scholarly journals Elucidating the Mechanisms of Hugan Buzure Granule in the Treatment of Liver Fibrosis via Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yi Zhu ◽  
Ming Qiao ◽  
Jianhua Yang ◽  
Junping Hu
Keyword(s):  
Liver Fibrosis ◽  
Rna Polymerase Ii ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Docking Simulation ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Transcription Activator ◽  
Active Ingredients ◽  
Oxidoreductase Activity

Objective. To holistically explore the latent active ingredients, targets, and related mechanisms of Hugan buzure granule (HBG) in the treatment of liver fibrosis (LF) via network pharmacology. Methods. First, we collected the ingredients of HBG by referring the TCMSP server and literature and filtered the active ingredients though the criteria of oral bioavailability ≥30% and drug-likeness index ≥0.18. Second, herb-associated targets were predicted and screened based on the BATMAN-TCM and SwissTargetPrediction platforms. Candidate targets related to LF were collected from the GeneCards and OMIM databases. Furthermore, the overlapping target genes were used to construct the protein-protein interaction network and “drug-compound-target-disease” network. Third, GO and KEGG pathway analyses were carried out to illustrate the latent mechanisms of HBG in the treatment of LF. Finally, the combining activities of hub targets with active ingredients were further verified based on software AutoDock Vina. Results. A total of 25 active ingredients and 115 overlapping target genes of HBG and LF were collected. Besides, GO enrichment analysis exhibited that the overlapping target genes were involved in DNA-binding transcription activator activity, RNA polymerase II-specific, and oxidoreductase activity. Simultaneously, the key molecular mechanisms of HBG against LF were mainly involved in PI3K-AKT, MAPK, HIF-1, and NF-κB signaling pathways. Also, molecular docking simulation demonstrated that the key targets of HBG for antiliver fibrosis were IL6, CASP3, EGFR, VEGF, and MAPK. Conclusion. This work validated and predicted the underlying mechanisms of multicomponent and multitarget about HBG in treating LF and provided a scientific foundation for further research.

scholarly journals Insights into the molecular mechanisms of Huangqi decoction on liver fibrosis via computational systems pharmacology approaches

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Biting Wang ◽  
Zengrui Wu ◽  
Weihua Li ◽  
Guixia Liu ◽  
Yun Tang
Keyword(s):  
Molecular Docking ◽  
Liver Fibrosis ◽  
Molecular Mechanisms ◽  
Docking Simulation ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Bipartite Network ◽  
Metabolomics Data ◽  
Metabolic Products ◽  
Compound Target

Abstract Background The traditional Chinese medicine Huangqi decoction (HQD) consists of Radix Astragali and Radix Glycyrrhizae in a ratio of 6: 1, which has been used for the treatment of liver fibrosis. In this study, we tried to elucidate its action of mechanism (MoA) via a combination of metabolomics data, network pharmacology and molecular docking methods. Methods Firstly, we collected prototype components and metabolic products after administration of HQD from a publication. With known and predicted targets, compound-target interactions were obtained. Then, the global compound-liver fibrosis target bipartite network and the HQD-liver fibrosis protein–protein interaction network were constructed, separately. KEGG pathway analysis was applied to further understand the mechanisms related to the target proteins of HQD. Additionally, molecular docking simulation was performed to determine the binding efficiency of compounds with targets. Finally, considering the concentrations of prototype compounds and metabolites of HQD, the critical compound-liver fibrosis target bipartite network was constructed. Results 68 compounds including 17 prototype components and 51 metabolic products were collected. 540 compound-target interactions were obtained between the 68 compounds and 95 targets. Combining network analysis, molecular docking and concentration of compounds, our final results demonstrated that eight compounds (three prototype compounds and five metabolites) and eight targets (CDK1, MMP9, PPARD, PPARG, PTGS2, SERPINE1, TP53, and HIF1A) might contribute to the effects of HQD on liver fibrosis. These interactions would maintain the balance of ECM, reduce liver damage, inhibit hepatocyte apoptosis, and alleviate liver inflammation through five signaling pathways including p53, PPAR, HIF-1, IL-17, and TNF signaling pathway. Conclusions This study provides a new way to understand the MoA of HQD on liver fibrosis by considering the concentrations of components and metabolites, which might be a model for investigation of MoA of other Chinese herbs.

scholarly journals A Network Pharmacology-Based Study on the Anti-Lung Cancer Effect of Dipsaci Radix

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Jiayan Wu ◽  
Shengkun Hong ◽  
Xiankuan Xie ◽  
Wangmi Liu
Keyword(s):  
Lung Cancer ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Active Compounds

Objective. Dipsaci Radix (DR) has been used to treat fracture and osteoporosis. Recent reports have shown that myeloid cells from bone marrow can promote the proliferation of lung cancer. However, the action and mechanism of DR has not been well defined in lung cancer. The aim of the present study was to define molecular mechanisms of DR as a potential therapeutic approach to treat lung cancer. Methods. Active compounds of DR with oral bioavailability ≥30% and drug-likeness index ≥0.18 were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform. The potential target genes of the active compounds and bone were identified by PharmMapper and GeneCards, respectively. The compound-target network and protein-protein interaction network were built by Cytoscape software and Search Tool for the Retrieval of Interacting Genes webserver, respectively. GO analysis and pathway enrichment analysis were performed using R software. Results. Our study demonstrated that DR had 6 active compounds, including gentisin, sitosterol, Sylvestroside III, 3,5-Di-O-caffeoylquinic acid, cauloside A, and japonine. There were 254 target genes related to these active compounds as well as to bone. SRC, AKT1, and GRB2 were the top 3 hub genes. Metabolisms and signaling pathways associated with these hub genes were significantly enriched. Conclusions. This study indicated that DR could exhibit the anti-lung cancer effect by affecting multiple targets and multiple pathways. It reflects the traditional Chinese medicine characterized by multicomponents and multitargets. DR could be considered as a candidate for clinical anticancer therapy by regulating bone physiological functions.

scholarly journals Potential Molecular Target Prediction and Docking Verification of Hua-Feng-Dan in Stroke Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Ping Yang ◽  
Haifeng He ◽  
Shangfu Xu ◽  
Ping Liu ◽  
Xinyu Bai
Keyword(s):  
Molecular Docking ◽  
Signaling Pathways ◽  
Target Genes ◽  
Target Prediction ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Core Network ◽  
Active Ingredients ◽  
Protein Protein Interaction ◽  
Highly Correlated

Objective. Hua-Feng-Dan (HFD) is a Chinese medicine for stroke. This study is to predict and verify potential molecular targets and pathways of HFD against stroke using network pharmacology. Methods. The TCMSP database and TCMID were used to search for the active ingredients of HFD, and GeneCards and DrugBank databases were used to search for stroke-related target genes to construct the “component-target-disease” by Cytoscape 3.7.1, which was further filtered by MCODE to build a core network. The STRING database was used to obtain interrelationships by topology and to construct a protein-protein interaction network. GO and KEGG were carried out through DAVID Bioinformatics. Autodock 4.2 was used for molecular docking. BaseSpace was used to correlate target genes with the GEO database. Results. Based on OB ≥ 30% and DL ≥ 0.18, 42 active ingredients were extracted from HFD, and 107 associated targets were obtained. PPI network and Cytoscape analysis identified 22 key targets. GO analysis suggested 51 cellular biological processes, and KEGG suggested that 60 pathways were related to the antistroke mechanism of HFD, with p53, PI3K-Akt, and apoptosis signaling pathways being most important for HFD effects. Molecular docking verified interactions between the core target (CASP8, CASP9, MDM2, CYCS, RELA, and CCND1) and the active ingredients (beta-sitosterol, luteolin, baicalein, and wogonin). The identified gene targets were highly correlated with the GEO biosets, and the stroke-protection effects of Xuesaitong in the database were verified by identified targets. Conclusion. HFD could regulate the symptoms of stroke through signaling pathways with core targets. This work provided a bioinformatic method to clarify the antistroke mechanism of HFD, and the identified core targets could be valuable to evaluate the antistroke effects of traditional Chinese medicines.

scholarly journals Deciphering of Key Pharmacological Pathways of Poria Cocos Intervention in Breast Cancer Based on Integrated Pharmacological Method

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xiaoran Ma ◽  
Jibiao Wu ◽  
Cun Liu ◽  
Jie Li ◽  
Shixia Dong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Network Pharmacology ◽  
Breast Cancers ◽  
Active Ingredients ◽  
Poria Cocos ◽  
Pharmacological Method

Objective. Poria cocos (Fuling), a natural plant, has recently emerged as a promising strategy for cancer treatment. However, the molecular mechanisms of Poria cocos action in breast cancer remain poorly understood. Methods. TCMSP database was used to screen the potential active ingredients in Poria cocos. GEO database was used to identify differentially expressed genes. Network pharmacology was used to identify the specific pathways and key target proteins related to breast cancer. Finally, molecular docking was used to validate the results. Results. In our study, 237 targets were predicted for 15 potential active ingredients found in Poria cocos. An interaction network of predicted targets and genes differentially regulated in breast cancers was constructed. Based on the constructed network and further analysis including network topology, KEGG, survival analysis, and gene set enrichment analysis, 3 primary nodes were identified as key potential targets that were significantly enriched in the PPAR signaling pathway. Conclusion. The results showed that potential active ingredients of Poria cocos might interfere with breast cancer through synergistic regulation of PTGS2, ESR1, and FOS.

scholarly journals Based on Network Pharmacology Tools to Investigate the Molecular Mechanism of Cordyceps sinensis on the Treatment of Diabetic Nephropathy

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yan Li ◽  
Lei Wang ◽  
Bojun Xu ◽  
Liangbin Zhao ◽  
Li Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Diabetic Nephropathy ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Cordyceps Sinensis ◽  
Network Pharmacology ◽  
Active Ingredients

Background. Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus and is a major cause of end-stage kidney disease. Cordyceps sinensis (Cordyceps, Dong Chong Xia Cao) is a widely applied ingredient for treating patients with DN in China, while the molecular mechanisms remain unclear. This study is aimed at revealing the therapeutic mechanisms of Cordyceps in DN by undertaking a network pharmacology analysis. Materials and Methods. In this study, active ingredients and associated target proteins of Cordyceps sinensis were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Swiss Target Prediction platform, then reconfirmed by using PubChem databases. The collection of DN-related target genes was based on DisGeNET and GeneCards databases. A DN-Cordyceps common target interaction network was carried out via the STRING database, and the results were integrated and visualized by utilizing Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the molecular mechanisms and therapeutic effects of Cordyceps on the treatment of DN. Results. Seven active ingredients were screened from Cordyceps, 293 putative target genes were identified, and 85 overlapping targets matched with DN were considered potential therapeutic targets, such as TNF, MAPK1, EGFR, ACE, and CASP3. The results of GO and KEGG analyses revealed that hub targets mainly participated in the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. These targets were correlated with inflammatory response, apoptosis, oxidative stress, insulin resistance, and other biological processes. Conclusions. Our study showed that Cordyceps is characterized as multicomponent, multitarget, and multichannel. Cordyceps may play a crucial role in the treatment of DN by targeting TNF, MAPK1, EGFR, ACE, and CASP3 signaling and involved in the inflammatory response, apoptosis, oxidative stress, and insulin resistance.

scholarly journals Aberrant expression of BDNF might serve as a candidate target for cocaine-induced psychosis: insights from bioinformatics analysis and microarray validation

2021 ◽  
Vol 34 (5) ◽  
pp. e100587
Author(s):  
Youwei Zhu ◽  
Yan Zhao ◽  
Xiaomin Xu ◽  
Hang Su ◽  
Xiaotong Li ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Treatment Options ◽  
Interaction Network ◽  
Mendelian Inheritance ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Aberrant Expression ◽  
Holistic View ◽  
Risk Genes

BackgroundCocaine use disorder (CUD) and associated psychosis are major public health issues worldwide, along with high relapse outcome and limited treatment options. Exploring the molecular mechanisms underlying cocaine-induced psychosis (CIP) could supply integrated insights for understanding the pathogenic mechanism and potential novel therapeutic targets.AimsThe aim of the study was to explore common alterations of CUD-schizophrenia-target genes and identify core risk genes contributing to CIP through data mining and network pharmacology approach.MethodsTarget genes of CUD were obtained from GeneCards, Comparative Toxicogenomics Database, Swiss Target Prediction platform and PubChem. Schizophrenia-related target genes were derived from DisGeNET, GeneCards, MalaCards and Online Mendelian Inheritance in Man databases. Then, the overlap genes of these two sets were regarded as risk genes contributing to CIP. Based on these CUD-schizophrenia-target genes, functional annotation and pathway analysis were performed using the clusterProfiler package in R. Protein–protein interaction network construction and module detection were performed based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. Gene expression datasets GSE54839 and GSE93577 were applied for data validation and diagnostic capacity evaluation of interested hub genes.ResultsA total of 165 CUD-schizophrenia-target genes were obtained. These genes were mainly contributing to chemical synaptic transmission, neuropeptide hormone activity, postsynaptic membrane and neuroactive ligand–receptor interaction pathway. Network analysis and validation analysis indicated that BDNF might serve as an important risk gene in mediating CIP.ConclusionsThis study generates a holistic view of CIP and provides a basis for the identification of potential CUD-schizophrenia-target genes involved in the development of CIP. The abnormal expression of BDNF would be a candidate therapeutic target underlying the pathogenesis of CUD and associated CIP.

scholarly journals Network Pharmacological Study of Achyranthis bidentatae Radix Effect on Bone Trauma

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Liying Wu ◽  
Youguo Hao ◽  
Chuanqiang Dai ◽  
Zhibang Zhang ◽  
Munazza Ijaz ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Pharmacological Study ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Docking Studies ◽  
Network Pharmacology ◽  
Extensive Literature ◽  
Positive Regulation ◽  
Oxidoreductase Activity ◽  
Bone Trauma

Purpose. Bone trauma is a clinical condition that afflicts the majority of the world’s population. For the management of bone trauma, the underlying mechanisms of the drugs effective for bone healing are deemed necessary. Achyranthis bidentatae Radix (ABR) is a popular alternative medicine recommended in the treatment of bone trauma and injury, yet its mechanism of action persists to be vague. This study was conducted for the evaluation of the mode of action of ABR through network pharmacology in treating bone trauma. Methods. An extensive survey of published works led to the development of a drug-target database, after which multiple protein targets for bone trauma were discerned. The protein-protein interaction network was developed by utilizing the STITCH database and gene ontology (GO) enrichment analysis using Cytoscape and ClueGO. Moreover, docking studies were performed for revealing the affinity of various ingredients with IL6. Results. The extensive literature survey yielded the presence of 176 components in ABR, and 151 potential targets were acquired. Scrutinization of these targets revealed that 21 potential targets were found to be associated with bone trauma. Out of which, some remarkable targets such as IL6, MAPK14, MAPK8, SRC, PTGS2, and MMP2 were observed to be associated in the functional interaction of ABR. According to docking results, several ingredients of ABR such as Baicalien, Copistine, Epiberberine, Kaempferol, and Palmatine have the lowest docking scores (range between -6 and -7). Conclusions. The results of the study elucidated that ABR can positively be utilized for the management of bone trauma, which can be mediated by multiple molecular mechanisms such as ERBB2 signaling pathway, positive regulation of oxidoreductase activity, JNK cascade pathway, multicellular organism metabolic process, T cell costimulation, and the positive regulation of MAPK activity. The findings also suggest that several ingredients of ABR such as Baicalien, Copistine, Epiberberine, Kaempferol, and Palmatine have good affinity with IL6, suggesting the promising potential of ABR in treating bone trauma, likely through IL6.

Exploration of  the mechanism of Ziyin Tongluo Formula on preventing and treating postmenopausal osteoporosis based on the network pharmacology

2020 ◽  
Author(s):  
Rong-Bin Chen ◽  
Ying-Dong Yang ◽  
Kai Sun ◽  
Shan Liu ◽  
Wei Guo ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Postmenopausal Osteoporosis ◽  
Target Genes ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Regulation Of Transcription ◽  
Active Ingredients ◽  
Active Components ◽  
Kegg Pathways ◽  
Key Genes

Abstract Background Postmenopausal osteoporosis (PMOP) is a global chronic and metabolic bone disease that poses huge challenges to individuals and society. Previous studies have confirmed that Ziyin Tongluo Formula (ZYTLF) has a good clinical effect in the treatment of PMOP. However, the material basis and mechanism of ZYLTF against PMOP has not been thoroughly explained. Methods TCMSP, TCMID, and BATMAN-TCM databases were used to identify the active ingredients and their putative targets. Genes associated with PMOP were mined from GeneCards, OMIM, DisGeNET databases, and then mapped with the putative targets to obtain overlapping target genes. A network model of "herb-active ingredient-overlapping target genes" was constructed and a protein-protein interaction network of overlapping target genes was built and the key genes were selected based on the MCC algorithm. The key genes were imported to the DAVID database to performs GO and KEGG pathway enrichment analyses. Results Ninety-two active components of ZYTLF corresponded to 243 targets, with 129 target genes interacting with PMOP, and 50 key genes were selected. GO analysis results showed that biological process mainly included positive regulation of transcription, negative regulation of apoptosis, and cell components were mainly nucleus, cytoplasm, and molecular functions mainly included enzyme binding, protein binding and transcription factor binding. There were two main types of significant KEGG pathways in PMOP, hormone-related signaling pathways (estrogen, prolactin, thyroid hormone) and inflammation-related pathways (TNF, PI3K-Akt, MAPK ). Conclusions The underlying therapeutic mechanisms of ZYTLF action on PMOP maybe is that, the active ingredients such as quercetin, kaempferol, luteolin act on ESR1, TNF, IL6, MAPK8 and other key genes, which mainly enrich in estrogen, TNF, PI3K-Akt, MAPK and other signaling pathways.

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

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.

Discussion on the Mechanism of Lithospermum erythrorhizon in the Treatment of Cervical Cancer Based on Network Pharmacology and Molecular Docking Technology

2021 ◽  
Vol 7 (5) ◽  
pp. 3927-3933
Author(s):  
Qiong Yan ◽  
Fangwu Ye
Keyword(s):  
Cervical Cancer ◽  
Molecular Docking ◽  
Drug Targets ◽  
Target Genes ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Drug Candidate ◽  
Pathway Enrichment Analysis ◽  
Active Ingredients ◽  
Stable Conformation

Objective To explore the “multi-component, multi-target, multi-pathway” mechanism of Lithospermum erythrorhizonagairtst cervical cancer. Methods The active ingredients and corresponding targets were screened through TCMSP, PubChem and SwissTargetPrediction databases. The GeneCarts platform was used to collect cervical cancer-related genes, and the intersection of drug targets and cervical cancer targets was analyzed. Use STRING to analyze protein interaction network, use Cytoscape software to construct component-target and core target interaction network, perform KEGG pathway enrichment analysis on core target genes, and conduct molecular docking verification.Results After screening, 12 main active ingredients of comfrey (including Shikonin A, 1-methoxyacetylshikonin, Shikonin B, etc.) and 35 key targets related to comfrey and cervical cancer were obtained (including ESR1, SRC, MMP9, PTGS2, etc.). And these genes were mainly enriched in 39 signaling pathways such as PI3K-Akt and estrogen. Molecular docking reminder that Lithospermum A has a higher affinity with ESR1, and Lithospermum B can form a stable conformation with SRC, MMP9, and PTGS2. Conclusion Lithospermum erythrorhizon is a potential drug candidate for the treatment of cervical cancer. It can treat cervical cancer through multi-component, multi-target, and multi-channel action.

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