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

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.

Integrated Serum Pharmacochemistry, Metabolomics, and Network Pharmacology to Reveal the Material Basis and Mechanism of Danggui Shaoyao San in the Treatment of Primary Dysmenorrhea

“…Scholars have reported that the material basis of DSS against atherosclerosis was paeoniflorin, ferulic acid, and Poria acid, and the material basis of DSS against senile dementia are ferulic acid, A. macrocephala I, gallic acid, etc. ( Wu et al, 2020 ; Bi et al, 2021 ). Nevertheless, for hundreds of years, due to the complexity of the components and internal mechanisms of DSS, tremendous efforts have been made to reveal the active components and pharmacological mechanisms of DSS, but it still has not been effectively solved.…”

DPHB, a diarylheptane from Alpinia officinarum Hance, ameliorates insulin resistance: A network pharmacology and in vitro study

“…Network pharmacology, in combination with the system biology theory, utilizes high-throughput omics data analysis, computer simulation, network database retrieval, and other technologies to construct drug–target–disease interaction networks as well as to systematically clarify the potential targets and pharmacological effects of traditional Chinese medicine (TCM) components to evaluate the role of TCM in diseases ( Nogales et al, 2022 ). Therefore, an increasing number of studies have applied network pharmacology to clarify the pharmacodynamic basis and the molecular mechanism of TCM/drugs in disease treatment ( Luo et al, 2020 ; Wu et al, 2020 ; Cai et al, 2021 ).…”

Anti-Inflammatory Effects and Mechanisms of Pudilan Antiphlogistic Oral Liquid

“… 13 Studies have found that the construction of complex biochemical networks of living organisms such as cells presented a large-scale period from transients (such as metabolic reactions) to long-term regulation (such as cell development), from different localities within cells to tissues and organs. 14 Large-scale leaps will also present multiple dimensions of the three-dimensional network from small chemical molecules, genes to proteins. 15 Therefore, systemic pharmacology can solve a series of problems brought about by the complexity of TCM, which provides a new approach to predict the active ingredients and candidate targets through a holistic process of active compound screening, target “fishing”, component–target–disease (C–T–D) network construction, and target enrichment analysis.…”

“…Systemic pharmacology is built to study the interaction between drugs and the body from a systemic level, which helps to study the discipline and mechanisms of the action of the drugs, especially some ancient but potent formulae . Studies have found that the construction of complex biochemical networks of living organisms such as cells presented a large-scale period from transients (such as metabolic reactions) to long-term regulation (such as cell development), from different localities within cells to tissues and organs . Large-scale leaps will also present multiple dimensions of the three-dimensional network from small chemical molecules, genes to proteins .…”