scholarly journals Unveiling the Mechanism of Principal Drugs of Lianpu Drink on Chronic Gastritis by Network Pharmacology

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Shuhan Zhou ◽  
Xiaohui Xu ◽  
Jiangqin Zeng ◽  
Zhiyi Liu ◽  
Miao Wang ◽  
...  
Keyword(s):  
Chronic Gastritis ◽  
Animal Experiments ◽  
Network Pharmacology ◽  
Clinical Effects ◽  
Main Research ◽  
Protein Protein Interaction ◽  
Coptidis Rhizoma ◽  
Research Objects ◽  
Magnolia Officinalis ◽  
P38 Pathway

Lianpu drink (LPD) is a traditional Chinese medicine (TCM) formula for the treatment of chronic gastritis (CG), and its clinical effects have been effectively verified. However, due to the complexity of the chemical composition of TCM formulas, its mechanism of action has not yet been clearly explained. Many studies have shown that the principal drugs in the TCM formula play a major therapeutic role. Therefore, in this study, the principal drugs Coptidis Rhizoma (CR) and Magnolia officinalis Rehd. et Wils. (MOR) in LPD were used as the main research objects to predict the mechanism of LPD on CG. We contrasted a “compounds-targets-diseases” network and screened the putative targets of CR and MOR in LPD related to CG, respectively. Furthermore, common targets of CR and MOR related to CG were selected as candidate targets. In this study, the specific target proteins of CR, MOR, and CG were combined by protein-protein interaction (PPI) to construct a pharmacological network of “components-targets-diseases.” In addition, we investigated the effects of CR and MOR on the TNF signaling pathway, which mediated the remission of CG. This study preliminarily revealed that CR and MOR play a key role in the treatment of CG. Animal experiments also showed that CR and MOR could significantly improve CG by inhibiting MKK6/p38 and RIP/p38 pathway.

scholarly journals Exploring the mechanism of Bushenhuoxue formula acting on postmenopausal osteoporosis via network pharmacology and experimental validation

2021 ◽  
Author(s):  
Chunhai Ke ◽  
Yizhou Chen ◽  
Yi Wang ◽  
Guonong He ◽  
Hongkai Lou ◽  
...  
Keyword(s):  
Postmenopausal Osteoporosis ◽  
Experimental Validation ◽  
Animal Experiments ◽  
Network Pharmacology ◽  
Overlapping Genes ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Vegf Signaling ◽  
Endothelial Growth Factor

Abstract Background: Bushenhuoxue (BSHX) formula, a ten-compound herbal decoction, has been used to treat postmenopausal osteoporosis (PMOP) in China for decades. Our previous study also revealed the anti-PMOP effects of BSHX formula in ovariectomized (OVX) mice. However, its pharmacological mechanisms remain unknown. Methods: Network pharmacology followed by animal experiments was used to explore the action mechanism of BSHX formula. Firstly, we obtained the chemical compounds and potential targets of BSHX formula using TCMSP and TCMID databases. Simultaneously, GeneCards and DisGeNET databases were used to determine the targets in PMOP. Based on their overlapping genes between BSHX formula and PMOP, a protein-protein interaction (PPI) network was constructed for screening hub-targets. GO and KEGG enrichment analyses were further performed to identify the critical biological processes and signaling pathways. In vivo experimental study, an OVX mouse model was established to determine the anti-PMOP effects of BSHX formula via Micro-CT assay and ABH staining. The expressions of β-catenin, alkaline phosphatase (ALP), vascular endothelial growth factor (VEGF) and CD31 were detected by immunohistochemistry.Results: A total of 218 active ingredients and 274 related targets were identified in BSHX formula. After matching with 292 therapeutic targets of PMOP, 64 overlapping genes were obtained and further used to build a PPI network in which CTNNB1 and VEGFA played a central role. GO and KEGG enrichment analyses indicated that the anti-PMOP effects of BSHX formula were mainly associated with cell proliferation, angiogenesis and their regulated pathways including β-catenin signaling and VEGF signaling. In mouse experiments, we revealed that bone mass and blood vessels in the OVX mice were significantly enhanced after treated with BSHX formula for 8 weeks. Moreover, down-regulations of β-catenin, ALP, VEGF and CD31 caused by OVX surgery were significantly restored by BSHX formula.Conclusions: Through network pharmacology and an experimental validation, we have revealed that BSHX formula exerts anti-PMOP effects mainly through promoting β-catenin-mediated osteogenesis and VEGF-mediated angiogenesis. BSHX formula can be considered as a new option for the treatment of PMOP.

scholarly journals Elucidating the Mechanisms of Action of Lianhua Qingwen decoction for the Treatment of COVID-19 via Systems Pharmacology Approaches

2021 ◽  
Author(s):  
Xiting Wang ◽  
Tao Lu
Keyword(s):  
Molecular Docking ◽  
Blood Circulation ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Detection Algorithm ◽  
Network Pharmacology ◽  
Systems Pharmacology ◽  
Protein Protein Interaction ◽  
Further Development ◽  
Protein Protein Interaction Network

Abstract Due to the severity of the COVID-19 epidemic, to identify a proper treatment for COVID-19 is of great significance. Traditional Chinese Medicine (TCM) has shown its great potential in the prevention and treatment of COVID-19. One of TCM decoction, Lianhua Qingwen decoction displayed promising treating efficacy. Nevertheless, the underlying molecular mechanism has not been explored for further development and treatment. Through systems pharmacology and network pharmacology approaches, we explored the potential mechanisms of Lianhua Qingwen treating COVID-19 and acting ingredients of Lianhua Qingwen decoction for COVID-19 treatment. Through this way, we generated an ingredients-targets database. We also used molecular docking to screen possible active ingredients. Also, we applied the protein-protein interaction network and detection algorithm to identify relevant protein groupings of Lianhua Qingwen. Totally, 605 ingredients and 1,089 targets were obtained. Molecular Docking analyses revealed that 35 components may be the promising acting ingredients, 7 of which were underlined according to the comprehensive analysis. Our enrichment analysis of the 7 highlighted ingredients showed relevant significant pathways that could be highly related to their potential mechanisms, e.g. oxidative stress response, inflammation, and blood circulation. In summary, this study suggests the promising mechanism of the Lianhua Qingwen decoction for COVID-19 treatment. Further experimental and clinical verifications are still needed.

scholarly journals Investigating drug–target interactions in frontotemporal dementia using a network pharmacology approach

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Archana Balasubramanian ◽  
Raksha Sudarshan ◽  
Jhinuk Chatterjee
Keyword(s):  
Substance Abuse ◽  
Targeted Therapy ◽  
Drug Interactions ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Specific Drug ◽  
Protein Protein Interaction ◽  
App Gene ◽  
Protein Protein Interaction Network

Abstract Background Frontotemporal dementia (FTD) is the second most common type of dementia in individuals aged below 65 years with no current cure. Current treatment plan is the administration of multiple medications. This has the issue of causing adverse effects due to unintentional drug–drug interactions. Therefore, there exists an urgent need to propose a novel targeted therapy that can maximize the benefits of FTD-specific drugs while minimizing its associated adverse side effects. In this study, we implemented the concept of network pharmacology to understand the mechanism underlying FTD and highlight specific drug–gene and drug–drug interactions that can provide an interesting perspective in proposing a targeted therapy against FTD. Results We constructed protein–protein, drug–gene and drug–drug interaction networks to identify highly connected nodes and analysed their importance in associated enriched pathways. We also performed a historeceptomics analysis to determine tissue-specific drug interactions. Through this study, we were able to shed light on the APP gene involved in FTD. The APP gene which was previously known to cause FTD cases in a small percentage is now being extensively studied owing to new reports claiming its participation in neurodegeneration. Our findings strengthen this hypothesis as the APP gene was found to have the highest node degree and betweenness centrality in our protein–protein interaction network and formed an essential hub node between disease susceptibility genes and neuroactive ligand–receptors. Our findings also support the study of FTD being presented as a case of substance abuse. Our protein–protein interaction network highlights the target genes common to substance abuse (nicotine, morphine and cocaine addiction) and neuroactive ligand–receptor interaction pathways, therefore validating the cognitive impairment caused by substance abuse as a symptom of FTD. Conclusions Our study abandons the one-target one-drug approach and uses networks to define the disease mechanism underlying FTD. We were able to highlight important genes and pathways involved in FTD and analyse their relation with existing drugs that can provide an insight into effective medication management.

scholarly journals Comparative studies of the anti-thrombotic effects of saffron and HongHua based on network pharmacology

2020 ◽  
Vol 19 (7) ◽  
pp. 1441-1448
Author(s):  
Jinyan Jiang ◽  
Susu Lin ◽  
Qiaoqiao Li ◽  
Shanshan Jiang ◽  
Yingjie Hu ◽  
...  
Keyword(s):  
Animal Experiments ◽  
Blood Stasis ◽  
Erythrocyte Aggregation ◽  
Network Pharmacology ◽  
Control Group ◽  
Clotting Time ◽  
Aggregation Index ◽  
Model Control

Purpose: To investigate the comparative anti-thrombotic effects of saffron and Honghua, and also to explore possible mechanisms in thrombosis based on network pharmacology. Methods: A network pharmacology model was used for bioactive components, targets and pathways for saffron and HongHua via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper, Genecard, Uniprot and KEGG databases. In animal experiments, 72 rats were randomly divided into 9 groups: normal control group (NC), model control group (MC), crocetin groups (80, 40, 20 mg/kg), hydroxysafflor yellow A(HSYA) groups (80, 40, 20 mg/kg), and aspirin group (40 mg/kg). Using in vitro thrombosis models and an acute blood stasis model in vivo, the anti-thrombotic effects of these treatments on clotting time, hemorheology parameters, Thromboxane B2 (TXB2), plasmin activator inhibitor (PAI), protein C (PC), protein S (PS), and thrombinantithrombin complex (TAT) were determined and comparisons made for saffron and HongHua. Results: Five potential compounds, 16 anti-thrombotic targets and 27 pathways were predicted for saffron, while 22 compounds, 37 disease targets and 35 pathways were found for HongHua (p < 0.05). Pharmacological experiments revealed that crocetin and HSYA had significant effects on thrombus length, thrombus wet/dry mass, whole blood viscosity (WBV), erythrocyte aggregation index (EAI), clotting time and D-dimer for the high and middle groups. Unlike HSYA, crocetin also had significant and dose-dependent effects on PAI, prothrombin fragment 1+2 (F1+2) and PS and had highly significant effects on TXB2 and TAT. Conclusion: This research provides a systematic, comprehensive and comparative analysis of component, target and anti-thrombotic pathways of saffron and HongHua based on network pharmacology, and also shows that saffron has more significant anti-thrombotic effect than HongHua. Keywords: Saffron; HongHua; Network pharmacology; Anti-thrombosis; Network model

scholarly journals Identification of the Active Constituents and Significant Pathways of Shen-qi-Yi-zhu Decoction on Antigastric Cancer: A Network Pharmacology Research and Experimental Validation

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shuhong Zeng ◽  
Zhibao Yu ◽  
Xintian Xu ◽  
Yuanjie Liu ◽  
Jiepin Li ◽  
...  
Keyword(s):  
Experimental Validation ◽  
Target Genes ◽  
Cell Model ◽  
Network Pharmacology ◽  
Disease Network ◽  
Systematic Method ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Underlying Mechanisms

Shen-qi-Yi-zhu decoction (SQYZD) is an empirical prescription with antigastric cancer (GC) property created by Xu Jing-fan, a National Chinese Medical Master. However, its underlying mechanisms are still unclear. Based on network pharmacology and experimental verification, this study puts forward a systematic method to clarify the anti-GC mechanism of SQYZD. The active ingredients of SQYZD and their potential targets were acquired from the TCMSP database. The target genes related to GC gathered from GeneCards, DisGeNET, OMIM, TTD, and DrugBank databases were imported to establish protein-protein interaction (PPI) networks in GeneMANIA. Cytoscape was used to establish the drug-ingredients-targets-disease network. The hub target genes collected from the SQYZD and GC were parsed via GO and KEGG analysis. Our findings from network pharmacology were successfully validated using an in vitro HGC27 cell model experiment. In a word, this study proves that the combination of network pharmacology and in vitro experiments is effective in clarifying the potential molecular mechanism of traditional Chinese medicine (TCM).

scholarly journals Study on the Mechanism of Lianpu Drink for the Treatment of Chronic Gastritis Based on Network Pharmacology

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shuhan Zhou ◽  
Yanjun Duan ◽  
Yu Deng ◽  
Miao Wang ◽  
Chaoqun Huang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Chronic Gastritis ◽  
Mechanisms Of Action ◽  
Network Pharmacology ◽  
Biological Pathway ◽  
Disease Network ◽  
Target Disease ◽  
Compound Target

Chronic gastritis (CG) places a considerable burden on the healthcare system worldwide. Traditional Chinese Medicine (TCM) formulas characterized by multicompounds and multitargets have been acknowledged with striking effects in the treatment of CG in China’s history. Nevertheless, their accurate mechanisms of action are still ambiguous. In this study, we analyzed the effective compounds, potential targets, and related biological pathway of Lianpu Drink (LPD), a TCM formula which has been reported to have a therapeutic effect on CG, by contrasting a “compound-target-disease” network. According to the results, 92 compounds and 5762 putative targets of LPD were screened; among them, 8 compounds derived from different herbs in LPD and 30 common targets related to LPD and CG were selected as candidate compounds and precision targets, respectively. Meanwhile, the predicted common targets were verified by Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis and pharmacological experiments. The results demonstrated that quercetin, ephedrine, trigonelline, crocetin, and β-sitosterol were major effective compounds of LPD responsible for the CG treatment by inhibiting the activation of the JAK 2-STAT 3 signaling pathway to reduce the expressions of cyclin D1 and Bcl-2 proteins. The study provides evidence for the mechanism of understanding of LPD for the treatment of CG.

scholarly journals The Mechanisms of Sijunzi Decoction in the Treatment of Chronic Gastritis Revealed by Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ting Wang ◽  
Yuyin Feng ◽  
Hesong Wang ◽  
Guiyang Huo ◽  
Yanan Cai ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Inflammatory Response ◽  
Chronic Gastritis ◽  
Peripheral Blood ◽  
Network Pharmacology ◽  
Rna Seq ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Superficial Gastritis ◽  
Chronic Superficial Gastritis

Chronic gastritis is characterized by inflammation in the gastric mucosa with a vicious circle in inflammatory cells and inflammatory mediators. Stomach adenocarcinoma would occur in the metaplastic gastric mucosa of chronic gastritis. Sijunzi decoction is a famous classical formula for the treatment of chronic gastritis. Although previous studies revealed some functions of Sijunzi decoction in treating chronic gastritis, the underlying mechanisms have not been illustrated clearly. In this study, we used network pharmacology to investigate the mechanism of Sijunzi decoction in treating chronic gastritis. Firstly, online datasets TCMSP, SWISS, and DisGeNET were used to investigate the functional mechanism of Sijunzi decoction against chronic gastritis and 18 genes were identified as targets of Sijunzi decoction in chronic gastritis. These 18 genes can be categorized into immunologically related genes and cancer-related genes. GO analysis showed that the 18 target genes were mainly enriched in angiogenesis, nitric oxide biosynthetic process, ERK1 and ERK2 cascade, cellular response to drug, and MAPK cascade. So, Sijunzi decoction alleviated chronic gastritis by inhibiting the local inflammatory response. Furthermore, we also investigated the impact of Sijunzi decoction on the peripheral blood leukocytes with our own RNA sequencing (RNA-seq) data of 11 chronic superficial gastritis patients. 102 differentially expressed genes (DEGs) were identified by comparing RNA-seq data of chronic superficial gastritis patients with healthy control groups. After performing a functional analysis on 102 DEGs and Sijunzi decoction potential targets and taking the intersection of these pathways, we found that platelet activation, angiogenesis, and pathways in cancer were candidate target pathways regulated by Sijunzi decoction. Thus, Sijunzi decoction also alleviates chronic gastritis by suppressing inflammatory response of peripheral blood leukocytes. Our results showed that Sijunzi decoction can ameliorate the local gastric inflammation and inflammations in peripheral blood leukocytes and might also reduce the incidence of stomach cancer in chronic gastritis.

scholarly journals Venn-diaNet : venn diagram based network propagation analysis framework for comparing multiple biological experiments

2019 ◽  
Vol 20 (S23) ◽  
Author(s):  
Benjamin Hur ◽  
Dongwon Kang ◽  
Sangseon Lee ◽  
Ji Hwan Moon ◽  
Gung Lee ◽  
...  
Keyword(s):  
Interaction Network ◽  
Venn Diagram ◽  
Analysis Framework ◽  
Seed Selection ◽  
Systematic Analysis ◽  
Main Research ◽  
Protein Protein Interaction ◽  
Propagation Analysis ◽  
Network Propagation ◽  
Main Research Topic

Abstract Background The main research topic in this paper is how to compare multiple biological experiments using transcriptome data, where each experiment is measured and designed to compare control and treated samples. Comparison of multiple biological experiments is usually performed in terms of the number of DEGs in an arbitrary combination of biological experiments. This process is usually facilitated with Venn diagram but there are several issues when Venn diagram is used to compare and analyze multiple experiments in terms of DEGs. First, current Venn diagram tools do not provide systematic analysis to prioritize genes. Because that current tools generally do not fully focus to prioritize genes, genes that are located in the segments in the Venn diagram (especially, intersection) is usually difficult to rank. Second, elucidating the phenotypic difference only with the lists of DEGs and expression values is challenging when the experimental designs have the combination of treatments. Experiment designs that aim to find the synergistic effect of the combination of treatments are very difficult to find without an informative system. Results We introduce Venn-diaNet, a Venn diagram based analysis framework that uses network propagation upon protein-protein interaction network to prioritizes genes from experiments that have multiple DEG lists. We suggest that the two issues can be effectively handled by ranking or prioritizing genes with segments of a Venn diagram. The user can easily compare multiple DEG lists with gene rankings, which is easy to understand and also can be coupled with additional analysis for their purposes. Our system provides a web-based interface to select seed genes in any of areas in a Venn diagram and then perform network propagation analysis to measure the influence of the selected seed genes in terms of ranked list of DEGs. Conclusions We suggest that our system can logically guide to select seed genes without additional prior knowledge that makes us free from the seed selection of network propagation issues. We showed that Venn-diaNet can reproduce the research findings reported in the original papers that have experiments that compare two, three and eight experiments. Venn-diaNet is freely available at: http://biohealth.snu.ac.kr/software/venndianet

scholarly journals Analysis of the Molecular Mechanisms of the Effects of Prunella vulgaris against Subacute Thyroiditis Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xin Shen ◽  
Rui Yang ◽  
Jianpeng An ◽  
Xia Zhong
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Subacute Thyroiditis ◽  
Network Pharmacology ◽  
Pharmacokinetic Parameters ◽  
Pathway Enrichment Analysis ◽  
Prunella Vulgaris ◽  
Protein Protein Interaction

Prunella vulgaris (PV) has a long history of application in traditional Chinese and Western medicine as a remedy for the treatment of subacute thyroiditis (SAT). This study applied network pharmacology to elucidate the mechanism of the effects of PV against SAT. Components of the potential therapeutic targets of PV and SAT-related targets were retrieved from databases. To construct a protein-protein interaction (PPI) network, the intersection of SAT-related targets and PV-related targets was input into the STRING platform. Gene ontology (GO) analysis and KEGG pathway enrichment analysis were carried out using the DAVID database. Networks were constructed by Cytoscape for visualization. The results showed that a total of 11 compounds were identified according to the pharmacokinetic parameters of ADME. A total of 126 PV-related targets and 2207 SAT-related targets were collected, and 83 overlapping targets were subsequently obtained. The results of the KEGG pathway and compound-target-pathway (C-T-P) network analysis suggested that the anti-SAT effect of PV mainly occurs through quercetin, luteolin, kaempferol, and beta-sitosterol and is most closely associated with their regulation of inflammation and apoptosis by targeting the PIK3CG, MAPK1, MAPK14, TNF, and PTGS2 proteins and the PI3K-Akt and TNF signaling pathways. The study demonstrated that quercetin, luteolin, kaempferol, and beta-sitosterol in PV may play a major role in the treatment of SAT, which was associated with the regulation of inflammation and apoptosis, by targeting the PI3K-Akt and TNF signaling pathways.

scholarly journals Screening and Identification of Molecular Targets Involved in Preventing Gastric Precancerous Lesions in Chronic Atrophic Gastritis by Qilianshupi Decoction

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Yameng Zhang ◽  
Chao Li ◽  
Shanmei Sun ◽  
Zhiqun Cao ◽  
Jian Chen ◽  
...  
Keyword(s):  
Atrophic Gastritis ◽  
Telomere Length ◽  
Precancerous Lesions ◽  
Animal Experiments ◽  
Molecular Targets ◽  
Chronic Atrophic Gastritis ◽  
Telomerase Activity ◽  
Network Pharmacology ◽  
Screening And Identification ◽  
Tract Disease

Chronic atrophic gastritis (CAG) is a common and possibly precancerous digestive tract disease. Development of drugs with effect of preventing precancerous lesions draws the eyes of global researchers. Qilianshupi decoction (QLSP) is a Traditional Chinese Medicine (TCM) that is commonly used to treat CAG, but few studies have explored the mechanism of QLSP on treating CAG. This study investigated the molecular targets of the component herbs of QLSP in preventing precancerous lesions based on network pharmacology. Network pharmacology analysis revealed that the 6 herbs regulated multiple CAG-related genes, among which the most important were cancer-related pathway (apoptosis, p53, and VEGF) and epithelial cell signaling in Helicobacter pylori infection. Further animal experiments showed that the expression of survivin and p53 in precancerous lesions of CAG rats was significantly increased which was suppressed by QLSP. Moreover, telomerase activity was inhibited in precancerous lesions of CAG rats, and telomere length of gastric mucosa was increased, which was reversed by QLSP. Our results suggest that the components of QLSP prevents gastric precancerous lesions through decreasing the expression of survivin and p53 and regulating telomerase activity and telomere length in CAG.

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