Integrating network pharmacology and pharmacological evaluation for deciphering the action mechanism of herbal formula Zuojin Pill in suppressing hepatocellular carcinoma

Wei Guo, Jihan Huang, Ning Wang, Hor-Yue Tan, Fan Cheung, Feiyu Chen, Yibin Feng*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

73 Citations (Scopus)

Abstract

Hepatocellular carcinoma (HCC) is a kind of complicated disease with an increasing incidence all over the world. A classic Chinese medicine formula, Zuojin pill (ZJP), was shown to exert therapeutic effects on HCC. However, its chemical and pharmacological profiles remain to be elucidated. In the current study, network pharmacology approach was applied to characterize the action mechanism of ZJP on HCC. All compounds were obtained from the corresponding databases, and active compounds were selected according to their oral bioavailability and drug-likeness index. The potential proteins of ZJP were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database and the traditional Chinese medicine integrated database (TCMID), whereas the potential genes of HCC were obtained from OncoDB.HCC and Liverome databases. The potential pathways related to genes were determined by gene ontology (GO) and pathway enrichment analyses. The compound-target and target-pathway networks were constructed. Subsequently, the potential underlying action mechanisms of ZJP on HCC predicted by the network pharmacology analyses were experimentally validated in HCC cellular and orthotopic HCC implantation murine models. A total of 224 components in ZJP were obtained, among which, 42 were chosen as bioactive components. The compound-target network included 32 compounds and 86 targets, whereas the target-pathway network included 70 proteins and 75 pathways. The in vitro and in vivo experiments validated that ZJP exhibited its prominent therapeutic effects on HCC mainly via the regulation of cell proliferation and survival though the EGFR/MAPK, PI3K/NF-êB, and CCND1 signaling pathways. In conclusion, our study suggested combination of network pharmacology prediction with experimental validation may offer a useful tool to characterize the molecular mechanism of traditional Chinese medicine (TCM) ZJP on HCC.

Original languageEnglish
Article number01185
Number of pages21
JournalFrontiers in Pharmacology
Volume10
DOIs
Publication statusPublished - 9 Oct 2019

Scopus Subject Areas

  • Pharmacology
  • Pharmacology (medical)

User-Defined Keywords

  • Zuojin pill
  • hepatocellular carcinoma
  • network pharmacology
  • pharmacological evaluation, cell proliferation and survival

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