Network pharmacology based research into the effect and potential mechanism of Portulaca oleracea L. polysaccharide against ulcerative colitis.
Molecular docking
Network pharmacology
Polysaccharides
Portulaca oleracea L
Ulcerative colitis
Journal
Computers in biology and medicine
ISSN: 1879-0534
Titre abrégé: Comput Biol Med
Pays: United States
ID NLM: 1250250
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
06
10
2022
revised:
11
03
2023
accepted:
02
05
2023
medline:
5
6
2023
pubmed:
23
5
2023
entrez:
22
5
2023
Statut:
ppublish
Résumé
Ulcerative colitis (UC) as a chronic inflammatory bowel disease (IBD) has received extensive concerns worldwide. As a traditional herbal medicine, Portulaca oleracea L. (POL) has a wide application in gastrointestinal diseases such as diarrhea and dysentery. This study aims to investigate the target and potential mechanisms of Portulaca oleracea L. polysaccharide (POL-P) in the treatment of UC. The active ingredients and relevant targets of POL-P were searched through the TCMSP and Swiss Target Prediction databases. UC related targets were collected through the GeneCards and DisGeNET databases. The intersection of POL-P targets with UC targets was done using Venny. Then, protein-protein interaction (PPI) network of the intersection targets was constructed through the STRING database and analyzed using Cytohubba to identify the key targets of POL-P in the treatment of UC. In addition, GO and KEGG enrichment analyses were performed on the key targets and the binding mode of POL-P to the key targets was further analyzed by molecular docking technology. Finally, the efficacy and target of POL-P were verified using animal experiments and immunohistochemical staining. A total of 316 targets were obtained based on POL-P monosaccharide structures, among which 28 were related to UC. Cytohubba analysis showed that VEGFA, EGFR, TLR4, IL-1β, STAT3, IL-2, PTGS2, FGF2, HGF, and MMP9 were the key targets for UC treatment and were mainly involved in multiple signaling pathways such as proliferation, inflammation, and immune response. Molecular docking results revealed that POL-P had a good binding potential to TLR4. In vivo validation results showed that POL-P significantly reduced the overexpression of TLR4 and its downstream key proteins (MyD88 and NF-κB) in intestinal mucosa of UC mice, which indicated that POL-P improved UC by mediating TLR4 related proteins. POL-P may be a potential therapeutic agent for UC and its mechanism is closely related to the regulation of TLR4 protein. This study will provide novel insights for the treatment of UC with POL-P.
Sections du résumé
BACKGROUND
Ulcerative colitis (UC) as a chronic inflammatory bowel disease (IBD) has received extensive concerns worldwide. As a traditional herbal medicine, Portulaca oleracea L. (POL) has a wide application in gastrointestinal diseases such as diarrhea and dysentery. This study aims to investigate the target and potential mechanisms of Portulaca oleracea L. polysaccharide (POL-P) in the treatment of UC.
METHOD
The active ingredients and relevant targets of POL-P were searched through the TCMSP and Swiss Target Prediction databases. UC related targets were collected through the GeneCards and DisGeNET databases. The intersection of POL-P targets with UC targets was done using Venny. Then, protein-protein interaction (PPI) network of the intersection targets was constructed through the STRING database and analyzed using Cytohubba to identify the key targets of POL-P in the treatment of UC. In addition, GO and KEGG enrichment analyses were performed on the key targets and the binding mode of POL-P to the key targets was further analyzed by molecular docking technology. Finally, the efficacy and target of POL-P were verified using animal experiments and immunohistochemical staining.
RESULTS
A total of 316 targets were obtained based on POL-P monosaccharide structures, among which 28 were related to UC. Cytohubba analysis showed that VEGFA, EGFR, TLR4, IL-1β, STAT3, IL-2, PTGS2, FGF2, HGF, and MMP9 were the key targets for UC treatment and were mainly involved in multiple signaling pathways such as proliferation, inflammation, and immune response. Molecular docking results revealed that POL-P had a good binding potential to TLR4. In vivo validation results showed that POL-P significantly reduced the overexpression of TLR4 and its downstream key proteins (MyD88 and NF-κB) in intestinal mucosa of UC mice, which indicated that POL-P improved UC by mediating TLR4 related proteins.
CONCLUSION
POL-P may be a potential therapeutic agent for UC and its mechanism is closely related to the regulation of TLR4 protein. This study will provide novel insights for the treatment of UC with POL-P.
Identifiants
pubmed: 37216777
pii: S0010-4825(23)00464-X
doi: 10.1016/j.compbiomed.2023.106999
pii:
doi:
Substances chimiques
Toll-Like Receptor 4
0
Drugs, Chinese Herbal
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
106999Informations de copyright
Copyright © 2023. Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.