Shen-Xiong-Tong-Mai granule suppresses nerve cell apoptosis to ameliorate ischemic stroke via activating PI3K/Akt signaling pathway.

Abstract

BACKGROUND: Ischemic stroke (IS) is a common subtype of stroke in China, accounting for 60 %-80 % of all stroke cases. Shen-Xiong-Tong-Mai granule (SXTMG) is one of the commonly used herbal medicine formulas in TCM. The present work aimed to explore the predominant active substances and molecular mechanisms underlying SXTMG against IS. METHODS: IS animal model and cell model were constructed using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) methods, respectively. The SXTMG and IS targets were predicted using four databases. UPLC/MS analysis was employed to identify the active compounds of SXTMG. The pathway changes were detected using western blot and immunofluorescence staining. RESULTS: Firstly, SXTMG significantly reduced the ischemic area, brain edema, and nerve function injury of MCAO rats, exhibiting crucial anti-IS effects. Totally 22 active compounds were identified in SXTMG based on HPLC-MS/MS results. After bioinformatics analysis, 89 common targets were identified, which were significantly enriched in pathways including apoptosis pathway and PI3K/Akt signaling. Finally, in vitro experiments indicated that SXTMG treatment significantly inhibited the OGD/R HT22 cell apoptosis and activated the PI3K/Akt signaling in OGD/R HT22 cells. CONCLUSION: SXTMG possessed promising protective effects against IS through triggering PI3K/Akt signaling to suppress nerve cell apoptosis.