Unveiling the molecular mechanisms of Danggui-Shaoyao-San against Alzheimer’s disease in APP/PS1 mice via integrating proteomic and metabolomic approaches

作者：Qihui Wu, Wei Wang, Zhuangzi Huang, Xianghao Lin, Mao-Zhong Yao, Chuipu Cai, Guohu Weng, Yong Gu, Hongying Li, Jinman Liu, Jiansong Fang, Weirong Li · 发表于：Alzheimer s Research & Therapy · 年份：2024 · DOI：10.1186/s13195-024-01618-1 · 被引用次数：17 · 研究领域：Alzheimer's disease research and treatments、Traditional Chinese Medicine Analysis、Metabolomics and Mass Spectrometry Studies

BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder for which no effective therapy is currently available. Given that various attempts to target beta-amyloid (Aβ) have been unsuccessful in clinical trials, other potential pathogenic factors such as brain energy metabolism (EM) have attracted increasing attention. Traditional Chinese medicines, including danggui-shaoyao-san (DSS), play a notable role in AD. However, it remains unclear whether DSS exerts therapeutic effects on AD through EM regulation. METHODS: In this study, we conducted behavioural tests, Nissl staining, haematoxylin and eosin staining, and thioflavin S staining, in APP/PS1 mice to assess the pharmacodynamic effect of DSS on AD. Subsequently, we integrated the drug target network of herbal ingredients in DSS and evaluated their absorption, distribution, metabolism, excretion, and toxicity properties to identify the core ingredients. We used proteomic and metabolomic approaches to explore the potential mechanisms of action of DSS against AD. Consequently, we verified the mechanism underlying EM using qPCR, western blotting, and ELISA. RESULTS: In vivo experimental results revealed that DSS ameliorated cognitive impairment in APP/PS1 mice, attenuated neuronal apoptosis, and reduced Aβ burden. Furthermore, the drug-target network comprised 6,514 drug-target interactions involving 1,118 herbal ingredients and 218 AD genes, of which 253 were identified as the core ingredients in D...