Exploring the pharmacological mechanism of Xianlian Jiedu decoction in the treatment of colorectal Cancer based on network pharmacology, molecular docking and experimental validation
Background: Xianlian Jiedu Decoction (XLJDD) is a clinical effective prescription for the treatment of colorectal cancer (CRC) for several decades. However, the effective mechanism and targets of action of XLJDD are still unclear. This study aims to discover the pharmacological mechanism of XLJDD by...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Pharmacological Research - Modern Chinese Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667142523001100 |
| _version_ | 1797388599566532608 |
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| author | Ke Cai Xin-Yue Cao Fan Chen Yue Zhu Dong-Dong Sun Hai-Bo Cheng Jin-Ao Duan Shu-Lan Su |
| author_facet | Ke Cai Xin-Yue Cao Fan Chen Yue Zhu Dong-Dong Sun Hai-Bo Cheng Jin-Ao Duan Shu-Lan Su |
| author_sort | Ke Cai |
| collection | DOAJ |
| description | Background: Xianlian Jiedu Decoction (XLJDD) is a clinical effective prescription for the treatment of colorectal cancer (CRC) for several decades. However, the effective mechanism and targets of action of XLJDD are still unclear. This study aims to discover the pharmacological mechanism of XLJDD by employing a combination of network pharmacology, molecular docking and in vitro and in vivo experimental validation. Methods: Multiple databases, including TCMSP, Swiss Target Prediction, Drugbank, Geencards, Malacards, Therapeutic Target Database (TTD) and Disgenet, were searched and identified the targets of ingredients from XLJDD and the targets associated with CRC. The common targets of ingredients and disease were analyzed, and the visualization network of protein-protein interaction (PPI) were constructed using STRING database and to identified the core targets based on Cytoscape software. Metascape database was employed for GO and KEGG enrichment analysis of common targets. The active ingredients of XLJDD and core targets were verified through molecular docking test. Subsequently, in vitro and in vivo experiments were performed to validate the analysis results using CT-26 and HCT116 cell lines and AOM/DSS mice model. Results: A total of 36 active components and 122 targets were identified for XLJDD, while 1728 targets associated with CRC were obtained. Among them, there were 71 common targets between ingredients and disease. And 19 core targets (AKT1, TNF, PTGS2, CASP3, EGFR, ESR1, MMP9, IL1B, CCND1, PPARG, ERBB2, SIRT1, MMP2, BCL2L1, MAPK1, PPARA, PGR, AR and SERPINE1.) were finally screened from PPI network. GO analysis enriched a total of 99 entries, with 74 related to biological processes, 20 to molecular functions, and 5 to cellular components. The KEGG enrichment pathway analysis demonstrated that the biological discrepancy was mainly focused on the tumorigenesis-, inflammation-, and mechanism-related pathways. Molecular docking presented the great bonding ability of 19 key targets with 17 active constituents. Experiments based on CT-26 and HCT116 cells verified that XLJDD could inhibit the proliferation of colorectal cancer cells. In addition, XLJDD inhibited tumor progression in mice. Finally, the results of molecular biology experiments showed that XLJDD could activate the colorectal cancer-related PTEN/AKT/FoXO1 pathway, and up-regulate the expression levels of key genes such as AKT1, TNF, PTGS2 and down-regulate the expression levels of CASP3. Conclusions: This study revealed comprehensively the targets and mechanism for the efficacy of XLJDD in treatment of CRC. Furthermore, the results were achieved through in vitro experiment of CT-26 and HCT116 cell lines, and in vivo experiment of AOM/DSS mice. |
| first_indexed | 2024-03-08T22:43:06Z |
| format | Article |
| id | doaj.art-371a75dac03d4ea8becb58d516787c66 |
| institution | Directory Open Access Journal |
| issn | 2667-1425 |
| language | English |
| last_indexed | 2024-03-08T22:43:06Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research - Modern Chinese Medicine |
| spelling | doaj.art-371a75dac03d4ea8becb58d516787c662023-12-17T06:42:59ZengElsevierPharmacological Research - Modern Chinese Medicine2667-14252023-12-019100324Exploring the pharmacological mechanism of Xianlian Jiedu decoction in the treatment of colorectal Cancer based on network pharmacology, molecular docking and experimental validationKe Cai0Xin-Yue Cao1Fan Chen2Yue Zhu3Dong-Dong Sun4Hai-Bo Cheng5Jin-Ao Duan6Shu-Lan Su7Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaJiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaThe First Clinical Medical College of Nanjing University of Chinese Medicine Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaThe First Clinical Medical College of Nanjing University of Chinese Medicine Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China; Corresponding authors at: 138 Xianlin Road, Nanjing 210023, P.R.China.Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Corresponding authors at: 138 Xianlin Road, Nanjing 210023, P.R.China.Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Corresponding authors at: 138 Xianlin Road, Nanjing 210023, P.R.China.Background: Xianlian Jiedu Decoction (XLJDD) is a clinical effective prescription for the treatment of colorectal cancer (CRC) for several decades. However, the effective mechanism and targets of action of XLJDD are still unclear. This study aims to discover the pharmacological mechanism of XLJDD by employing a combination of network pharmacology, molecular docking and in vitro and in vivo experimental validation. Methods: Multiple databases, including TCMSP, Swiss Target Prediction, Drugbank, Geencards, Malacards, Therapeutic Target Database (TTD) and Disgenet, were searched and identified the targets of ingredients from XLJDD and the targets associated with CRC. The common targets of ingredients and disease were analyzed, and the visualization network of protein-protein interaction (PPI) were constructed using STRING database and to identified the core targets based on Cytoscape software. Metascape database was employed for GO and KEGG enrichment analysis of common targets. The active ingredients of XLJDD and core targets were verified through molecular docking test. Subsequently, in vitro and in vivo experiments were performed to validate the analysis results using CT-26 and HCT116 cell lines and AOM/DSS mice model. Results: A total of 36 active components and 122 targets were identified for XLJDD, while 1728 targets associated with CRC were obtained. Among them, there were 71 common targets between ingredients and disease. And 19 core targets (AKT1, TNF, PTGS2, CASP3, EGFR, ESR1, MMP9, IL1B, CCND1, PPARG, ERBB2, SIRT1, MMP2, BCL2L1, MAPK1, PPARA, PGR, AR and SERPINE1.) were finally screened from PPI network. GO analysis enriched a total of 99 entries, with 74 related to biological processes, 20 to molecular functions, and 5 to cellular components. The KEGG enrichment pathway analysis demonstrated that the biological discrepancy was mainly focused on the tumorigenesis-, inflammation-, and mechanism-related pathways. Molecular docking presented the great bonding ability of 19 key targets with 17 active constituents. Experiments based on CT-26 and HCT116 cells verified that XLJDD could inhibit the proliferation of colorectal cancer cells. In addition, XLJDD inhibited tumor progression in mice. Finally, the results of molecular biology experiments showed that XLJDD could activate the colorectal cancer-related PTEN/AKT/FoXO1 pathway, and up-regulate the expression levels of key genes such as AKT1, TNF, PTGS2 and down-regulate the expression levels of CASP3. Conclusions: This study revealed comprehensively the targets and mechanism for the efficacy of XLJDD in treatment of CRC. Furthermore, the results were achieved through in vitro experiment of CT-26 and HCT116 cell lines, and in vivo experiment of AOM/DSS mice.http://www.sciencedirect.com/science/article/pii/S2667142523001100Xianlian Jiedu decoctionColorectal cancerNetwork pharmacologyMolecular dockingAOM/DSS mice |
| spellingShingle | Ke Cai Xin-Yue Cao Fan Chen Yue Zhu Dong-Dong Sun Hai-Bo Cheng Jin-Ao Duan Shu-Lan Su Exploring the pharmacological mechanism of Xianlian Jiedu decoction in the treatment of colorectal Cancer based on network pharmacology, molecular docking and experimental validation Pharmacological Research - Modern Chinese Medicine Xianlian Jiedu decoction Colorectal cancer Network pharmacology Molecular docking AOM/DSS mice |
| title | Exploring the pharmacological mechanism of Xianlian Jiedu decoction in the treatment of colorectal Cancer based on network pharmacology, molecular docking and experimental validation |
| title_full | Exploring the pharmacological mechanism of Xianlian Jiedu decoction in the treatment of colorectal Cancer based on network pharmacology, molecular docking and experimental validation |
| title_fullStr | Exploring the pharmacological mechanism of Xianlian Jiedu decoction in the treatment of colorectal Cancer based on network pharmacology, molecular docking and experimental validation |
| title_full_unstemmed | Exploring the pharmacological mechanism of Xianlian Jiedu decoction in the treatment of colorectal Cancer based on network pharmacology, molecular docking and experimental validation |
| title_short | Exploring the pharmacological mechanism of Xianlian Jiedu decoction in the treatment of colorectal Cancer based on network pharmacology, molecular docking and experimental validation |
| title_sort | exploring the pharmacological mechanism of xianlian jiedu decoction in the treatment of colorectal cancer based on network pharmacology molecular docking and experimental validation |
| topic | Xianlian Jiedu decoction Colorectal cancer Network pharmacology Molecular docking AOM/DSS mice |
| url | http://www.sciencedirect.com/science/article/pii/S2667142523001100 |
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