Investigating the effects and mechanisms of Erchen Decoction in the treatment of colorectal cancer by network pharmacology and experimental validation
Objective: Erchen Decoction (ECD), a well-known traditional Chinese medicine, exerts metabolism-regulatory, immunoregulation, and anti-tumor effects. However, the action and pharmacological mechanism of ECD remain largely unclear. In the present study, we explored the effects and mechanisms of ECD i...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1000639/full |
| _version_ | 1828725390497021952 |
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| author | Yanfei Shao Yanfei Shao Jingxian Chen Yujie Hu Yuan Wu Hualin Zeng Shuying Lin Qiying Lai Xiaodong Fan Xiaodong Fan Xueliang Zhou Xueliang Zhou Minhua Zheng Minhua Zheng Bizhen Gao Jing Sun Jing Sun |
| author_facet | Yanfei Shao Yanfei Shao Jingxian Chen Yujie Hu Yuan Wu Hualin Zeng Shuying Lin Qiying Lai Xiaodong Fan Xiaodong Fan Xueliang Zhou Xueliang Zhou Minhua Zheng Minhua Zheng Bizhen Gao Jing Sun Jing Sun |
| author_sort | Yanfei Shao |
| collection | DOAJ |
| description | Objective: Erchen Decoction (ECD), a well-known traditional Chinese medicine, exerts metabolism-regulatory, immunoregulation, and anti-tumor effects. However, the action and pharmacological mechanism of ECD remain largely unclear. In the present study, we explored the effects and mechanisms of ECD in the treatment of CRC using network pharmacology, molecular docking, and systematic experimental validation.Methods: The active components of ECD were obtained from the TCMSP database and the potential targets of them were annotated by the STRING database. The CRC-related targets were identified from different databases (OMIM, DisGeNet, GeneCards, and DrugBank). The interactive targets of ECD and CRC were screened and the protein-protein interaction (PPI) networks were constructed. Then, the hub interactive targets were calculated and visualized from the PPI network using the Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. In addition, the molecular docking was performed. Finally, systematic in vitro, in vivo and molecular biology experiments were performed to further explore the anti-tumor effects and underlying mechanisms of ECD in CRC.Results: A total of 116 active components and 246 targets of ECD were predicted based on the component-target network analysis. 2406 CRC-related targets were obtained from different databases and 140 intersective targets were identified between ECD and CRC. 12 hub molecules (STAT3, JUN, MAPK3, TP53, MAPK1, RELA, FOS, ESR1, IL6, MAPK14, MYC, and CDKN1A) were finally screened from PPI network. GO and KEGG pathway enrichment analyses demonstrated that the biological discrepancy was mainly focused on the tumorigenesis-, immune-, and mechanism-related pathways. Based on the experimental validation, ECD could suppress the proliferation of CRC cells by inhibiting cell cycle and promoting cell apoptosis. In addition, ECD could inhibit tumor growth in mice. Finally, the results of molecular biology experiments suggested ECD could regulate the transcriptional levels of several hub molecules during the development of CRC, including MAPKs, PPARs, TP53, and STATs.Conclusion: This study revealed the potential pharmacodynamic material basis and underlying molecular mechanisms of ECD in the treatment of CRC, providing a novel insight for us to find more effective anti-CRC drugs. |
| first_indexed | 2024-04-12T13:26:34Z |
| format | Article |
| id | doaj.art-b040ea246a534da9a1a847800ec69ef8 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T13:26:34Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-b040ea246a534da9a1a847800ec69ef82022-12-22T03:31:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.10006391000639Investigating the effects and mechanisms of Erchen Decoction in the treatment of colorectal cancer by network pharmacology and experimental validationYanfei Shao0Yanfei Shao1Jingxian Chen2Yujie Hu3Yuan Wu4Hualin Zeng5Shuying Lin6Qiying Lai7Xiaodong Fan8Xiaodong Fan9Xueliang Zhou10Xueliang Zhou11Minhua Zheng12Minhua Zheng13Bizhen Gao14Jing Sun15Jing Sun16Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Traditional Chinese Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCollege of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaDepartment of Traditional Chinese Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCollege of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaCollege of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaCollege of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCollege of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaObjective: Erchen Decoction (ECD), a well-known traditional Chinese medicine, exerts metabolism-regulatory, immunoregulation, and anti-tumor effects. However, the action and pharmacological mechanism of ECD remain largely unclear. In the present study, we explored the effects and mechanisms of ECD in the treatment of CRC using network pharmacology, molecular docking, and systematic experimental validation.Methods: The active components of ECD were obtained from the TCMSP database and the potential targets of them were annotated by the STRING database. The CRC-related targets were identified from different databases (OMIM, DisGeNet, GeneCards, and DrugBank). The interactive targets of ECD and CRC were screened and the protein-protein interaction (PPI) networks were constructed. Then, the hub interactive targets were calculated and visualized from the PPI network using the Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. In addition, the molecular docking was performed. Finally, systematic in vitro, in vivo and molecular biology experiments were performed to further explore the anti-tumor effects and underlying mechanisms of ECD in CRC.Results: A total of 116 active components and 246 targets of ECD were predicted based on the component-target network analysis. 2406 CRC-related targets were obtained from different databases and 140 intersective targets were identified between ECD and CRC. 12 hub molecules (STAT3, JUN, MAPK3, TP53, MAPK1, RELA, FOS, ESR1, IL6, MAPK14, MYC, and CDKN1A) were finally screened from PPI network. GO and KEGG pathway enrichment analyses demonstrated that the biological discrepancy was mainly focused on the tumorigenesis-, immune-, and mechanism-related pathways. Based on the experimental validation, ECD could suppress the proliferation of CRC cells by inhibiting cell cycle and promoting cell apoptosis. In addition, ECD could inhibit tumor growth in mice. Finally, the results of molecular biology experiments suggested ECD could regulate the transcriptional levels of several hub molecules during the development of CRC, including MAPKs, PPARs, TP53, and STATs.Conclusion: This study revealed the potential pharmacodynamic material basis and underlying molecular mechanisms of ECD in the treatment of CRC, providing a novel insight for us to find more effective anti-CRC drugs.https://www.frontiersin.org/articles/10.3389/fphar.2022.1000639/fullErchen decoctioncolorectal cancernetwork pharmacologycell cyclecell apoptosis |
| spellingShingle | Yanfei Shao Yanfei Shao Jingxian Chen Yujie Hu Yuan Wu Hualin Zeng Shuying Lin Qiying Lai Xiaodong Fan Xiaodong Fan Xueliang Zhou Xueliang Zhou Minhua Zheng Minhua Zheng Bizhen Gao Jing Sun Jing Sun Investigating the effects and mechanisms of Erchen Decoction in the treatment of colorectal cancer by network pharmacology and experimental validation Frontiers in Pharmacology Erchen decoction colorectal cancer network pharmacology cell cycle cell apoptosis |
| title | Investigating the effects and mechanisms of Erchen Decoction in the treatment of colorectal cancer by network pharmacology and experimental validation |
| title_full | Investigating the effects and mechanisms of Erchen Decoction in the treatment of colorectal cancer by network pharmacology and experimental validation |
| title_fullStr | Investigating the effects and mechanisms of Erchen Decoction in the treatment of colorectal cancer by network pharmacology and experimental validation |
| title_full_unstemmed | Investigating the effects and mechanisms of Erchen Decoction in the treatment of colorectal cancer by network pharmacology and experimental validation |
| title_short | Investigating the effects and mechanisms of Erchen Decoction in the treatment of colorectal cancer by network pharmacology and experimental validation |
| title_sort | investigating the effects and mechanisms of erchen decoction in the treatment of colorectal cancer by network pharmacology and experimental validation |
| topic | Erchen decoction colorectal cancer network pharmacology cell cycle cell apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1000639/full |
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