Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma

Abstract Background Cholangiocarcinoma refers to an epithelial cell malignancy with poor prognosis. Yinchenhao decoction (YCHD) showed positive effects on cancers, and associations between YCHD and cholangiocarcinoma remain unclear. This study aimed to screen out the effective active components of Y...

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Main Authors: Zhiqiang Chen, Tong Lin, Xiaozhong Liao, Zeyun Li, Ruiting Lin, Xiangjun Qi, Guoming Chen, Lingling Sun, Lizhu Lin
Format: Article
Language:English
Published: BMC 2021-01-01
Series:Chinese Medicine
Subjects:
Online Access:https://doi.org/10.1186/s13020-021-00423-4
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spelling doaj-b5040e242920405882daef79775626e12021-01-24T12:25:37ZengBMCChinese Medicine1749-85462021-01-0116112010.1186/s13020-021-00423-4Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against CholangiocarcinomaZhiqiang Chen0Tong Lin1Xiaozhong Liao2Zeyun Li3Ruiting Lin4Xiangjun Qi5Guoming Chen6Lingling Sun7Lizhu Lin8The First School of Clinical Medical Sciences, Guangzhou University of Chinese MedicineThe First School of Clinical Medical Sciences, Guangzhou University of Chinese MedicineThe First School of Clinical Medical Sciences, Guangzhou University of Chinese MedicineThe First School of Clinical Medical Sciences, Guangzhou University of Chinese MedicineThe First School of Clinical Medical Sciences, Guangzhou University of Chinese MedicineThe First School of Clinical Medical Sciences, Guangzhou University of Chinese MedicineThe First School of Clinical Medical Sciences, Guangzhou University of Chinese MedicineDepartment of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese MedicineDepartment of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese MedicineAbstract Background Cholangiocarcinoma refers to an epithelial cell malignancy with poor prognosis. Yinchenhao decoction (YCHD) showed positive effects on cancers, and associations between YCHD and cholangiocarcinoma remain unclear. This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma. Methods By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods. Results 32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions. Conclusions As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effectsthrough multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.https://doi.org/10.1186/s13020-021-00423-4Yinchenhao decoctionNetwork pharmacologyMechanismCholangiocarcinoma
collection DOAJ
language English
format Article
sources DOAJ
author Zhiqiang Chen
Tong Lin
Xiaozhong Liao
Zeyun Li
Ruiting Lin
Xiangjun Qi
Guoming Chen
Lingling Sun
Lizhu Lin
spellingShingle Zhiqiang Chen
Tong Lin
Xiaozhong Liao
Zeyun Li
Ruiting Lin
Xiangjun Qi
Guoming Chen
Lingling Sun
Lizhu Lin
Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma
Chinese Medicine
Yinchenhao decoction
Network pharmacology
Mechanism
Cholangiocarcinoma
author_facet Zhiqiang Chen
Tong Lin
Xiaozhong Liao
Zeyun Li
Ruiting Lin
Xiangjun Qi
Guoming Chen
Lingling Sun
Lizhu Lin
author_sort Zhiqiang Chen
title Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma
title_short Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma
title_full Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma
title_fullStr Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma
title_full_unstemmed Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma
title_sort network pharmacology based research into the effect and mechanism of yinchenhao decoction against cholangiocarcinoma
publisher BMC
series Chinese Medicine
issn 1749-8546
publishDate 2021-01-01
description Abstract Background Cholangiocarcinoma refers to an epithelial cell malignancy with poor prognosis. Yinchenhao decoction (YCHD) showed positive effects on cancers, and associations between YCHD and cholangiocarcinoma remain unclear. This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma. Methods By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods. Results 32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions. Conclusions As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effectsthrough multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.
topic Yinchenhao decoction
Network pharmacology
Mechanism
Cholangiocarcinoma
url https://doi.org/10.1186/s13020-021-00423-4
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