Abstract

Ischemic cerebrovascular disease is a global health problem. According to the World Health Organization, ischemic stroke is actually the most common cause of death in the world. Ligustrazine (4-methyl-pyrazine [tetramethylpyrazine]) protects neurons against toxicity and plays a central role in regulating the brain’s response to injury. In the present study, we investigated the mechanisms involved in the neuroprotective effects of ligustrazine in a model of hypoxic-ischemic brain disease. We found that ligustrazine effectively increases the survival rate of PC12 cells and relieves OGD (oxygen-glucose deprivation) damage. The effects of ligustrazine on the ActA/Smad pathway and on the up-regulation of inducible nitric oxide synthase (NOS) and superoxide dismutase (SOD) were investigated using OGD in PC12 cells for clarifying the neuroprotective mechanisms of ligustrazine. The results show that ligustrazine increases the expression of ActRIIA, Smad3 and Smad4; and that 50 and 100 ng/ml of ligustrazine reduces NO levels and increases SOD activity by 78.9 and 79.9%, respectively. These results suggest that the neuroprotective effects of ligustrazine in ischemia are related to the activation of the ActA/Smad signaling pathway and to its anti-oxidant activities.

Key words: Oxygen-glucose deprivation, ischemia tolerance model, ligustrazine, ActA/Smad pathway.