ETHNOPHARMACOLOGICAL RELEVANCE: Amygdalin, a key component of Peach kernel (semen persicae), also known as Taoren, is a traditional Chinese herb known for promoting blood circulation and alleviating blood stasis, especially in stroke treatment. This study aimed to explore the effects of amygdalin on neurological function in a rat model of acute ischemic stroke. METHODS: We induced acute ischemic stroke in Sprague-Dawley rats by occluding the right middle cerebral artery (MCAO) for 30 min, followed by reperfusion. Amygdalin was administered intraperitoneally at doses of 5 mg, 10 mg, and 20 mg per kilogram starting 24 h post-reperfusion for three consecutive days. We assessed cerebral infarct volume and neurological function, and analyzed the brain tissue using western blotting. RESULTS: Amygdalin significantly reduced cerebral infarct volume resulting from MCAO in the 5-mg group (amygdalin 5 mg/kg
18.02 ± 7.51 %), 10-mg group (amygdalin 10 mg/kg
16.25 % ± 6.35 %) and 20-mg group (amygdalin 20 mg/kg
12.26 ± 6.69 %) compared to the sham group (phosphate buffer saline
28.99 ± 6.36 %) (all p <
0.001). The 10-mg and 20-mg groups showed significantly lower modified neurological severity scores (mNSS) than the sham group 5 days post-reperfusion (p <
0.05, p <
0.0001, respectively). Performance on the rotarod test also improved significantly in the 10-mg group (p <
0.05) and 20-mg group (p <
0.0001) compared to the sham group, and the distance traveled in the open-field test increased significantly in the 5-mg group (p <
0.001), 10-mg group (p <
0.0001) and 20-mg group (p <
0.0001) compared to the sham group. Western blotting revealed that the expression of uncleaved caspase-3 in the cerebral cortex was greater in the sham group compared to the control (without MCAO and treatment) and the 20-mg groups (both p <
0.05), while the expression of caspase-9 was greater in the control and 20-mg groups than in the sham group (both p <
0.05). CONCLUSION: Intraperitoneal administration of amygdalin for three days reduced cerebral infarct volume and improved neurological function in a rat model of acute ischemic stroke. Additionally, amygdalin decreased uncleaved caspase-3 expression and increased caspase-9 expression. The findings suggest that amygdalin plays a neuroprotective role through modulation of apoptosis process via the intrinsic pathway.