Neuroprotective effects of breviscapine against apoptosis induced by transient focal cerebral ischaemia in rats.
Breviscapine, a flavonoid isolated from the traditional Chinese medicinal herb Erigerin breviscapus, has been proved to be effective in protecting the brain against ischaemic damage, but the mechanisms remain unknown. In this study, we have demonstrated the effects of breviscapine on neuronal apoptosis in a rat model of transient focal cerebral ischaemia. Rats were administered with breviscapine (50 or 100 mg kg(-1)/day) intragastrically for seven successive days, then subjected to 2-h brain ischaemia induced by middle cerebral artery occlusion, followed by 24-h reperfusion. After reperfusion, the rats were killed and the brain samples were collected. Haematoxylin-eosin staining was used to evaluate the histopathological changes. Terminal deoxynucleotidyl transferase-mediated biotiny-lated UTP nick end labeling (TUNEL) and flow cytometry (FCM) analysis were used to detect the level of apoptosis. The expressions of bcl-2 and caspase-3 in the cortex were determined by Western blot. Significant increases in the number of haematoxylin-eosin- and TUNEL-positive staining cells and DNA fragmentation were observed at 24 h after reperfusion, and the increases were inhibited by breviscapine (50 and 100 mg kg(-1)). Breviscapine at both doses markedly inhibited the expression and activation of caspase-3 and up-regulated the expression of bcl-2. These findings suggested that breviscapine attenuated neuroapoptosis and regulated the protein expression related to apoptosis after transient focal cerebral ischaemia, which may have contributed, in part, to the protective effects of breviscapine on cerebral ischaemic damage.
Yiming
Liu
L
Central Laboratory of Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou 510120, China. lyming2000@163.com
Wei
He
H
Aihua
Lin
L
Fandian
Zeng
Z
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D049919:Erigeron / Q000737:chemistry; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D008516:Medicine, Chinese Traditional; D020768:Middle Cerebral Artery / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D005419:Flavonoids; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C061097:breviscapine; D053148:Caspase 3