Exploring the mechanism of Celastrol in the treatment of rheumatoid arthritis based on systems pharmacology and multi-omics

Abstract

To explore the molecular network mechanism of Celastrol in the treatment of rheumatoid arthritis (RA) based on a novel strategy (integrated systems pharmacology, proteomics, transcriptomics and single-cell transcriptomics). Firstly, the potential targets of Celastrol and RA genes were predicted through the database, and the Celastrol-RA targets were obtained by taking the intersection. Then, transcriptomic data and proteomic data of Celastrol treatment of RA were collected. Subsequently, Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were imported into Metascape for enrichment analysis, and related networks were constructed. Finally, the core targets of Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were mapped to synoviocytes of RA mice to find potential cell populations for Celastrol therapy. A total of 195 Celastrol-RA targets, 2068 differential genes, 294 differential proteins were obtained. The results of enrichment analysis showed that these targets, genes and proteins were mainly related to extracellular matrix organization, TGF-β signaling pathway, etc. The results of single cell sequencing showed that the main clusters of these targets, genes, and proteins could be mapped to RA synovial cells. For example, Mmp9 was mainly distributed in Hematopoietic cells, especially in Ptprn+fibroblast. The results of molecular docking also suggested that Celastrol could stably combine with molecules predicted by network pharmacology. In conclusion, this study used systems pharmacology, transcriptomics, proteomics, single-cell transcriptomics to reveal that Celastrol may regulate the PI3K/AKT signaling pathway by regulating key targets such as TNF and IL6, and then play an immune regulatory role.

Non-coding RNAs: targets for Chinese herbal medicine in treating myocardial fibrosis

“…Chinese herb Tripterygium wilfordii Hook. F. has the effects of dispelling dampness, relieving swelling and pain, and resisting inflammation ( Zeng et al, 2024 ). Triptolide and tripterine are the two most active components in the extract of Tripterygium wilfordii Hook.…”

Implementation of multiomic mass spectrometry approaches for the evaluation of human health following environmental exposure

“…Zeng et al 145 reported that post analysis integration of transcriptomics and proteomics data of synovial cells and fibroblasts has been performed to better understand inflammation pathways in which the drug celastrol impacts rheumatic arthritis cells by modulating inflammation, inhibiting chemokine pathways and osteoclast differentiation, and promoting synovial cell apoptosis.…”