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Utilizing network pharmacology to explore the underlying mechanism of Radix Salviae in diabetic retinopathy.

ABSTRACT: Introduction:Radix 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. Methods:A 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. Results:A 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. Conclusions:Radix 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.

SUBMITTER: Piao CL

PROVIDER: S-EPMC6936117 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Utilizing network pharmacology to explore the underlying mechanism of <i>Radix Salviae</i> in diabetic retinopathy.

Piao Chun-Li CL Luo Jin-Li JL Jin De Tang Cheng C Wang Li L Lian Feng-Mei FM Tong Xiao-Lin XL

Chinese medicine 20191230

<h4>Introduction</h4><i>Radix Salviae</i> (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 <i>Radix Salviae</i> remain vague. The aim of this study was to decrypt the underlying mechanisms of <i>Radix Salviae</i> in the treatment of diabetic retinopathy using a systems pharmacology approach.<h4>Methods</h4>A network pharmacology-based strategy was proposed ...[more]

PMID: 31892939

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Project description:BackgroundGuizhi Fuling Wan (GZFLW) is a widely used classical Chinese herbal formulae prescribed for the treatment of endometriosis (EMs). This study aimed to predict the key targets and mechanisms of GZFLW in the treatment of EMs by network pharmacology and molecular docking.MethodsFirstly, related compounds and targets of GZFLW were identified through the TCMSP, BATMAN-TCM and CASC database. Then, the EMs target database was built by GeneCards. The overlapping targets between GZFLW and EMs were screened out, and then data of the PPI network was obtained by the STRING Database to analyze the interrelationship of these targets. Furthermore, a topological analysis was performed to screen the hub targets. After that, molecular docking technology was used to confirm the binding degree of the main active compounds and hub targets. Finally, the DAVID database and Metascape database were used for GO and KEGG enrichment analysis.ResultsA total of 89 GZFLW compounds and 284 targets were collected. One hundred one matching targets were picked out as the correlative targets of GZFLW in treating EMs. Among these, 25 significant hub targets were recognized by the PPI network. Coincidently, molecular docking simulation indicated that the hub targets had a good bonding activity with most active compounds (69.71%). Furthermore, 116 items, including the inflammatory reaction, RNA polymerase, DNA transcription, growth factor activity, and steroid-binding, were selected by GO enrichment analysis. Moreover, the KEGG enrichment analysis results included 100 pathways focused on the AGE-RAGE pathway, HIF pathway, PI3K Akt pathway, MAPK pathway, and TP53 pathway, which exposed the potential mechanisms of GZFLW in treating EMs. Also, the MTT colorimetric assay indicated that the cell proliferation could be inhibited by GZFLW. Compared with the control group, the protein levels of P53, BAX, and caspase3 in the drug groups were all increased in Western blotting results. The results of flow cytometry showed that the percentage of apoptotic cells in the GZFLW group was significantly higher than that in the control group.ConclusionThrough the exploration of network pharmacology and molecular docking technology, GZFLW has a therapeutic effect on EMs through multi-target mechanism. This study provided a good foundation for further experimental research.

Project description:Radix Salviae (Danshen)-Angelicae Sinensis Radix (Danggui)-Lycii Fructus (Gouqizi)-Rehmanniae Radix Praeparata (Shudihuang)-Ginkgo Folium (Yinxinye) (RALRG) are commonly used herbs in China that have shown positive effects on retinitis pigmentosa (RP). However, little research has been performed on the impact of RALRG and RP. Herein, this study aimed to predict the mechanism and potential components of RALRG in treating RP. The ingredients of RALRG were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP); the potential targets of RP and RALRG were obtained from TCMSP, GeneCards, and the Online Mendelian Inheritance in Man (OMIM) database. A protein-protein interaction (PPI) network was constructed to visualize PPIs. The functional enrichment was performed with the R program. A visual RALRG-RP-pathway pharmacology network was established by Cytoscape 3.9.1. Molecular docking was used to perform molecular docking and calculate the binding affinity. A total of 132 effective active ingredients in RALRG with 248 target genes were screened; 92 intersection target genes were acquired from the intersection of RP- and RALRG-related genes. Gene Ontology (GO) enrichment indicated that these intersection targets were mainly involved in oxidative stress, metal ion response, and chemical stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the PI3K-AKT, cellular senescence, and MAPK signaling pathways were closely related to the therapy of RP. In addition, a potential pharmacology network for RALRG-RP-pathway was constructed. AKT1 and JUN were considered the primary targets. Luteolin, quercetin, and kaempferol were identified as the vital three active ingredients. RALRG was found to be the main regulator for oxidative stress and PI3K/AKT signaling pathways. Luteolin, quercetin, and kaempferol were three promising complementary ingredients for RP treatment. This study may provide a theoretical basis for applying RALRG to screen potential drugs for RP.

Dataset Information

Utilizing network pharmacology to explore the underlying mechanism of Radix Salviae in diabetic retinopathy.

Publications

Utilizing network pharmacology to explore the underlying mechanism of <i>Radix Salviae</i> in diabetic retinopathy.

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