Xingnaojing injection alleviates cerebral ischemia/reperfusion injury through regulating endoplasmic reticulum stress in Vivo and in Vitro

Background: Xingnaojing (XNJ) injection, an extract derived from traditional Chinese medicine, is commonly used to treat ischemic stroke (IS). Previous studies have shown that XNJ has the ability to alleviate apoptosis in cerebral ischemia-reperfusion injury. However, the potential mechanisms have not been clarified. Objective: To identify the neuroprotective effect of XNJ and explore whether XNJ inhibits cell apoptosis associated with endoplasmic reticulum stress (ERS) after IS. Methods: In this study, cultured hippocampal neurons from mouse embryos and Sprague-Dawley rats were assigned randomly to four groups: sham, model, XNJ, and edaravone. The treatment groups were administered 2 h after modelling. Neurological deficit scores and motor performance tests were performed after 24 h of modelling. Additionally, pathomorphology, cell apoptosis and calcium content were evaluated. To ascertain the expression of ERS proteins, western blotting and polymerase chain reaction were employed. Results: The results indicated that XNJ treatment resulted in a notable decrease in infarct volume, apoptosis and missteps compared with the model group. XNJ also exhibited improvements in neurological function, grip strength and motor time. The calcium content significantly reduced in XNJ group. The XNJ administration resulted in a reduction in the levels of proteins associated with ERS including CHOP, GRP78, Bax, caspase-12, caspase-9, and cleaved-caspase-3, but an increase of the Bcl-2/Bax ratio. Furthermore, the downregulation of mRNA expression of CHOP, GRP78, caspase-12, caspase-9, and caspase-3 was confirmed in both cultured neurons and rat model. Conclusion: These findings suggest that XNJ may alleviate apoptosis by modulating the ERSinduced apoptosis pathway, making it a potential novel therapeutic approach for ischemic stroke.