Dataset Information

Exploring the mechanisms underlying the therapeutic effect of the drug pair Rhubarb-Coptis in diabetic nephropathy using network pharmacology and molecular docking analysis.

ABSTRACT:

Background

To use network pharmacology to explore the mechanism of the drug pair Rhubarb-Coptis in the treatment of diabetic nephropathy (DN).

Methods

The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredients of drug pair Rhubarb-Coptis. Targets were obtained using the TCMSP and SwissTargetPrediction databases. DN disease targets were extracted from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and Therapeutic Target database (TTD) databases. A "drug-compound-target" network and protein-protein interaction (PPI) network were constructed and analyzed through the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape software. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Molecular docking was performed using AutoDock Vina and PyMOL software.

Results

A total of 30 active components and 609 targets of Rhubarb-Coptis were screened out, and 98 common targets of DN and Rhubarb-Coptis were obtained. Quercetin, berberine, epiruberine, epautin, and moupinamide were the main active components in the treatment of DN. The STAT3, CTNNB1, PIK3R1, PIK3CA, and TP53 genes were identified as the potential 5 key targets. The GO enrichment analysis showed that these 5 key targets mainly involved in inflammation, oxidative stress, and apoptosis. KEGG enrichment analysis showed that the pathways were mainly enriched in the AGE-RAGE and HIF-1 signaling pathways. Molecular docking revealed that the 5 key targets could combine well with their corresponding active compounds.

Conclusions

This study expounds the therapeutic effect of Rhubarb-Coptis on DN from a holistic perspective, and provides a valuable basis for clinical application and academic research.

SUBMITTER: Wu C

PROVIDER: S-EPMC9843313 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Exploring the mechanisms underlying the therapeutic effect of the drug pair Rhubarb-Coptis in diabetic nephropathy using network pharmacology and molecular docking analysis.

Wu Chunwei C Cao Lei L Liu Miao M Zhang Wenlong W Chen Hailong H Wang Ruolin R Liu Chang C He Ze Z

Annals of translational medicine 20221201 24

<h4>Background</h4>To use network pharmacology to explore the mechanism of the drug pair Rhubarb-Coptis in the treatment of diabetic nephropathy (DN).<h4>Methods</h4>The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredients of drug pair Rhubarb-Coptis. Targets were obtained using the TCMSP and SwissTargetPrediction databases. DN disease targets were extracted from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and Therapeutic Target ...[more]

PMID: 36660658

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Project description:Diabetic nephropathy (DN) is one of the most serious complications of diabetes and the main cause of end-stage renal failure. Rhubarb is a widely used traditional Chinese herb, and it has exhibited efficacy in reducing proteinuria, lowering blood sugar levels and improving kidney function in patients with DN. However, the exact pharmacological mechanism by rhubarb improves DN remain unclear due to the complexity of its ingredients. Hence, we systematically explored the underlying mechanisms of rhubarb in the treatment of DN. We adopted a network pharmacology approach, focusing on the identification of active ingredients, drug target prediction, gene collection, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment. Molecular docking technology was used to verify the binding ability between the main active compounds and central therapeutic targets, and screen out the core active ingredients in rhubarb for the treatment of DN. Finally, molecular dynamics simulation was performed for the optimal core protein-ligand obtained by molecular docking using GROMACS software. The network analysis identified 16 active compounds in rhubarb that were linked to 37 possible therapeutic targets related to DN. Through protein-protein interaction analysis, TP53, CASP8, CASP3, MYC, JUN and PTGS2 were identified as the key therapeutic targets. By validation of molecular docking, finding that the central therapeutic targets have good affinities with the main active compounds of rhubarb, and rhein, beta-sitosterol and aloe-emodin were identified as the core active ingredients in rhubarb for the treatment of DN. Results from molecular dynamics simulations showed that TP53 and aloe-emodin bound very stably with a binding free energy of - 26.98 kcal/mol between the two. The results of the gene enrichment analysis revealed that the PI3K-Akt signalling pathway, p53 signalling pathway, AGE-RAGE signalling pathway and MAPK signalling pathway might be the key pathways for the treatment of DN, and these pathways were involved in podocyte apoptosis, glomerular mesangial cell proliferation, inflammation and renal fibrosis. Based on the network pharmacology approach and molecular docking technology, we successfully predicted the active compounds and their respective targets. In addition, we illustrated the molecular mechanisms that mediate the therapeutic effects of rhubarb against DN. These findings provided an important scientific basis for further research of the mechanism of rhubarb in the treatment of DN.

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Dataset Information

Exploring the mechanisms underlying the therapeutic effect of the drug pair Rhubarb-Coptis in diabetic nephropathy using network pharmacology and molecular docking analysis.

Background

Methods

Results

Conclusions

Publications

Exploring the mechanisms underlying the therapeutic effect of the drug pair Rhubarb-Coptis in diabetic nephropathy using network pharmacology and molecular docking analysis.

Similar Datasets

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