Integrated Network Pharmacology and Experimental Validation Approach to Investigate the Mechanisms of Stigmasterol in the Treatment of Rheumatoid Arthritis

Abstract

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints associated with systemic comorbidities. Sinomenium acutum is regarded as an effective traditional Chinese medicine (TCM) for the treatment of RA. Materials and Methods: Based on network pharmacology and Gene Expression Omnibus (GEO) database, 33 RA-related differentially-expressed genes (DEGs) targeting active compounds of Sinomenium acutum were initially screened in our investigation. Results: Gene Ontology (GO) and Kyoto encyclopaedia of genes and genome (KEGG) analyses found the important involvement of these DEGs in osteoclast differentiation, and finally 5 core DEGs, including NCF4, NFKB1, CYBA, IL-1β and NCF1 were determined through protein-protein interaction (PPI) network. We also identified the related active component of Sinomenium acutum include Stigmasterol. Finally, in order to experimentally verify these results, a rat model of collagen-induced arthritis (CIA) was established, and subsequently treated with Stigmasterol solution. Conclusion: Similar to the healing effect of Indomethacin, Stigmasterol was observed to reduce the levels of inflammatory factors (IL-6 and IL-1β) and osteoclast differentiation-related factors (RANKL, ACP5 and Cathepsin K), which can also reduce the arthritis index score and alleviate the degree of pathological injury of rat ankle joints. The predictions and experimental data uncover the involvement of Stigmasterol, an active component of Sinomenium acutum, in regulation of osteoclast differentiation, exerting great medicinal potential in the treatment of RA.

Critical Response to Article “Integrated Network Pharmacology and Experimental Validation Approach to Investigate the Mechanisms of Stigmasterol in the Treatment of Rheumatoid Arthritis” [Letter]

“…We have read, reviewed and appreciated the work performed by Xie et al regarding the integrated network pharmacology and experimental approaches in order to investigate the mechanisms of Stigmasterol, the active components of Sinomenium acutum used in arthritis treatment. 1 Based on their results, 5 main differentially expressed genes involved in osteoclast differentiation, the major mediators of bone destruction, including NCF4, NFKB1, CYBA, IL-1β and NCF1 were determined to be targeted by the through protein-protein interaction (PPI) network. Sinomenium acutum (Thumb.)…”

Anti-inflammatory properties and characterization of water extracts obtained from Callicarpa kwangtungensis Chun using in vitro and in vivo rat models

“…Its main pathological features are cell proliferation, microvascular proliferation 8 , inflammatory cell infiltration, and synovial tissue proliferation 9 . Although RA is a common chronic-inflammatory disease in the clinic and the therapeutic strategies for RA are continually improving, there is a lack of specific medicines with low toxicity and high efficiency for treating this disease 10 – 12 . Therefore, developing drugs for treating RA is a priority.…”

Dispelling Dampness, Relieving Turbidity and Dredging Collaterals Decoction, Attenuates Potassium Oxonate-Induced Hyperuricemia in Rat Models

“…This study used network pharmacology and molecular docking to screen for the potential pharmacological components and targets of compounds. 14 , 15 Network pharmacology plays an important role in elucidating the therapeutic mechanisms of traditional Chinese medicine, especially for the targeting characteristics of the multiple pathways of traditional Chinese medicine, and combined with animal model verification, it elucidates the mechanism of DED in hyperuricemia treatment.…”