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pmid:36267726

Exploring the molecular mechanism of Sishen Decoction in the treatment of rheumatoid arthritis.

Jiannan Zheng · Yeyu Zhao · Qing Qi · Mingli Gao · Jing Yu

Annals of translational medicine · 2022 doi:10.21037/atm-22-3888

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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title
Exploring the molecular mechanism of Sishen Decoction in the treatment of rheumatoid arthritis.
doi
10.21037/atm-22-3888
pmid
36267726
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Jiannan Zheng
[1]
Yeyu Zhao
[2]
Qing Qi
[3]
Mingli Gao
[4]
Jing Yu
journal
Annals of translational medicine
year
2022
abstract
Background: To explore the potential targets and mechanism of action of Sishen Decoction in the treatment of rheumatoid arthritis (RA) using a network pharmacology approach. Methods: Firstly, we analyzed the differentially expressed genes in the Gene Expression Omnibus (GEO) database and constructed a protein-protein interaction (PPI) network using potential core target proteins determined by the STRING platform and Cytoscape software. We also performed gene ontology functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis, and gene set enrichment analysis (GSEA) on the potential targets, and then used the disease target database to download targets related to RA pathogenesis. The relevant targets were intersected with the action targets of Sishen Decoction to obtain the potential targets considered for the treatment of RA with Sishen Decoction. Results: The GSE55235 and GSE77298 datasets were downloaded from the GEO database for analysis, and 73 genes with abnormally high expression in RA and 26 genes with abnormally low expression in RA were obtained by taking the intersection of highly expressed genes and low expression genes in RA. The results of KEGG and Metascape showed that the differential genes were enriched in inflammation-related signaling pathways such as leukocyte migration, myeloid leukocyte-mediated immunity, and lymphocyte activation, as well as bone activation and bone development, which are closely related to RA. In the exploration of the drug targets of Sishen Decoction for the treatment of RA, it was found that Sishen Decoction may regulate the interleukin (IL)-17) signaling pathway, tumour necrosis factor (TNF) signaling pathway, and chemokine signaling pathway in RA by targeting MMP9 and CXCR4. Conclusions: This study explored the potential targets and signaling pathways of Sishen Decoction in the treatment of RA, which may help to illustrate the mechanisms involved in the action of Sishen Decoction and better understand its anti-RA role in the inhibition of angiogenesis, synovial proliferation, and bone destruction.
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Next, gene set enrichment analysis (GSEA) was conducted with P<0.05 as a screening condition of significant enrichment, followed by visualization of the results.
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Then, the up-regulated and down-regulated genes in the GSE55235 and GSE77298 datasets were intersected, which yielded 73 genes with abnormally high expression and 26 genes with abnormally low expression in RA (Figure 1E).
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We also performed gene ontology functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis, and gene set enrichment analysis (GSEA) on the potential targets, and then used the disease target database to download targets related to RA pathogenesis. The relevant targets were intersected with the action targets of Sishen Decoction to obtain the potential targets considered for the treatment of RA with Sishen Decoction.\nResults: The GSE55235 and GSE77298 datasets were downloaded from the GEO database for analysis, and 73 genes with abnormally high expression in RA and 26 genes with abnormally low expression in RA were obtained by taking the intersection of highly expressed genes and low expression genes in RA. The results of KEGG and Metascape showed that the differential genes were enriched in inflammation-related signaling pathways such as leukocyte migration, myeloid leukocyte-mediated immunity, and lymphocyte activation, as well as bone activation and bone development, which are closely related to RA. In the exploration of the drug targets of Sishen Decoction for the treatment of RA, it was found that Sishen Decoction may regulate the interleukin (IL)-17) signaling pathway, tumour necrosis factor (TNF) signaling pathway, and chemokine signaling pathway in RA by targeting MMP9 and CXCR4.\nConclusions: This study explored the potential targets and signaling pathways of Sishen Decoction in the treatment of RA, which may help to illustrate the mechanisms involved in the action of Sishen Decoction and better understand its anti-RA role in the inhibition of angiogenesis, synovial proliferation, and bone destruction.", "claims": [{"id": "claim-method", "statement": "Next, gene set enrichment analysis (GSEA) was conducted with P<0.05 as a screening condition of significant enrichment, followed by visualization of the results.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36267726", "locator": "sections[4] \"Functional enrichment analysis\" paragraph 2", "quote": "Next, gene set enrichment analysis (GSEA) was conducted with P<0.05 as a screening condition of significant enrichment, followed by visualization of the results."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Datasets including GSE55235 and GSE77298 were mined from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov), which comprised 43 human-derived samples [17 healthy control (HC) joints and 26 RA patients].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36267726", "locator": "sections[3] \"Identification of differentially expressed genes (DEGs) in RA\" paragraph 2", "quote": "Datasets including GSE55235 and GSE77298 were mined from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov), which comprised 43 human-derived samples [17 healthy control (HC) joints and 26 RA patients]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Intersecting the differentially expressed genes in GSE55235 and GSE77298 identified 73 genes with abnormally high expression and 26 genes with abnormally low expression in RA.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36267726", "locator": "sections[8] \"Retrieval of DEGs in RA\" paragraph 2", "quote": "Then, the up-regulated and down-regulated genes in the GSE55235 and GSE77298 datasets were intersected, which yielded 73 genes with abnormally high expression and 26 genes with abnormally low expression in RA (Figure 1E)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Intersecting the differentially expressed genes in GSE55235 and GSE77298 identified 73 genes with abnormally high expression and 26 genes with abnormally low expression in RA.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36267726"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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