scholarly journals Network Pharmacology-based to Investigate Pharmacological Mechanisms of Active Ingredients in Gegen Qinlian Pill to Ameliorate Irinotecan-induced Diarrhea

2020 ◽  
Author(s):  
Yihan Wu ◽  
Yanfen Cheng ◽  
Yuhan Yang ◽  
Di Wang ◽  
Xiaoqin Yang ◽  
...  
Keyword(s):  
Serum Sample ◽  
Interaction Network ◽  
Chemical Compounds ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Active Components ◽  
Promising Strategy ◽  
Gut Toxicity ◽  
Underlying Mechanisms ◽  
Compound Target

Abstract Background: The application of natural extracts or compounds derived from Chinese medicine is deemed to a promising strategy to prevent irinotecan (CPT-11)-induced gut toxicity. Based on the protective activity of Gegen Qinlian decoction in our previous study, we speculated that Gegen Qinlian Pill (GQP) would exhibit similar therapeutic effects. However, the effective material basis and the potential mechanisms underlying the effect of GQP in the treatment of diarrhea induced by CPT-11 have not been fully elucidated. Herein, we primarily investigated amelioration effect of GQP on the CPT-11 induced gut toxicity, and further explore its anti-diarrhea mechanism.Methods: Firstly, the protective effect of GQP towards alleviating diarrhea in mice following CPT-11 administration was investigated. Furthermore, the effective ingredients of GQP in serum sample of mice by HPLC-Q-TOF-MS analysis was obtained. Next, based on these active components, an interaction network linking “compound-target-pathway” was established. Finally, a predicted mechanism within vivo validation of GQP based on Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were obtained. Results: A total of 19 chemical compounds derived from the GQP were identified in its serum sample. Then, an interaction network linking “compound-target-pathway” was established to illuminate the interaction between these components absorbed into serum and their targets for diarrhea. GQP exerted a curative effect on diarrhea and diarrhea-related diseases by targeting different targets, regulating inflammation, oxidative stress, and proliferation processes. Conclusion: Taken together, this study provides a novel and scientific strategy to discover the potential effective constituents of herbs or herbal formula, and elucidated basic pharmacological effects and underlying mechanisms of GQP in the treatment of CPT-11 induced gut toxicity.

scholarly journals Study on the Mechanism of Salvia miltiorrhiza in the Treatment of Traumatic Bone Defects

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Qian Tan ◽  
Yaoxi Liu ◽  
Ting Lei ◽  
Weihua Ye ◽  
Xin Hu ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Salvia Miltiorrhiza ◽  
Interaction Network ◽  
Bone Defects ◽  
Biological Properties ◽  
Bone Diseases ◽  
Network Pharmacology ◽  
Active Components ◽  
Compound Target

Traumatic bone defect is one of the major orthopedic diseases in clinics, and its incidence is increasing year by year. And repairing traumatic bone defects is a very difficult problem in clinics at present. The surface of medical titanium-based alloy has good biological properties, and its implant has a certain role in promoting bone in bone tissue. However, titanium-based materials are biologically inert and have no biological activity. As a traditional Chinese medicine, Salvia miltiorrhiza has the efficacy of treating bone diseases and promoting bone healing. The curative effect can be better exerted by loading the traditional Chinese medicine active compound Salvia miltiorrhiza on the surface of the titanium implant in a certain way. At present, due to the complex chemical composition of Salvia miltiorrhiza, the mechanism of its use for the treatment of traumatic bone defects is still unclear. Therefore, in this study, we mainly discussed the potential target and mechanism of Salvia miltiorrhiza in the treatment of traumatic bone defects through network pharmacology, which may provide a scientific basis for the treatment of traumatic bone defects with Salvia miltiorrhiza loaded on the surface of medical titanium-based alloy. We screened out effective compounds and targets of Salvia miltiorrhiza and targets related to traumatic bone defects with the help of relevant databases. The targets of Salvia miltiorrhiza for traumatic bone defects were analyzed by STRING and GeneCards databases, and the results were visualized by constructing a compound-target network, protein-protein interaction network, and compound-target-disease network with Cytoscape 3.7.1 analysis software. Finally, the selected core targets carried out GO and KEGG enrichment. The results showed that 60 main active components were screened from Salvia miltiorrhiza Bunge, which could act on 149 targets. There were 33 active components and 70 targets related to traumatic bone defects, respectively. The core targets of Salvia miltiorrhiza in the treatment of traumatic bone defects were MAPK1, MAPK10, MAPK14, TGFB1, and TNF. The results of enrichment analysis showed that Salvia miltiorrhiza might treat traumatic bone defects through an osteogenic differentiation pathway.

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pathway Enrichment ◽  
Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt 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.

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 Therapeutic Efficacy Evaluation and Underlying Mechanisms Prediction of Jianpi Liqi Decoction for Hepatocellular Carcinoma

2021 ◽  
pp. 1-11
Author(s):  
Shi Bing Su ◽  
Xiaole Chen ◽  
Peng Wang ◽  
Yunquan Luo ◽  
Yi Yu Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Signaling Pathways ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Efficacy Evaluation ◽  
Underlying Mechanisms ◽  
Multiple Signaling

Objective: The aim of this study was to assess the therapeutic effects of Jianpi Liqi decoction (JPLQD) in hepatocellular carcinoma (HCC) and explore its underlying mechanisms. Methods: The characteristics and outcomes of HCC patients with intermediate stage B who underwent sequential conventional transcatheter arterial chemoembolization (cTACE) and radiofrequency ablation (RFA) only or in conjunction with JPLQD were analysed retrospectively. The plasma proteins were screened using label-free quantitative proteomics analysis. The effective mechanisms of JPLQD were predicted through network pharmacology approach and partially verified by ELISA. Results: Clinical research demonstrated that the Karnofsky Performance Status (KPS), traditional Chinese medicine (TCM) syndrome scores, neutropenia and bilirubin, median progression-free survival (PFS), and median overall survival (OS) in HCC patients treated with JPLQD were superior to those in patients not treated with JPLQD (all P<0.05). The analysis of network pharmacology, combined with proteomics, suggested that 52 compounds targeted 80 potential targets, which were involved in the regulation of multiple signaling pathways, especially affecting the apoptosis-related pathways including TNF, p53, PI3K-AKT, and MAPK. Plasma IGFBP3 and CA2 were significantly up-regulated in HCC patients with sequential cTACE and RFA therapy treated with JPLQD than those in patients not treated with JPLQD (P<0.001). The AUC of the IGFBP3 and CA2 panel, estimated using ROC analysis for JPLQD efficacy evaluation, was 0.867. Conclusion: These data suggested that JPLQD improves the quality of life, prolongs the overall survival, protects liver function in HCC patients, and exhibits an anticancer activity against HCC. IGFBP3 and CA2 panels may be potential therapeutic targets and indicators in the efficacy evaluation for JPLQD treatment, and the effective mechanihsms involved in the regulation of multiple signaling pathways, possibly affected the regulation of apoptosis.

scholarly journals Exploring the Pharmacological Mechanism of the modified Chinese medicine formulas “Shenfu-Linguizhugan decoction” treating Dilated cardiomyopathy Based on Network Pharmacology

2020 ◽  
Author(s):  
Wuxia Quan ◽  
Yandong Miao
Keyword(s):  
Gene Expression ◽  
Chinese Medicine ◽  
Dilated Cardiomyopathy ◽  
Target Genes ◽  
Muscle Disease ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Bioactive Components ◽  
Ppi Network ◽  
Compound Target

Abstract Background: Dilated cardiomyopathy (DCM) is a non-ischaemic cardiac muscle disease with structural and functional myocardial aberration can lead to extensive morbidity and mortality due to complications in particular heart failure and arrhythmia. Two classic Chinese medicine formulas, Shenfu decoction and Linguizhugan decoction, were both shown to exert therapeutic effects on heart disease. Thus, modified Shenfu and Linguizhugan decoction (SFLGZGD) is recommended for treatment DCM. However, its chemical and pharmacological characteristics remain to be elucidated. In the current study, a network pharmacology approach was applied to characterize the action mechanism and target genes of SFLGZGD on DCM.Methods: The gene expression of DCM was obtained from the Gene Expression Omnibus (GEO). All compounds were obtained from the correlative databases, and active mixture were selected according to their oral bioavailability (OB) and drug-likeness (DL) index. The potential targets of SFLGZGD were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database. The compound-target and target-pathway networks were constructed. The protein-protein interactive (PPI) network generated by R software was visualized by Cytoscape, and the topology scores, functional regions, and gene annotations were analyzed using plugins of Bisogenet and CytoNCA. The potential pathways related to target genes were determined by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.Results: A total of 963 differentially expressed genes (DEGs), including 538 upregulated genes and 425 downregulated, were obtained from GSE19303. A total of 636 ingredients in SFLGZGD were obtained, among which, 93 were chosen as bioactive components. The compound-target network included 10 bioactive components and 18 potential targets and a total of 1939 genes obtained in the PPI network, among them, a total of 16 genes were screened out. Moreover,129 terms on the GO analysis and six pathways obtained. Among these potential targets, EGFR, CDKN1A, MMP1, COL1A1, COL3A1, MMP3, ICAM1, and HSPB1 were identified as relatively high-degree targets.Conclusions: The network pharmacology-based approach in the current study has shown promising potential in identifying major therapeutic targets from TCM formulations. Besides, our study suggested that network pharmacology prediction may provide a useful tool for describing the molecular mechanism of SFLGZGD on DCM.

scholarly journals Network pharmacology, molecular docking, and experimental study for the mechanisms of Qishen Yiqi Pills against Cardiovascular Diseases

2021 ◽  
Author(s):  
Jie-wen Zhao ◽  
Hai-dong Liu ◽  
Ming-yin Man ◽  
Lv-ya Wang ◽  
Ning Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cardiovascular Diseases ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Literature Mining ◽  
Therapeutic Effects ◽  
Active Components

Abstract Background Qishen Yiqi Pills (QSYQP) is a traditional Chinese compound recipe. However, our understanding of its mechanism has been hindered due to the complexity of its components and targets. In this work, the network pharmacology-based approaches were used to explore QSYQP’s pharmacological mechanism on treating cardiovascular diseases (CVD). Results From ETCM and TCM MESH databases we collected QSYQP’s 333 active components and their 674 putative targets. We constructed the sub-network influence by CVD genes and found that 40% QSYQP targets appeared in 20 modules, in which QSYQP’s targets and CVD genes co-existed as hub nodes in the sub-network. Functional enrichment analysis suggested that the 42 key targets were mainly expressed in platelets, blood vessels, cardiomyocytes, and other tissues. The main signaling pathways regulated and controlled by the key targets were inflammation, immunity, blood coagulation and energy metabolism. Network and pathway analysis identified 7 key targets, which were regulated by 7 compounds of QSYQP. 26 of the 42 important targets, including the 7 key targets were verified by literature mining. Twelve pairs of interactions between key targets and QSYQP’s compounds were validated by molecular docking. Further validation experiments suggested that QSYQP suppressed H/R induced apoptosis and cytoskeleton disruption of cardiomyocytes. Western blotting showed that the expression of cardiovascular diseases-related genes including ACTC1, FoxO1 and DIAPH1 was significantly decreased by establishing the hypoxia-reoxygenation model in vitro, while the protein expression of experimental group was significantly increased by adding QSYQP or its ingredients. Conclusion These results indicated the correlation of QSYQP treatment to the therapeutic effects of CVD. At the molecular level, this study revealed the multicomponent and multitargeting mechanisms of QSYQP in the regulation and treatment of cardiovascular diseases, potentially providing a reference for the further utilization of QSYQP.

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 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.

scholarly journals Unveiling Potential Active Constituents and Pharmacological Mechanisms of Pudilanxiaoyan Oral Liquid for Anti-Coronavirus Pneumonia Using Network Pharmacology

2021 ◽  
Author(s):  
Ying-Peng Tong ◽  
Xiao-Fei Shen ◽  
Qi Zhou ◽  
Chun-Xiao Jiang ◽  
Na Li ◽  
...  
Keyword(s):  
Target Genes ◽  
Inflammatory Responses ◽  
Interaction Network ◽  
In Vitro Study ◽  
Network Pharmacology ◽  
Active Components ◽  
Active Constituents ◽  
Network Analyses ◽  
Oral Liquid

AbstractThe outbreak of novel coronavirus pneumonia (COVID-19), defined as a worldwide pandemic, has been a public health emergency of international concern. Pudilanxiaoyan oral liquid (PDL), an effective drug of Traditional Chinese Medicine (TCM), is considered to be an effective and alternative means for clinical prevention of COVID-19. The purpose of this study was to identify potential active constituents of PDL, and explore its underlying anti-COVID-19 mechanism using network pharmacology. Integration of target prediction (SwissTargetPrediction and STITCH database) was used to elucidate the active components of PDL. Protein–protein interaction network analyses, gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, network construction, and molecular docking were applied to analyze the prospective mechanisms of the predicted target genes. Our results showed that the key active ingredients in PDL were luteolin, apigenin, esculetin, chrysin, baicalein, oroxylin A, baicalin, wogonin, cymaroside, and gallic acid. A majority of the predicted targets were mainly involved in the pathways related to viral infection, lung injury, and inflammatory responses. An in vitro study further inferred that inhibiting the activity of nuclear factor (NF)-кB signaling pathway was a key mechanism by which PDL exerted anti-COVID-19 effects. This study not only provides chemical basis and pharmacology of PDL but also the rationale for strategies to exploring future TCM for COVID-19 therapy.

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