Huatuo Zaizao pill alleviates cerebral ischemia-reperfusion injury in rhesus macaque and rat with middle cerebral artery obstruction

Objective To investigate how Huatuo Zaizao pill (HZP) enhances neurological function and to explore the underlying mechanism in acute phase of the middle cerebral artery occlusion (MCAO) ischemia-reperfusion model. Methods MCAO ischemia-reperfusion models were established in rhesus monkeys and rats to evaluate cerebral infarct volume and neurological impairment. Additionally, immunofluorescence staining and Western blotting (WB) were utilized to determine the expression levels of glial fibrillary acidic protein (GFAP) and Bax proteins. Results In the rhesus monkey MCAO ischemia-reperfusion model, the HZP group exhibited a greater reduction in infarct volume than the model group. The NHPSS scores in the HZP group began to decrease at 16 hours after stroke; compared with the model group, the NHPSS scores were significantly lower from 48 hours to 14 days. Compared with the control group, the percentages of cerebral infarction volume in rats of the model group was significantly increased, while that in the HZP groups was significantly decreased. Additionally, the time in the adhesive removal test was significantly shortened in the HZP groups. Immunofluorescence and WB revealed that the expression of GFAP and Bax was increased in the model group, whereas this change could be reversed to a certain extent after HZP treatment. Conclusions HZP significantly alleviates acute-phase symptoms in the rhesus macaque MCAO model, with these beneficial effects persisting into the recovery phase. This protective action may counteract cerebral ischemia-reperfusion injury by mitigating neuroinflammation and inhibiting neuronal apoptosis. Findings from both rhesus macaque and rat models in this study support the potential of HZP as an adjunctive therapeutic agent for acute cerebral infarction.