Systems-mapping of herbal effects on complex diseases using the network-perturbation signatures

Xuetong Chen, Chunli Zheng, Chun Wang, Zihu Guo, Shuo Gao, Zhangchi Ning, Chao Huang, Cheng Lu, Yingxue Fu, Daogang GUAN*, Aiping LYU, Yonghua Wang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

The herbs have proven to hold great potential to improve people's health and wellness during clinical practice over the past millennia. However, herbal medicine for the personalized treatment of disease is still under investigation owing to the complex multi-component interactions in herbs. To reveal the valuable insights for herbal synergistic therapy, we have chosen Traditional Chinese Medicine (TCM) as a case to illustrate the art and science behind the complicated multi-molecular, multi-genes interaction systems, and how the good practices of herbal combination therapy are applicable to personalized treatment. Here, we design system-wide interaction map strategy to provide a generic solution to establish the links between diseases and herbs based on comprehensive testing of molecular signatures in herb-disease pairs. Firstly, we integrated gene expression profiles from 189 diseases to characterize the disease-pathological feature. Then, we generated the perturbation signatures from the huge chemical informatics data and pharmacological data for each herb, which were represented the targets affected by the ingredients in the herb. So that we could assess the effects of herbs on the individual. Finally, we integrated the data of 189 diseases and 502 herbs, yielding the optimal herbal combinations for the diseases based on the strategy, and verifying the reliability of the strategy through the permutation testing and literature verification. Furthermore, we propose a novel formula as a candidate therapeutic drugs of rheumatoid arthritis and demonstrate its therapeutic mechanism through the systematic analysis of the influencing targets and biological processes. Overall, this computational method provides a systematic approach, which blended herbal medicine and omics data sets, allowing for the development of novel drug combinations for complex human diseases.

Original languageEnglish
Article number1174
JournalFrontiers in Pharmacology
Volume9
Issue numberOCT
DOIs
Publication statusPublished - 18 Oct 2018

Scopus Subject Areas

  • Pharmacology
  • Pharmacology (medical)

User-Defined Keywords

  • Herbal medicines
  • Mathematical modeling
  • Network pharmacology
  • Personalized medicine
  • Perturbation signatures
  • Systems pharmacology

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