Dataset Information

Potential Molecular Mechanisms of Zhibai Dihuang Wan in Systemic Lupus Erythematosus Based on Network Biology.

ABSTRACT: Systemic lupus erythematosus (SLE) is a refractory autoimmune disease. Zhibai Dihuang Wan (ZDW) has frequently been used for treating SLE in China and been proved to have a prominent role in decreasing SLE patients' morality rate. However, the active substances in ZDW and the molecular mechanisms of ZDW in SLE remain unclear. This study identified the bioactive compounds and delineated the molecular targets and potential pathways of ZDW by using a network biology approach. First, we collected putative targets of ZDW based on TCMSP, GeneCards, and STITCH databases and built a network containing the interactions between the putative targets of ZDW and known therapeutic targets of SLE. Then, the key hubs were imported to DAVID Bioinformatics Resources 6.7 to perform gene ontology biological process (GOBP) and pathway enrichment analysis. A total of 95 nodes including 73 putative targets of ZDW were determined as major hubs in terms of their node degree. The results of GOBP and pathway enrichment analysis indicated that putative targets of ZDW mostly were involved in various pathways associated with inflammatory response and apoptosis. More importantly, eleven putative targets of ZDW (CASP3, BCL2, BAX, CYCS, NFKB1, NFKBIA, IL-6, IL-1?, PTGS2, CCL2, and TNF-?) were recognized as active factors involved in the main biological functions of treatment, implying the underlying mechanisms of ZDW acting on SLE. This study provides novel insights into the mechanisms of ZDW in SLE, from the molecular level to the pathway level.

SUBMITTER: Yang Z

PROVIDER: S-EPMC7178533 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Potential Molecular Mechanisms of <i>Zhibai Dihuang Wan</i> in Systemic Lupus Erythematosus Based on Network Biology.

Yang Zi Z Xie Rui-Fei RF Zhong Min-Hong MH Xie Guan-Qun GQ Fan Yong-Sheng YS Zhao Ting T

Evidence-based complementary and alternative medicine : eCAM 20200413

Systemic lupus erythematosus (SLE) is a refractory autoimmune disease. <i>Zhibai Dihuang Wan</i> (ZDW) has frequently been used for treating SLE in China and been proved to have a prominent role in decreasing SLE patients' morality rate. However, the active substances in ZDW and the molecular mechanisms of ZDW in SLE remain unclear. This study identified the bioactive compounds and delineated the molecular targets and potential pathways of ZDW by using a network biology approach. First, we colle ...[more]

PMID: 32351603

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Project description:Complex disease is a cascade process which is associated with functional abnormalities in multiple proteins and protein-protein interaction (PPI) networks. One drug one target has not been able to perfectly intervene complex diseases. Increasing evidences show that Chinese herb formula usually treats complex diseases in the form of multi-components and multi-targets. The key step to elucidate the underlying mechanism of formula in traditional Chinese medicine (TCM) is to optimize and capture the important components in the formula. At present, there are several formula optimization models based on network pharmacology has been proposed. Most of these models focus on the 2D/3D similarity of chemical structure of drug components and ignore the functional optimization space based on relationship between pathogenetic genes and drug targets. How to select the key group of effective components (KGEC) from the formula of TCM based on the optimal space which link pathogenic genes and drug targets is a bottleneck problem in network pharmacology. To address this issue, we designed a novel network pharmacological model, which takes Lang Chuang Wan (LCW) treatment of systemic lupus erythematosus (SLE) as the case. We used the weighted gene regulatory network and active components targets network to construct disease-targets-components network, after filtering through the network attribute degree, the optimization space and effective proteins were obtained. And then the KGEC was selected by using contribution index (CI) model based on knapsack algorithm. The results show that the enriched pathways of effective proteins we selected can cover 96% of the pathogenetic genes enriched pathways. After reverse analysis of effective proteins and optimization with CI index model, KGEC with 82 components were obtained, and 105 enriched pathways of KGEC targets were consistent with enriched pathways of pathogenic genes (80.15%). Finally, the key components in KGEC of LCW were evaluated by in vitro experiments. These results indicate that the proposed model with good accuracy in screening the KGEC in the formula of TCM, which provides reference for the optimization and mechanism analysis of the formula in TCM.

Project description:BackgroundThe risk of acute myocardial infarction (AMI) is elevated in patients with systemic lupus erythematosus (SLE), and it is of great clinical value to identify potential molecular mechanisms and diagnostic markers of AMI associated with SLE by analyzing public database data and transcriptome sequencing data.MethodsAMI and SLE-related sequencing datasets GSE62646, GSE60993, GSE50772 and GSE81622 were downloaded from the Gene Expression Omnibus (GEO) database and divided into prediction and validation cohorts. To identify the key genes associated with AMI related to SLE, WGCNA and DEGs analysis were performed for the prediction and validation cohorts, respectively. The related signaling pathways were identified by GO/KEGG enrichment analysis. Peripheral blood mononuclear cells (PBMCs) from patients with AMI were collected for transcriptome sequencing to validate the expression of key genes in patients with AMI. Least absolute shrinkage and selection operator (LASSO) regression analysis was applied to screen diagnostic biomarkers. The diagnostic efficacy of biomarkers was validated by ROC analysis, and the CIBERSORTx platform was used to analyze the composition of immune cells in AMI and SLE.ResultsA total of 108 genes closely related to AMI and SLE were identified in the prediction cohort, and GO/KEGG analysis showed significantly enriched signaling pathways. The results of differential analysis in validation cohort were consistent with them. By transcriptional sequencing of PBMCs from peripheral blood of AMI patients, combined with the results of prediction and validation cohort analysis, seven genes were finally screened out. LASSO analysis finally identifies DYSF, LRG1 and CSF3R as diagnostic biomarkers of SLE-related-AMI. CIBERSORTx analysis revealed that the biomarkers were highly correlated with neutrophils.ConclusionNeutrophil degranulation and NETs formation play important roles in SLE-related AMI, and DYSF, LRG1 and CSF3R were identified as important diagnostic markers for the development and progression of SLE-related AMI.

Dataset Information

Potential Molecular Mechanisms of Zhibai Dihuang Wan in Systemic Lupus Erythematosus Based on Network Biology.

Publications

Potential Molecular Mechanisms of <i>Zhibai Dihuang Wan</i> in Systemic Lupus Erythematosus Based on Network Biology.

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