Synergistic protective effect of astragaloside IV-tetramethylpyrazine against cerebral ischemic-reperfusion injury induced by transient focal ischemia.
BACKGROUND
Astragaloside IV and tetramethylpyrazine have been extensively used in the cardio-cerbrovascular diseases of medicine as a chief ingredient of glycoside or alkaloid formulations for the treatment of stroke and myocardial ischemia diseases.


OBJECTIVE
To investigate the effects of astragaloside IV (ASG IV) and tetramethylpyrazine (TMPZ) on cerebral ischemia-reperfusion (IR) injury model in rat model.


METHODS
Rats were randomly divided into the following five groups: sham group, IR group and treatment group including ASG IV, ASG IV-TMPZ and nimodipine treatment. The therapeutic effect was evaluated by micro-positron emission tomography (Micro-PET) using (18)F-fluoro-2-deoxy-d-glucose. The neurological examination, infarct volume and the levels of oxidative stress- and cell apoptosis-related molecules were assessed.


RESULTS
Micro-PET imaging showed that glucose metabolism in the right hippocampus was significantly decreased in the IR group compared to the sham group (P<0.01). ASG IV and ASG IV-TMPZ treatments reversed the decreased glucose metabolism in the model group (P<0.05 and P<0.01, respectively). IR induced the increase of Caspase-3 mRNA levels, MDA content and iNOS activity, but it caused the decrease of SOD activity and Bcl-2 expression compared the sham group (P<0.01). ASG IV-TMPZ and ASG IV reversed the IR-induced changes of these parameters, i.e. the down regulation of Caspase-3 mRNA, MDA content and iNOS activity, and the up regulation of SOD activity and Bcl-2 expression (P<0.05).


CONCLUSIONS
This study showed that ASG IV-TMPZ played a pivotal synergistic protective role against focal cerebral ischemic reperfusion damage in a rat experimental model.
Institute of Cardio-Cerbrovascular Diseases, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
Jiehong
J
Yang
Jinhui
J
Li
Jing
J
Lu
Yuyan
Y
Zhang
Zhenhong
Z
Zhu
Haitong
H
Wan
D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D002317:Cardiovascular Agents / Q000494:pharmacology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004357:Drug Synergism; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009553:Nimodipine / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*
D002317:Cardiovascular Agents; D018696:Neuroprotective Agents; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D011719:Pyrazines; D012333:RNA, Messenger; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D008315:Malondialdehyde; D009553:Nimodipine; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D053148:Caspase 3; D005947:Glucose; C017953:tetramethylpyrazine