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Celastrol may regulate core target proteins to alleviate the inflammatory response.
A bioinformatics analysis identified the CLEC2B gene as a potential diagnostic marker of psoriatic arthritis (PsA) and celastrol as a candidate drug for PsA. The study was published in the Journal of Orthopaedic Surgery and Research.1
“Celastrol may regulate core target proteins (interleukin-6 [IL6], tumor necrosis factor [TNF], glyceraldehyde 3-phosphate dehydrogenase [GAPDH], and AKT1) to alleviate the inflammatory response in PsA,” reported Xichao Yang, of Xi’an Jiaotong University in Shaanxi, China, and colleagues.
The limited diagnostic markers and effective therapeutic options in PsA may be explained by the lack of understanding of its pathogenesis. Celastrol is a plant-derived compound that has shown potential in the treatment of various diseases, including rheumatoid arthritis, by regulating immunity and inflammation. Its role in the treatment of PsA is unknown.
In this study, the researchers aimed to identify potential diagnostic markers for PsA and screen therapeutic compounds for the disease.
Bioinformatics analysis of the GEO database’s GSE61281 dataset, which contained 20 PsA samples and 12 control samples, obtained 734 differentially expressed genes in PsA. Weighed gene co-expression network analysis (WGCNA) was used to identify PSA-related modules and prognostic biomarkers. The researchers collected blood samples from patients with PsA for real-time quantitative reverse transcription polymerase chain reaction (PCR) to verify the findings. Nine natural compounds (celastrol, prunetin, piceid, securinine, strychnine, arecaidine, farnesol, solanine, and taurodeoxycholic-acid) were evaluated as potential drugs for PsA.
CLEC2B was significantly up-regulated in PsA in both the GSE61281 dataset (P <.001) and clinical samples (P <.01). The diagnostic area under the curve (AUC) value of the gene was .88 in GSE61281 and .84 in clinical samples, suggesting that the CLEC2B gene as a potential biomarker for PsA.
CMap analysis results identified celastrol as a candidate drug for PSA. Subsequently, network pharmacology analysis identified 4 core targets of celastrol – IL6, TNF, GAPDH, and AKT1 – and showed that celastrol could treat PsA by modulating inflammatory-related pathways. Stable binding of celastrol to the 4 core targets in the treatment of PsA was shown with molecular docking. Further, animal experiments suggested that celastrol alleviated the inflammatory response in mannan-induced PsA.
“Whether celastrol can be a natural drug for PsA and the exact mechanism of its action still needs to be investigated and proven experimentally, and our results will hopefully provide new clinical insights,” investigators concluded.