Exploration of the Immuno-Inflammatory Potential Targets of Xinfeng Capsule in Patients with Ankylosing Spondylitis Based on Data Mining, Network Pharmacology, and Molecular Docking

Fang, Yanyan; Liu, Jian; Xin, Ling; Wen, Jianting; Guo, Jing; Huang, Dan; Xu, Li

doi:10.1155/2022/5382607

Cited by 9 publications

(6 citation statements)

References 32 publications

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“…A previous study also found that overexpression of microRNA-26a-5p by human bone mesenchymal stem cell-derived exosomes alleviates osteoarthritis by downregulating PTGS2, and the abovementioned studies suggest that PTGS2 is involved in the pathogenesis of knee osteoarthritis [32]. A recent study also demonstrated that quercetin may inhibit the inflammatory response in ankylosing spondylitis (AS) by downregulating PTGS2 in the NF-κB signaling pathway [33]. Our study confirmed that PTGS2 was highly expressed in peripheral blood and bone tissue samples from patients with hormonal femoral head necrosis and in a mouse model of hormonal femoral head necrosis and that quercetin treatment reduced PTGS2 expression and significantly improved femoral head necrosis.…”

Section: Discussionmentioning

confidence: 93%

A network pharmacology approach and validation experiments to investigate the mechanism of the Chinese medicine Wen-Dan Decoction in the treatment of steroid-induced femoral head necrosis

Li²,

Wu³

et al. 2022

Preprint

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Objective: The present work studied the mechanism of action of Wen-Dan Decoction in treating steroid-induced necrosis of the femoral head (SINFH) via network pharmacology and in vivo experiments.Methods: The microarray dataset GSE123568 (peripheral blood), which includes 30 SINFH patients and 10 non-SINFH samples (after using steroids), is included in the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene coexpression network analysis (WGCNA) were used to identify key SINFH-related genes. To investigate the functions of key SINFH-related genes, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed. We constructed a protein–protein interaction (PPI) network based on the STRING database. In addition, we screened active components in Wen-Dan Decoction and their possible role in treating hormonal osteonecrosis using the Traditional Chinese Medicine System Pharmacology (TCMSP) Database. Subsequently, the potential mechanisms of action of Wen-Dan Decoction in the treatment of SINFH obtained via network pharmacology analyses were validated in in vivo experiments.Results: A total of 608 DEGs were obtained (230 upregulated, 378 downregulated). In GO functional enrichment analysis, SINFH-related genes were mainly involved in neutrophil activation and immune response, and KEGG pathway analysis revealed that SINFH genes were mainly associated with cytokine receptor interactions, lipids and atherosclerosis, and tuberculosis. In addition, a total of 147 active ingredients were obtained for Wen-Dan Decoction, of which the core ingredient was quercetin, an active ingredient in licorice. Meanwhile, 277 target genes were identified for the treatment of SINFH with Wen-Dan Decoction, and NCF1, PTGS2, and RUNX2 were selected as core target genes. Furthermore, the results of quantitative real-time polymerase chain reaction (qRT–PCR) on peripheral blood and bone tissue samples from SINFH patients and non-SINFH samples showed that PGTS2 and NCF1 were upregulated in patient blood and necrotic bone tissues. In quercetin-treated mice, the appearance of femoral head necrosis was significantly improved, and micro-CT suggested that the bone density was significantly better. Finally, the results of qRT–PCR analysis of peripheral blood and femoral bone tissue from a mouse model of SINFH treated with quercetin showed that PGTS2 and NCF1 levels were downregulated compared with those of controls, which was consistent with the results of bioinformatics analysis.Conclusion: This study provides new insights into the genes and related pathways involved in SINFH and shows that PTGS2 and NCF1 could be used as potential drug targets in SINFH.

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Section: Discussionmentioning

confidence: 93%

A network pharmacology approach and validation experiments to investigate the mechanism of the Chinese medicine Wen-Dan Decoction in the treatment of steroid-induced femoral head necrosis

Li²,

Wu³

et al. 2022

Preprint

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“…To identify the core of ceRNA networks, we got 4 hub targets including JUN, CCND1, MAPK1, and MAPK14 by PPI analysis. en AutoDock Vina was used to verify the binding activity among hub targets and their related components with binding energy less than -5.0 kcal/mol, which showed good and stable combination with each other [34].…”

Section: Discussionmentioning

confidence: 99%

Zuogui Pill Ameliorates Glucocorticoid-Induced Osteoporosis through ZNF702P-Based ceRNA Network: Bioinformatics Analysis and Experimental Validation

Zhang

Chen

Shang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Glucocorticoid-induced osteoporosis (GIOP) is a musculoskeletal disease with increased fracture risk caused by long-term application of glucocorticoid, but there exist few effective interventions. Zuogui Pill (ZGP) has achieved clinical improvement for GIOP as an ancient classical formula, but its molecular mechanisms remain unclear due to scanty relevant studies. This study aimed to excavate the effective compounds and underlying mechanism of ZGP in treating GIOP and construct relative ceRNA network by using integrated analysis of bioinformatics analysis and experimental validation. Results show that ZNF702P is significantly upregulated in GIOP than normal cases based on gene chip sequencing analysis. Totally, 102 ingredients and 535 targets of ZGP as well as 480 GIOP-related targets were selected, including 122 common targets and 8 intersection targets with the predicted mRNAs. The ceRNA network contains one lncRNA (ZNF702P), 6 miRNAs, and 8 mRNAs. Four hub targets including JUN, CCND1, MAPK1, and MAPK14 were identified in the PPI network. Six ceRNA interaction axes including ZNF702P-hsa-miR-429-JUN, ZNF702P-hsa-miR-17-5p/hsa-miR-20b-5p-CCND1, ZNF702P-hsa-miR-17-5p/hsa-miR-20b-5p-MAPK1, and ZNF702P-hsa-miR-24-3p-MAPK14 were obtained. By means of molecular docking, we found that all the hub targets could be effectively combined with related ingredients. GO enrichment analysis showed 649 biological processes, involving response to estrogen, response to steroid hormone, inflammatory response, macrophage activation, and osteoclast differentiation, and KEGG analysis revealed 102 entries with 36 relative signaling pathways, which mainly contained IL-17 signaling pathway, T cell receptor signaling pathway, FoxO signaling pathway, the PD-L1 expression and PD-1 checkpoint pathway, MAPK signaling pathway, TNF signaling pathway, Estrogen signaling pathway, and Wnt signaling pathway. Our experiments confirmed that ZNF702P exhibited gradually increasing expression levels during osteoclast differentiation of human peripheral blood monocytes (HPBMs) induced by RANKL, while ZGP could inhibit osteoclast differentiation of HPBMs induced by RANKL in a concentration-dependent manner. Therefore, by regulating inflammatory response, osteoclast differentiation, and hormone metabolism, ZGP may treat GIOP by regulating hub target genes, such as JUN, CCND1, MAPK1, and MAPK14, and acting on numerous key pathways, which involve the ZNF702P-based ceRNA network.

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“…e a nities between ligands and receptors were evaluated as docking energies by AutoDock Vina software (version 1.2.0). ey were considered to bind well with each other when the docking energy was less than −5 kcal/mol [23].…”

Section: Molecular Dockingmentioning

confidence: 99%

Potential Mechanisms of White Peony against Primary Sjögren’s Syndrome Based on Network Pharmacology and Molecular Docking

Zhuang

Liang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Multiple system and organ damage occurs with the continuous progression of primary Sjögren’s syndrome (pSS), and the lack of specific drugs against this disease is a huge challenge. White peony (WP), a widely used traditional Chinese herb, has been confirmed to have a therapeutic value in pSS. However, the specific mechanisms of WP in the treatment of pSS are unknown. Methods. The active ingredients and their targets in WP were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and disease-related targets were collected from GeneCards, Online Mendelian Inheritance in Man (OMIM), and the Therapeutic Target Database (TTD). The overlapping targets were acquired by taking the intersection. A protein-protein interaction (PPI) network was structured using the STRING database. A disease-drug-ingredient-target (D-D-I-T) network was built using Cytoscape software. By filtering twice, core targets were acquired. Gene Ontology (GO) and Kyoto Encyclopedia Gene and Genome (KEGG) pathway enrichment analysis were accompanied by R packages. Finally, molecular docking was used to verify the abovementioned results. Results. In total, we screened 88 WP-related targets, 1480 pSS-related targets, and 32 overlapping targets. D-D-I-T Network analysis displayed six main active ingredients of WP, which played a significant therapeutic role in pSS. Further topological analysis selected seven core target genes, including IL-6, TNF, PPARγ, AKT1, CASP3, NOS3, and JUN. GO and KEGG analysis were used to elucidate pharmacological mechanisms, mainly acting in the AGE-RAGE signaling pathway. Molecular docking proved that paeoniflorin bound well with core targets. Conclusion. Our study revealed that IL-6, TNF, AKT1, CASP3, NOS3, and JUN may be pathogenic target genes, and PPARγ may be a protective target gene. The main active ingredients of WP mainly played a therapeutic role via the AGE-RAGE signaling pathway. These findings provide a fundamental and theoretical basis for the clinical application of WP.

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Exploration of the Immuno-Inflammatory Potential Targets of Xinfeng Capsule in Patients with Ankylosing Spondylitis Based on Data Mining, Network Pharmacology, and Molecular Docking

Cited by 9 publications

References 32 publications

A network pharmacology approach and validation experiments to investigate the mechanism of the Chinese medicine Wen-Dan Decoction in the treatment of steroid-induced femoral head necrosis

A network pharmacology approach and validation experiments to investigate the mechanism of the Chinese medicine Wen-Dan Decoction in the treatment of steroid-induced femoral head necrosis

Zuogui Pill Ameliorates Glucocorticoid-Induced Osteoporosis through ZNF702P-Based ceRNA Network: Bioinformatics Analysis and Experimental Validation

Potential Mechanisms of White Peony against Primary Sjögren’s Syndrome Based on Network Pharmacology and Molecular Docking

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