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

• Published in: Fitoterapia Vol. 165; p. 105398
• Main Authors: Lijuan, Tan, Xiaolu, Cao, Xin, Wan, Yuying, He, Xi, Lan, Xiliang, Yang, Ting, Wang, Zhenli, Min, Yu, Zou
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2023
• Subjects: Animals; Anti-platelet aggregation; Ischemic stroke; Molecular docking; Molecular Structure; MRTF-A; Neuroprotective Agents - pharmacology; Piperlongumine; Proto-Oncogene Proteins c-bcl-2; Rats; Stroke - drug therapy; Piperlongumine; Ischemic stroke; MRTF-A; Molecular docking; Anti-platelet aggregation
• ISSN: 0367-326X; 1873-6971
• DOI: 10.1016/j.fitote.2022.105398

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 previous 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. [Display omitted]