TY - JOUR
T1 - Integrating network pharmacology and pharmacological evaluation for deciphering the action mechanism of herbal formula Zuojin Pill in suppressing hepatocellular carcinoma
AU - Guo, Wei
AU - Huang, Jihan
AU - Wang, Ning
AU - Tan, Hor-Yue
AU - Cheung, Fan
AU - Chen, Feiyu
AU - Feng, Yibin
N1 - Funding Information:
Tis study was supported by the Research Grant Council, the HKSAR (Project code: RGC GRF 17152116), the Commissioner for Innovation Technology, the HKSAR (Project code: ITS/091/16FX), and the Health and Medical Research Fund (HMRF) (Project code: 16172751).*%blankline%*
Funding Information:
This study was supported by the Research Grant Council, the HKSAR (Project code: RGC GRF 17152116), the Commissioner for Innovation Technology, the HKSAR (Project code: ITS/091/16FX), and the Health and Medical Research Fund (HMRF) (Project code: 16172751).
Publisher Copyright:
© 2019 Guo, Huang, Wang, Tan, Cheung, Chen and Feng.
PY - 2019/10/9
Y1 - 2019/10/9
N2 - 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.
AB - 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.
KW - Zuojin pill
KW - hepatocellular carcinoma
KW - network pharmacology
KW - pharmacological evaluation, cell proliferation and survival
UR - http://www.scopus.com/inward/record.url?scp=85074212361&partnerID=8YFLogxK
U2 - 10.3389/fphar.2019.01185
DO - 10.3389/fphar.2019.01185
M3 - Journal article
AN - SCOPUS:85074212361
SN - 1663-9812
VL - 10
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 01185
ER -
