Abstract
Bushen-Yizhi prescription (BSYZ) has been an effective traditional Chinese medicine (TCM) prescription in treating Alzheimer’s disease (AD) for hundreds of years. However, the underlying mechanisms have not been fully elucidated yet. In this work, a systems pharmacology approach was developed to reveal the underlying molecular mechanisms of BSYZ in treating AD. First, we obtained 329 candidate compounds of BSYZ by in silico ADME/T filter analysis and 138 AD-related targets were predicted by our in-house WEGA algorithm via mapping predicted targets into AD-related proteins. In addition, we elucidated the mechanisms of BSYZ action on AD through multiple network analysis, including compound-target network analysis and target-function network analysis. Furthermore, several modules regulated by BSYZ were incorporated into AD-related pathways to uncover the therapeutic mechanisms of this prescription in AD treatment. Finally, further verification experiments also demonstrated the therapeutic effects of BSYZ on cognitive dysfunction in APP/PS1 mice, which was possibly via regulating amyloid-β metabolism and suppressing neuronal apoptosis. In conclusion, we provide an integrative systems pharmacology approach to illustrate the underlying therapeutic mechanisms of BSYZ formula action on AD.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that impairs memory and cognitive judgement
A total of 688 chemical moieties derived from the Bushen-Yizhi formula (BSYZ) formula were collected from traditional Chinese medicine systems pharmacology (TCMSP)[24] and traditional Chinese medicine (TCM)[25] databases
We developed an integrative systems pharmacology approach to uncover the pharmacological mechanisms of BSYZ against AD with a network pharmacology analysis and experimental validations
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that impairs memory and cognitive judgement. Chinese medicine has been widely applied in the prevention and treatment of diseases for two thousand years and a number of TCM formulas are employed to improve cognitive function[9]. As a novel strategy to identify the active compounds of herbs and their therapeutic targets, systems pharmacology has been used to facilitate a comprehensive understanding of the MOAs of Chinese herbal medicines[19,20,21,22]. We employed a systems pharmacology approach to investigate the active ingredients, potential targets and therapeutic MOAs of BSYZ in AD treatment (Fig. 1). The predicted targets were mapped into AD-relevant databases to determine their biological functions and corresponding AD pathways Based on these results, we constructed networks to illuminate the MOAs of BSYZ on AD. We used an APP/PS1 mouse model to validate the proposed mechanisms for BSYZ as an anti-AD agent
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