Neuroprotective effects of leonurine on ischemia/reperfusion-induced mitochondrial dysfunctions in rat cerebral cortex.
Ischemic brain is particularly susceptible to free radicals mediated secondary neuronal damage, especially mitochondrial dysfunctions. Chinese Herbal Medicine with antioxidant properties is believed to have potential therapeutic effect. Leonurine, an alkaloid present in Herba Leonuri (HL), has shown biological effects such as antioxidant, anticoagulant, anti-apoptosis and protection against ischemic heart disease. In this study, neuroprotective effects of leonurine against cerebral ischemia/reperfusion-induced mitochondrial dysfunctions in cortex were evaluated. We used transient rat middle cerebral artery occlusion (MCAO) model of brain ischemia. The rats were treated with their respective treatments for 1 week prior to the MCAO. We found that leonurine significantly improved neurological outcome and reduced ischemia/reperfusion (I/R)-induced cerebral infarction 24 h after MCAO. Leonurine decreased reactive oxygen species (ROS) level in mitochondria isolated from ischemic cortex, which was increased by MCAO. Terminal deoxyuridine triphosphate (dUTP) Nick-End Labeling (TUNEL) staining showed anti-apoptotic effect of leonurine on ischemic cortex. Western blot analysis showed a marked decrease in the expression of Bax and an increase of Bcl-2 as a result of leonurine treatment. The attenuation of mitochondrial membrane swelling, restore of mitochondrial membrane potential and content of cytochrome c (Cyt-C) in mitochondria isolated from ischemic cortex could also be observed in leonurine treated group. The findings of this study suggest that leonurine has promising therapeutic effect for ischemic stroke treatment through antioxidant and anti-apoptotic mechanisms.
Department of Pharmacology, Institute of Biomedical Sciences, Fudan University, Shanghai, China.
Jia
J
Qi
Zhen Yi
ZY
Hong
Hong
H
Xin
Yi Zhun
YZ
Zhu
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D002544:Cerebral Infarction / Q000503:physiopathology / Q000517:prevention & control; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D031332:Leonurus / Q000737:chemistry*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C013587:leonurine; D005707:Gallic Acid; D045304:Cytochromes c