Xiao Tian, Yu Xingling, Tao Jie, Tan Jiaoyang, Zhao Zhourong, Zhang Chao, Duan Xiaohua
Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine, Kunming 650500, China.
Int J Mol Sci. 2025 Jan 1;26(1):317. doi: 10.3390/ijms26010317.
Stroke is the leading cause of death and disability worldwide, with ischemic stroke accounting for the majority of these. HBA is the active ingredient in and has potential therapeutic effects on central nervous system diseases. In this study, the cell model of cerebral ischemia was replicated by the culture method of oxygen-glucose deprivation/reoxygenation, and the rat model of vascular dementia was established by the two-vessel occlusion method. Metabolomics technology was employed to analyze the metabolic changes in ischemic neurons induced by HBA, and potential therapeutic targets were verified. The protective effects of HBA on ischemic neurons and their mitochondria were examined through multiple indicators, and the related mechanisms were verified. HBA can improve post-ischemic cognitive impairment in rats, and its mechanism is related to the regulation of the choline-activated phospholipase D2/Sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α pathway to improve mitochondrial function and reduce autophagic activity to maintain mitochondrial homeostasis. It is concluded that HBA has a protective effect on neuronal damage and cognitive impairment caused by cerebral ischemia by regulating key metabolites and signaling pathways, and that it provides a new molecular target for the treatment of cerebral ischemia.
中风是全球范围内导致死亡和残疾的主要原因,其中缺血性中风占大多数。HBA是[具体药物名称]中的活性成分,对中枢神经系统疾病具有潜在治疗作用。在本研究中,采用氧糖剥夺/复氧培养法复制脑缺血细胞模型,通过双血管闭塞法建立血管性痴呆大鼠模型。运用代谢组学技术分析HBA诱导的缺血神经元代谢变化,并验证潜在治疗靶点。通过多项指标检测HBA对缺血神经元及其线粒体的保护作用,并验证相关机制。HBA可改善大鼠缺血后认知障碍,其机制与调节胆碱激活的磷脂酶D2/沉默信息调节因子1/过氧化物酶体增殖物激活受体γ共激活因子1α通路以改善线粒体功能、降低自噬活性从而维持线粒体稳态有关。结论是,HBA通过调节关键代谢物和信号通路对脑缺血所致神经元损伤和认知障碍具有保护作用,为脑缺血治疗提供了新的分子靶点。