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A Network Pharmacology to Explore the Mechanism of Astragalus Membranaceus in the Treatment of Diabetic Retinopathy.

ABSTRACT: Background:Diabetic retinopathy (DR) includes a series of typical lesions affected by retinal microvascular damage caused by diabetes mellitus (DM), which not only seriously damages the vision, affecting the life's quality of patients, but also brings a considerable burden to the family and society. Astragalus Membranaceus (AM) is a commonly used medicine in clinical therapy of eye disorders in traditional Chinese medicine (TCM). In recent years, it is also used for treating DR, but the specific mechanism is unclear. Therefore, this study explores the potential mechanism of AM in DR treatment by using network pharmacology. Methods:Based on the oral bioavailability (OB) and drug likeness (DL) of two ADME (absorption, distribution, metabolism, excretion) parameters, Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Swiss Target Prediction platform, GeneCards, and OMIM database were used to predict and screen the active compounds of AM, the core targets of AM in DR treatment. The Metascape data platform was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the core targets. Results:24 active compounds were obtained, such as quercetin, kaempferol, and astragaloside IV. There were 169 effective targets of AM in DR treatment, and the targets were further screened and finally, 38 core targets were obtained, such as VEGFA, AKT1, and IL-6. EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, and other metabolic pathways participated in oxidative stress, cell apoptosis, angiogenesis signal transduction, inflammation, and other biological processes. Conclusion:AM treats DR through multiple compounds, multiple targets, and multiple pathways. AM may play a role in the treatment of DR by targeting VEGFA, AKT1, and IL-6 and participating in oxidative stress, angiogenesis, and inflammation.

SUBMITTER: Jin Q

PROVIDER: S-EPMC7652614 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Network Pharmacology to Explore the Mechanism of <i>Astragalus</i> Membranaceus in the Treatment of Diabetic Retinopathy.

Jin Qi Q Hao Xiao-Feng XF Xie Li-Ke LK Xu Jing J Sun Mei M Yuan Hang H Wang Shi-Hui SH Wu Gai-Ping GP Miao Meng-Lu ML

Evidence-based complementary and alternative medicine : eCAM 20201102

<h4>Background</h4>Diabetic retinopathy (DR) includes a series of typical lesions affected by retinal microvascular damage caused by diabetes mellitus (DM), which not only seriously damages the vision, affecting the life's quality of patients, but also brings a considerable burden to the family and society. <i>Astragalus</i> Membranaceus (AM) is a commonly used medicine in clinical therapy of eye disorders in traditional Chinese medicine (TCM). In recent years, it is also used for treating DR, b ...[more]

PMID: 33204295

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Project description:Background:Diabetic nephropathy (DN), characterized by hyperglycemia, hypertension, proteinuria, and edema, is a unique microvascular complication of diabetes. Traditional Chinese medicine (TCM) Astragalus membranaceus (AM) has been widely used for DN in China while the pharmacological mechanisms are still unclear. This work is aimed at undertaking a network pharmacology analysis to reveal the mechanism of the effects of AM in DN. Materials and Methods. In this study, chemical constituents of AM were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the potential targets of AM were identified using the Therapeutic Target Database (TTD). DisGeNET and GeneCards databases were used to collect DN-related target genes. DN-AM common target protein interaction network was established by using the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the DN mechanism and therapeutic effect of AM. The network diagrams of the active component-action target and protein-protein interaction (PPI) networks were constructed using Cytoscape software. Results:A total of 16 active ingredients contained and 78 putative identified target genes were screened from AM, of which 42 overlapped with the targets of DN and were considered potential therapeutic targets. The analysis of the network results showed that the AM activity of component quercetin, formononetin, calycosin, 7-O-methylisomucronulatol, and quercetin have a good binding activity with top ten screened targets, such as VEGFA, TNF, IL-6, MAPK, CCL3, NOS3, PTGS2, IL-1?, JUN, and EGFR. GO and KEGG analyses revealed that these targets were associated with inflammatory response, angiogenesis, oxidative stress reaction, rheumatoid arthritis, and other biological process. Conclusions:This study demonstrated the multicomponent, multitarget, and multichannel characteristics of AM, which provided a novel approach for further research of the mechanism of AM in the treatment of DN.

Project description:AbstractDiabetic nephropathy (DN) is a common microvascular complication of diabetic patients, along with hypertension, hyperlipemia, proteinuria, edema, and other clinical manifestations. Astragalus membranaceus (AM) is a traditional Chinese medicine and has shown significant clinical efficacy against DN. However, the overall molecular mechanism of this therapeutic effect has not been entirely elucidated. Using network pharmacology, we aimed to identify the key active ingredients and potential pharmacological mechanisms of AM in treating DN and provide scientific evidence of its clinical efficacy.The active ingredients of AM were obtained from the traditional Chinese medicine systems pharmacology database, and the potential targets of AM were identified using the therapeutic target database. DN-related target genes were acquired from the Gene Expression Omnibus microarray dataset GSE1009 and 3 widely used databases-DisGeNET, GeneCards, and Comparative Toxicogenomics Database. The DN-AM common target protein interaction network was established by using the STRING database. Active ingredients candidate targets proteins networks were constructed using Cytoscape software for visualization. Additionally, gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathway analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery database. Target-regulating microRNAs (miRNAs) of these hub genes were obtained from the therapeutic target database, which could then be used for further identification of AM-regulated key miRNAs.A total of 17 active ingredients and 214 target proteins were screened from AM. 61 candidate co-expressed genes with therapeutic effects against DN were obtained and considered as potential therapeutic targets. GO and Kyoto encyclopedia of genes and genomes enrichment analysis showed that these genes were mainly involved in inflammatory response, angiogenesis, oxidative stress reaction, HIF signaling pathway, tumor necrosis factor signaling pathway, and VEGF signaling pathway. In all, 636 differentially expressed genes were identified between the DN patients and control group by using microarray data, GSE1009. Lastly, VEGFA, epidermal growth factor receptor, STAT1, and GJA1 were screened as hub genes. The relationships between miRNAs and hub genes were constructed, which showed that miR-302-3p, miR-372-3p, miR-373-3p, and miR-520-3p were regulated by VEGFA and epidermal growth factor receptor. Meanwhile, VEGFA also influenced miR-15-5p, miR-16-5p, miR-17-5p, miR-20-5p, miR-93-5p, miR-106-5p, miR-195-5p, miR-424-5p, miR-497-5p, and miR-519-3p. In addition, miR-1-3p and miR-206 were regulated by VEGFA and GJA1, and miR-23-3p was regulated by STAT1 and GJA1.To our knowledge, this study revealed for the first time the characteristic multiple components, multiple targets, and multiple pathways of AM that seem to be the underlying mechanisms of action of AM in the treatment of DN with respect to miRNAs.Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.

Project description:IntroductionRadix Salviae (Dan-shen in pinyin), a classic Chinese herb, has been extensively used to treat diabetic retinopathy in clinical practice in China for many years. However, the pharmacological mechanisms of Radix Salviae remain vague. The aim of this study was to decrypt the underlying mechanisms of Radix Salviae in the treatment of diabetic retinopathy using a systems pharmacology approach.MethodsA network pharmacology-based strategy was proposed to elucidate the underlying multi-component, multi-target, and multi-pathway mode of action of Radix Salviae against diabetic retinopathy. First, we collected putative targets of Radix Salviae based on the Traditional Chinese Medicine System Pharmacology database and a network of the interactions among the putative targets of Radix Salviae and known therapeutic targets of diabetic retinopathy was built. Then, two topological parameters, "degree" and "closeness certainty" were calculated to identify the major targets in the network. Furthermore, the major hubs were imported to the Database for Annotation, Visualization and Integrated Discovery to perform a pathway enrichment analysis.ResultsA total of 130 nodes, including 18 putative targets of Radix Salviae, were observed to be major hubs in terms of topological importance. The results of pathway enrichment analysis indicated that putative targets of Radix Salviae mostly participated in various pathways associated with angiogenesis, protein metabolism, inflammatory response, apoptosis, and cell proliferation. The putative targets of Radix Salviae (vascular endothelial growth factor, matrix metalloproteinases, plasminogen, insulin-like growth factor-1, and cyclooxygenase-2) were recognized as active factors involved in the main biological functions of treatment, which implied that these were involved in the underlying mechanisms of Radix Salviae on diabetic retinopathy.ConclusionsRadix Salviae could alleviate diabetic retinopathy via the molecular mechanisms predicted by network pharmacology. This research demonstrates that the network pharmacology approach can be an effective tool to reveal the mechanisms of traditional Chinese medicine from a holistic perspective.

Project description:Background and objectiveHuangZhi YiShen Capsule (HZYS) is a Chinese patent herbal drug that protects kidney function in diabetic kidney disease (DKD) patients. However, the pharmacologic mechanisms of HZYS remain unclear. This study would use network pharmacology to explore the pharmacologic mechanisms of HZYS.MethodsChemical constituents of HZYS were obtained through the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and literature search. Potential targets of HZYS were identified by using the TCMSP and the SwissTarget Prediction databases. DKD-related target genes were collected by using the Online Mendelian Inheritance in Man, Therapeutic Target Database, GeneCards, DisGeNET, and Drugbank databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the mechanisms of HZYS in treating DKD. Molecular docking was conducted to verify the potential interactions between the prime compounds and the hub genes.Results179 active compounds and 620 target genes were obtained, and 571 common targets were considered potential therapeutic targets. The top 10 main active compounds of HZYS were heparin, quercetin, kaempferol, luteolin, methyl14-methylpentadecanoate, methyl (Z)-11-hexadecenoate, 17-hydroxycorticosterone, 4-pregnene-17α, 20β, 21-triol-3, 11-dione, wogonin, and hydroxyecdysone. Hub signaling pathways by which HZYS treating DKD were PI3K-Akt, MAPK, AGE-RAGE in diabetic complications, TNF, and apoptosis. The top 10 target genes associated with these pathways were IL6, MAPK1, AKT1, RELA, BCL2, JUN, MAPK3, MAP2K1, CASP3, and TNF. Quercetin and Luteolin were verified to have good binding capability with the hub potential targets IL6, MAPK1, AKT1 through molecular docking.ConclusionHZYS appeared to treat DKD by regulating the inflammatory, oxidative stress, apoptotic, and fibrosis signaling pathways. This study provided a novel perspective for further research of HZYS.

Dataset Information

A Network Pharmacology to Explore the Mechanism of Astragalus Membranaceus in the Treatment of Diabetic Retinopathy.

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A Network Pharmacology to Explore the Mechanism of <i>Astragalus</i> Membranaceus in the Treatment of Diabetic Retinopathy.

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