Systems pharmacology-based approach to investigate the mechanisms of Danggui-Shaoyao-san prescription for treatment of Alzheimer’s disease

BMC Complementary Medicine and Therapies

Qihui Wu¹  Yong Gu¹  Yunbo Chen²  Chuipu Cai²  Weirong Li²  Shuhuan Fang²  Jiansong Fang²  Qi Wang² 

[1] Clinical Research Center, Hainan Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine;Science and Technology Innovation Center, Guangzhou University of Chinese Medicine;

关键词: Systems pharmacology;    Danggui-Shaoyao-san;    Alzheimer’s disease;    Mechanism of action;   

DOI  :  10.1186/s12906-020-03066-4

来源: DOAJ

【 摘 要 】

Abstract Background Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, characterized by a progressive and irreversible loss of memory and cognitive abilities. Currently, the prevention and treatment of AD still remains a huge challenge. As a traditional Chinese medicine (TCM) prescription, Danggui-Shaoyao-san decoction (DSS) has been demonstrated to be effective for alleviating AD symptoms in animal experiments and clinical applications. However, due to the complex components and biological actions, its underlying molecular mechanism and effective substances are not yet fully elucidated. Methods In this study, we firstly systematically reviewed and summarized the molecular effects of DSS against AD based on current literatures of in vivo studies. Furthermore, an integrated systems pharmacology framework was proposed to explore the novel anti-AD mechanisms of DSS and identify the main active components. We further developed a network-based predictive model for identifying the active anti-AD components of DSS by mapping the high-quality AD disease genes into the global drug-target network. Results We constructed a global drug-target network of DSS consisting 937 unique compounds and 490 targets by incorporating experimental and computationally predicted drug–target interactions (DTIs). Multi-level systems pharmacology analyses revealed that DSS may regulate multiple biological pathways related to AD pathogenesis, such as the oxidative stress and inflammatory reaction processes. We further conducted a network-based statistical model, drug-likeness analysis, human intestinal absorption (HIA) and blood-brain barrier (BBB) penetration prediction to uncover the key ani-AD ingredients in DSS. Finally, we highlighted 9 key ingredients and validated their synergistic role against AD through a subnetwork. Conclusion Overall, this study proposed an integrative systems pharmacology approach to disclose the therapeutic mechanisms of DSS against AD, which also provides novel in silico paradigm for investigating the effective substances of complex TCM prescription.

【 授权许可】

Unknown