A Network Pharmacology Approach to Investigate the Anticancer Mechanism and Potential Active Ingredients of Rheum palmatum L. Against Lung Cancer via Induction of Apoptosis

Rheum palmatum L. (RPL) is a known traditional herbal medicine with the functions of “heat-clearing and damp-drying” in traditional Chinese medicine. Its anti-cancer effect against lung cancer has been confirmed previously, but the related mechanisms and active substances for its action has been lit...

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Main Authors: Qing Zhang, Jia Liu, Ruolan Li, Rong Zhao, Mengmeng Zhang, Shujun Wei, Dong Ran, Wei Jin, Chunjie Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-11-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2020.528308/full
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author Qing Zhang
Jia Liu
Ruolan Li
Rong Zhao
Mengmeng Zhang
Shujun Wei
Dong Ran
Wei Jin
Chunjie Wu
author_facet Qing Zhang
Jia Liu
Ruolan Li
Rong Zhao
Mengmeng Zhang
Shujun Wei
Dong Ran
Wei Jin
Chunjie Wu
author_sort Qing Zhang
collection DOAJ
description Rheum palmatum L. (RPL) is a known traditional herbal medicine with the functions of “heat-clearing and damp-drying” in traditional Chinese medicine. Its anti-cancer effect against lung cancer has been confirmed previously, but the related mechanisms and active substances for its action has been little studied. This study adopted the network pharmacology, built the network map of drug ingredients and disease targets (DDN), and discussed the effective components of RPL and its possible mechanisms. All constituents of RPL were collected through database search and literature mining, and the potential active constituents were screened. The inverse pharmacophore matching model was used to predict the targets of active ingredients, and the method was supplemented by database retrieval and literature mining. Compounds-target data were inputted into Cytoscape software to build the DDN of RPL, and functional annotation analysis and pathway enrichment analysis were carried out. Finally, 20 active compounds were screened, which acted on 817 targets. A total of 22,418 lung cancer-related targets were collected, and 761 overlapped with drug targets. By bioinformatics annotation of these overlapping genes, a total of 235 gene ontology (GO) functional annotation analyses and 46 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained. It was found that the enrichment of GO and KEGG was associated with apoptosis, suggesting RPL plays an anti-lung cancer role via inducing cell apoptosis. Subsequent cell experiment results showed RPL and its active constituents inhibited the proliferation of A549 cells and reduced clone formation rate of A549 cells via induction of apoptosis. In this study, the pharmacodynamic basis and mechanism of RPL against lung cancer were studied from the perspective of systematic pharmacology, which would be beneficial for further elucidating the anticancer effect of RPL on lung cancer.
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spelling doaj.art-bd0b736e9acb40f9aef248e6e3eb7cd82022-12-22T00:58:24ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-11-011110.3389/fphar.2020.528308528308A Network Pharmacology Approach to Investigate the Anticancer Mechanism and Potential Active Ingredients of Rheum palmatum L. Against Lung Cancer via Induction of ApoptosisQing Zhang0Jia Liu1Ruolan Li2Rong Zhao3Mengmeng Zhang4Shujun Wei5Dong Ran6Wei Jin7Chunjie Wu8School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaEmergency Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaEmergency Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaRheum palmatum L. (RPL) is a known traditional herbal medicine with the functions of “heat-clearing and damp-drying” in traditional Chinese medicine. Its anti-cancer effect against lung cancer has been confirmed previously, but the related mechanisms and active substances for its action has been little studied. This study adopted the network pharmacology, built the network map of drug ingredients and disease targets (DDN), and discussed the effective components of RPL and its possible mechanisms. All constituents of RPL were collected through database search and literature mining, and the potential active constituents were screened. The inverse pharmacophore matching model was used to predict the targets of active ingredients, and the method was supplemented by database retrieval and literature mining. Compounds-target data were inputted into Cytoscape software to build the DDN of RPL, and functional annotation analysis and pathway enrichment analysis were carried out. Finally, 20 active compounds were screened, which acted on 817 targets. A total of 22,418 lung cancer-related targets were collected, and 761 overlapped with drug targets. By bioinformatics annotation of these overlapping genes, a total of 235 gene ontology (GO) functional annotation analyses and 46 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained. It was found that the enrichment of GO and KEGG was associated with apoptosis, suggesting RPL plays an anti-lung cancer role via inducing cell apoptosis. Subsequent cell experiment results showed RPL and its active constituents inhibited the proliferation of A549 cells and reduced clone formation rate of A549 cells via induction of apoptosis. In this study, the pharmacodynamic basis and mechanism of RPL against lung cancer were studied from the perspective of systematic pharmacology, which would be beneficial for further elucidating the anticancer effect of RPL on lung cancer.https://www.frontiersin.org/articles/10.3389/fphar.2020.528308/fullnetwork pharmacologytraditional Chinese medicinelung cancerapoptosisRheum palmatum L. (Dahuang)
spellingShingle Qing Zhang
Jia Liu
Ruolan Li
Rong Zhao
Mengmeng Zhang
Shujun Wei
Dong Ran
Wei Jin
Chunjie Wu
A Network Pharmacology Approach to Investigate the Anticancer Mechanism and Potential Active Ingredients of Rheum palmatum L. Against Lung Cancer via Induction of Apoptosis
Frontiers in Pharmacology
network pharmacology
traditional Chinese medicine
lung cancer
apoptosis
Rheum palmatum L. (Dahuang)
title A Network Pharmacology Approach to Investigate the Anticancer Mechanism and Potential Active Ingredients of Rheum palmatum L. Against Lung Cancer via Induction of Apoptosis
title_full A Network Pharmacology Approach to Investigate the Anticancer Mechanism and Potential Active Ingredients of Rheum palmatum L. Against Lung Cancer via Induction of Apoptosis
title_fullStr A Network Pharmacology Approach to Investigate the Anticancer Mechanism and Potential Active Ingredients of Rheum palmatum L. Against Lung Cancer via Induction of Apoptosis
title_full_unstemmed A Network Pharmacology Approach to Investigate the Anticancer Mechanism and Potential Active Ingredients of Rheum palmatum L. Against Lung Cancer via Induction of Apoptosis
title_short A Network Pharmacology Approach to Investigate the Anticancer Mechanism and Potential Active Ingredients of Rheum palmatum L. Against Lung Cancer via Induction of Apoptosis
title_sort network pharmacology approach to investigate the anticancer mechanism and potential active ingredients of rheum palmatum l against lung cancer via induction of apoptosis
topic network pharmacology
traditional Chinese medicine
lung cancer
apoptosis
Rheum palmatum L. (Dahuang)
url https://www.frontiersin.org/articles/10.3389/fphar.2020.528308/full
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