scholarly journals Region-Specific Biomarkers and Their Mechanisms in the Treatment of Lung Adenocarcinoma: A Study of Panax quinquefolius from Wendeng, China

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6829
Author(s):  
Xuanming Zhang ◽  
Liwen Han ◽  
Peihai Li ◽  
Shanshan Zhang ◽  
Mengqi Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Panax Quinquefolius ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Chemical Characteristics ◽  
Functional Activities ◽  
Ginsenoside Rc ◽  
Cancer Suppression ◽  
Metabolomics Analysis

Panax quinquefolius, a popular medicinal herb, has been cultivated in China for many years. In this work, the region-specific profiles of metabolites in P. quinquefolius from Wendeng was investigated using liquid-chromatography–quadrupole–time-of-flight-(LC–Q–TOF)-based metabolomics analysis. The three most abundant biomarkers, identified as ginsenoside Rb3, notoginsenoside R1, and ginsenoside Rc, were the representative chemical components employed in the network pharmacology analysis. In addition, molecular docking and western blotting analyses revealed that the three compounds were effective binding ligands with Hsp90α, resulting in the inactivation of SRC and PI3K kinase, which eventually led to the inactivation of the Akt and ERK pathways and lung cancer suppression. The outcomes obtained herein demonstrated the intriguing chemical characteristics and potential functional activities of P. quinquefolius from Wendeng.

scholarly journals Immunoregulatory mechanism studies of ginseng leaves on lung cancer based on network pharmacology and molecular docking

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zao-Hui Li ◽  
Dan Yu ◽  
Nan-Nan Huang ◽  
Jun-Kai Wu ◽  
Xiao-Wei Du ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Target Prediction ◽  
Ginseng Root ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Signaling Proteins ◽  
P53 Expression ◽  
Docking Analysis ◽  
Anticancer Properties

AbstractPanax ginseng is one of the oldest and most generally prescribed herbs in Eastern traditional medicine to treat diseases. Several studies had documented that ginseng leaves have anti-oxidative, anti-inflammatory, and anticancer properties similar to those of ginseng root. The aim of this research was to forecast of the molecular mechanism of ginseng leaves on lung cancer by molecular docking and network pharmacology so as to decipher ginseng leaves' entire mechanism. The compounds associated with ginseng leaves were searched by TCMSP. TCMSP and Swiss Target Prediction databases were used to sort out the potential targets of the main chemical components. Targets were collected from OMIM, PharmGKB, TTD, DrugBank and GeneCards which related to immunity and lung cancer. Ginseng leaves exert its lung cancer suppressive function by regulating the several signaling proteins, such as JUN, STAT3, AKT1, TNF, MAPK1, TP53. GO and KEGG analyses indicated that the immunoreaction against lung cancer by ginseng leaves might be related to response to lipopolysaccharide, response to oxidative stress, PI3K-Akt, MAPK and TNF pathway. Molecular docking analysis demonstrated that hydrogen bonding was interaction's core forms. The results of CCK8 test and qRT-PCR showed that ginseng leaves inhibit cell proliferation and regulates AKT1 and P53 expression in A549. The present study clarifies the mechanism of Ginseng leaves against lung cancer and provides evidence to support its clinical use.

scholarly journals Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer based on network pharmacology and molecular docking

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoling Li ◽  
Baixin Lin ◽  
Zhiping Lin ◽  
Yucui Ma ◽  
Qu Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Erk Signaling ◽  
Network Pharmacology ◽  
Protein Interaction Data ◽  
Small Cell Lung

AbstractFucosterol, a sterol isolated from brown algae, has been demonstrated to have anti-cancer properties. However, the effects and underlying molecular mechanism of fucosterol on non-small cell lung cancer remain to be elucidated. In this study, the corresponding targets of fucosterol were obtained from PharmMapper, and NSCLC related targets were gathered from the GeneCards database, and the candidate targets of fucosterol-treated NSCLC were predicted. The mechanism of fucosterol against NSCLC was identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein–protein interaction data were collected from STRING database. The hub gene GRB2 was further screened out and verified by molecular docking. Moreover, the relationship of GRB2 expression and immune infiltrates were analyzed by the TIMER database. The results of network pharmacology suggest that fucosterol acts against candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8, and SRC, which regulate biological processes including negative regulation of the apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf/MEK/ERK signaling pathway initiated by GRB2 showed to be significant in treating NSCLC. In conclusion, our study indicates that fucosterol may suppress NSCLC progression by targeting GRB2 activated the Raf/MEK/ERK signaling pathway, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.

Network pharmacology and molecular docking reveal the mechanism of Scopoletin against non-small cell lung cancer

Life Sciences ◽  
2021 ◽  
Vol 270 ◽  
pp. 119105
Author(s):  
Chong Yuan ◽  
Meng-Heng Wang ◽  
Fei Wang ◽  
Peng-Yu Chen ◽  
Xin-Ge Ke ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Network Pharmacology ◽  
Small Cell Lung

scholarly journals Mechanism of Compound Houttuynia Mixture as an Anti-COVID-19 Drug Based on Network Pharmacology and Molecular Docking

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110167
Author(s):  
Xing-Pan Wu ◽  
Tian-Shun Wang ◽  
Zi-Xin Yuan ◽  
Yan-Fang Yang ◽  
He-Zhen Wu
Keyword(s):  
Molecular Docking ◽  
Target Prediction ◽  
Interaction Network ◽  
Scientific Basis ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Active Components ◽  
Discovery Studio ◽  
The Core ◽  
Pathway Annotation

Objective To explore the anti-COVID-19 active components and mechanism of Compound Houttuynia mixture by using network pharmacology and molecular docking. Methods First, the main chemical components of Compound Houttuynia mixture were obtained by using the TCMSP database and referring to relevant chemical composition literature. The components were screened for OB ≥30% and DL ≥0.18 as the threshold values. Then Swiss Target Prediction database was used to predict the target of the active components and map the targets of COVID-19 obtained through GeneCards database to obtain the gene pool of the potential target of COVID-19 resistance of the active components of Compound Houttuynia mixture. Next, DAVID database was used for GO enrichment and KEGG pathway annotation of targets function. Cytoscape 3.8.0 software was used to construct a “components-targets-pathways” network. Then String database was used to construct a “protein-protein interaction” network. Finally, the core targets, SARS-COV-2 3 Cl, ACE2 and the core active components of Compound Houttuyna Mixture were imported into the Discovery Studio 2016 Client database for molecular docking verification. Results Eighty-two active compounds, including Xylostosidine, Arctiin, ZINC12153652 and ZINC338038, were screened from Compound Houttuyniae mixture. The key targets involved 128 targets, including MAPK1, MAPK3, MAPK8, MAPK14, TP53, TNF, and IL6. The HIF-1 signaling, VEGF signaling, TNF signaling and another 127 signaling pathways associated with COVID-19 were affected ( P < 0.05). From the results of molecular docking, the binding ability between the selected active components and the core targets was strong. Conclusion Through the combination of network pharmacology and molecular docking technology, this study revealed that the therapeutic effect of Compound Houttuynia mixture on COVID-19 was realized through multiple components, multiple targets and multiple pathways, which provided a certain scientific basis of the clinical application of Compound Houttuynia mixture.

scholarly journals Network Pharmacology and Experiment Verification to Explore the Potential Mechanism of Yin-Huo-Tang for Lung Adenocarcinoma Recurrence

2021 ◽  
Author(s):  
Dianna Liu ◽  
Shicheng Lin ◽  
Yuan Li ◽  
Tian Zhou ◽  
Kaiwen Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Rna Sequencing ◽  
Network Pharmacology ◽  
Phytochemical Analysis ◽  
Sequencing Analysis ◽  
Lewis Lung ◽  
Hub Genes

Abstract BackgroundLung adenocarcinoma (LUAD) is one of the most common malignancies with a rise in new cases worldwide each year. Recurrence significantly influences the survival in patients with LUAD. Yin-Huo-Tang (YHT) is a classic traditional Chinese prescription, used to prevent lung cancer relapse by “nourishing yin and clearing heat”. MethodsIn this study, the mechanism of YHT in LUAD recurrence was investigated. Firstly, the bioactive compounds-targets network and the protein–protein interaction network were constructed, and functional annotation and pathway enrichment analyses were performed. Pivotal compounds and hub genes were selected from the networks. Subsequently, the effectiveness of YHT was confirmed in lewis lung carcinoma mice. RNA sequencing was used to explore the mRNA expression differences between tumor tissues in the model mouses and YHT-treated mouses. The pathways screened by network pharmacology and RNA sequencing analysis at the same time were considered the most important pathways. At last, qualitative phytochemical analysis, molecular docking technology, PCR and WB analysis were used to validate the pivotal active ingredients, hub genes and main pathways.ResultsThere were 128 active compounds, 419 targets interacting with LUAD recurrence. Network analysis identified 4 pivotal compounds, 28 hub genes and 30 main pathways. Target genes mainly focused on inflammation, metabolism, immune responses and apoptosis. We confirmed that YHT could inhibit the recurrence of lung adenocarcinoma through animal experimental study. Sphingolipid signaling pathway was the common main pathway in network pharmacology and RNA sequencing results. The hub genes related with the sphingolipid signaling pathway was S1PR5. Qualitative phytochemical analysis of the water extract of YHT confirmed the presence of 3 pivotal compounds, namely stigmasterol, nootkatone and ergotamine. The results of molecular docking verified the pivotal compounds of YHT could good affinity with the S1PR5. The PCR and WB analysis verified YHT suppressed lewis lung cancer cells proliferation by inhibiting S1P/S1PR5/Gi/Ras/Raf/MEK/ERK pathway, and inhibited migration through S1P/S1PR5/Gi/PI3K/RAC pathway.ConclusionThe results confirmed the therapeutic effect of YHT on the recurrence of LUAD by multi-component-multi-target mode, the sphingolipid signaling pathway was one of the most relevant potential signaling pathways.

scholarly journals Mechanisms of Compound Kushen Injection for the Treatment of Lung Cancer Based on Network Pharmacology

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Ziqi Meng ◽  
Xinkui Liu ◽  
Jiarui Wu ◽  
Wei Zhou ◽  
Kaihuan Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Small Cell Lung Cancer ◽  
Docking Simulation ◽  
Small Cell ◽  
Network Pharmacology ◽  
Small Cell Lung ◽  
Molecular Docking Simulation ◽  
Target Network ◽  
Compound Kushen Injection

Background. Compound Kushen Injection (CKI) is a Chinese patent drug that shows good efficacy in treating lung cancer (LC). However, its underlying mechanisms need to be further clarified.Methods. In this study, we adopted a network pharmacology method to gather compounds, predict targets, construct networks, and analyze biological functions and pathways. Moreover, molecular docking simulation was employed to assess the binding potential of selected target-compound pairs.Results. Four networks were established, including the compound-putative target network, protein-protein interaction (PPI) network of LC targets, compound-LC target network, and herb-compound-target-pathway network. Network analysis showed that 8 targets (CHRNA3, DRD2, PRKCA, CDK1, CDK2, CHRNA5, MMP1, and MMP9) may be the therapeutic targets of CKI in LC. In addition, molecular docking simulation indicated that CHRNA3, DRD2, PRKCA, CDK1, CDK2, MMP1, and MMP9 had good binding activity with the corresponding compounds. Furthermore, enrichment analysis indicated that CKI might exert a therapeutic role in LC by regulating some important pathways, namely, pathways in cancer, proteoglycans in cancer, PI3K-Akt signaling pathway, non-small-cell lung cancer, and small cell lung cancer.Conclusions. This study validated and predicted the mechanism of CKI in treating LC. Additionally, this study provides a good foundation for further experimental studies and promotes the reasonable application of CKI in the clinical treatment of LC.

scholarly journals Ginsenoside Rc Protects Neurons From Oxygen-glucose Deprivation Injuries and Its Mechanistic Investigation via a Network Pharmacology-based Analysis

2020 ◽  
Author(s):  
Mingmin Huang ◽  
Shaoru Chen ◽  
Kening Zheng ◽  
Qu Liu ◽  
Kening Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Viability ◽  
Neuroprotective Effect ◽  
Glucose Deprivation ◽  
Network Pharmacology ◽  
Oxygen Glucose Deprivation ◽  
Cell Toxicity ◽  
Tnf Α ◽  
Neuron Damage ◽  
Ginsenoside Rc

Abstract Background: Ginsenoside Rc (Rc) is one of the major active components of Panax ginseng Meyer. Studies have shown that Rc has remarkable effect in protection of nervous system. However, the potential molecular mechanism of its neuroprotective effect remains unclear. Our study aim to investigate the neuroprotective effect of Rc on neuron damage and explore the potential mechanism on its regulation of TNF-α and DRP-1.Methods: Oxygen-glucose deprivation reperfusion (OGD/R) cell neuron damage modle was induced by Na2S2O4 and EBSS solution. After preventive administration, cell viability and cell toxicity were detected to evaluate the putative neuroprotective properties of Rc. Network pharmacology and molecular docking simulation studies were performed to predict the potential targets and pharmacological mechanism. Furthermore, the prediction was validated via western blot assay and specific antagonist. Results: In OGD/R injured cells, Rc significantly improved cell viability (Rc middle dose vs. OGD/R model: 67.3±2.33% vs. 55.7±1.14%, P<0.05) and obviously decreased cell toxicity (Rc middle dose vs. OGD/R model: 147±39.7% vs. 232±29.4%, P<0.01). Analysis of network pharmacology and molecular docking indicated that the key targets of Rc are TNF-α and DRP-1. Subsequently molecular biological studies showed a significant increase on expression of TNF-α and DRP-1 in model group. Conversely, administration of Rc reversed the alteration significantly and presented a dose dependence. By adding antagonist, we validated that Rc had an indirect regulation on TNF-α and DRP-1. Conclusions: Rc possess protective properties against OGD-induced neuron damage by regulating the expression of TNF-α and DRP-1.

Network Pharmacology-Based Identification of Pharmacological Mechanisms of Inula japonica Thunb. on Non-small Cell Lung Cancer

2020 ◽  
Author(s):  
Huiqin Qian ◽  
Bai-Ling Wang ◽  
Ling-Yun Zhang ◽  
Jia-Xiang Li ◽  
Xiu-Xiu Huang
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Protein Kinase ◽  
Small Cell Lung Cancer ◽  
Enrichment Analysis ◽  
Small Cell ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Small Cell Lung ◽  
Compound Target

Abstract Background Inula japonica Thunb. (IJT) is an extensively applied herbal medicine for treating non-small cell lung cancer (NSCLC) due to its anti-asthma, antitussive, and expectorant properties. However, the mechanism of IJT against NSCLC remains to be elucidated. Methods Network pharmacology analysis was applied to determine the function mechanism of IJT against NSCLC. Databases were used to collect compounds and their related and known therapeutic targets. The compound–target (C–T) and target–target networks were then constructed to screen the kernel compounds and NSCLC-related targets of IJT. Moreover, the NSCLC-related targets of IJT were input in the DAVID Bioinformatics Resources (version 6.8) for Gene Ontology Biological Processes (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the binding affinity of major compounds with the NSCLC-relevant targets of IJT was further verified by molecular docking. Results Two active compounds (quercetin and luteolin) and six putative targets (RAC-alpha serine/threonine-protein kinase, G1/S-specific cyclin-D1, cyclin-dependent kinase inhibitor 2A, epidermal growth factor receptor, receptor tyrosine-protein kinase erbB-2, and cellular tumor antigen p53) were screened as the effective compounds and NSCLC-related targets of IJT. GOBP and KEGG enrichment analysis indicated that NSCLC was the major pathway of IJT in the treatment of NSCLC and the mediation of apoptosis, cell cycle, tumor progression, and proliferation of biological processes, including the Ras, ERBB, MAPK, PI3K–Akt, calcium, and p53 signaling pathways. The results of molecular docking validated that 10 of the 12 pairs of compound-target had effective binding. Conclusions The mechanisms of IJT against NSCLC through multi-compounds, multi-targets, and multi-pathways were elucidated.

scholarly journals Network Pharmacology Integrated Molecular Docking Reveals the Anti-COVID-19 Mechanism of Yinma Jiedu Granules

2021 ◽  
Vol 16 (2) ◽  
pp. 1934578X2199171
Author(s):  
ZiXin Yuan ◽  
Can Zeng ◽  
Bing Yu ◽  
Ying Zhang ◽  
TianShun Wang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Signaling Pathways ◽  
Hypoxia Inducible Factor ◽  
Growth Factor Receptor ◽  
Interaction Network ◽  
Mitogen Activated Protein Kinase ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Active Components ◽  
Discovery Studio

To investigate the mechanism of action of components of Yinma Jiedu granules in the treatment of coronavirus disease 2019 (COVID-19) using network pharmacology and molecular docking. The main chemical components of Yinma Jiedu granules were collected in the literature and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. Using the SwissTargetPrediction database, the targets of the active component were identified and further correlated to the targets of COVID-19 through the GeneCards database. The overlapping targets of Yinma Jiedu granules components and COVID-19 were identified as the research target. Using the Database for Annotation, Visualization and Integrated Discovery database to carry out the target gene function Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway annotation and Cytoscape 3.6.1 software was used to construct a “component-target-pathway” network. The protein-protein interaction network was built using Search Tool for the Retrieval of Interacting Genes/Proteins database. Using Discovery Studio 2016 Client software to study the virtual docking of key protein and active components. One hundred active components were screened from the Yinma Jiedu Granules that involved 67 targets, including mitogen-activated protein kinase 3 (MAPK3), epidermal growth factor receptor, tumor necrosis factor, tumor protein 53, and MAPK1. These targets affected 109 signaling pathways including hypoxia-inducible factor-1, apoptosis, and Toll-like receptor signaling pathways. Molecular docking results showed that the screened active components have a strong binding ability to the key targets. In this study, through network pharmacology and molecular docking, we justified the multicomponent, multitarget, and multipathways of Yinma Jiedu Granules in the treatment of COVID-19.

scholarly journals Exploration in the mechanism of fucosterol  for the treatment of  non-small cell lung cancer Based on network pharmacology and molecular docking

2020 ◽  
Author(s):  
Xiaoling Li ◽  
Baixin Lin ◽  
Zhiping Lin ◽  
Qu Wang ◽  
Yushi Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
New Drugs ◽  
Network Pharmacology ◽  
Protein Interaction Data ◽  
Small Cell Lung

Abstract Background: It has been demonstrated that fucosterol induces a therapeutic effect on cancer. However, the molecular mechanisms underlying the effects of fucosterol in the treatment of non-small cell lung cancer are still unclear.Methods: In this study, pharmMapper and GeneCards databases were utilized to gather the prediction of fucosterol targets and NSCLC-related targets. The mechanisms of fucosterol against NSCLC were identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein-protein interaction data was obtained from Sting Database. Molecular docking was used to predict the docking of GRB2. Moreover, the relationship of GRB2 expression and immune infiltrates was analyzed by TIMER database.Results: The results suggest that fucosterol acts against by candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8 and SRC, which regulate biological processes including negative regulation of apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf / MEK / ERK signaling pathway initiated by GRB2 maybe the most significant pathway for fucosterol to treat NSCLC.Conclusions: These results show that GRB2 is the key target for fucosterol in the treatment of NSCLC, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.

Sign in / Sign up

Export Citation Format

Share Document