scholarly journals Exploring the Mechanism of Action Compound-Xueshuantong Capsule in Diabetic Retinopathy Treatment Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Haoran Li ◽  
Biao Li ◽  
Yanlin Zheng
Keyword(s):  
Diabetic Retinopathy ◽  
Active Ingredient ◽  
Diabetic Complications ◽  
Interaction Network ◽  
Signal Pathway ◽  
Tanshinone Iia ◽  
Network Pharmacology ◽  
Active Components ◽  
Disease Treatment

Aim of the Study. To study the mechanism of Compound-Xueshuantong Capsule in diabetic retinopathy treatment based on network pharmacology. Materials and Methods. The components with oral bioavailability ≥30% and drug similarity ≥0.18 were screened by the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and the effective grouping of Compound-Xueshuantong Capsule was obtained. At the same time, the targets of each drug active component in the Compound-Xueshuantong Capsule were obtained by searching the TCMSP. The effective components and targets of the Compound-Xueshuantong Capsule were annotated by the UniProt database, and the disease treatment targets were searched by the GeneCards database. The disease treatment target is intersected with the drug target and the Wayne diagram is drawn by VennDiagram. The active ingredient targets of the intersection and Compound-Xueshuantong Capsule were inputted into Cytoscape 3.7.2 software to construct the active ingredient-target-disease interaction network. The above targets were inputted into the String database for protein-protein interaction network prediction. Finally, by using the DAVID database, GO and KEGG enrichment analysis was carried out to reveal the potential signal pathway of the Compound-Xueshuantong Capsule in diabetic retinopathy treatment. Results. 93 active components of the Compound-Xueshuantong Capsule and 92 targets for treating diabetic retinopathy were screened. The main active components of the Compound-Xueshuantong Capsule in treating diabetic retinopathy were quercetin, luteolin, kaempferol, beta-sitosterol, isorhamnetin, and tanshinone IIa. The effect of the Compound-Xueshuantong Capsule on diabetic retinopathy may be related to IL6, EFGR, CASP3, and VEGFA. In addition, the treatment of diabetic retinopathy mainly involves in the regulation of nuclear receptors and transcription factors in vivo. The target of the Compound-Xueshuantong Capsule in diabetic retinopathy treatment is significantly enriched in the AGE-RAGE signal pathway, TNF signal pathway, HIF-1 signal pathway, and VEGF signal pathway in diabetic complications. Conclusion. Compound-Xueshuantong Capsule can treat diabetic retinopathy through multitarget, multipathway, and multipathway regulation of the biomolecular network. The potential biological mechanism of the Compound-Xueshuantong Capsule in diabetic retinopathy treatment may be related to the AGE-RAGE signal pathway, TNF signal pathway, HIF-1 signal pathway, and VEGF signal pathway in diabetic complications, but these findings still need to be confirmed by further clinical research.

The Mechanism of Compound Danshen Dripping Pills in the Treatment of Diabetic Retinopathy Based on Network Pharmacology and Molecular Docking

2021 ◽  
Author(s):  
Xuedong An ◽  
LiYun Duan ◽  
YueHong Zhang ◽  
De Jin ◽  
Shenghui Zhao ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Cell Proliferation ◽  
Diabetic Retinopathy ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Active Ingredient ◽  
Network Pharmacology ◽  
Asiatic Acid ◽  
Active Components ◽  
The Core

Abstract BackgroundOur previous randomized, double-blind, placebo-controlled, multi-center clinical study showed that Compound Danshen Dripping Pills (CDDP) had a significant and safe effect in the treatment of diabetic retinopathy (DR), but its mechanism is still unclear, which we would explain based on network pharmacology and molecular docking.MethodThe active ingredients of CDDP (composed of Panax notoginseng, Salvia miltiorrhiza Bge., and Borneol) were searched in the TCMSP database. The validated target and Smiles number of the active ingredient are queried through the PubChem database, and the predicted target of the active ingredient is obtained through the Swisstarget Prediction database. The Drugbank, TTD, and DisGeNET databases were retrieved to obtain the related targets of DR. The core targets were obtained by the cluster analysis function of Cytoscape, and then the Protein-Protein Interaction was performed. The GO and KEGG signal pathways were enriched and clustered in David database. The potential active components and targets were docking with Autodock Vina, and the results were visualized by PyMOL.Result51 active components and 922 validation and prediction targets of CDDP, 715 targets of DR and 154 co-targets were obtained. Cluster analysis showed that there were two clusters, a total of 64 targets. Go and KEGG signal pathway enrichment analysis showed that the top 20 mainly included TNF and HIF-1 signaling pathway. In GO analysis, BP mainly includes positive regulation of smooth muscle cell proliferation and response to hypoxia, CC mainly includes extracellular space and extracellular domain, MF mainly includes protein binding and protein binding recognition. In KEGG database, the key genes in the TNF signaling pathway were TNF, NFkB and VEGF, in HIF-1 signaling pathway were the IL-6, STAT3, HIF1A and VEGF. Molecular docking results showed that all components of CDDP had a certain docking ability with TNF, NFkB, VEGF, IL-6, STAT3 and HIF1A, which of Asiatic acid and Salvianolic acid j was the strongest.Conclusion Based on the network pharmacology and molecular docking, the core active components of CDDP, mainly including Asiatic acid and Salvianolic acid j, which may play a role in regulating cell proliferation and response to inflammation and hypoxia by regulating the binding and recognition of intracellular and extracellular proteins, that is, mainly through TNF signaling pathway and HIF-1 signaling pathway.

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.

Molecular Mechanism of The Effect of Huanglian Jiedu Decoction On Ulcerative Colitis Based On Network Pharmacology And Molecular Docking

2021 ◽  
Author(s):  
Jing Yang ◽  
Chao-Tao Tang ◽  
Ruiri Jin ◽  
Bixia Liu ◽  
Peng Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Molecular Docking ◽  
Molecular Mechanism ◽  
Target Genes ◽  
Signal Pathway ◽  
Intestinal Barrier Function ◽  
Network Pharmacology ◽  
Bioactive Components ◽  
Ppi Network ◽  
Active Components

Abstract Huanglian jiedu decoction (HLJDD) is a heat-clearing and detoxifying agent composed of four kinds of Chinese herbal medicine. Previous studies have shown that HLJDD can improve the inflammatory response of ulcerative colitis (UC) and maintain intestinal barrier function. However, its molecular mechanism is not completely clear. In this study, we verified the bioactive components (BCI) and potential targets of HLJDD in the treatment of UC by means of network pharmacology and molecular docking, and constructed the pharmacological network and PPI network. Then the core genes were enriched by GO and KEGG. Finally, the bioactive components were docked with the key targets to verify the binding ability between them. A total of 54 active components related to UC were identified. Ten genes are considered to be very important to PPI network. Functional analysis showed that these target genes were mainly involved in the regulation of cell response to different stimuli, IL-17 signal pathway and TNF signal pathway. The results of molecular docking showed that the active components of HLJDD had good affinity with Hub gene. This study systematically elucidates the "multi-component, multi-target, multi-pathway" mechanism of anti-UC with HLJDD for the first time, suggesting that HLJDD or its active components may be candidate drugs for the treatment of ulcerative colitis.

scholarly journals Advanced Glycation End Products: Formation, Role in Diabetic Complications, and Potential in Clinical Applications

2020 ◽  
Author(s):  
Rujman Khan ◽  
Xin Yee Ooi ◽  
Matthew Parvus ◽  
Laura Valdez ◽  
Andrew Tsin
Keyword(s):  
Diabetic Retinopathy ◽  
Advanced Glycation End Products ◽  
Diabetic Complications ◽  
Tanshinone Iia ◽  
Future Research ◽  
Advanced Glycation ◽  
Reactive Aldehydes ◽  
Glycation End Products ◽  
End Products ◽  
Lysine Residues

Hyperglycemic conditions and disruptions to glucose-regulating pathways lead to increased formation of highly reactive aldehydes, methylglyoxal and glyoxal, which react with certain arginine and lysine residues in proteins to form advanced glycation end products (AGEs). These AGEs damage the integrity of the retinal vasculature predominantly through two mechanisms: non-receptor-mediated damage, which pertains to the interaction with extracellular matrix and its functional properties, and receptor-mediated damage through AGE interactions with their receptors (RAGE) on pericytes and Muller cells. Damage occurring between AGE and RAGE potentially generates reactive oxygen species, inflammatory cytokines, and growth factors. Both mechanisms result in increased permeability of endothelial tight junctions, and this increased permeability can lead to leaking and eventually ischemia. Once this ischemia becomes significant, neovascularization can occur, the hallmark of proliferative diabetic retinopathy. Current pharmaceutical studies have shown the potential of AGE inhibitors, such as aminoguanidine, in decreasing AGE production, thus minimizing its effects in hyperglycemic conditions. Other pharmaceutical interventions, such as Tanshinone IIA, aim to protect cells from the impacts of AGEs. Future research will not only continue to understand the properties of AGEs and their effects on diabetes and diabetic complications like diabetic retinopathy but will also explore how they impact other diseases.

scholarly journals Ganghuo Kanggan Decoction in Influenza: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation

2020 ◽  
Vol 11 ◽  
Author(s):  
Yanni Lai ◽  
Qiong Zhang ◽  
Haishan Long ◽  
Tiantian Han ◽  
Geng Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Influenza A ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
New Drugs ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Active Components ◽  
Compound Screening

Background: Ganghuo Kanggan decoction (GHKGD) is a clinical experience prescription used for the treatment of viral pneumonia in the Lingnan area of China, and its clinical effect is remarkable. However, the mechanism of GHKGD in influenza is still unclear.Objective: To predict the active components and signaling pathway of GHKGD and to explore its therapeutic mechanism in influenza and to verified it in vivo using network pharmacology.Methods: The potential active components and therapeutic targets of GHKGD in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including compound screening, target prediction and pathway enrichment analysis. Based on the target network and enrichment results, a mouse model of influenza A virus (IAV) infection was established to evaluate the therapeutic effect of GHKGD on influenza and to verify the possible molecular mechanism predicted by network pharmacology.Results: A total of 116 candidate active compounds and 17 potential targets were identified. The results of the potential target enrichment analysis suggested GHKGD may involve the RLR signaling pathway to reduce inflammation in the lungs. In vivo experiments showed that GHKGD had a protective effect on pneumonia caused by IAV-infected mice. Compared with the untreated group, the weight loss in the GHKGD group in the BALB/c mice decreased, and the inflammatory pathological changes in lung tissue were reduced (p &lt; 0.05). The expression of NP protein and the virus titers in lung were significantly decreased (p &lt; 0.05). The protein expression of RIG-I, NF-kB, and STAT1 and the level of MAVS and IRF3/7 mRNA were remarkably inhibited in GHKGD group (p &lt; 0.05). After the treatment with GHKGD, the level of Th1 cytokines (IFN-γ, TNF-α, IL-2) was increased, while the expression of Th2 (IL-5, IL4) cytokines was reduced (p &lt; 0.05).Conclusion: Through a network pharmacology strategy and in vivo experiments, the multi-target and multi-component pharmacological characteristics of GHKGD in the treatment of influenza were revealed, and regulation of the RLR signaling pathway during the anti-influenza process was confirmed. This study provides a theoretical basis for the research and development of new drugs from GHKGD.

scholarly journals Investigation of the Mechanisms of Neuroprotection Mediated by Lobelia Species via Computational Network Pharmacology and Molecular Modeling

2020 ◽  
Author(s):  
Qinfang Zheng ◽  
Liangzi Fang ◽  
Xiaolong Huang ◽  
Ye Wang ◽  
Shuihan Zhang
Keyword(s):  
Molecular Modeling ◽  
Neurodegenerative Diseases ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Docking Studies ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Active Components ◽  
Neuroprotective Actions ◽  
Gaba Transporter 1

Abstract BackgroundSeveral species of the medicinally valuable genus Lobelia (Campanulaceae) exhibit neuroprotection. While the neuroprotective mechanisms of some components (e.g. lobeline, lobelanine, and lobelanidine) belonging to the L. nicotianaefolia or L. inflata are extensively characterized, there remains the need to study and elucidate the mechanism of action of other species and their active components. In this work, we have studied the neuroprotective mechanism of the pharmacokinetically favorable active compounds of 17 Lobelia species.MethodsNetwork pharmacology approach and molecular modeling were employed. We have conducted drug-likeness evaluation, oral bioavailability prediction followed by the Gene Ontology (GO) terms and pathways enrichment analysis, protein-protein and protein-compound interaction network construction and analysis, and molecular docking studies. Five neurodegenerative diseases viz. Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, epilepsy, and Amyotrophic lateral sclerosis along with the common neuroprotection mechanism-associated genes were evaluated.ResultsWe revealed the neuroprotective mechanism of the active ingredients of Lobelia species. Our study strongly indicates that 12 unique active ingredients viz. luteolin, kaempferol, acacetin, chryseriol, norlobelanine, lobelanine, 2-[(2R,6S)-6-[(2R)-2-hydroxy-2-phenylethyl]-1-methylpiperidin-2-yl]-1-phenylethanone, hydroxygenkwanin, lobelanidine, quercetin, and diosmetin regulates 31 targets within multiple signaling pathways. The nitric oxide synthase, brain (NOS1), androgen receptor (ANDR), sodium- and chloride-dependent GABA transporter 1 (SC6A1), apoptosis regulator Bcl-2 (BCL2), RAC-alpha serine/threonine-protein kinase (AKT1), cellular tumor antigen p53, apoptosis regulator BAX, and tumor necrosis factor (TNFA) were identified as the majorly regulated genes. A majority of these target proteins act via several cancer-related pathways proven to have cross-talks with the pathogenesis of neurodegenerative diseases.ConclusionsThis study explains how the active ingredients of the Lobelia species exhibit their neuroprotective actions and provide a reference basis to investigate their pharmacological effects in detail.

scholarly journals A Network Pharmacology and Molecular Docking Approach to Investigate the Anticoronavirus-Induced Diseases Effect of Yinqiao Powder Combined With Modified Sangju Decoction

2021 ◽  
Vol 16 (9) ◽  
pp. 1934578X2110352
Author(s):  
Tian-Shun Wang ◽  
Xing-Pan Wu ◽  
Qiu-Yuan Jian ◽  
Yan-Fang Yang ◽  
Wu He-Zhen
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Treatment Strategies ◽  
Interaction Network ◽  
Mitogen Activated Protein Kinase ◽  
Network Pharmacology ◽  
Common Mechanism ◽  
Active Components ◽  
Discovery Studio ◽  
The Core

Severe acute respiratory syndrome (SARS) once caused great harm in China, but now it is the coronavirus disease 2019 (COVID-19) pandemic that has become a huge threat to global health, which raises urgent demand for developing effective treatment strategies to avoid the recurrence of tragedies. Yinqiao powder, combined with modified Sangju decoction (YPCMSD), has been clinically proven to have a good therapeutic effect on COVID-19 in China. This study aimed to analyze the common mechanism of YPCMSD in the treatment of SARS and COVID-19 through network pharmacology and molecular docking and further explore the potential application value of YPCMSD in the treatment of coronavirus infections. Firstly, the active components were collected from the literature and Traditional Chinese Medicine Systems Pharmacology database platform. The COVID-19 and SARS associated targets of the active components were forecasted by the SwissTargetPrediction database and GeneCards. A protein–protein-interaction network was drawn and the core targets were obtained by selecting the targets larger than the average degree. By importing the core targets into database for annotation, visualization, and integrated discovery, enrichment analysis of gene ontology, and construction of a Kyoto Encyclopedia of genes and genomes pathway was conducted. Cytoscape 3.6.1 software was used to construct a “components–targets–pathways” network. Active components were selected to dock with acute respiratory syndrome coronavirus type 2 (SARS-COV-2) 3CL and angiotensin-converting enzyme 2 (ACE2) through Discovery Studio 2016 software. A network of “components–targets–pathways” was successfully constructed, with key targets involving mitogen-activated protein kinase 1, caspase-3 (CASP3), tumor necrosis factor (TNF), and interleukin 6. Major metabolic pathways affected were those in cancer, the hypoxia-inducible factor 1 signaling pathway, the TNF signaling pathway, the Toll-like receptor signaling pathway, and the PI3K-Akt signaling pathway. The core components, such as arctiin, scopolin, linarin, and isovitexin, showed a strong binding ability with SARS-COV-2 3CL and ACE2. We predicted that the mechanism of action of this prescription in the treatment of COVID-19 and SARS might be associated with multicomponents that bind to SARS-COV-2 3CL and ACE2, thereby regulating targets that coexpressed with them and pathways related to inflammation and the immune system.

scholarly journals A Network Pharmacology-based Study of the Potential Mechanism of Bushenhuoxue Formula in Treating Osteoarthritis

2020 ◽  
Author(s):  
Xiong Wen ◽  
Cai Xianhua
Keyword(s):  
Signaling Pathway ◽  
Protein Interactions ◽  
Diabetic Complications ◽  
Target Genes ◽  
Endocrine Resistance ◽  
Network Pharmacology ◽  
Potential Mechanism ◽  
Apoptosis Rate

Abstract Background: To investigate the potential mechanism underlying the efficacy of BuShenHuoXue (BSHX) formula on Osteoarthritis (OA) and its molecular mechanism. Materials and Methods: Data as for bioactive chemicals of individual herb in BSHX formula and their targets were collected from Traditional Chinese Medicine Systems Pharmacology database and OA-associated targets from Gene Expression Omnibus database, compound-disease target network and protein-protein interactions network were built, picturized and analyzed by Cytoscape. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment of key targets were carried out and analyzed to probe into the core pathway and their main functions further. The chondrocytes of SD rats were cultured in vitro, and 50μg/ml IL-1βwas added to the chondrocytes to induce apoptosis. Different concentrations of quercetin were added to the experimental group and the apoptosis rate of chondrocytes, the difference of the expression of SELE, MMP2, and COL1 genes and their protein expression level were further detected. Results: A total of 104 candidate chemicals and 42 crossing targets were screened out. Leading target genes are PTGS2, NCOA2 and HSP90AA1, whereas quercetin and luteolin are principal ingredients. Potential pathways against OA are AGE-RAGE signaling pathway in diabetic complications, Relaxin signaling pathway, IL-17 signaling pathway, Tyrosine metabolism and Endocrine resistance. Our study showed that quercetin could inhibit the apoptosis of chondrocytes induced by IL-1β, decrease SELE, MMP2 and COL1 mRNA expression, likewise decrease the expression of SELE, MMP2 and COL1 protein. Conclusion: This study investigated the bioactive chemicals, crossing targets and possible mechanisms of BSHX formula against OA by network pharmacology strategy, results suggests that quercetin in BSHX formula may target on SELE, MMP2, and COL1 genes and then inhibit the progression of OA through the AGE-RAGE signaling pathway in diabetic complications. By the mechanism of reducing the apoptosis rate of SD rat chondrocytes and down-regulation the expression of genes involved in inflammation, we made sure that quercetin as principal ingredient can protect the cartilage. In addition, the conclusion of this study still need to be confirmed by in vivo and vitro experiments.

scholarly journals Study on the Mechanism of Mulberry Root Bark Decoction in the Treatment of Chronic Obstructive Pulmonary Disease based on Network Pharmacology

2021 ◽  
Vol 5 (5) ◽  
pp. 90-95
Author(s):  
Jie Meng ◽  
Xuanguo Zhang
Keyword(s):  
Oxidative Stress ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Signal Pathway ◽  
Network Pharmacology ◽  
Chronic Obstructive ◽  
Root Bark ◽  
Active Components ◽  
Obstructive Pulmonary Disease ◽  
R Language

Objective: Study the mechanism of Mulberry Root Bark Decoction in the treatment of COPD based on network pharmacology. Methods: The active components and predictive targets of Mulberry Root Bark Decoction were screened by TCMSP database. The disease targets of COPD were collected by searching GeneCards, DisGeNET, PhamGKB and TTD databases. Using R language to draw Venn diagram, and get the key target of Mulberry Root Bark Decoction in the treatment of COPD. Cytoscape was used to construct the regulatory network of drug active ingredient disease target. The key targets were imported into string database to construct protein-protein interaction network, and the core targets were obtained by network topology analysis with Cytoscape software. Finally, the Bioconductor platform and R language were used for GO and KEGG enrichment analysis. Results: There were 142 active components and 255 drug targets in Mulberry Root Bark Decoction. 1941 COPD targets were retrieved. There were 129 common targets of Mulberry Root Bark Decoction and COPD; Eight core targets of PPI network were obtained. GO function analysis is involved in oxidative stress, cellular chemical stress and other biological processes. Cell components such as cell membrane raft and membrane region involve molecular functions such as ubiquitin like protein ligase and DNA binding transcription factor. KEGG mainly includes PI3K-Akt signal pathway, tumor necrosis factor signal pathway, IL-17 signal pathway, etc. Conclusion: Quercetin, luteolin, kaempferol, wogonin and other active components in Mulberry Root Bark Decoction act on PI3K / Akt, TNF, IL-17, TCR and other signal pathways through Jun, TP53, MAPK1, IL6 and other targets to play an anti-inflammatory and reduce oxidative stress response role. The results of this study can provide a reference for further study on the mechanism of Mulberry Root Bark Decoction in the treatment of chronic obstructive pulmonary disease.

scholarly journals Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma

2021 ◽  
Author(s):  
Zhiqiang Chen ◽  
Tong Lin ◽  
Xiaozhong Liao ◽  
Zeyun Li ◽  
Ruiting Lin ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Experimental Results ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Active Components ◽  
Active Compounds ◽  
Apoptosis Rate

Abstract Background: Cholangiocarcinoma refers to an epithelial cell malignancy with poor prognosis. Yinchenhao decoction (YCHD) showed positive effects on cancers, and associations between YCHD and cholangiocarcinoma remain unclear. This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma. Methods: By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods. Results: 32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions. Conclusion:As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effectsthrough multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.

Sign in / Sign up

Export Citation Format

Share Document