scholarly journals Revealing active components, action targets and molecular mechanism of Gandi capsule for treating diabetic nephropathy based on network pharmacology strategy

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Qiqiang Zhang ◽  
Qing Ye ◽  
Xiaohui Huang ◽  
Ajing Xu ◽  
Yan Liu ◽  
...  
Keyword(s):  
Oral Administration ◽  
Molecular Mechanism ◽  
Blood Stasis ◽  
Pharmacological Action ◽  
Rat Plasma ◽  
Network Pharmacology ◽  
Active Components ◽  
Protein Targets ◽  
Discovery Studio ◽  
Network Analyses

Abstract Background Gandi capsule is a traditional Chinese herbal formula used to promote blood circulation and removing blood stasis in clinical. Our previous study has shown that it reduces proteinuria with routine treatment in diabetic nephrophy (DN), but its pharmacological action mechanism is still unknown. Methods To facilitate the identification of components, a component database of Gandi capsule and target database of DN were established by ourselves. The components absorbed in blood circle were identified in rat plasma after oral administration of Gandi capsule by UHPLC-QQQ-MS/MS. The potential targets were screened by using Libdock tolls in Discovery studio 3.0. Then Pathway and Network analyses were used to enrich the screened targets. The possible targets were verified by using a surface plasmon resonance (SPR) test and the molecular mechanism focusing these targets for treating DN was clarified by western blot. Results Six components in Gandi capsule were identified detected in rat plasma after oral administration by UHPLC-QQQ-MS/MS. After molecular docking analyses in KEGG and Discovery studio, four protein targets including HNF4A, HMGCR, JAK3, and SIRT1, were screened out, and proved as effective binding with baicalin, wogonoside by SPR. And the molecular mechanism was clarified that baicalin and wogonoside inhibit the effect of high glucose (HG)-induced decreased cell viability and podocin expression, and strengthen the activation p-AKT, p-PI3K, and p-AMPK. Conclusion Baicalin and wogonoside were screened out to be the active compounds in Gandi capsule and can ameliorate HG-induced podocyte damage by influencing the AMPK and PI3K-AKT signaling pathways by binding with HNF4A, HMGCR, JAK3, and SIRT1. Graphical abstract

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 An LC-MS/MS Method for Simultaneous Determination of the Toxic and Active Components of Cortex Periplocae in Rat Plasma and Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Zhen Li ◽  
Yang Li ◽  
Jin Li ◽  
Rui Liu ◽  
Jia Hao ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Simple Liquid ◽  
Active Components ◽  
Limit Of Quantification ◽  
Liquid Chromatography Tandem Mass

A sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the toxic and other active components including isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract to rats. Plasma samples were prepared by protein precipitation with methanol. All compounds were separated on a C18 column with gradient elution using acetonitrile and formic acid aqueous solution (0.1%, v/v) as the mobile phase at a flow rate of 0.3 mL/min. The detection of all compounds was accomplished by multiple-reaction monitoring (MRM) in the positive electrospray ionization mode. The LC-MS/MS method exhibited good linearity for five analytes. The lower limit of quantification (LLOQ) was 0.48 ng/mL for scopoletin, periplogenin, and periplocymarin; 2.4 ng/mL for isovanillin and periplocin. The extraction recoveries of all compounds were more than 90% and the RSDs were below 10%. It was found that the absorption of scopoletin and periplocin was rapid in vivo after oral administration of cortex periplocae extract. Furthermore, periplocymarin possessed abundant plasma exposure. The results demonstrated that the validated method was efficiently applied for the pharmacokinetic studies of isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract.

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 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.

scholarly journals Evidence-Based Complementary and Alternative Medicine Exploring Active Components and Mechanism of Jinhua Qinggan Granules in Treatment of COVID-19 Based on Virus-Host Interaction

2020 ◽  
Vol 15 (9) ◽  
pp. 1934578X2094721
Author(s):  
Yan Ren ◽  
Zheng-hao Yin ◽  
Jian-xing Dai ◽  
Zhuo Yang ◽  
Bin-bin Ye ◽  
...  
Keyword(s):  
Chemical Constituents ◽  
Enrichment Analysis ◽  
Holistic Approach ◽  
Network Pharmacology ◽  
Cytokine Signaling ◽  
Active Components ◽  
Protein Targets ◽  
S Protein ◽  
Host Interaction ◽  
Analysis Platform

This study aimed at exploring the active components and mechanisms of Jinhua Qinggan granules (JQG) in the prevention and treatment of coronavirus disease 2019 (COVID-19) using network pharmacology and molecular docking technology. These efforts were accomplished by employing the holistic approach of traditional Chinese medicine (TCM) and considering the virus-host interaction consisting of viral characteristics, the entry pathway into the host, and the resulting immune response. The chemical constituents and molecular targets of the 12 herbs from JQG were obtained using the TCM Systems Pharmacology database and analysis platform. UniProt was used to search for genes corresponding to JQG protein targets and Cytoscape 3.7.2 to construct the component-target (gene) network. Database for Annotation, Visualization and Integrated Discovery was used to perform enrichment analysis of gene ontology functions and the Kyoto Encyclopedia of Genes and Genomes pathways to predict the mechanism of action. The components ranked high in the network, and the major active components of the principal medicines, based on published literature, were docked with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL hydrolase, SARS-CoV-2 spike glycoprotein (S protein), angiotensin conversion enzyme II (ACE2), and suppressor of cytokine signaling 1 (SOCS1). Visualization analysis demonstrated that the core active components of JQG had a strong affinity for SARS-CoV-2 3CL hydrolase, SARS-CoV-2 S protein, ACE2, and SOCS1. These data imply that the potential active components of JQG may act on multiple signaling pathways by binding to targets such as SARS-CoV-2 3CL hydrolase, S protein, ACE2, and SOCS1, thereby inhibiting virus replication and targeting cell binding, reducing host inflammation, and activating antiviral immunity to a certain extent.

scholarly journals Simultaneous Determination of Seven Active Components in Rat Plasma by UHPLC-MS/MS and Application to a Quantitative Study after Oral Administration of Huang-Lian Jie-Du Decoction in High Fat-Induced Atherosclerosis Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Li Jiang ◽  
Yanling Xiong ◽  
Lanbin Yu ◽  
Yu Chen ◽  
Qiyun Zhang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Simultaneous Determination ◽  
Quantitative Study ◽  
High Performance ◽  
Rat Plasma ◽  
Dependent Manner ◽  
High Fat ◽  
Active Components ◽  
Validation Parameters

Huang-Lian Jie-Du decoction (HLJDD) has been used to treat cardiovascular and cerebrovascular disease for many years in China. Currently, the determination of effect components in HLJDD is focusing either on the formula or on the extract, while quantification of that in biological samples is scarce, especially simultaneous determination of multicomponent. In this paper, a rapid, specific, and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry method was developed and fully validated for the simultaneous determination of seven main active constituents, i.e., baicalin, baicalein, wogonoside, wogonin, berberine, palmatine, jatrorrhizine in rat plasma. The method was also successfully applied to a quantitative study after oral administration of HLJDD at different doses of 1.5, 3, and 6 g/kg body weight to high fat-induced atherosclerosis rats. The analytes were detected by ESI source and multiple reactions monitoring (MRM) using positive scanning mode. The blood was collected from the abdominal aorta of rats at predetermined time and preprepared with icariin and tetrahydropalmatine as internal standards (IS). Sample preparation was achieved by protein precipitation (PPT). The validation parameters (linearity, sensitivity, intra-/interday precision and accuracy, extraction recovery, and matrix effect) were within acceptable ranges, and biological extracts were stable during the entire storing and preparing process. And the result of determination of HLJDD-containing plasma, baicalin, baicalein, wogonoside, and wogonin could be highly detected in a dose-dependent manner while berberine, jatrorrhizine, and palmatine were determined in a very low level and in a dose-independent mode. Thus, the established method was sensitive enough and successfully applied to the determination of seven effective components in plasma taken from 24 high fat-induced atherosclerosis rats after oral administration of three dosages of HLJDD.

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