Neuroprotective Effects of Leonurine on Ischemia/Reperfusion-Induced Mitochondrial Dysfunctions in Rat Cerebral Cortex

被引:81
作者
Qi, Jia [1 ,2 ,3 ]
Hong, Zhen Yi [1 ,2 ]
Xin, Hong [1 ,2 ]
Zhu, Yi Zhun [1 ,2 ,4 ]
机构
[1] Fudan Univ, Dept Pharmacol, Sch Pharm, Shanghai 201203, Peoples R China
[2] Fudan Univ, Inst Biomed Sci, Shanghai 201203, Peoples R China
[3] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Pharm, Shanghai 200092, Peoples R China
[4] Natl Univ Singapore, Ctr Life Sci, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117456, Singapore
基金
英国医学研究理事会; 美国国家科学基金会;
关键词
ischemia; Leonurine; apoptosis; mitochondrial; dysfunction; ACUTE ISCHEMIC-STROKE; OXIDATIVE STRESS; APOPTOSIS; MECHANISMS; INJURY; DAMAGE; BRAIN; CELL; BAX; CYCLOSPORINE;
D O I
10.1248/bpb.33.1958
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Ischemic brain is particularly susceptible to free radicals mediated secondary neuronal damage, especially mitochondria! 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 I 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
引用
收藏
页码:1958 / 1964
页数:7
相关论文
共 29 条
[11]   Cytosol-to-membrane redistribution of Bax and Bcl-X-L during apoptosis [J].
Hsu, YT ;
Wolter, KG ;
Youle, RJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :3668-3672
[12]  
Hu S, 1976, AM J CHINESE MED, V4, P18
[13]   Mechanisms of ischemic brain injury [J].
Janardhan V. ;
Qureshi A.I. .
Current Cardiology Reports, 2004, 6 (2) :117-123
[14]   Cyclosporin A and its nonimmunosuppressive analogue N-Me-Val-4-cyclosporin A mitigate glucose/oxygen deprivation-induced damage to rat cultured hippocampal neurons [J].
Khaspekov, L ;
Friberg, H ;
Halestrap, A ;
Viktorov, I ;
Wieloch, T .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1999, 11 (09) :3194-3198
[15]  
KONG Y C, 1976, American Journal of Chinese Medicine, V4, P373, DOI 10.1142/S0192415X76000470
[16]   NXY-059 for acute ischemic stroke [J].
Lees, KR ;
Zivin, JA ;
Ashwood, T ;
Davalos, A ;
Davis, SM ;
Diener, H ;
Grotta, J ;
Lyden, P ;
Shuaib, A ;
Hårdemark, H ;
Wasiewski, WW .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (06) :588-600
[17]   Reactive species mechanisms of cellular hypoxia-reoxygenation injury [J].
Li, CY ;
Jackson, RM .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2002, 282 (02) :C227-C241
[18]   4-Guanidino-n-butyl Syringate (Leonurine, SCM 198) Protects H9c2 Rat Ventricular Cells From Hypoxia-induced Apoptosis [J].
Liu, Xin-hua ;
Chen, Pei-fang ;
Pan, Li-long ;
De Silva, Ranil ;
Zhu, Yi-zhun .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2009, 54 (05) :437-444
[19]   PROTECTIVE EFFECTS OF LEONURINE IN NEONATAL RAT HYPOXIC CARDIOMYOCYTES AND RAT INFARCTED HEART [J].
Liu, Xin-Hua ;
Xin, Hong ;
Hou, Ai-Jun ;
Zhu, Yi-Zhun .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2009, 36 (07) :696-703
[20]   Cerebral protection of purified Herba Leonuri extract on middle cerebral artery occluded rats [J].
Loh, Kok Poh ;
Huang, Shan Hong ;
Tan, Benny Kwong Huat ;
Zhu, Yi Zhun .
JOURNAL OF ETHNOPHARMACOLOGY, 2009, 125 (02) :337-343