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Front. Pharmacol. | doi: 10.3389/fphar.2018.00668

A Computational Systems Pharmacology Approach to Investigate Molecular Mechanisms of Herbal Formula Tian-Ma-Gou-Teng-Yin for Treatment of Alzheimer’s Disease

  • 1School of Pharmacy, East China University of Science and Technology, China

Traditional Chinese Medicine (TCM) is typically prescribed as formula to treat certain symptoms. A TCM formula contains hundreds of chemical components, which makes it complicated to elucidate the molecular mechanisms of TCM. Here, we proposed a computational systems pharmacology approach consisting of network link prediction, statistical analysis and bioinformatics tools to investigate the molecular mechanisms of TCM formulae. Taking formula Tian-Ma-Gou-Teng-Yin as an example, which shows pharmacological effects on Alzheimer’s disease (AD) and its mechanism is unclear, we first identified 494 formula components together with corresponding 178 known targets, and then predicted 364 potential targets for these components with our balanced substructure-drug-target network-based inference method. With Fisher’s exact test and statistical analysis we identified 12 compounds to be most significantly related to AD. The target genes of these compounds were further enriched onto pathways involved in AD, such as neuroactive ligand-receptor interaction, serotonergic synapse, inflammatory mediator regulation of transient receptor potential channel and calcium signaling pathway. By regulating key target genes, such as ACHE, HTR2A, NOS2 and TRPA1, the formula could have neuroprotective and anti-neuroinflammatory effects against the progression of AD. Our approach provided a holistic perspective to study the relevance between TCM formulae and diseases, and implied possible pharmacological effects of TCM components.

Keywords: Traditional Chinese Medicine, Compound-protein interactions, Network-based inference, Computational systems pharmacology, Alzheimer’s disease

Received: 17 Mar 2018; Accepted: 04 Jun 2018.

Edited by:

Yuanjia Hu, University of Macau, Macau

Reviewed by:

Junguk Hur, University of North Dakota, United States
István Zupkó, University of Szeged, Hungary  

Copyright: © 2018 Wang, Wu, Sun, Li, Liu and Tang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yun Tang, East China University of Science and Technology, School of Pharmacy, 130 Meilong Road, Shanghai, 200237, China,