Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China; Interdisciplinary Institute for Personalized Medicine in Brain Disorders, Jinan University, Guangzhou, China.
Phytomedicine. 2021 Oct;91:153648. doi: 10.1016/j.phymed.2021.153648. Epub 2021 Jul 12.
Alzheimer's disease (AD) is the most common neurodegenerative disease. Deposition of amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs) is the key pathological hallmark of AD. Accumulating evidence suggest that impairment of autophagy-lysosomal pathway (ALP) plays key roles in AD pathology.
The present study aims to assess the neuroprotective effects of Qingyangshen (QYS), a Chinese herbal medicine, in AD cellular and animal models and to determine its underlying mechanisms involving ALP regulation.
QYS extract was prepared and its chemical components were characterized by LC/MS. Then the pharmacokinetics and acute toxicity of QYS extract were evaluated. The neuroprotective effects of QYS extract were determined in 3XTg AD mice, by using a series of behavioral tests and biochemical assays, and the mechanisms were examined in vitro.
Oral administration of QYS extract improved learning and spatial memory, reduced carboxy-terminal fragments (CTFs), amyloid precursor protein (APP), Aβ and Tau aggregates, and inhibited microgliosis and astrocytosis in the brains of 3XTg mice. Mechanistically, QYS extract increased the expression of PPARα and TFEB, and promoted ALP both in vivo and in vitro.
QYS attenuates AD pathology, and improves cognitive function in 3XTg mice, which may be mediated by activation of PPARα-TFEB pathway and the subsequent ALP enhancement. Therefore, QYS may be a promising herbal material for further anti-AD drug discovery.
阿尔茨海默病（AD）是最常见的神经退行性疾病。淀粉样β斑块（Aβ）和神经纤维缠结（NFTs）的沉积是 AD 的关键病理标志。越来越多的证据表明，自噬溶酶体途径（ALP）的损伤在 AD 病理学中起关键作用。
本研究旨在评估中药青羊参（QYS）在 AD 细胞和动物模型中的神经保护作用，并确定其涉及 ALP 调节的潜在机制。
制备 QYS 提取物，并用 LC/MS 对其化学组成进行表征。然后评估 QYS 提取物的药代动力学和急性毒性。通过一系列行为测试和生化测定，在 3XTg AD 小鼠中评估 QYS 提取物的神经保护作用，并在体外研究其机制。
口服 QYS 提取物可改善 3XTg 小鼠的学习和空间记忆，减少羧基末端片段（CTFs）、淀粉样前体蛋白（APP）、Aβ 和 Tau 聚集体，并抑制大脑中的小胶质细胞和星形胶质细胞增生。在体内和体外，QYS 提取物均增加了 PPARα 和 TFEB 的表达，并促进了 ALP。
QYS 可减轻 AD 病理，改善 3XTg 小鼠的认知功能，这可能是通过激活 PPARα-TFEB 途径和随后的 ALP 增强介导的。因此，QYS 可能是一种有前途的抗 AD 药物发现的草药材料。
