Abstract: Objective To compare the protective effects of three classic Mongolian medicinal formulas—Saurile, Zhenbao pills, and Zandan-3 decoction—against cerebral ischemia-reperfusion injury in mice, and to identify the optimal formula for subsequent mechanistic investigations. Methods A total of 120 C57BL/6J mice were randomly divided into six groups: sham-operated group, model group, nimodi-pine group (46.8 mg·kg^-1), Saurile group (338 mg·kg^-1), Zhenbao pill group (780 mg·kg^-1), and Zandan-3 decoction group (1 950 mg·kg^-1), with 20 mice in each group. The treatment groups were administered with respective formulas via gavage for 10 days, while the sham-operated and model groups received an equivalent volume of saline. A transient middle cerebral artery occlusion model was established using the filament method, involving 1.5 hours of ischemia followed by 24 hours of reperfusion. The sham-operated group underwent the surgical procedure without filament insertion. After 24 hours of reperfusion, brain tissues were harvested for TTC staining to assess the ischemic area, HE and Nissl staining were used to observe pathological changes, and behavioral scoring was recorded. Serum samples were collected to measure levels of SOD, MDA, and LDH. The protective effects of Saurile, Zhenbao pills, and Zandan-3 decoction against cerebral ischemia-reperfusion injury were compared, and network pharmacology was employed to predict the targets of Saurile. Results Compared to the sham-operated group, there was a significant increase in the infarct area based on TTC staining, a markedly reduced neurobehavioral score (P<0.001), evident infarct lesions as evidenced by HE staining, and pronounced neuronal damage after Nissl staining in the model group (P<0.001). Serum levels of SOD, MDA, and LDH were significantly decreased (P<0.001). Compared with the model group, the nimodipine, Saurile, Zhenbao Pill, and Zandan-3 Decoction groups showed a significant decrease in the infarct area according to TTC staining (P<0.05), an increased neurobehavioral score (P<0.05), a decrease in lesions based on HE and Nissl staining (P<0.05), and higher serum levels of SOD, MDA, and LDH (P<0.05). Saurile proved to be the most effective, followed by Zhenbao pills and Zandan-3 decoction. Conclusion This study has found that, compared to the model group, the classic Mongolian medicinal formulas Saurile, Zhenbao pills, and Zandan-3 decoction can significantly ameliorate cerebral ischemia-reperfusion injury in mice. Saurile delivers the best effect, potentially by regulating the MAPK signaling pathway and inhibiting inflammatory responses. However, the specific active components and precise mechanisms require more study.

Key words: Saurile, Zhenbao Pill, Zandan-3, Classic Mongolian Medicine, Cerebral Ischemia-Reperfusion Injury, Mice