appreciably enriched in pathways associated with nitrogen metabolism and antigen presentation. 485 upregulated genes and 635 downregulated genes were notably enriched in autophagy and neutrophil extracellular trap formation. WGCNA identified 204 hub genes, including TNFSF10, IL-1β, DCBLD2, and TNF, which were also potential action targets of GPS. The core targets were substantially enriched in necroptosis and TNF/MAPK/NF-κB pathways. In MCAO model, intragastric GPS (400 mg/kg/day) in mice reduced neurological scores, brain injury area, neuronal damage, lowered serum inflammatory factors, and downregulated pyroptosis-related indicators and nuclear NF-κB, while upreguated cytoplasm NF-κB.

CONCLUSIONS

GPS exerted neuroprotective effects against CIRI induced by MCAO. Correlative evidence suggested that these effects may be associated with the regulation of inflammation and pyroptosis related signaling pathway, consistent with network pharmacology predictions. These insights offer viability of GPS as a treatment option for MCAO.