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Utilising network pharmacology to explore the underlying mechanism of Wumei Pill in treating pancreatic neoplasms.

ABSTRACT: BACKGROUND:Wumei Pill (WMP), a famous herbal formula, has been widely used to treat digestive system diseases in clinical practice in China for centuries. We have found a correlation between the indications of WMP and the typical symptoms of pancreatic neoplasms. However, the pharmacological mechanisms of WMP still remain unknown. METHODS:In the present work, we used a network pharmacological method to predict its underlying complex mechanism of treating pancreatic neoplasms. Firstly, we obtained relative compounds of WMP based on TCMSP database, TCM database@Taiwan and TCMID database and collected potential targets of these compounds by target fishing. Then we built the pancreatic neoplasms target database by CTD, TTD, PharmGKB. Based on the matching results between WMP potential targets and pancreatic neoplasms targets, we built a PPI network to analyze the interactions among these targets and screen the hub targets by topology. Furthermore, DAVID bioinformatics resources were utilized for the enrichment analysis on GO_BP and KEGG. RESULTS:A total of 80 active ingredients and 77 targets of WMP were picked out. The results of DAVID enrichment analysis indicated that 58 cellular biological processes (FDR

SUBMITTER: Wan Y

PROVIDER: S-EPMC6611005 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Utilising network pharmacology to explore the underlying mechanism of Wumei Pill in treating pancreatic neoplasms.

Wan Yuxiang Y Xu Lin L Liu Zeyu Z Yang Ming M Jiang Xin X Zhang Qiaoli Q Huang Jinchang J

BMC complementary and alternative medicine 20190704 1

<h4>Background</h4>Wumei Pill (WMP), a famous herbal formula, has been widely used to treat digestive system diseases in clinical practice in China for centuries. We have found a correlation between the indications of WMP and the typical symptoms of pancreatic neoplasms. However, the pharmacological mechanisms of WMP still remain unknown.<h4>Methods</h4>In the present work, we used a network pharmacological method to predict its underlying complex mechanism of treating pancreatic neoplasms. Firs ...[more]

PMID: 31272505

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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:BackgroundDry eye disease (DED) is a multifactorial disease of the ocular surface, which affects the quality of life and work efficiency of affected patients. The traditional Chinese medicine formula Qiju Dihuang Pill (QJDHP) has a good therapeutic effect on DED. However, the pharmacological mechanism is not clear.ObjectiveTo explore the mechanism of QJDHP in the treatment of DED based on network pharmacology.MethodThe active components in QJDHP were screened in Traditional Chinese Medicine Systems Pharmacology (TCMSP), and putative molecular targets of QJDHP were identified using the SwissTargetPrediction database. DED-related targets were screened by GeneCards and OMIM. We established protein-protein interaction (PPI) and core targets and corresponding active compound network by Cytoscape to identify the core targets and main compounds of QJDHP against DED. DAVID database was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking was used to evaluate the binding activity between key active compounds and core targets.ResultsThe results of network pharmacology showed that 253 targets of QJDHP were related to DED. PPI network analysis showed the 18 core targets. The binding affinity of docking results ranged from -5.7 to -9.3 kcal/mol, indicating a good docking effect. The results of GO enrichment analysis showed that the mechanism of QJDHP in the treatment of DED mainly involved biological processes such as apoptosis, oxidative stress, response to estrogen, angiogenesis, and the regulation of transcription factors. KEGG analysis showed that QJDHP may be regulated by the TNF signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway, and estrogen signaling pathway in the treatment of DED.ConclusionIn this study, we demonstrated the multicomponent, multitarget, and multichannel action mechanism of QJDHP in the treatment of DED and provided a foundation for further drug development research.

Project description:ObjectiveHyperuricemia (HUA) is a common metabolic disease caused by disordered purine metabolism. We aim to reveal the mechanisms underlying the anti-HUA function of Simiao pill and provide therapeutic targets.MethodsSimiao pill-related targets were obtained using Herbal Ingredients' Targets (HIT), Traditional Chinese Medicine Systems Pharmacology (TCMSP), and Traditional Chinese Medicine Integrated Database (TCMID). HUA-associated targets were retrieved from GeneCards, DisGeNET, and Therapeutic Targets Database (TTD). Protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, ggraph and igraph R packages. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using ClusterProfiler. The top 10 core targets were identified through cytoHubba. Molecular docking was conducted using PyMOL and AutoDock high-performance liquid chromatograph (HPLC) analysis was performed to identify effective compounds of Simiao pill.ResultsSimiao pill-HUA target network contained 80 targets. The key targets were mainly involved in inflammatory responses. Insulin (INS), tumor necrosis factor (TNF), interleukin-6 (IL6), interleukin 1 beta (IL1B), vascular endothelial growth factor A (VEGFA), leptin (LEP), signal transducer and activator of transcription 3 (STAT3), C-C motif chemokine ligand 2 (CCL2), interleukin-10 (IL10), and toll like receptor 4 (TLR4) were the top 10 targets in the PPI network. GO analysis demonstrated the main implication of the targets in molecular responses, production, and metabolism. KEGG analysis revealed that Simiao pill might mitigate HUA through advanced glycation end-product- (AGE-) receptor for AGE- (RAGE-) and hypoxia-inducible factor-1- (HIF-1-) associated pathways. IL1B, IL6, IL10, TLR4, and TNF were finally determined as the promising targets of Simiao pill treating HUA. Through molecular docking and HPLC analysis, luteolin, quercetin, rutaecarpine, baicalin, and atractylenolide I were the main active compounds.ConclusionsSimiao pill can mitigate HUA by restraining inflammation, mediating AGE-RAGE- and HIF-1-related pathways, and targeting IL1B, IL6, IL10, TLR4, and TNF.

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.

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Project description:BackgroundHyperlipidemia, due to the practice of unhealthy lifestyles of modern people, has been a disturbance to a large portion of population worldwide. Recently, several scholars have turned their attention to Chinese medicine (CM) to seek out a lipid-lowering approach with high efficiency and low toxicity. This study aimed to explore the mechanism of Huatan Jiangzhuo decoction (HTJZD, a prescription of CM) in the treatment of hyperlipidemia and to determine the major regulation pathways and potential key targets involved in the treatment process.MethodsData on the compounds of HTJZD, compound-related targets (C-T), and known disease-related targets (D-T) were collected from databases. The intersection targets (I-T) between C-T and D-T were filtered again to acquire the selected targets (S-T) according to the specific index. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, as well as network construction, were applied to predict the putative mechanisms of HTJZD in treating hyperlipidemia. Thereafter, an animal experiment was conducted to validate the therapeutic effect of HTJZD. In addition, regulated differentially expressed genes (DEGs) were processed from the RNA sequencing analysis results. Common genes found between regulated DEGs and S-T were analyzed by KEGG pathway enrichment to select the key targets. Lastly, key targets were validated by real-time quantitative reverse transcription PCR (qRT-PCR) analysis.ResultsA total of 210 S-T were filtered out for enrichment analysis and network construction. The enrichment results showed that HTJZD may exert an effect on hyperlipidemia through the regulation of lipid metabolism and insulin resistance. The networks predict that the therapeutic effect of HTJZD may be based on the composite pharmacological action of these active compounds. The animal experiment results verify that HTJZD can inhibit dyslipidemia in rats with hyperlipidemia, suppress lipid accumulation in the liver, and reverse the expression of 202 DEGs, which presented an opposite trend in the model and HTJZD groups. Six targets were selected from the common targets between 210 S-T and 202 regulated DEGs, and the qRT-PCR results showed that HTJZD could effectively reverse Srebp-1c, Cyp3a9, and Insr mRNA expression (P < 0.01).ConclusionIn brief, network pharmacology predicted that HTJZD exerts a therapeutic effect on hyperlipidemia. The animal experimental results confirmed that HTJZD suppressed the pathological process induced by hyperlipidemia by regulating the expression of targets involved in lipid metabolism and insulin resistance.

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Utilising network pharmacology to explore the underlying mechanism of Wumei Pill in treating pancreatic neoplasms.

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Utilising network pharmacology to explore the underlying mechanism of Wumei Pill in treating pancreatic neoplasms.

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