Identification of ligustrazine-based analogs of piperlongumine as potential anti-ischemic stroke agents

摘要

Piper longum has a specific aroma and spicy taste. In addition to edible value, current studies have shown that piper longum also has pharmacological activities such as anti-platelet aggregation, anti-inflammation, anti-cancer, anti-diabetes and anti-depression. Piperlongumine is an alkaloid isolated from Piper longum. Based on our pre-vious studies, four Piperlongumine analogs were synthesized, and their anti-platelet aggregation activities were evaluated. Among them, compound 8 has the strongest anti-platelet aggregation activity. Therefore, compound 8 was docked with stroke-related protein targets, and it was found that compound 8 had good binding affinity to MRTF-A complex and Bcl-2. Through animal experiments, it was found that compound 8 could significantly improve the pathological damage of brain tissue after ischemia and could increase the expression of MRTF-A and Bcl-2 in cerebral cortex in rats. These results suggest that compound 8 may have a good inhibitory effect on apoptosis and tissue structurel disorders induced by cerebral ischemia-reperfusion, so as to reduce the injury caused by ischemic stroke.

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