Dataset Information

Network Pharmacology-Based Prediction and Verification of the Targets and Mechanism for Panax Notoginseng Saponins against Coronary Heart Disease.

ABSTRACT: Coronary heart disease (CHD) is the worldwide leading cause for cardiovascular death. Panax notoginseng saponin (PNS), which is the main bioactive compound of panax notoginseng, has been generally accepted to exert a remarkable effect on CHD for a long time. However, to reveal the underlying treatment target and corresponding mechanism of PNS against CHD is still a substantial challenge. In this work, the targets and mechanism of PNS against CHD were successfully achieved by pharmacology-based prediction and experimental verification. 36 common targets were screened out through integrating the gene expression profile of CHD and the chemical-protein data of PNS. Then, two key nodes were further selected for verification by experiment after analyzing GO function, KEGG pathway, coexpression, and topology analysis. Results showed that PNS has protected the human umbilical vein endothelial cells from H2O2-induced oxidative stress by inhibiting early cell apoptosis via upregulating VEGFA mRNA expression. Therefore, our research has successfully pointed out one treatment target and apoptotic inhibition caused by PNS with method of integrating bioinformatics prediction and experimental verification, which has partially explained the pharmacological mechanism of PNS against CHD.

SUBMITTER: Dong Y

PROVIDER: S-EPMC6636530 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Network Pharmacology-Based Prediction and Verification of the Targets and Mechanism for Panax Notoginseng Saponins against Coronary Heart Disease.

Dong Yan Y Duan Lian L Chen Heng-Wen HW Liu Yong-Mei YM Zhang Yun Y Wang Jie J

Evidence-based complementary and alternative medicine : eCAM 20190703

Coronary heart disease (CHD) is the worldwide leading cause for cardiovascular death. Panax notoginseng saponin (PNS), which is the main bioactive compound of panax notoginseng, has been generally accepted to exert a remarkable effect on CHD for a long time. However, to reveal the underlying treatment target and corresponding mechanism of PNS against CHD is still a substantial challenge. In this work, the targets and mechanism of PNS against CHD were successfully achieved by pharmacology-based p ...[more]

PMID: 31354855

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Project description:Background:Panax notoginseng saponins (PNS) may have an inhibitory effect against coronary artery disease (CAD); however, the mechanism is unclear. Recent research has begun to evaluate the role of epigenetics in CAD. Our team found that hypomethylation of miR-194 could be an important mechanism of CAD. Purpose: The aim of this study was to investigate the effect of PNS against CAD and evaluate whether the mechanism is related to methylation of mi-R194. Methods: We conducted a randomized controlled trial with a double-blind placebo design on 84 patients with CAD. Treatment was continued for 4 weeks, and the clinical effect of PNS on CAD was observed. Methylation of miR-194, its promoter, and the key nodes of the MAPK pathway were measured by pyrosequencing and qRT-PCR. We then conducted a pharmacological analysis of the active components of PNS. The effects of PNS on oxidized human umbilical vein endothelial cells and the methylation of miR-194, its promoter, and the key nodes of the MAPK pathway were measured in vitro through methylation-specific PCR (MSPCR), qRT-PCR, Western blot analysis, and annexin V/propidium iodide apoptosis assay. Results: PNS improved symptoms of CAD. High-density lipoprotein and white blood cell count demonstrated significant changes after treatment in the PNS group. No significant difference was observed between miR-194 and mRNA MAPK, FAS, RAS, and FOS in the PNS group after treatment. However, some notable trends were observed in these genes. The targets of PNS were predicted by the pharmacological components. Some targets were found to be differentially expressed genes in CAD sequencing. Six genes, including MAPK1, RAS, and FASL, were common targets of PNS in CAD sequencing. Correlations were observed between genes in the interaction network and clinical parameters. In vitro experiments confirmed that PNS could change the methylation of miR-194, its promoter, and MAPK, FAS, RAS, and FOS. Intervention with PNS is likely to improve apoptosis. Conclusion: We reported the regulation of miR-194 promoter, miR-194, and MAPK methylation by PNS through cell experiments and a randomized controlled trial. PNS can be used for intervention in CAD by targeting the miR-194 promoter-miR-194-MAPK signaling pathway. Clinical Trial Registration: https://www.clinicaltrials.gov/, NCT03083119.

Project description:BackgroundPanax notoginseng saponins (PNS) have been deemed effective herb compounds for treating ischaemic stroke (IS) and improving the quality of life of IS patients. This study aimed to investigate the underlying mechanisms of PNS in the treatment of IS based on network pharmacology.MethodsPNS were identified from the Traditional Chinese Medicine System Pharmacology (TCMSP) database, and their possible targets were predicted using the PharmMapper database. IS-related targets were identified from the GeneCards database, OMIM database, and DisGeNET database. A herb-compound-target-disease network was constructed using Cytoscape, and protein-protein interaction (PPI) networks were established with STRING. GO enrichment and KEGG pathway analysis were performed using DAVID. The binding of the compounds and key targets was validated by molecular docking studies using AutoDock Vina. The neuroprotective effect of TFCJ was substantiated in terms of oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde) and the levels of IGF1/PI3K/Akt pathway proteins.ResultsA total of 375 PNS targets and 5111 IS-related targets were identified. Among these targets, 241 were common to PNS, and IS network analysis showed that MAPK1, AKT1, PIK3R1, SRC, MAPK8, EGFR, IGF1, HRAS, RHOA, and HSP90AA1 are key targets of PNS against IS. Furthermore, GO and KEGG enrichment analysis indicated that PNS probably exert therapeutic effects against IS by regulating many pathways, such as the Ras, oestrogen, FoxO, prolactin, Rap1, PI3K-Akt, insulin, PPAR, and thyroid hormone signalling pathways. Molecular docking studies further corroborated the experimental results.The network pharmacology results were further verified by molecular docking and in vivo experiments.ConclusionsThe ameliorative effects of PNS against IS were predicted to be associated with the regulation of the IGF1-PI3K-Akt signalling pathway. Ginsenoside Re and ginsenoside Rb1 may play an important role in the treatment of IS.

Project description:Panax notoginseng (Burk) F. H. Chen, as traditional Chinese medicine, has a long history of high clinical value, such as anti-inflammatory, anti-oxidation, inhibition of platelet aggregation, regulation of blood glucose and blood pressure, inhibition of neuronal apoptosis, and neuronal protection, and its main ingredients are Panax notoginseng saponins (PNS). Currently, Panax notoginseng (Burk) F. H. Chen may improve mental function, have anti-insomnia and anti-depression effects, alleviate anxiety, and decrease neural network excitation. However, the underlying effects and the mechanisms of Panax notoginseng (Burk) F. H. Chen and its containing chemical constituents (PNS) on these depression-related or anxiety-related diseases has not been completely established. This review summarized the antidepressant or anxiolytic effects and mechanisms of PNS and analyzed network targets of antidepressant or anxiolytic actions with network pharmacology tools to provide directions and references for further pharmacological studies and new ideas for clinical treatment of nervous system diseases and drug studies and development. The review showed PNS and its components may exert these effects through regulating neurotransmitter mechanism (5-HT, DA, NE), modulation of the gamma-amino butyric acid (GABA) neurotransmission, glutamatergic system, hypo-thalamus-pituitary-adrenal (HPA) axis, brain-derived neurotrophic factor (BDNF), and its intracellular signaling pathways in the central nervous system; and produce neuronal protection by anti-inflammatory, anti-oxidation, or inhibition of neuronal apoptosis, or platelet aggregation and its intracellular signaling pathways. Network target analysis indicated PNS and its components also may have anti-inflammatory and anti-apoptotic effects, which leads to the preservation of brain nerves, and regulate the activity and secretion of nerve cells, exerting anti-depression and anxiolytic effects, which may provide new directions for further in-depth researches of related mechanisms.

Dataset Information

Network Pharmacology-Based Prediction and Verification of the Targets and Mechanism for Panax Notoginseng Saponins against Coronary Heart Disease.

Publications

Network Pharmacology-Based Prediction and Verification of the Targets and Mechanism for Panax Notoginseng Saponins against Coronary Heart Disease.

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