Shuxuening injection ameliorates poststroke cognitive impairment by regulating multiple cell death pathways.

BACKGROUND

Poststroke cognitive impairment (PSCI) frequently occurs after ischaemic stroke (IS). Despite its widespread clinical application in treating ischaemic cardio-cerebrovascular diseases, the effect of Shuxuening injection (SXNI) on PSCI is unknown.

METHODS

The therapeutic effects of SXNI were assessed with a modified neurological severity score (mNSS), Y-maze tests, cerebral infarction volume measurements, and histopathological examinations. To identify key targets and pathways involved in SXNI treatment, we conducted integrated multiomics studies combining transcriptomic and proteomic analyses, supplemented by biochemical assays and transmission electron microscopy (TEM). Validation was performed through qPCR, enzyme-linked immunosorbent assay (ELISA), immunofluorescence and Western blotting analysis. Finally, the components in SXNI were analyzed both qualitatively and quantitatively using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) and LC-MS/MS.

RESULTS

Integrated multiomics analyses suggested that SXNI may exert therapeutic effects on PSCI through multiple signalling pathways. By modulating key pathways linked to oxidative stress, immune, and inflammatory response signaling, SXNI thereby demonstrated a significant role in acute ischaemic stroke (AIS) pathogenesis. Building on monotherapy investigations, we subsequently explored the therapeutic potential of combining SXNI with Edaravone (EDA).

CONCLUSIONS

SXNI suppresses pyroptotic and oxeiptotic signaling in the ischaemic brain by concurrently regulating the HIF-1α/NLRP3 and KEAP1/PGAM5/AIFM1 axes. By targeting ROS mediated death, SXNI effectively mitigates injury and offers a promising therapeutic strategy for AIS.