Breviscapine confers a neuroprotective efficacy against transient focal cerebral ischemia by attenuating neuronal and astrocytic autophagy in the penumbra

• Published in: Biomedicine & pharmacotherapy Vol. 90; pp. 69 - 76
• Main Authors: Pengyue, Zhang, Tao, Guo, Hongyun, He, Liqiang, Yang, Yihao, Deng
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.06.2017
• Subjects: Animals; Astrocytes - drug effects; Astrocytes - metabolism; Autophagy - drug effects; Autophagy inhibition; Beclin-1 - metabolism; Brain - drug effects; Brain - metabolism; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Breviscapine; Cerebral ischemia; Disease Models, Animal; Flavonoids - pharmacology; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - metabolism; Internal Medicine; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - metabolism; Male; Medical Education; Neurons - drug effects; Neurons - metabolism; Neuroprotection; Neuroprotection - drug effects; Neuroprotective Agents - pharmacology; Penumbra; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Stroke - drug therapy; Stroke - metabolism; Neuroprotection; Cerebral ischemia; Penumbra; Breviscapine; Autophagy inhibition
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.03.039

Abstract Breviscapine is a flavonoid derived from a traditional Chinese herb Erigerin breviscapus (Vant.) Hand-Mazz, and has been extensively used in clinical treatment for cerebral stroke in China, but the underlying pharmacological mechanisms are still unclear. In present study, we investigated whether breviscapine could confer a neuroprotection against cerebral ischemia injury by targeting autophagy mechanisms. A cerebral stroke model in Sprague-Dawley rats was prepared by middle cerebral artery occlusion (MCAO), rats were then randomly divided into 5 groups: MCAO + Bre group, rats were treated with breviscapine; MCAO + Tat-Beclin-1 group, animals were administrated with specific autophagy inducer Tat-Beclin-1; MCAO + Bre + Tat-Beclin-1 group, rats were treated with both breviscapine and Tat-Beclin-1, MCAO + saline group, rats received the same volume of physiological saline, and Sham surgery group. The autophagy levels in infarct penumbra were evaluated by western blotting, real-time PCR and immunofluorescence 7 days after the insult. Meanwhile, infarct volume, brain water content and neurological deficit score were assessed. The results illustrated that the infarct volume, brain water content and neurofunctional deficiency were significantly reduced by 7 days of breviscapine treatment in MCAO + Bre group, compared with those in MCAO + saline group. Meanwhile, the western blotting, quantitative PCR and immunofluorescence showed that the autophagy in both neurons and astrocytes at the penumbra were markedly attenuated by breviscapine admininstration. Moreover, these pharmacological effects of breviscapine could be counteracted by autophagy inducer Tat-Beclin-1. Our study suggests that breviscapine can provide a neuroprotection against transient focal cerebral ischemia, and this biological function is associated with attenuating autophagy in both neurons and astrocytes.