Synergistic protective effect of astragaloside IV–tetramethylpyrazine against cerebral ischemic-reperfusion injury induced by transient focal ischemia

ETHNOPHARMACOLOGICAL RELEVANCE: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. AIM OF THE STUDY:To investigate the effects of astragaloside IV (ASG IV) and tetramethylpyrazine (TMPZ) on cerebral ischemia-reperfusion (IR) injury model in rat model. MATERIALS AND 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). CONCLUSION:This study showed that ASG IV-TMPZ played a pivotal synergistic protective role against focal cerebral ischemic reperfusion damage in a rat experimental model.