Breviscapine ameliorates autophagy by activating the JAK2/STAT5/BCL2 pathway in a transient cerebral ischemia rat model.

Breviscapine (Bre), an extract from Erigeron breviscapus, has been widely used to treat cerebral ischemia but the mechanisms of its neuroprotective effects need to be clarified. The present study investigated whether Bre could alleviate excessive autophagy induced by cerebral ischemia in the rat middle cerebral artery occlusion (MCAO) ischemia model via activating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5)/B-cell lymphoma 2 (BCL2) pathway. Rats were randomly divided into 5 groups, i.e. Sham group, MCAO+saline group, MCAO+Bre group, MCAO+DMSO (Dimethyl sulfoxide) group, and MCAO+Bre+AG490 (Tyrphostin AG490, the inhibitor of STAT5) group. The model was established and neuroprotection was evaluated by determining infarct volumes and conducting neurological behavioral tests. Autophagy levels in the infarct penumbra were detected using transmission electron microscopy and Western blotting. The expression of proteins in the JAK2/STAT5/BCL2 pathway was tested by Western blotting. Compared to the MCAO+saline group, the infarct volumes in the MCAO+Bre group were significantly reduced and neurological behavior improved. Breviscapine administration also significantly increased p-JAK2, p-STAT5, and BCL2 expression but decreased autolysosome numbers; it also downregulated Beclin-1 expression and the LC3II/LCI ratio. The JAK2 inhibitor AG490 reversed these effects. These findings indicate that breviscapine can improve neural recovery following ischemia through alleviating excessive autophagy and activation of the JAK2/STAT5/BCL2 axis.