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Article: Integrating Network Pharmacology and Pharmacological Evaluation for Deciphering the Action Mechanism of Herbal Formula Zuojin Pill in Suppressing Hepatocellular Carcinoma

TitleIntegrating Network Pharmacology and Pharmacological Evaluation for Deciphering the Action Mechanism of Herbal Formula Zuojin Pill in Suppressing Hepatocellular Carcinoma
Authors
KeywordsCell proliferation and survival
Hepatocellular carcinoma
Network pharmacology
Pharmacological evaluation
Zuojin pill
Issue Date2019
PublisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/pharmacology
Citation
Frontiers in Pharmacology, 2019, v. 10, article no. 01185 How to Cite?
AbstractHepatocellular 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-κB, 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.
Persistent Identifierhttp://hdl.handle.net/10722/282261
ISSN
2020 Impact Factor: 5.81
2020 SCImago Journal Rankings: 1.384
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGuo, W-
dc.contributor.authorHuang, J-
dc.contributor.authorWang, N-
dc.contributor.authorTan, HYH-
dc.contributor.authorCheung, F-
dc.contributor.authorChen, F-
dc.contributor.authorFeng, Y-
dc.date.accessioned2020-05-05T14:32:51Z-
dc.date.available2020-05-05T14:32:51Z-
dc.date.issued2019-
dc.identifier.citationFrontiers in Pharmacology, 2019, v. 10, article no. 01185-
dc.identifier.issn1663-9812-
dc.identifier.urihttp://hdl.handle.net/10722/282261-
dc.description.abstractHepatocellular 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-κB, 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.-
dc.languageeng-
dc.publisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/pharmacology-
dc.relation.ispartofFrontiers in Pharmacology-
dc.rightsThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCell proliferation and survival-
dc.subjectHepatocellular carcinoma-
dc.subjectNetwork pharmacology-
dc.subjectPharmacological evaluation-
dc.subjectZuojin pill-
dc.titleIntegrating Network Pharmacology and Pharmacological Evaluation for Deciphering the Action Mechanism of Herbal Formula Zuojin Pill in Suppressing Hepatocellular Carcinoma-
dc.typeArticle-
dc.identifier.emailWang, N: ckwang@hku.hk-
dc.identifier.emailTan, HYH: hyhtan@hku.hk-
dc.identifier.emailFeng, Y: yfeng@hku.hk-
dc.identifier.authorityWang, N=rp02075-
dc.identifier.authorityFeng, Y=rp00466-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fphar.2019.01185-
dc.identifier.scopuseid_2-s2.0-85074212361-
dc.identifier.hkuros309781-
dc.identifier.volume10-
dc.identifier.spagearticle no. 01185-
dc.identifier.epagearticle no. 01185-
dc.identifier.isiWOS:000497520300001-
dc.publisher.placeSwitzerland-
dc.identifier.issnl1663-9812-

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