System pharmacology-based strategy to decode the synergistic mechanism of Zhi-zhu Wan for functional dyspepsia

Chun Wang, Qing Ren, Xue Tong Chen, Zhi Qian Song, Zhang Chi Ning, Jia He Gan, Xin Ling Ma, Dong Rui Liang, Daogang GUAN*, Zhen Li Liu, Aiping LYU

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Functional dyspepsia (FD) is a widely prevalent gastrointestinal disorder throughout the world, whereas the efficacy of current treatment in the Western countries is limited. As the symptom is equivalent to the traditional Chinese medicine (TCM) term "stuffiness and fullness," FD can be treated with Zhi-zhu Wan (ZZW) which is a kind of Chinese patent medicine. However, the "multi-component" and "multi-target" feature of Chinese patent medicine makes it challenge to elucidate the potential therapeutic mechanisms of ZZW on FD. Presently, a novel system pharmacology model including pharmacokinetic parameters, pharmacological data, and component contribution score (CS) is constructed to decipher the potential therapeutic mechanism of ZZW on FD. Finally, 61 components with favorable pharmacokinetic profiles and biological activities were obtained through ADME (absorption, distribution, metabolism, and excretion) screening in silico. The related targets of these components are identified by component targeting process followed by GO analysis and pathway enrichment analysis. And systematic analysis found that through acting on the target related to inflammation, gastrointestinal peristalsis, and mental disorder, ZZW plays a synergistic and complementary effect on FD at the pathway level. Furthermore, the component CS showed that 29 components contributed 90.18% of the total CS values of ZZW for the FD treatment, which suggested that the effective therapeutic effects of ZZW for FD are derived from all active components, not a few components. This study proposes the system pharmacology method and discovers the potent combination therapeutic mechanisms of ZZW for FD. This strategy will provide a reference method for other TCM mechanism research.

Original languageEnglish
Article number841
JournalFrontiers in Pharmacology
Volume9
Issue numberAUG
DOIs
Publication statusPublished - 6 Aug 2018

Scopus Subject Areas

  • Pharmacology
  • Pharmacology (medical)

User-Defined Keywords

  • Baizhu
  • Functional dyspepsia
  • System pharmacology
  • Therapeutic mechanism
  • Zhi-zhu Wan
  • Zhishi

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