Chlorogenic acid alleviates middle cerebral artery occlusion-induced changes of Bcl-2/Bad and Bcl-xL/Bad interaction in adult male rats

Abstract

Ischemic stroke is caused by a blockage of the cerebral artery, which leads to a severe neurological disorder. Chlorogenic acid is a phenolic acid found mainly in plants such as coffee beans, eggplants, and carrots. It exerts a neuroprotective effect against cerebral ischemic damage. Bcl-2 family protein is a representative apoptosis regulatory protein. Bcl-2 and Bcl-xL act as apoptosis inhibitors, while Bax and Bad act as apoptosis inducers.The interaction of Bcl-2 family protein plays an important role in determining cell fate. The aim of this study was to investigate whether chlorogenic acid modulates the interaction of Bcl-2 family proteins during ischemic injury. Middle cerebral artery occlusion (MCAO) surgery was performed to induce cerebral ischemia. Chlorogenic acid (30 mg/kg) or phosphate buffered saline was intraperitoneally injected to adult male rats 2 h after MCAO surgery. Neurobehavioral tests were performed to confirm the neuroprotective effect of chlorogenic acid 24 h after MCAO injury, and immunoprecipitation analysis was performed to investigate the interaction of Bcl-2 family protein. MCAO damage showed signs of severe neurological disorders, while chlorogenic acid improved these disorders. Results of immunoprecipitation analysis were as follows. Interaction between Bax and Bcl-2 or Bcl-xL was decreased in MCAO injury, chlorogenic acid prevents these decreases. In contrast to Bax, Interaction between Bad and Bcl-2 or Bcl-xL was increased in MCAO injury, chlorogenic acid prevents these increases. Furthermore, chlorogenic acid attenuated MCAO-induced increase of capase-9. In conclusion, our findings demonstrate that chlorogenic acid exerts a neuroprotective effect against cerebral ischemic injury by modulating interaction of Bcl-2 family proteins.