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Uncovering the Mechanism of Curcuma in the Treatment of Ulcerative Colitis Based on Network Pharmacology, Molecular Docking Technology, and Experiment Verification
AIM: The incidence of ulcerative colitis (UC) is increasing steadily in developed countries, it is plaguing nearly 1 million people in the United States and European countries, while developing countries have had a rapidly increased incidence over the past decades. Curcuma is widely used in treating...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225429/ https://www.ncbi.nlm.nih.gov/pubmed/34221084 http://dx.doi.org/10.1155/2021/6629761 |
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author | Liu, Suxian Li, Qiaodong Liu, Fengzhi Cao, Hui Liu, Jun Shan, Jingyi Dan, Wenchao Yuan, Jianye Lin, Jiang |
author_facet | Liu, Suxian Li, Qiaodong Liu, Fengzhi Cao, Hui Liu, Jun Shan, Jingyi Dan, Wenchao Yuan, Jianye Lin, Jiang |
author_sort | Liu, Suxian |
collection | PubMed |
description | AIM: The incidence of ulcerative colitis (UC) is increasing steadily in developed countries, it is plaguing nearly 1 million people in the United States and European countries, while developing countries have had a rapidly increased incidence over the past decades. Curcuma is widely used in treating malaria, UC, Crohn's disease, and colon cancer, which lead to diarrhea and bloody stool. However, the systemic mechanism of curcuma in treating UC is still unclear. Our work was supposed to expound how does curcuma alleviate UC in a comprehensive and systematic way by network pharmacology, molecular docking, and experiment verification. METHODS: Traditional Chinese Medicine System Pharmacology Database (TCMSP), Shanghai Chemistry & Chemical Industry Data Platform (SGST), and papers published in Chinese Network Knowledge Infrastructure (CNKI) and PubMed were used to collect the chemical constituents of curcuma based on ADME (absorption, distribution, metabolism, and excretion). And effective targets were predicted by Swiss Target Prediction to establish the curcuma-related database. The disease targets of UC were screened by GeneCards and DrugBank databases, and Wayne (Venn) analysis was carried out with curcuma targets to determine the intersection targets. AutoDock software and TCMNPAS system were used to dock the core chemical components of curcuma with key UC targets. Protein interaction (PPI) network was constructed based on the STRING database and Cytoscape software. Gene function GO analysis and KEGG pathway enrichment analysis were carried out by using Metascape database. Finally, HE staining was performed to identify the inflammatory infiltration and expression difference in TNF-α and STAT3 before and after the treatment of curcuma which was verified by immunoblotting. RESULTS: Twelve active components containing 148 target genes were selected from curcuma. Potential therapeutic targets of curcuma in the treatment of UC were acquired from 54 overlapped targets from UC and curcuma. Molecular docking was used to filter the exact 24 core proteins interacting with compounds whose docking energy is lower than −5.5 and stronger than that of 5-aminosalicylic acid (5-ASA). GO and KEGG analyses showed that these targets were highly correlated with EGFR tyrosine kinase inhibitor resistance, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, MAPK signaling pathway, and inflammatory bowel disease (IBD). Experiments verified curcuma relieved pathological manifestation and decreased the expression of TNF-α and STAT3. CONCLUSION: Curcuma relieved the colon inflammation of ulcerative colitis via inactivating TNF pathway, inflammatory bowel disease pathway, and epithelial cell signaling in Helicobacter pylori infection pathway, probably by binding to STAT3 and TNF-α. |
format | Online Article Text |
id | pubmed-8225429 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-82254292021-07-02 Uncovering the Mechanism of Curcuma in the Treatment of Ulcerative Colitis Based on Network Pharmacology, Molecular Docking Technology, and Experiment Verification Liu, Suxian Li, Qiaodong Liu, Fengzhi Cao, Hui Liu, Jun Shan, Jingyi Dan, Wenchao Yuan, Jianye Lin, Jiang Evid Based Complement Alternat Med Research Article AIM: The incidence of ulcerative colitis (UC) is increasing steadily in developed countries, it is plaguing nearly 1 million people in the United States and European countries, while developing countries have had a rapidly increased incidence over the past decades. Curcuma is widely used in treating malaria, UC, Crohn's disease, and colon cancer, which lead to diarrhea and bloody stool. However, the systemic mechanism of curcuma in treating UC is still unclear. Our work was supposed to expound how does curcuma alleviate UC in a comprehensive and systematic way by network pharmacology, molecular docking, and experiment verification. METHODS: Traditional Chinese Medicine System Pharmacology Database (TCMSP), Shanghai Chemistry & Chemical Industry Data Platform (SGST), and papers published in Chinese Network Knowledge Infrastructure (CNKI) and PubMed were used to collect the chemical constituents of curcuma based on ADME (absorption, distribution, metabolism, and excretion). And effective targets were predicted by Swiss Target Prediction to establish the curcuma-related database. The disease targets of UC were screened by GeneCards and DrugBank databases, and Wayne (Venn) analysis was carried out with curcuma targets to determine the intersection targets. AutoDock software and TCMNPAS system were used to dock the core chemical components of curcuma with key UC targets. Protein interaction (PPI) network was constructed based on the STRING database and Cytoscape software. Gene function GO analysis and KEGG pathway enrichment analysis were carried out by using Metascape database. Finally, HE staining was performed to identify the inflammatory infiltration and expression difference in TNF-α and STAT3 before and after the treatment of curcuma which was verified by immunoblotting. RESULTS: Twelve active components containing 148 target genes were selected from curcuma. Potential therapeutic targets of curcuma in the treatment of UC were acquired from 54 overlapped targets from UC and curcuma. Molecular docking was used to filter the exact 24 core proteins interacting with compounds whose docking energy is lower than −5.5 and stronger than that of 5-aminosalicylic acid (5-ASA). GO and KEGG analyses showed that these targets were highly correlated with EGFR tyrosine kinase inhibitor resistance, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, MAPK signaling pathway, and inflammatory bowel disease (IBD). Experiments verified curcuma relieved pathological manifestation and decreased the expression of TNF-α and STAT3. CONCLUSION: Curcuma relieved the colon inflammation of ulcerative colitis via inactivating TNF pathway, inflammatory bowel disease pathway, and epithelial cell signaling in Helicobacter pylori infection pathway, probably by binding to STAT3 and TNF-α. Hindawi 2021-06-16 /pmc/articles/PMC8225429/ /pubmed/34221084 http://dx.doi.org/10.1155/2021/6629761 Text en Copyright © 2021 Suxian Liu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Liu, Suxian Li, Qiaodong Liu, Fengzhi Cao, Hui Liu, Jun Shan, Jingyi Dan, Wenchao Yuan, Jianye Lin, Jiang Uncovering the Mechanism of Curcuma in the Treatment of Ulcerative Colitis Based on Network Pharmacology, Molecular Docking Technology, and Experiment Verification |
title | Uncovering the Mechanism of Curcuma in the Treatment of Ulcerative Colitis Based on Network Pharmacology, Molecular Docking Technology, and Experiment Verification |
title_full | Uncovering the Mechanism of Curcuma in the Treatment of Ulcerative Colitis Based on Network Pharmacology, Molecular Docking Technology, and Experiment Verification |
title_fullStr | Uncovering the Mechanism of Curcuma in the Treatment of Ulcerative Colitis Based on Network Pharmacology, Molecular Docking Technology, and Experiment Verification |
title_full_unstemmed | Uncovering the Mechanism of Curcuma in the Treatment of Ulcerative Colitis Based on Network Pharmacology, Molecular Docking Technology, and Experiment Verification |
title_short | Uncovering the Mechanism of Curcuma in the Treatment of Ulcerative Colitis Based on Network Pharmacology, Molecular Docking Technology, and Experiment Verification |
title_sort | uncovering the mechanism of curcuma in the treatment of ulcerative colitis based on network pharmacology, molecular docking technology, and experiment verification |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225429/ https://www.ncbi.nlm.nih.gov/pubmed/34221084 http://dx.doi.org/10.1155/2021/6629761 |
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