Liu Sai, Chen Long, Li Jinran, Sun Yuan, Xu Yue, Li Zhaoxing, Zhu Zheying, Li Xinuo
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Int J Mol Sci. 2023 Jul 26;24(15):11976. doi: 10.3390/ijms241511976.
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, hallmarked by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles. Due to the uncertainty of the pathogenesis of AD, strategies aimed at suppressing neuroinflammation and fostering synaptic repair are eagerly sought. Asiaticoside (AS), a natural triterpenoid derivative derived from Centella asiatica, is known for its anti-inflammatory, antioxidant, and wound-healing properties; however, its neuroprotective function in AD remains unclear. Our current study reveals that AS, when administered (40 mg/kg) in vivo, can mitigate cognitive dysfunction and attenuate neuroinflammation by inhibiting the activation of microglia and proinflammatory factors in Aβ-induced AD mice. Further mechanistic investigation suggests that AS may ameliorate cognitive impairment by inhibiting the activation of the p38 MAPK pathway and promoting synaptic repair. Our findings propose that AS could be a promising candidate for AD treatment, offering neuroinflammation inhibition and enhancement of synaptic function.
阿尔茨海默病（AD）是一种常见的神经退行性疾病，其特征是β淀粉样蛋白（Aβ）斑块和神经原纤维缠结的积累。由于AD发病机制的不确定性，人们急切地寻求旨在抑制神经炎症和促进突触修复的策略。积雪草苷（AS）是一种从积雪草中提取的天然三萜衍生物，以其抗炎、抗氧化和伤口愈合特性而闻名；然而，其在AD中的神经保护功能仍不清楚。我们目前的研究表明，AS在体内以40mg/kg的剂量给药时，可以减轻Aβ诱导的AD小鼠的认知功能障碍，并通过抑制小胶质细胞的激活和促炎因子来减轻神经炎症。进一步的机制研究表明，AS可能通过抑制p38丝裂原活化蛋白激酶（MAPK）途径的激活和促进突触修复来改善认知障碍。我们的研究结果表明，AS可能是一种有前途的AD治疗候选药物，具有抑制神经炎症和增强突触功能的作用。
