Utilizing Network Pharmacology to Explore the Possible Mechanism of Coptidis Rhizoma in Kawasaki Disease

Background: The purpose of the research is to identify the main active ingredients in Coptidis Rhizoma (CR) and explore the possible molecular mechanisms in the treatment of Kawasaki disease (KD).Materials and Methods: A total of 58 children with KD were randomly divided into a control group and a Berberine treatment group. The therapeutic indicators of the two groups before and after treatment were compared. Then, compounds and drug targets of CR from the TCMSP, SWISS, SEA, and the STITCH were collected, and targeted KD genes were retrieved from the DisGeNET, DrugBank, and GeneCards databases. The network pharmacology approach involved network construction, target prediction, and module analysis. GO and KEGG enrichment analysis were performed to investigate the possible pathways related to CR for KD treatments. Finally, protein expression was determined to verify the core targets using Western blotting in the cell experiment.Results: In total, nine compounds, 369 relative drug targets, and 624 KD target genes were collected in the above database. The network analysis revealed that 41 targets might be the therapeutic targets of CR on KD. GO and KEGG enrichment analysis revealed that the biological processes, namely, response to hormone, response to inorganic substance, and enzyme-linked receptor protein signaling pathway, and Pathways in cancer, Toll-like receptor signaling pathway, and Pancreatic cancer are the most significant. Protein expression of CASP3, PTGS2, and SRC was upregulated and AKT1 and ERK were downregulated.Conclusion: We provided useful resources to understand the molecular mechanism and the potential targets for novel therapy of KD.

Download Full-text

Utilizing Network Pharmacology to Explore the Possible Mechanism of Coptidis Rhizoma in Kawasaki Disease

10.21203/rs.3.rs-124429/v1 ◽

2020 ◽

Author(s):

Xue Fan ◽

Xin Guo ◽

Ying Li ◽

Mingguo Xu

Keyword(s):

Kawasaki Disease ◽

Signaling Pathway ◽

Drug Targets ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Control Group ◽

Pathway Enrichment Analysis ◽

Routine Treatment ◽

Coptidis Rhizoma

Abstract Background: Kawasaki disease (KD) is an acute self-limiting systemic vasculitis. In study, a randomized controlled trial regarding berberine (main component of Coptidis Rhizoma) function in treating KD was carried out and possible pharmacological mechanisms of Coptidis Rhizoma (CR) on KD therapy were investigated using an integrated network pharmacology approach. Methods: A total of 58 children with KD, younger than 5 years old, were enrolled in the study from October 2018 to May 2019. The patients were randomly divided into control group and BBR treatment group. The therapeutic indicators of the 2 groups before and after treatments were compared. Then, compounds and drug targets of CR from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the SWISS database, the SEA database and the STITCH database were collected, and targeted KD genes were retrieved from the DisGeNET databases, the DrugBank databases and the GeneCards databases. The network pharmacology approach involved network construction, target prediction, and module analysis. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to CR for KD treatments. Results: The berberine group was able to reduce the values of CRP, NLR and PLR significantly. Also, the effect of berberine improved the resistance rate of intravenous injection of gamma globulin significantly. In total, 9 compounds and 369 relative drug targets were collected from TCMSP, SWISS, SEA and STITCH database and 624 KD target genes were collected in DisGeNET, DrugBank and GeneCards database. The network analysis revealed that 41 targets might be the therapeutic targets of CR on KD, among which ATK1, RELA, SRC, CASP3 and MTOR ranked in top 5. Gene ontology enrichment analysis revealed that the reaction to bacteria-derived molecules and to lipopolysaccharide and the apoptosis process were the key biological procedures for CR treating KD. The KEGG pathway enrichment analysis pointed out that the four signaling pathways closely related to CR treating KD including age-rage signaling pathway, fluid shear stress and atherosclerosis, TNF signaling pathway and Toll-like receptor signaling pathway in diabetic complications. Conclusions: we concluded that the introduction of routine treatment combined with berberine in treating KD has advantages than routine treatment and can be considered as a preferred approach in KD. Network pharmacology showed that CR exerted the effect of prevention KD by regulating multi-targets and multi-components.

Download Full-text

A Network Pharmacology Approach to Uncover the Mechanisms of Shen-Qi-Di-Huang Decoction against Diabetic Nephropathy

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/7043402 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 9

Author(s):

Sha Di ◽

Lin Han ◽

Qing Wang ◽

Xinkui Liu ◽

Yingying Yang ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Interaction Network ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Protein Protein Interaction ◽

Regulation Of Blood Pressure ◽

Protein Protein Interaction Network

Shen-Qi-Di-Huang decoction (SQDHD), a well-known herbal formula from China, has been widely used in the treatment of diabetic nephropathy (DN). However, the pharmacological mechanisms of SQDHD have not been entirely elucidated. At first, we conducted a comprehensive literature search to identify the active constituents of SQDHD, determined their corresponding targets, and obtained known DN targets from several databases. A protein-protein interaction network was then built to explore the complex relations between SQDHD targets and those known to treat DN. Following the topological feature screening of each node in the network, 400 major targets of SQDHD were obtained. The pathway enrichment analysis results acquired from DAVID showed that the significant bioprocesses and pathways include oxidative stress, response to glucose, regulation of blood pressure, regulation of cell proliferation, cytokine-mediated signaling pathway, and the apoptotic signaling pathway. More interestingly, five key targets of SQDHD, named AKT1, AR, CTNNB1, EGFR, and ESR1, were significant in the regulation of the above bioprocesses and pathways. This study partially verified and predicted the pharmacological and molecular mechanisms of SQDHD on DN from a holistic perspective. This has laid the foundation for further experimental research and has expanded the rational application of SQDHD in clinical practice.

Download Full-text

A network pharmacology-based study on Alzheimer disease prevention and treatment of Qiong Yu Gao

10.21203/rs.2.24495/v2 ◽

2020 ◽

Author(s):

Jieshu You ◽

Chen-yue Li ◽

Wei Chen ◽

Xia-lin Wu ◽

Li-jie Huang ◽

...

Keyword(s):

Signaling Pathway ◽

Molecular Mechanisms ◽

Kegg Pathway ◽

Herbal Medicines ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Resistance Pathway ◽

Prevention And Treatment ◽

Ad Prevention

Abstract Background and objective: As the pathological mechanisms of AD are complex, increasing evidence have demonstrated Chinese Medicine with multi-ingredients and multi-targets may be more suitable for the treatment of diseases with complex pathogenesis. Therefore, the study was to preliminarily decipher the bioactive compounds and potential mechanisms of Qiong Yu Gao (QYG) for AD prevention and treatment by an integrated network pharmacology approach. Methods: Putative ingredients of QYG and significant genes of AD were retrieved from public database after screening. Then QYG ingredients target proteins/genes were obtained by target fishing. Compound-target-disease network was constructed using Cytoscape to decipher the mechanism of QYG for AD. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to QYG for AD treatments. Results: Finally, 70 compounds and 511 relative drug targets were collected. In which, 17 representative direct targets were found. Gene ontology enrichment analysis revealed that the adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway was the key biological processes and were regulated simultaneously by the 17 direct targets. The KEGG pathway enrichment analysis found that three signaling pathways were closely related to AD prevention and treatment by QYG, including PI3K-Akt signaling pathway, regulation of actin cytoskeleton pathway and insulin resistance pathway. Conclusion: This study demonstrated that QYG exerted the effect of preventing and treating AD by regulating multi-targets with multi-components. Furthermore, the study demonstrated that a network pharmacology-based approach was useful for elucidation of the interrelationship between complex diseases and interventions of Chinese herbal medicines.

Download Full-text

Network Pharmacology-Based Prediction of the Active Ingredients and Potential Targets of Chinese Herbal Danyu Gukang Pills for Application to Osteonecrosis of the Femoral Head Disease

10.21203/rs.3.rs-143355/v1 ◽

2021 ◽

Author(s):

Yongchang Guo ◽

Dapeng Zhang ◽

Yuju Cao ◽

Xiaoyan Feng ◽

Caihong Shen ◽

...

Keyword(s):

Molecular Docking ◽

Femoral Head ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

In Vitro Experiments ◽

Active Components

Abstract Ethnopharmacological relevanceOsteonecrosis of the femoral head (ONFH) is still a challenge for orthopedists worldwide, which may lead to disability in patients without effective treatment. A newly developed formula of Chinese medicine, Danyu Gukang Pills (DGP), was recognized to be effective for ONFH. Nevertheless, its molecular mechanisms remain to be clarified. MethodsNetwork pharmacology was adopted to detect the mechanism of DGP on ONFH. The compounds of DGP were collected from the online databases, and active components were selected based on their OB and DL index. The potential proteins of DGP were acquired from TCMSP database, while the potential genes of ONFH were obtained from Gene Cards and Pubmed Gene databases. The function of Gene and potential pathways were researched by GO and KEGG pathway enrichment analysis. The compounds-targets and targets-pathways network were constructed in an R and Cytosacpe software. The mechanism was further investigated via molecular docking. Finally, in-vitro experiments were validated in the BMSCs. ResultsA total of 2305 compounds in DGP were gained, among which, 370 were selected as active components for which conforming to criteria. Combined the network analysis, molecular docking and in-vitro experiments, the results firstly demonstrated that the treatment effect of DGP on ONFH may be closely related to HIF-1α, VEGFA and HIF-1 signaling pathway. ConclusionThe current study firstly researched the molecular mechanism of DGP on ONFH based on network pharmacology. The results indicated that DGP may exert the effect on ONFH targeting on HIF-1α and VEGFA via HIF-1 signaling pathway.

Download Full-text

A Network Pharmacology-Based Study on Alzheimer disease prevention and treatment of Qiong Yu Gao

10.21203/rs.2.24495/v1 ◽

2020 ◽

Author(s):

Jieshu You ◽

Chen-yue Li ◽

Wei Chen ◽

Xia-lin Wu ◽

Li-jie Huang ◽

...

Keyword(s):

Signaling Pathway ◽

Molecular Mechanisms ◽

Kegg Pathway ◽

Herbal Medicines ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Integrated Network ◽

Resistance Pathway ◽

Prevention And Treatment

Abstract Background and objective: As the pathological mechanisms of AD is complex, increasing evidence have demonstrated Chinese Medicine with multi-ingredients and multi-targets may be more suitable for the treatment of diseases with complex pathogenesis. Therefore, the study was to preliminarily decipher the bioactive compounds and potential mechanisms of Qiong Yu Gao (QYG) for AD prevention and treatment by an integrated network pharmacology approach. Methods: Putative ingredients of QYG and significant genes of AD were retrieved from public database after screening. Then QYG ingredients target proteins/genes were obtained by target fishing. Compound-target-disease network was constructed using Cytoscape to decipher the mechanism of QYG for AD. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to QYG for AD treatments. Results: Finally, 70 compounds and 511 relative drug targets were collected. In which, 17 representative direct targets were found. Gene ontology enrichment analysis revealed that the adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway was the key biological processes and were regulated simultaneously by the 17 direct targets. KEGG pathway enrichment analysis found that three signaling pathways were closely related with AD treatment by QYG, including PI3K-Akt signaling pathway, regulation of actin cytoskeleton pathway and insulin resistance pathway. Conclusion: This study demonstrated that QYG exerted the effect of treating AD by regulating multi-targets with multi-components. Furthermore, the study demonstrated that a network pharmacology-based approach was useful for elucidation of the interrelationship between complex diseases and interventions of Chinese herbal medicines.

Download Full-text

A Study on the Mechanism of Milkvetch Root in the treatment of Diabetic Nephropathy based on Network Pharmacology

10.21203/rs.3.rs-22529/v1 ◽

2020 ◽

Author(s):

Chunli Piao ◽

Qi Zhang ◽

De Jin ◽

Li Wang ◽

Cheng Tang ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Signaling Pathway ◽

Diabetic Complications ◽

Drug Targets ◽

Topological Analysis ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Systems Pharmacology ◽

Pathway Enrichment

Abstract Background: Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. Milkvetch Root has been extensively used to treat DN in clinical practice in China for many years, but the active ingredients, drug targets, and its exact molecular mechanism are not known. The aim of this study was to decrypt the underlying mechanisms of Milkvetch Root in the treatment of DN by using a systems pharmacology approach. Methods: The components and targets of Milkvetch Root were analyzed using the Traditional Chinese Medicine Systems Pharmacology database. Then we found the common target of Milkvetch Root and disease, constructed a protein-protein interaction (PPI) network using String, and screened the key targets from these common targets through topological analysis. Analyses of enrichment of Gene Ontology (GO) pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Subsequently, the major hubs were imported to the Database for Annotation, Visualization and Integrated Discovery to perform a pathway enrichment analysis. Results: There were 20 active compounds of Milkvetch Root and 10 diabetic nephropathy -associated targets (AKT1, VEGFA, IL6, PPARG, CCL2, NOS3, SERPINE1, CRP, ICAM1, SLC2A4) that were obtained. Then, the results of GO and KEGG pathway enrichment analyses suggested that the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, PI3K-Akt signaling pathway and TNF signaling pathway in diabetic complications might serve as the key points and principal pathways for DN treatment. Conclusions: In brief, Milkvetch Root has multiple components, multiple targets and multiple pharmacological effects in the treatment of DN, which provides clues for further research on DN.

Download Full-text

Utilizing Network Pharmacology to Explore the Possible Mechanism of CoptidisRhizoma in Kawasaki Disease

10.21203/rs.3.rs-90022/v1 ◽

2020 ◽

Author(s):

Xue Fan ◽

Xin Guo ◽

Mingguo Xu

Keyword(s):

Kawasaki Disease ◽

Signaling Pathway ◽

Target Genes ◽

Fluid Shear Stress ◽

Controlled Trial ◽

Enrichment Analysis ◽

Resistance Rate ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Routine Treatment

Abstract Background: Kawasaki disease (KD) isan acute self-limiting systemic vasculitis.In this study, a randomized controlled trial regarding berberine (main component of CoptidisRhizoma) function in treating KD was carried out and possible pharmacological mechanisms of CoptidisRhizoma (CR) on Kawasaki disease therapy were investigated using an integrated network pharmacology approach.Results: The BBR group was able to reduce the values of CRP, NLR and PLR significantly. Also, the effect of BBR improved the resistance rate of intravenous injection of gamma globulin significantly. In total, 9 compounds and 369 relative drug targets were collected from TCMSP, SWISS, SEA and STITCH database and 624 KD target genes were collected in DisGeNET, DrugBank and GeneCards database. The network analysis revealed that 41 targets might be the therapeutic targets of CR on KD, among which ATK1, RELA, SRC, CASP3 and MTOR ranked in top 5. Gene ontology enrichment analysis revealed that the reaction to bacteria-derived molecules and to lipopolysaccharide and the apoptosis process were the key biological procedures for CR treating KD. The KEGG pathway enrichment analysis pointed out that the four signaling pathways closely related to CR treating KD including age-rage signaling pathway, fluid shear stress and atherosclerosis, TNF signaling pathway and Toll-like receptor signaling pathway in diabetic complications.Conclusion: We concluded that the introduction of routine treatment combined with BBR in treating KD has advantages than routine treatment and can be considered as a preferred approach in KD. Network pharmacology showed that CR exerted the effect of prevention KD by regulating multi-targets and multi-components.

Download Full-text

Decoding the Mechanism of Huanglian Jiedu Decoction in Treating Pneumonia Based on Network Pharmacology and Molecular Docking

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.638366 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xianhai Li ◽

Hua Tang ◽

Qiang Tang ◽

Wei Chen

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Clinical Symptoms ◽

Interaction Network ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Interleukin 17 ◽

Active Ingredients ◽

Hub Genes

Huang-Lian-Jie-Du decoction (HLJDD) has been used to treat pneumonia for thousands of years in China. However, our understanding of its mechanisms on treating pneumonia is still unclear. In the present work, network pharmacology was used to analyze the potential active ingredients and molecular mechanisms of HLJDD on treating pneumonia. A total of 102 active ingredients were identified from HLJDD, among which 54 were hit by the 69 targets associated with pneumonia. By performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we obtained the main pathways associated with pneumonia and those associated with the mechanism of HLJDD in the treatment of pneumonia. By constructing the protein–protein interaction network of common targets, 10 hub genes were identified, which were mainly involved in the tumor necrosis factor (TNF) signaling pathway, interleukin 17 (IL-17) signaling pathway, and nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway. Moreover, the results of molecular docking showed that the active ingredients of HLJDD had a good affinity with the hub genes. The final results indicate that HLJDD has a greater effect on bacterial pneumonia than on viral pneumonia. The therapeutic effect is mainly achieved by regulating the host immune inflammatory response and oxidative stress reaction, antibacterial microorganisms, alleviating the clinical symptoms of pneumonia, repairing damaged cells, and inhibiting cell migration.

Download Full-text

Study on Intervention Mechanism of Yiqi Huayu Jiedu Decoction on ARDS Based on Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/4782470 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Xu Liang ◽

Changyong Luo ◽

Yan Li ◽

Xin Li ◽

Qian Wang ◽

...

Keyword(s):

Western Blot ◽

Lung Tissue ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Expression Level ◽

Network Pharmacology ◽

Control Group ◽

Pathway Enrichment Analysis ◽

Protective Effects ◽

Lung Tissue Damage

Background. Yiqi Huayu Jiedu (YQHYJD) is a traditional Chinese medicine decoction made up of eight traditional Chinese medicines. Although YQHYJD is effectively used to prevent and treat ARDS/acute lung injury (ALI) in rats, the molecular mechanisms supporting its clinical application remain elusive. The purpose of the current study was to understand its lung protective effects at the molecular level using network pharmacology approach. Methods. In an ARDS animal model, the beneficial pharmacological activities of YQHYJD were confirmed by reduced lung tissue damage levels observed on drug treated rats versus control group. We then proposed a network analysis to discover the key nodes based on drugs and disease network. Subsequently, we analyzed interaction networks and screened key targets. Using Western blot to detect the expression level of key targets, the intervention effect of changes in expression level of key targets on ARDS was evaluated. Results. Pathway enrichment analysis of highly ranked genes showed that ErbB pathways were highly related to ARDS. Finally, western blot results showed decreased level of the AKT1 and KRAS/NRAS/HRAS protein in the lung after treatment which confirmed the hypothesis. Conclusion. In conclusion, our results suggest that YQHYJD can exert lung tissue protective effect against the severe injury through multiple pathways, including the endothelial cells permeability improvement, inflammatory reaction inhibition, edema, and lung tissue hemorrhage reduction.

Download Full-text

Therapeutic Effects and Molecular Network Mechanism of Chinese herbs for Coronavirus Disease-19

10.21203/rs.3.rs-29056/v1 ◽

2020 ◽

Author(s):

Jingjing Da ◽

Xiangyan Zhang ◽

Fa Sun ◽

Kui Zhang ◽

Xianchun Zeng ◽

...

Keyword(s):

Molecular Mechanisms ◽

Familial Aggregation ◽

Clinical Signs ◽

Enrichment Analysis ◽

Chinese Herbs ◽

Network Pharmacology ◽

Control Group ◽

Therapeutic Effects ◽

Target Network

Abstract Background: The coronavirus disease-19 (COVID-19) outbreak on December 2019.The present study was aimed to explore the therapeutic effects and the network pharmacology mechanism of Chinese herbs in COVID-19 patients.Methods: In this retrospective study, demographic, clinical signs, radiography, and laboratory of 78 patients were analysis from patients' medical records. Network pharmacology was applied to characterize the action mechanism of herbs decoction. Results: Of all patients were imported cases with familial aggregation. Survival analysis showed that the proportion of cough (χ2 =3.864, P=0.049) and fever (χ2 =5.549, P=0.018) in TCM group declined faster than control group. There was a significant radiographic lesions remission difference between groups (χ2 =7.666, P=0.006). After adjusted by baseline data, the changes of Lymphocytes, ALT and LDH were greater in TCM group (P=0.023, 0.005, 0.015, respectively). A total of 1852 ingredients in 13 herbs were obtained, among which, the ingredients-target network included 168 compounds and 189 targets, 38 GO terms and 63 pathways were found in enrichment analysis. Conclusion: The therapeutic effect of Chinese herbs was amelioration of cough and fever, facilitated the absorption of inflammatory infiltrates seen in the lungs, and increased the number of lymphocytes, protection of liver function via the mechanism of inhibition of coronavirus attack organs and immune cells directly. Molecular mechanisms need to be further validate in vitro and vivo.

Download Full-text