Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.
Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Molecules. 2023 Mar 13;28(6):2598. doi: 10.3390/molecules28062598.
Vascular dementia (VD) is the second most common dementia syndrome worldwide, and effective treatments are lacking. Blume (GEB) has been used in traditional Chinese herbal medicine for centuries to treat cognitive impairment, ischemic stroke, epilepsy, and dizziness. Gastrodin (-hydroxymethylphenyl-b--glucopyranoside, Gas) and Gastrodigenin (-hydroxybenzyl alcohol, HBA) are the main bioactive components of GEB. This study explored the effects of Gas and HBA on cognitive dysfunction in VD and their possible molecular mechanisms. The VD model was established by bilateral common carotid artery ligation (2-vessel occlusion, 2-VO) combined with an intraperitoneal injection of sodium nitroprusside solution. One week after modeling, Gas (25 and 50 mg/kg, i.g.) and HBA (25 and 50 mg/kg, i.g.) were administered orally for four weeks, and the efficacy was evaluated. A Morris water maze test and passive avoidance test were used to observe their cognitive function, and H&E staining and Nissl staining were used to observe the neuronal morphological changes; the expressions of Aβ1-42 and p-tau396 were detected by immunohistochemistry, and the changes in energy metabolism in the brain tissue of VD rats were analyzed by targeted quantitative metabolomics. Finally, a Hippocampus XF analyzer measured mitochondrial respiration in HO-treated HT-22 cells. Our study showed that Gas and HBA attenuated learning memory dysfunction and neuronal damage and reduced the accumulation of Aβ1-42, P-Tau396, and P-Tau217 proteins in the brain tissue. Furthermore, Gas and HBA improved energy metabolism disorders in rats, involving metabolic pathways such as glycolysis, tricarboxylic acid cycle, and the pentose phosphate pathway, and reducing oxidative damage-induced cellular mitochondrial dysfunction. The above results indicated that Gas and HBA may exert neuroprotective effects on VD by regulating energy metabolism and mitochondrial function.
血管性痴呆（VD）是全球第二常见的痴呆综合征，目前缺乏有效的治疗方法。百令（GEB）在传统中药中已使用数百年，用于治疗认知障碍、缺血性中风、癫痫和头晕。天麻素（-羟甲基苯-β-D-吡喃葡萄糖苷，Gas）和天麻苷元（-羟基苯甲醇，HBA）是 GEB 的主要生物活性成分。本研究探讨了 Gas 和 HBA 对 VD 认知功能障碍的影响及其可能的分子机制。通过双侧颈总动脉结扎（2 血管闭塞，2-VO）联合腹腔注射硝普钠溶液建立 VD 模型。建模后 1 周，口服给予 Gas（25 和 50mg/kg）和 HBA（25 和 50mg/kg）4 周，评价疗效。采用 Morris 水迷宫试验和被动回避试验观察其认知功能，H&E 染色和尼氏染色观察神经元形态变化；免疫组化检测 Aβ1-42 和 p-tau396 的表达，采用靶向定量代谢组学分析 VD 大鼠脑组织能量代谢变化。最后，用 Hippocampus XF 分析仪检测 HO 处理的 HT-22 细胞中线粒体呼吸。我们的研究表明，Gas 和 HBA 可减轻学习记忆功能障碍和神经元损伤，减少脑组织中 Aβ1-42、P-Tau396 和 P-Tau217 蛋白的积累。此外，Gas 和 HBA 改善了大鼠的能量代谢紊乱，涉及糖酵解、三羧酸循环和戊糖磷酸途径等代谢途径，并减轻氧化损伤诱导的细胞线粒体功能障碍。上述结果表明，Gas 和 HBA 可能通过调节能量代谢和线粒体功能对 VD 发挥神经保护作用。
