The mechanisms of celastrol in treating papillary thyroid carcinoma based on network pharmacology and experiment verification

Abstract

Background: Celastrol, a triterpene present in the traditional Chinese medicine (TCM) Triptergium wilfordii, has been demonstrated to have remarkable anticancer activity. However, its specific mechanism on papillary thyroid carcinoma (PTC) remains to be elucidated.Methods: Potential targets of celastrol were screened from public databases. Through the Gene Expression Omnibus (GEO) online database, we obtained the bioinformatics analysis profile of PTC, GSE33630, and analyzed the differentially expressed genes (DEGs). Then, a protein-protein interaction (PPI) network was constructed by utilizing the STRING database. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted. Finally, drug interactions between hub genes and celastrol were verified by molecular docking.Results: Four core nodes (MMP9, JUN, ICAM1, and VCAM1) were discerned via constructing a PPI network of 47 common targets. Through functional enrichment analysis, it was confirmed that the above target genes were basically enriched in the interleukin-17 (IL-17), nuclear factor kappa-B (NF-κB), and tumor necrosis factor (TNF) signaling pathways, which are involved in the inflammatory microenvironment to inhibit the development and progression of tumors. Molecular docking results demonstrated that celastrol has a strong binding efficiency with the 4 key proteins. Conclusions:In this research, it was demonstrated that celastrol can regulate a variety of proteins and signaling pathways against PTC, providing a theoretical basis for future clinical applications.

In vitro activity of celastrol in combination with thymol against carbapenem-resistant Klebsiella pneumoniae isolates

“…In addition, a recent study used molecular docking to evaluate the effect of celastrol on some targets for treating thyroid carcinoma [ 62 ]. It is worth mentioning that free binding energy scores of celastrol on the selected targets in their study ranged from −7.0 to −9.9 Kcal mol −1 [ 62 ], which is much lower than the free binding energy scores in our study (ranged from −11.55 to −12.8 Kcal mol −1 ) which means superior activity of celastrol on bacterial carbapenemases compared to human targets.…”

Elucidation of the potential antioxidant compound and mechanism of mung bean using network pharmacology and in vitro anti-oxidative activity

“…The species was set to "Homo sapiens, " minimum interaction threshold was selected as "medium confidence >0.4, " and the other parameters were kept in the default setting (Wang et al, 2020). In the network, each node represented a target protein, and each edge represented the PPI (Yi et al, 2021).…”