scholarly journals Potential Mechanism of Tibetan Medicine Dali in the Treatment of Respiratory Diseases via Network Pharmacology

2021 ◽  
Author(s):  
Yuxin Fan ◽  
Yong Yang ◽  
Yunhong Wang ◽  
Jirui Wang ◽  
Lei Hua ◽  
...  
Keyword(s):  
Cell Growth ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Respiratory Diseases ◽  
Mapk Signaling ◽  
The Body ◽  
Tibetan Medicine ◽  
Network Pharmacology ◽  
Active Components ◽  
Protein Targets

Abstract Background: As a source of Tibetan medicine “Dali”, Rhododendron anthopogonoides Maxim (RAM) has good medically helpful effect on respiratory diseases. However, due to its complex components, there is still a lack of pharmacological and pharmacodynamic research on its active components. Methods: The research method of the network pharmacology was used in this study, to obtain the mechanism of RAM in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The active components of RAM were obtained by searching the relevant database, and the protein targets of each chemical component in RAM were screened by Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and PubChem. Then, the protein targets were normalized to the corresponding gene name through UniProt. Meanwhile, genes related to ALI were searched by Online Mendelian Inheritance in Man (OMIM) database, GeneCards database, DrugBank database and DisGeNET database. The “Component-Target-Protein” network was established by Cytoscape software, and the core targets were screened by combining with STRING software. Finally, GO and KEGG enrichment analysis were carried out by David database. Results: Combined with all above results, 92 active components of RAM and 176 gene targets of ALI/ARDS were screened, including 46 common targets, which were related to biological processes such as inflammation, immune and inflammatory response, cell growth and differentiation and apoptosis. Conclusions: It can be concluded through the investigation of network pharmacology that RAM regulates a variety of physiological processes such as cell growth, differentiation, apoptosis and death by activating the Toll-like receptor signaling pathway, TNF signaling pathway, cAMP signaling pathway, MAPK signaling pathway, as well as regulating the inflammatory response of cells, the immune response of the body and promoting the inflammatory cytokines NF‐κB dependent expression and other processes to treat ALI/ARDS. This study revealed the mechanism of RAM multi-component, multi-target and multi-pathway, and provided scientific basis and research ideas for its clinical application.

scholarly journals Exploration of the Mechanism and Active Targets of Chinese Herbal Formula, JTTZ, for the Treatment of Type 2 Diabetes with Obesity and Hyperlipidemia Based on Network Pharmacology

2021 ◽  
Author(s):  
Haiyu Zhang ◽  
Xuedong An ◽  
De Jin ◽  
Jiaxing Tian ◽  
Wenke Liu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Pathway Analysis ◽  
Kegg Pathway ◽  
Therapeutic Targets ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Bile Acid Metabolism ◽  
Ppi Networks ◽  
Kegg Pathway Analysis

Abstract BackgroundPrevious studies have indicated that the JTTZ formula exhibits clinical benefit in T2D with obesity and hyperlipidemia such as lowering blood glucose, blood lipids, weight, and ameliorating symptoms as well as regulating islet function. However, their mechanism of action remains unclear. T2D with obesity and hyperlipidemia is associated with a severely poor management duo to difficulty in achieving the clinical goals and lack of effective multi-targeted therapies. In this study, we explored its potential mechanisms and therapeutic targets by network pharmacology. MethodsThe active ingredients and targets of JTTZ were obtained in the TCMSP, TCMID, TCM Database@Taiwan, PubChem and Swiss Target Prediction. And the therapeutic targets were searched from TTD, DrugBank Database and DisGeNET. Then, topology analysis were used as secondary screens to identify key hubs of the network. Finally, the data was integrated by Cytoscape software to construct a common network module. PPI networks were visualized to identify the interaction of the candidate targets. GO and KEGG pathway analysis were implemented. Rerult: 110 active compounds and 166 candidate targets of JTTZ against T2D with obesity and hyperlipidemia were obtained to construct compound-targets network. And, the therapeutic targets AKT2, RELA, NFKB1 and GSK3B were identified. GO and KEGG pathway analysis indicated that the biological processes related to inflammatory response, insulin secretion, steroid and bile acid metabolism, and 13 pathways mainly including adipocytokine signaling pathway, cAMP signaling pathway and cGMP-PKG signaling pathway were enriched. ConclusionOur data established that JTTZ intervenes with adipose tissue dysfunction via regulating to the adipocytokine (leptin and adiponectin), AMPK signaling pathway, cAMP and cGMP-PKG signaling pathway, inhibits systematic inflammatory response by NF-κB and MAPK signaling pathway, and ameliorates insulin resistance through PI3K/AKT2 pathway, all of which could thus offer a promising therapeutic strategy. In addition, AKT2, RELA, NFKB1 and GSK3B were identified to be regarded as potential therapeutic targets as well.

scholarly journals Based on Network Pharmacology to Explore the Potential Bioactive Compounds and Mechanisms of Zuojin Pill for the Treatment of Ulcerative Colitis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Ying Wei ◽  
Sichen Ren ◽  
Ruilin Wang ◽  
Manyi Jing ◽  
Honghong Liu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Signaling Pathway ◽  
Bioactive Compounds ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Active Components

Background. Zuojin Pill (ZJP), a classic prescription, has the potential to prevent ulcerative colitis (UC). However, the active components and mechanisms of ZJP are still arcane. This study aimed to use a network pharmacology approach to find the bioactive compounds and potential action mechanisms of ZJP in the treatment of UC. Methods. Firstly, the components and putative targets of ZJP were collected based on herbal medicine target databases, and a network containing the interaction between the targets of ZJP and the potential therapeutic targets of UC was established. Then, topological parameters were calculated to identify the key targets in the network and, in turn, to import them into the David database to perform path enrichment analysis. Results. 14 potential therapeutic components of ZJP and 26 key targets were obtained. These targets were related to signal transduction, MAPK cascade, inflammatory response, immune response, and the apoptotic process of UC. Moreover, the PI3K-Akt signaling pathway, MAPK signaling pathway, toll-like receptor signaling pathway, and Prolactin signaling pathway were predicted to participate in ZJP treating UC. Among them, 14 active components of ZJP directly regulate these pathways. Conclusion. ZJP could alleviate UC through the predicted components and mechanisms. The 14 predicted active components of ZJP may mainly play a therapeutic role for UC through synergistic regulation of the PI3K-Akt signaling pathway and MAPK signaling pathway.

scholarly journals Based on Network Pharmacology to Explore the Active Ingredients and Molecular Targets of Zuojin Pill for the Treatment of Ulcerative Colitis

2021 ◽  
Author(s):  
Ying Wei ◽  
Sichen Ren ◽  
Ruilin Wang ◽  
Manyi Jing ◽  
Honghong Liu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Rna Polymerase Ii ◽  
Signaling Pathway ◽  
Cellular Response ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Active Components

Abstract Background: Zuojin Pill (ZJP), a classic prescription, has the potential to prevent ulcerative colitis (UC). However, the active component and mechanism of ZJP is still arcane. Objective: This study aims to use a network pharmacology approach to find the bioactive compounds and potential action mechanisms of ZJP in the treatment of UC.Methods: Firstly, the components and putative targets of ZJP were collected based on the herbal medicine target database, and a network containing the interaction between the putative targets of ZJP and the potential therapeutic targets of UC was established. Then topological parameters were calculated to identify the key targets in the network and the key targets were imported into David database to perform path enrichment analysis.Results: 7 potential therapeutic components of ZJP and 26 key targets were obtained. These targets were related to signal transduction, response to drug, cellular response to lipopolysaccharide, MAPK cascade, inflammatory response, immune response, transcription from RNA polymerase II promoter, apoptotic process, regulation of sequence-specific DNA binding transcription factor activity and lipopolysaccharide-mediated signaling pathway. Moreover, PI3K-Akt signaling pathway, MAPK signaling pathway and Toll-like receptor signaling pathway were predicted to participate in the treatment of UC, which directly regulated by 7 active components of ZJP. Quercetin and isorhamnetin have great development value in the treatment of UC. Moupinamide and palmidin A are of great value for exploration because of their safety and innovation.Conclusion: ZJP mainly were directly involved in UC through inflammation and immune regulation by PI3K-Akt signaling pathway and MAPK signaling pathway.

scholarly journals Studies of the Anti-Diabetic Mechanism of Pueraria lobata Based on Metabolomics and Network Pharmacology

Processes ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 1245
Author(s):  
Shu Zhang ◽  
Qi Ge ◽  
Liang Chen ◽  
Keping Chen
Keyword(s):  
Signaling Pathway ◽  
Diabetes Complications ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Pueraria Lobata ◽  
Insulin Deficiency ◽  
Active Ingredients ◽  
Foxo Signaling Pathway ◽  
Anti Inflammation

Diabetes mellitus (DM), as a chronic disease caused by insulin deficiency or using obstacles, is gradually becoming a principal worldwide health problem. Pueraria lobata is one of the traditional Chinese medicinal and edible plants, playing roles in improving the cardiovascular system, lowering blood sugar, anti-inflammation, anti-oxidation, and so on. Studies on the hypoglycemic effects of Pueraria lobata were also frequently reported. To determine the active ingredients and related targets of Pueraria lobata for DM, 256 metabolites were identified by LC/MS non targeted metabonomics, and 19 active ingredients interacting with 51 DM-related targets were screened. The results showed that puerarin, quercetin, genistein, daidzein, and other active ingredients in Pueraria lobata could participate in the AGE-RAGE signaling pathway, insulin resistance, HIF-1 signaling pathway, FoxO signaling pathway, and MAPK signaling pathway by acting on VEGFA, INS, INSR, IL-6, TNF and AKT1, and may regulate type 2 diabetes, inflammation, atherosis and diabetes complications, such as diabetic retinopathy, diabetic nephropathy, and diabetic cardiomyopathy.

scholarly journals The Underlying Mechanism of Chinese Herb of Regulating Marrow in the Treatment of  Osteonecrosis of the Femoral Head Based on Network Pharmacology and Molecular Docking

2021 ◽  
Author(s):  
Xiaojian Wang ◽  
Rui Wang ◽  
Ting Xu ◽  
Hongting Jin ◽  
Peijian Tong ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Active Components ◽  
Pathway Enrichment

Abstract Background The lesion of marrow is a crucial factor in orthopedic diseases, which is recognized by orthopedics-traumatology expert from "Zhe-School of Chinese Medicine". The Chinese herbs of regulating marrow has been widely used to treat osteonecrosis of the femoral head (ONFH) in China, while the interaction mechanisms were still elucidated. Thus, we conducted this study to explore the underlying mechanism of the five highest-frequency Chinese herbs of regulating marrow(HF-CHRM) in the treatment of ONFH with the aid of network pharmacology(NP) and molecular docking(MD). Methods The active components and potential targets of HF-CHRM were obtained through several online databases, such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), UniProt database. The gene targets related to ONFH were collected with the help of the OMIM and GeneCards disease-related databases. The "drug- component-target-disease" network and protein-protein interaction(PPI) network of the drug and disease intersecting targets were constructed by using Cytoscape software and the STRING database. R software was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The MD of critical components and targets was carried out using Autodock Vina and Pymol to validate the binding affinity. Results A total of 54 active components, 1074 drug targets and 195 gene targets were obtained. There were 1219 ONFH related targets. 39 drug and disease intersection targets(representative genes: IL6, TP53, VEGFA, ESR1, IL1B) were obtained and considered potential therapeutic targets. 1619 items were obtained by the GO enrichment analysis, including 1517 biological processes, 10 cellular components and 92 molecular functions, which is mainly related to angiogenesis, bone and lipid metabolism and inflammatory reaction. The KEGG pathway enrichment analysis revealed 119 pathways, including AGE-RAGE signaling pathway, PI3K-Akt signaling pathway and IL-17 signaling pathway. MD results showed that quercetin, wogonin, and kaempferol active components had good affinity with IL6, TP53, and VEGFA core proteins. Conclusion The HF-CHRM can treat ONFH by multi-component, multi-target, and multi-pathway comprehensive action.

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.

Glutathione S-transferase omega 2 regulates cell growth and the expression of E-cadherin via post-transcriptional down-regulation of β-catenin in human esophageal squamous cells

2019 ◽  
Vol 41 (7) ◽  
pp. 875-886
Author(s):  
Masayoshi Terayama ◽  
Kazuhiko Yamada ◽  
Teruki Hagiwara ◽  
Fumika Inazuka ◽  
Takuhito Sezaki ◽  
...  
Keyword(s):  
Cell Growth ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Mapk Signaling ◽  
Membrane Localization ◽  
Esophageal Mucosa ◽  
Glutathione S Transferase ◽  
Down Regulation ◽  
Transfected Cells ◽  
E Cadherin

Abstract Glutathione S-transferase omega 2 (GSTO2), which belongs to the superfamily of GST omega class, lacks any appreciable GST activity. Although GSTO2 exhibits thioltransferase and glutathione dehydrogenase activities, its precise expression and physiological functions are still unclear. In the present study, we found that GSTO2 is exclusively expressed in the basal cell layer in Ki67-negative non-proliferative cells in the human esophageal mucosa. GSTO2 overexpression in esophageal squamous cell carcinoma (ESCC) cell lines inhibited cell growth and colony formation, and GSTO2-transfected cells formed smaller tumors in nude mice compared with mock-transfected cells. Interestingly, GSTO2 induction suppressed the expressions of E-cadherin and β-catenin at the cell–cell contact site. We quantified the phosphorylation levels of key proteins of MAPK signaling pathway and identified phosphorylation of p38. Additionally, HSP27, a downstream molecule of p38, was accelerated in GSTO2-transfected cells, unlike in mock-transfected cells. When GSTO2-transfected cells were treated with a p38 inhibitor, the expression of β-catenin and the membrane localization of E-cadherin was recovered. We next examined GSTO2 expression in 61 ESCC tissues using quantitative reverse transcription polymerase chain reaction and immunostaining. The results showed that GSTO2 mRNA and protein were significantly reduced in ESCC compared with normal tissues. When human ESCC cell lines were treated with 5-aza-2′-deoxycytidine, a DNA-methyltransferase inhibitor, GSTO2 transcription was induced, suggesting that aberrant hypermethylation is the cause of the down-regulated expression. Our results indicate that GSTO2 expression inhibits the membrane localization of E-cadherin, probably by modulation of the p38 signaling pathway. Down-regulation of GSTO2 by DNA hypermethylation contributes to the growth and progression of ESCC.

scholarly journals Network Pharmacology of Yougui Pill Combined with Buzhong Yiqi Decoction for the Treatment of Sexual Dysfunction

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yangyun Wang ◽  
Wandong Yu ◽  
Chaoliang Shi ◽  
Wei Jiao ◽  
Junhong Li ◽  
...  
Keyword(s):  
Sexual Dysfunction ◽  
Signaling Pathway ◽  
Herbal Medicines ◽  
Mapk Signaling ◽  
Glycyrrhetinic Acid ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Chemical Components ◽  
Target Proteins ◽  
Yougui Pill

Purpose. We aimed to find the possible key targets of Yougui pill and Buzhong Yiqi decoction for the treatment of sexual dysfunction. Materials and Methods. The composition of Yougui pill combined with Buzhong Yiqi decoction was obtained, and its effective components of medicine were screened using ADME; the component target proteins were predicted and screened based on the TCMSP and BATMAN databases. Target proteins were cross-validated using the CTD database. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for target proteins using the Cytoscape plugin ClueGO + CluePedia and the R package clusterProfiler, respectively. Subsequently, protein-protein interaction (PPI) analyses were conducted using the STRING database. Finally, a pharmacological network was constructed. Results. The pharmacological network contained 89 nodes and 176 relation pairs. Among these nodes, there were 12 for herbal medicines (orange peel, licorice, Eucommia, Aconite, Astragalus, Chinese wolfberry, yam, dodder seed, ginseng, Cornus officinalis, Rehmannia, and Angelica), 9 for chemical components (18-beta-glycyrrhetinic acid, carvacrol, glycyrrhetinic acid, higenamine, nobilin, quercetin, stigmasterol, synephrine, and thymol), 62 for target proteins (e.g., NR3C1, ESR1, PTGS2, CAT, TNF, INS, and TP53), and 6 for pathways (MAPK signaling pathway, proteoglycans in cancer, dopaminergic synapse, thyroid hormone signaling pathway, cAMP signaling pathway, and neuroactive ligand-receptor interaction). Conclusion. NR3C1, ESR1, PTGS2, CAT, TNF, INS, and TP53 may be important targets for the key active elements in the decoction combining Yougui pill and Buzhong Yiqi. Furthermore, these target proteins are relevant to the treatment of sexual dysfunction, probably via pathways associated with cancer and signal transduction.

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 < 0.05). The expression of NP protein and the virus titers in lung were significantly decreased (p < 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 < 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 < 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.

Sign in / Sign up

Export Citation Format

Share Document