Dataset Information

[Therapeutic mechanism of emodin for treatment of rheumatoid arthritis: a network pharmacology-based analysis].

ABSTRACT:

Objective

To investigate the therapeutic mechanism of emodin in the treatment of rheumatoid arthritis (RA) using a network pharmacology-based method and validate this mechanism in a fibroblast-like synovial cell line.

Methods

The PubChem, Targetnet, SwissTargetPrediction, Genecards, OMIM, and DisGeNET databases were searched to obtain emodin targets and RA-related genes. A protein-protein interaction (PPI) network was constructed, and GO and KEGG pathway enrichment analyses were carried out to analyze the intersection genes. AutoDock4.2.6 software was used to simulate molecular docking between emodin and its candidate targets. In a cultured fibroblast-like synovial cell line (MH7A), the effects of different concentrations of emodin on proliferation of tumor necrosis factor-α (TNF-α)-induced cells were investigated using CCK-8 assay, cell scratch experiment and flow cytometry; the changes in the expressions of nuclear factor-κB (NF-κB) pathway proteins were detected using Western blotting, and the mRNA expressions of the hub genes were examined with RT-qPCR.

Results

We identified 32 intersection genes of emodin and RA, and the key targets including CAPS3, ESR1, and MAPK14 involved mainly the NF-κB signaling pathway. Cell scratch experiment and flow cytometry demonstrated a strong inhibitory effect of emodin on MH7A cell proliferation. Treatment with TNF-α significantly increased the cellular expressions of the NF-κB pathway proteins, which were obviously lowered by treatment with 80 μmol/L emodin. The results of RT-qPCR showed that TNF-α treatment obviously up-regulated the expressions of the hub genes COX2 and P38MAPK, and emodin treatment significantly down-regulated the expressions of MAPK and PTGS2 and up-regulated the expression of CASP3.

Conclusion

The therapeutic effect of emodin on RA is mediated mainly through regulation of cell proliferation, apoptosis, and the NF-κB pathway.

SUBMITTER: Cao C

PROVIDER: S-EPMC9257365 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

[Therapeutic mechanism of emodin for treatment of rheumatoid arthritis: a network pharmacology-based analysis].

Cao C C Zeng L L Rong X X

Nan fang yi ke da xue xue bao = Journal of Southern Medical University 20220601 6

<h4>Objective</h4>To investigate the therapeutic mechanism of emodin in the treatment of rheumatoid arthritis (RA) using a network pharmacology-based method and validate this mechanism in a fibroblast-like synovial cell line.<h4>Methods</h4>The PubChem, Targetnet, SwissTargetPrediction, Genecards, OMIM, and DisGeNET databases were searched to obtain emodin targets and RA-related genes. A protein-protein interaction (PPI) network was constructed, and GO and KEGG pathway enrichment analyses were c ...[more]

PMID: 35790443

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Project description:Traditional Chinese medicine (TCM) with the characteristics of "multi-component-multi-target-multi-pathway" has obvious advantages in the prevention and treatment of complex diseases, especially in the aspects of "treating the same disease with different treatments". However, there are still some problems such as unclear substance basis and molecular mechanism of the effectiveness of formula. Network pharmacology is a new strategy based on system biology and poly-pharmacology, which could observe the intervention of drugs on disease networks at systematical and comprehensive level, and especially suitable for study of complex TCM systems. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, causing articular and extra articular dysfunctions among patients, it could lead to irreversible joint damage or disability if left untreated. TCM formulas, Danggui-Sini-decoction (DSD), Guizhi-Fuzi-decoction (GFD), and Huangqi-Guizhi-Wuwu-Decoction (HGWD), et al., have been found successful in controlling RA in clinical applications. Here, a network pharmacology-based approach was established. With this model, key gene network motif with significant (KNMS) of three formulas were predicted, and the molecular mechanism of different formula in the treatment of rheumatoid arthritis (RA) was inferred based on these KNMSs. The results show that the KNMSs predicted by the model kept a high consistency with the corresponding C-T network in coverage of RA pathogenic genes, coverage of functional pathways and cumulative contribution of key nodes, which confirmed the reliability and accuracy of our proposed KNMS prediction strategy. All validated KNMSs of each RA therapy-related formula were employed to decode the mechanisms of different formulas treat the same disease. Finally, the key components in KNMSs of each formula were evaluated by in vitro experiments. Our proposed KNMS prediction and validation strategy provides methodological reference for interpreting the optimization of core components group and inference of molecular mechanism of formula in the treatment of complex diseases in TCM.

Project description:Rheumatoid arthritis is a chronic autoimmune disease characterized by persistent hyperplasia of the synovial membrane and progressive erosion of articular cartilage. Disequilibrium between the proliferation and death of RA fibroblast-like synoviocytes (RA-FLSs) is the critical factor in progression of RA. Naringin has been reported to exert anti-inflammatory and antioxidant effect in acute and chronic animal models of RA. However, the therapeutic effect and underlying mechanisms of naringin in human RA-FLS remain unclear. Based on network pharmacology, the corresponding targets of naringin were identified using SwissTargetPrediction database, STITCH database, and Comparative Toxicogenomics Database. Deferentially expressed genes (DEGs) in RA were obtained from the GEO database. The protein-protein interaction (PPI) networks of intersected targets were constructed using the STRING database and visualized using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the pathways directly related to pathogenesis of RA were integrated manually. Further, in vitro studies were carried out based on network pharmacology. 99 target genes were intersected between targets of naringin and DEGs. The PPI network and topological analysis indicated that IL-6, MAPK8, MMP-9, TNF, and MAPK1 shared the highest centrality among all. GO analysis and KEGG analysis indicated that target genes were mostly enriched in (hsa05200) pathways in cancer, (hsa05161) hepatitis B, (hsa04380) osteoclast differentiation, (hsa04151) PI3K-Akt signaling pathway, and (hsa05142) Chagas disease (American trypanosomiasis). In vitro studies revealed that naringin exposure was found to promote apoptosis of RA-FLS, increased the activation of caspase-3, and increased the ratio of Bax/Bcl-2 in a dose-dependent manner. Furthermore, treatment of naringin attenuated the production of inflammatory cytokines and matrix metalloproteinases (MMPs) in TNF-ɑ-induced RA-FLS. Moreover, treatment of naringin inhibited the phosphorylation of Akt and ERK in RA-FLS. Network pharmacology provides a predicative strategy to investigate the therapeutic effects and mechanisms of herbs and compounds. Naringin inhibits inflammation and MMPs production and promotes apoptosis in RA-FLS via PI3K/Akt and MAPK/ERK signaling pathways.

Dataset Information

[Therapeutic mechanism of emodin for treatment of rheumatoid arthritis: a network pharmacology-based analysis].

Objective

Methods

Results

Conclusion

Publications

[Therapeutic mechanism of emodin for treatment of rheumatoid arthritis: a network pharmacology-based analysis].

Similar Datasets

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