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Revealing the Mechanism of Friedelin in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Verification

OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. This study was designed to uncover the healing effect of friedelin, a bioactive compound against UC through bioinformatics of network pharmacology and experimental verifi...

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Autores principales: Shi, Bei, Liu, Suxian, Huang, Aoshuang, Zhou, Mengyun, Sun, Boyun, Cao, Hui, Shan, Jingyi, Sun, Bo, Lin, Jiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577922/
https://www.ncbi.nlm.nih.gov/pubmed/34765000
http://dx.doi.org/10.1155/2021/4451779
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author Shi, Bei
Liu, Suxian
Huang, Aoshuang
Zhou, Mengyun
Sun, Boyun
Cao, Hui
Shan, Jingyi
Sun, Bo
Lin, Jiang
author_facet Shi, Bei
Liu, Suxian
Huang, Aoshuang
Zhou, Mengyun
Sun, Boyun
Cao, Hui
Shan, Jingyi
Sun, Bo
Lin, Jiang
author_sort Shi, Bei
collection PubMed
description OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. This study was designed to uncover the healing effect of friedelin, a bioactive compound against UC through bioinformatics of network pharmacology and experimental verification of UC model mice. MATERIALS AND METHODS: Targets of friedelin and potential mechanism of friedelin on UC were predicted through target searching, PPI network establishing, and enrichment analyzing. We explored effects of friedelin on dextran sulfate sodium (DSS)-induced colitis. Severity of UC was investigated by body weight, disease activity index (DAI), and length of the colon. Inflammation severity was examined by determination of proinflammatory and anti-inflammatory cytokines. The numbers of autophagosome around the epithelial cells were observed by autophagy inhibition via a transmission electron microscope. The expressions of autophagy-related ATG5 protein and AMPK-mTOR signaling pathway were determined by immunofluorescence staining. RESULTS: In this study, 17 potential targets of friedelin and 1111 UC-related targets were identified. 10 therapeutic targets of friedelin against UC were acquired from overlapped targets of UC and friedelin. PPI network construction filtered 14 core targets through target amplification and confidence enhancement. The results of molecular docking showed that the docking scores of the top 5 active targets were higher than the threshold values. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out, showing friedelin alleviates UC through anti-inflammatory pathways and molecular function of autophagy. Subsequently, animal-based experiments revealed the intraperitoneal injection of friedelin ameliorated DSS-induced body weight loss, DAI decrease, colon length shortening and colonic pathological damage with lower myeloperoxidase and proinflammatory cytokines (IL-1β and IL-6) and higher IL-10 levels, and more autophagosomes in transmission electron microscope results. The AMPK-mTOR signaling pathway plays important role in the friedelin's effect in autophagy as KEGG pathway result and experiment verification. Furthermore, the 3 ma validated the role of autophagy as an improvement in the friedelin's pharmacologic effect to UC model mice. CONCLUSIONS: Friedelin ameliorated DSS-induced colitis in mice through of inflammatory inhibition and regulation of autophagy.
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spelling pubmed-85779222021-11-10 Revealing the Mechanism of Friedelin in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Verification Shi, Bei Liu, Suxian Huang, Aoshuang Zhou, Mengyun Sun, Boyun Cao, Hui Shan, Jingyi Sun, Bo Lin, Jiang Evid Based Complement Alternat Med Research Article OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. This study was designed to uncover the healing effect of friedelin, a bioactive compound against UC through bioinformatics of network pharmacology and experimental verification of UC model mice. MATERIALS AND METHODS: Targets of friedelin and potential mechanism of friedelin on UC were predicted through target searching, PPI network establishing, and enrichment analyzing. We explored effects of friedelin on dextran sulfate sodium (DSS)-induced colitis. Severity of UC was investigated by body weight, disease activity index (DAI), and length of the colon. Inflammation severity was examined by determination of proinflammatory and anti-inflammatory cytokines. The numbers of autophagosome around the epithelial cells were observed by autophagy inhibition via a transmission electron microscope. The expressions of autophagy-related ATG5 protein and AMPK-mTOR signaling pathway were determined by immunofluorescence staining. RESULTS: In this study, 17 potential targets of friedelin and 1111 UC-related targets were identified. 10 therapeutic targets of friedelin against UC were acquired from overlapped targets of UC and friedelin. PPI network construction filtered 14 core targets through target amplification and confidence enhancement. The results of molecular docking showed that the docking scores of the top 5 active targets were higher than the threshold values. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out, showing friedelin alleviates UC through anti-inflammatory pathways and molecular function of autophagy. Subsequently, animal-based experiments revealed the intraperitoneal injection of friedelin ameliorated DSS-induced body weight loss, DAI decrease, colon length shortening and colonic pathological damage with lower myeloperoxidase and proinflammatory cytokines (IL-1β and IL-6) and higher IL-10 levels, and more autophagosomes in transmission electron microscope results. The AMPK-mTOR signaling pathway plays important role in the friedelin's effect in autophagy as KEGG pathway result and experiment verification. Furthermore, the 3 ma validated the role of autophagy as an improvement in the friedelin's pharmacologic effect to UC model mice. CONCLUSIONS: Friedelin ameliorated DSS-induced colitis in mice through of inflammatory inhibition and regulation of autophagy. Hindawi 2021-11-02 /pmc/articles/PMC8577922/ /pubmed/34765000 http://dx.doi.org/10.1155/2021/4451779 Text en Copyright © 2021 Bei Shi 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
Shi, Bei
Liu, Suxian
Huang, Aoshuang
Zhou, Mengyun
Sun, Boyun
Cao, Hui
Shan, Jingyi
Sun, Bo
Lin, Jiang
Revealing the Mechanism of Friedelin in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Verification
title Revealing the Mechanism of Friedelin in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Verification
title_full Revealing the Mechanism of Friedelin in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Verification
title_fullStr Revealing the Mechanism of Friedelin in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Verification
title_full_unstemmed Revealing the Mechanism of Friedelin in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Verification
title_short Revealing the Mechanism of Friedelin in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Verification
title_sort revealing the mechanism of friedelin in the treatment of ulcerative colitis based on network pharmacology and experimental verification
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577922/
https://www.ncbi.nlm.nih.gov/pubmed/34765000
http://dx.doi.org/10.1155/2021/4451779
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