Tetrahydropiperine, a natural alkaloid with neuroprotective effects in ischemic stroke

作者：Hongyan Ren, Qianqian Yuan, Jiayuan Lu, Siyu Xi, Yanbo Liu, Guangyu Yang, Zhixi Xie, Bo Wang, Li Ma, Xueyan Fu, Juan Liu, Yiwei Zhang · 发表于：Journal of Chemical Neuroanatomy · 年份：2024 · DOI：10.1016/j.jchemneu.2024.102397 · 被引用次数：8 · 研究领域：Autophagy in Disease and Therapy、Berberine and alkaloids research、Neurological Disease Mechanisms and Treatments

BACKGROUND: Ischemic stroke (IS) is a life-threatening neurological disease with various pathological mechanisms. Tetrahydropiperine (THP) is a natural alkaloid with protective effects against multiple diseases, such as seizure, and pain. This study was to examine the impact of THP on IS and investigate its potential mechanism. MATERIAL AND METHODS: We employed network pharmacology and molecular docking techniques to identify the target proteins of THP for intervention in IS. Adult male Sprague-Dawley rats were used to create a permanent middle cerebral artery occlusion model. PC-12 cells were chosen to establish an oxygen-glucose deprivation (OGD) cell model. Disease modeling followed by nimodipine (NIMO); 3-methyladenine (3-MA) and rapamycin (RAP) interventions. Open field test, Longa score, balance beam test, and forelimb grip test were used to measure motor and neurological functions. The degree of neurological damage recovery was assessed through behavioral analysis, and cerebral infarction volume was determined using TTC staining. Morphological changes were examined through HE and Nissl staining, and ultrastructural changes in neurons were observed using transmission electron microscopy. The protein expression of autophagy and related pathways was analyzed through Western blot (WB). The appropriate hypoxia time and drug concentration were determined using CCK-8 assay, which also measured cell survival rate. RESULTS: The network pharmacology findings indicated that the i...