Network pharmacology based research into the effect and potential mechanism of Portulaca oleracea L. polysaccharide against ulcerative colitis

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.