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...
Guardado en:
Autores principales: | , , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Hindawi Limited
2021
|
Materias: | |
Acceso en línea: | https://doaj.org/article/77b50dc86011417592836e4dcbb10f92 |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:77b50dc86011417592836e4dcbb10f92 |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:77b50dc86011417592836e4dcbb10f922021-11-15T01:19:23ZRevealing the Mechanism of Friedelin in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Verification1741-428810.1155/2021/4451779https://doaj.org/article/77b50dc86011417592836e4dcbb10f922021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/4451779https://doaj.org/toc/1741-4288Objectives. 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.Bei ShiSuxian LiuAoshuang HuangMengyun ZhouBoyun SunHui CaoJingyi ShanBo SunJiang LinHindawi LimitedarticleOther systems of medicineRZ201-999ENEvidence-Based Complementary and Alternative Medicine, Vol 2021 (2021) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Other systems of medicine RZ201-999 |
spellingShingle |
Other systems of medicine RZ201-999 Bei Shi Suxian Liu Aoshuang Huang Mengyun Zhou Boyun Sun Hui Cao Jingyi Shan Bo Sun Jiang Lin Revealing the Mechanism of Friedelin in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Verification |
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. |
format |
article |
author |
Bei Shi Suxian Liu Aoshuang Huang Mengyun Zhou Boyun Sun Hui Cao Jingyi Shan Bo Sun Jiang Lin |
author_facet |
Bei Shi Suxian Liu Aoshuang Huang Mengyun Zhou Boyun Sun Hui Cao Jingyi Shan Bo Sun Jiang Lin |
author_sort |
Bei Shi |
title |
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_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_sort |
revealing the mechanism of friedelin in the treatment of ulcerative colitis based on network pharmacology and experimental verification |
publisher |
Hindawi Limited |
publishDate |
2021 |
url |
https://doaj.org/article/77b50dc86011417592836e4dcbb10f92 |
work_keys_str_mv |
AT beishi revealingthemechanismoffriedelininthetreatmentofulcerativecolitisbasedonnetworkpharmacologyandexperimentalverification AT suxianliu revealingthemechanismoffriedelininthetreatmentofulcerativecolitisbasedonnetworkpharmacologyandexperimentalverification AT aoshuanghuang revealingthemechanismoffriedelininthetreatmentofulcerativecolitisbasedonnetworkpharmacologyandexperimentalverification AT mengyunzhou revealingthemechanismoffriedelininthetreatmentofulcerativecolitisbasedonnetworkpharmacologyandexperimentalverification AT boyunsun revealingthemechanismoffriedelininthetreatmentofulcerativecolitisbasedonnetworkpharmacologyandexperimentalverification AT huicao revealingthemechanismoffriedelininthetreatmentofulcerativecolitisbasedonnetworkpharmacologyandexperimentalverification AT jingyishan revealingthemechanismoffriedelininthetreatmentofulcerativecolitisbasedonnetworkpharmacologyandexperimentalverification AT bosun revealingthemechanismoffriedelininthetreatmentofulcerativecolitisbasedonnetworkpharmacologyandexperimentalverification AT jianglin revealingthemechanismoffriedelininthetreatmentofulcerativecolitisbasedonnetworkpharmacologyandexperimentalverification |
_version_ |
1718428929658716160 |