This study aims to investigate the optimal dosage, time point, and underlying mechanism of Shanhu Qishiwei pills (SHQS) in the treatment of cerebral ischemia-reperfusion injury (CIRI). A rat model of CIRI was established using the suture occlusion method. Ten dosage groups and eight observation time points were set up. The therapeutic efficacy was comprehensively evaluated through a combination of neurobehavioral rating, cerebral infarction ratio, oxidative stress indicators in serum, and brain histopathological examination (HE staining and Nissl staining). Qualitative analysis of the chemical constituents was conducted using ultra-high-pressure liquid chromatography coupled with electrospray time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS). The mechanism of action was predicted by network pharmacology and subsequently validated through RT-qPCR and Western blot. The results revealed that 45 chemical constituents were identified in SHQS, with 15 confirmed. The network of 37 active ingredients and 75 targets revealed a multi-component, multi-target, and multi-pathway synergistic regulation pattern. SHQS reduced cerebral infarction rate, protected neurons, and inhibited oxidative stress, with the optimal effect observed at 83.35 mg/(kg·d) administered for 72 h. Mechanistically, its neuroprotective effects were associated with downregulated mRNA and protein expression of tumor necrosis factor-α (TNF-α), interleukin-β (IL-1β), IL-6, indicating anti-inflammatory actions. In conclusion, the optimal dosage of SHQS for treating CIRI is 83.35 mg/(kg·d), with the optimal time point at 72 h, and the mechanism may be related to the downregulation of inflammatory cytokine expression.

Shanhu Qishiwei pills, cerebral ischemia-reperfusion injury, dose-effect relationship; time-effect relationship, inflammation