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Systems Pharmacological Approach to Investigate the Mechanism of Ohwia caudata for Application to Alzheimer's Disease.

ABSTRACT: Ohwia caudata (OC)-a traditional Chinese medicine (TCM)-has been reported to have large numbers of flavonoids, alkaloids, and triterpenoids. The previous studies on OC for treating Alzheimer's disease (AD) only focused on single targets and its mechanisms, while no report had shown about the synergistic mechanism of the constituents from OC related to their potential treatment on dementia in any database. This study aimed to predict the bioactive targets constituents and find potential compounds from OC with better oral bioavailability and blood-brain barrier permeability against AD, by using a system network level-based in silico approach. The results revealed that two new flavonoids, and another 26 compounds isolated from OC in our lab, were highly connected to AD-related signaling pathways and biological processes, which were confirmed by compound-target network, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, respectively. Predicted by the virtual screening and various network pharmacology methods, we found the multiple mechanisms of OC, which are effective for alleviating AD symptoms through multiple targets in a synergetic way.

SUBMITTER: Sun YW

PROVIDER: S-EPMC6515364 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Systems Pharmacological Approach to Investigate the Mechanism of <i>Ohwia caudata</i> for Application to Alzheimer's Disease.

Sun Yi-Wei YW Wang Yue Y Guo Zi-Feng ZF Du Kai-Cheng KC Meng Da-Li DL

Molecules (Basel, Switzerland) 20190417 8

<i>Ohwia caudata</i> (OC)-a traditional Chinese medicine (TCM)-has been reported to have large numbers of flavonoids, alkaloids, and triterpenoids. The previous studies on OC for treating Alzheimer's disease (AD) only focused on single targets and its mechanisms, while no report had shown about the synergistic mechanism of the constituents from OC related to their potential treatment on dementia in any database. This study aimed to predict the bioactive targets constituents and find potential co ...[more]

PMID: 30999553

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Project description:BackgroundAlzheimer'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.MethodsIn 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.ResultsWe 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.ConclusionOverall, 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.

Dataset Information

Systems Pharmacological Approach to Investigate the Mechanism of Ohwia caudata for Application to Alzheimer's Disease.

Publications

Systems Pharmacological Approach to Investigate the Mechanism of <i>Ohwia caudata</i> for Application to Alzheimer's Disease.

Similar Datasets

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