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1.
Medicine (Baltimore) ; 101(35): e30096, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107605

RESUMO

This study aimed to explore the effectiveness and safety of Sishen pills for the treatment of diarrheal diabetic enteropathy (DDE). The Traditional Chinese Medicine (TCM) Systems Pharmacology and BATMAN-TCM databases were used to determine the chemical composition of Sishen pills and thus predict information on protein targets. We searched for potential targets of DDE in the GeneCards, DrugBank, Therapeutic Target (TTD), and DisGeNET databases. Using the intersection of the drug and disease targets, protein-protein interaction (PPI) networks and molecular interaction modules were constructed, and key targets were screened. The intersecting gene targets were imported into the Metascape database to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The core targets and active ingredients were then docked at the molecular level. Sishen pills contain 70 active ingredients, 463 targets, and 566 disease targets. A module analysis of the targets revealed that the module was mainly related to adrenergic receptor activity, the adenosine phosphate kinase signaling pathway, and the G protein-coupled receptor signaling pathway. The GO and KEGG pathway enrichment results indicated that the protein genes regulated by Sishen pills were mainly enriched in the response to lipopolysaccharides, the AMPK signaling pathway, the JAK-STAT signaling pathway, and other signaling pathways. The molecular docking results showed that the core active compounds exhibited good binding activity with the predicted targets. Sishen pills can regulate the immune function of the body through anti-inflammatory and antibacterial effects for the treatment of DDE.


Assuntos
Diabetes Mellitus , Medicamentos de Ervas Chinesas , Proteínas Quinases Ativadas por AMP , Nucleotídeos de Adenina , Antibacterianos/uso terapêutico , Anti-Inflamatórios , Diabetes Mellitus/tratamento farmacológico , Diarreia/tratamento farmacológico , Diclorodifenil Dicloroetileno , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Receptores Adrenérgicos , Receptores Acoplados a Proteínas G
2.
PLoS One ; 17(9): e0273498, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36094934

RESUMO

OBJECTIVE: In this study, we used network pharmacology to explore the possible therapeutic mechanism underlying the treatment of diabetic nephropathy with Yishen capsules. METHODS: The active chemical constituents of Yishen capsules were acquired using the Traditional Chinese Medicine Systems Pharmacology platform and the Encyclopedia of Traditional Chinese Medicine. Component target proteins were then searched and screened in the BATMAN database. Target proteins were cross-validated using the Comparative Toxicogenomics Database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the target proteins were performed. Then, protein-protein interaction (PPI) analysis was performed using the STRING database. Finally, a pharmacological network was constructed to show the component-target-pathway relationships. Molecular docking was used to analyse the interaction between drug components and target proteins. RESULTS: In total, 285 active chemical components were found, including 85 intersection targets against DN. In the pharmacological network, 5 key herbs (A. membranaceus, A. sinensis, E. ferox, A. orientale, and R. rosea) and their corresponding 12 key components (beta-sitosterol, beta-carotene, stigmasterol, alisol B, mairin, quercetin, caffeic acid, 1-monolinolein, kaempferol, jaranol, formononetin, and calycosin) were screened. Furthermore, the 12 key components were related to 24 target protein nodes (e.g., AGT, AKT1, AKT2, BCL2, NFKB1, and SIRT1) and enriched in 24 pathway nodes (such as the NF-kappa B, AGE-RAGE, toll-like receptor, and relaxin signaling pathways). Molecular docking revealed that hydrogen bond was formed between drug components and target proteins. CONCLUSION: In conclusion, the active constituents of Yishen capsules modulate targets or signaling pathways in DN pathogenesis.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Cápsulas , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede
3.
Front Cell Infect Microbiol ; 12: 964469, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046748

RESUMO

Hepatocellular carcinoma (HCC) is a serious global health problem, and hepatitis B virus (HBV) infection remains the leading cause of HCC. It is standard care to administer antiviral treatment for HBV-related HCC patients with concurrent anti-cancer therapy. However, a drug with repressive effects on both HBV infection and HCC has not been discovered yet. In addition, drug resistance and side effects have made existing therapeutic regimens suboptimal. Traditional Chinese medicine (TCM) has multi-ingredient and multi-target advantages in dealing with multifactorial HBV infection and HCC. TCM has long been served as a valuable source and inspiration for discovering new drugs. In present study, a target-driven reverse network pharmacology was applied for the first time to systematically study the therapeutic potential of TCM in treating HBV-related HCC. Firstly, 47 shared targets between HBV and HCC were screened as HBV-related HCC targets. Next, starting from 47 targets, the relevant chemical components and herbs were matched. A network containing 47 targets, 913 chemical components and 469 herbs was established. Then, the validated results showed that almost 80% of the herbs listed in chronic hepatitis B guidelines and primary liver cancer guidelines were included in the 469 herbs. Furthermore, functional analysis was conducted to understand the biological processes and pathways regulated by these 47 targets. The docking results indicated that the top 50 chemical components bound well to targets. Finally, the frequency statistical analysis results showed the 469 herbs against HBV-related HCC were mainly warm in property, bitter in taste, and distributed to the liver meridians. Taken together, a small library of 913 chemical components and 469 herbs against HBV-related HCC were obtained with a target-driven approach, thus paving the way for the development of therapeutic modalities to treat HBV-related HCC.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Vírus da Hepatite B , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Medicina Tradicional Chinesa/efeitos adversos , Farmacologia em Rede
4.
Mol Med Rep ; 26(5)2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36052855

RESUMO

Resveratrol (Res) serves a protective role in hepatic, cardiovascular and autoimmune hypertrophic disease. However, the mechanisms by which Res ameliorates cardiac hypertrophy have not yet been fully elucidated. In the present study, network pharmacology was used to construct a network and perform enrichment analysis to evaluate the effect of Res on cardiac hypertrophy. Experimental validation was performed using 40 Sprague­Dawley rats administered intragastric 80 mg/kg/day Res and 20 mg/kg/day 3­methyladenine (3­MA) for 4 weeks. A total of 444 targets associated with cardiac hypertrophy and 229 potential disease­associated targets of Res were identified, from which 8 overlapping genes were demonstrated. Gene Ontology function and 'Kyoto Encyclopedia of Genes and Genomes' pathway enrichment analysis demonstrated that Res affected STAT3 and was associated with autophagy signaling pathways, including 'negative regulation of autophagy for hypertrophic cardiomyopathy'. Furthermore, Res ameliorated isoprenaline­induced cardiac hypertrophy, significantly improving cardiac dysfunction in vivo experiment (echocardiography, the degree of ventricular hypertrophy, etc.); this effect may be associated with regulation of autophagy and apoptosis. The autophagy inhibitor 3­MA markedly reversed the anti­cardiac hypertrophy effects of Res. In conclusion, Res inhibited cardiac hypertrophy via downregulation of the apoptosis signaling pathway and upregulating the autophagy pathway.


Assuntos
Experimentação Animal , Animais , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Farmacologia em Rede , Ratos , Ratos Sprague-Dawley , Resveratrol/farmacologia
5.
Comput Math Methods Med ; 2022: 7364126, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105239

RESUMO

Objective: To explore the molecular targets and mechanism of YuPingFeng (YPF) for the treatment of asthma by using network pharmacology and molecular docking. Methods: The potential active ingredients and relevant targets of YPF were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Asthma-related gene targets were retrieved from GeneCards, OMIM, DrugBank, PharmGKB, and TTD databases. The protein-protein (PPI) network between YPF and asthma common targets was constructed by SRING online database and Cytoscape software. GO and KEGG analyses were performed to explore the complicated molecular biological processes and potential pathways. Finally, a molecular docking approach was carried out to verify the results. Results: We obtained 100 potential targets of the 35 active ingredients in YPF and 1610 asthma-related targets. 60 YPF-asthma common targets were selected to perform PPI analysis. Seven core genes were screened based on two topological calculation methods. GO and KEGG results showed that the main pathways of YPF in treating asthma include TNF signaling pathway and PI3K-Akt signaling pathway. Finally, the molecular docking results indicated that the key ingredients of YPF had a good affinity with the relevant core genes. Conclusion: This study reflects the multicomponent, multitarget, and multipathway characteristics of YPF in treating asthma, providing a theoretical and scientific basis for the intervention of asthma by traditional Chinese medicine YPF.


Assuntos
Asma , Fosfatidilinositol 3-Quinases , Asma/tratamento farmacológico , Asma/genética , Medicamentos de Ervas Chinesas , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Tecnologia
6.
J Healthc Eng ; 2022: 2457706, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061816

RESUMO

Objective: This study aimed to determine the active ingredients of Huanglian Jiedu decoction (HLJDD) and the targets for treating dyslipidemia through network pharmacology to facilitate further application of HJJDD in the treatment of dyslipidemia. Methods: Potential drug targets for dyslipidemia were identified with a protein-protein interaction network. Gene ontology (GO) enrichment analysis and KEGG pathway analysis were performed to elucidate the biological function and major pathways involved in the HLJDD-mediated treatment of dyslipidemia. Results: This approach revealed 22 components, 234 targets of HLJDD, and 221 targets of dyslipidemia. There were 14 components and 31 common targets between HLJDD and dyslipidemia treatment. GO enrichment analysis showed that these targets were mainly associated with the response to DNA-binding transcription factor activity, lipid localization and storage, reactive oxygen species metabolic process, and inflammatory response. The results of KEGG analysis indicated that the AGE-RAGE, NF-κB, HIF-1, IL-17, TNF, FoxO, and PPAR signalling pathways were enriched in the antidyslipidemic action of HLJDD. Conclusion: This study expounded the pharmacological actions and molecular mechanisms of HLJDD in treating dyslipidemia from a holistic perspective, which may provide a scientific basis for the clinical application of HLJDD.


Assuntos
Medicamentos de Ervas Chinesas , Dislipidemias , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Dislipidemias/tratamento farmacológico , Humanos , Farmacologia em Rede , Mapas de Interação de Proteínas
7.
Biomed Res Int ; 2022: 3353464, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046450

RESUMO

Primary hypertension is understood as a disease with diverse etiology, a complicated pathological mechanism, and progressive changes. Gedan Jiangya Decoction (GJD), with the patent publication number CN114246896A, was designed to treat primary hypertension. It contains six botanical drugs; however, the underlying mechanism is uncertain. We utilized network pharmacology to predict the active components, targets, and signaling pathways of GJD in the treatment of primary hypertension. We also investigated the potential molecular mechanism using molecular docking and animal experiments. The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Protein Database (UniProt), and a literature review were used to identify the active components and related targets of GJD's pharmacological effects. The GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and DrugBank databases were utilized to identify hypertension-related targets. Based on a Venn diagram of designed intersection targets, 214 intersection targets were obtained and 35 key targets for the treatment of hypertension were determined using the STRING data platform and Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of key targets revealed that the relevant molecular action pathways of GJD in the treatment of hypertension include the Toll-like receptor, MAPK, PI3K-Akt, and renin-angiotensin signaling pathways. A GJD active ingredient-key target-pathway connection diagram was created using Cytoscape software, and 11 essential active components were selected. Molecular docking was then used to verify the binding activity of key targets and key active ingredients in GJD to treat primary hypertension. The results of this study indicate that AGTR1, AKT1 with puerarin, EDNRA with tanshinone IIA, MAPK14 with daidzein, MAPK8 with ursolic acid, and CHRM2 with cryptotanshinone had high binding activity to the targets with active components, whereas AGTR1 was selected as target genes verified by our experiment. HPLC was utilized to identify the five active ingredients. Experiments in high-salt rats demonstrated that GJD might decrease the expression of AGTR1 in the kidney and thoracic aorta while increasing the expression of eNOS by preventing the activation of the renin-angiotensin pathway, thereby reducing lowering systolic and diastolic blood pressure.


Assuntos
Medicamentos de Ervas Chinesas , Hipertensão , Angiotensinas/uso terapêutico , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Ratos , Renina
8.
J Tradit Chin Med ; 42(5): 788-794, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36083487

RESUMO

OBJECTIVE: To study therapeutic effect of kaempferol on metabolic associated fatty liver disease (MAFLD) by network pharmacology and molecular docking combined with cell experiments. METHODS: First, use the SwissTargetPrediction database to predict the targets of kaempferol, and collect the targets of MAFLD through the Disgenet database and the GeneCards database. Then, the common target of kaempferol and MAFLD was enriched and analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes, and the protein-protein interaction (PPI) network was constructed through the string database to obtain the key targets, and carry out molecular docking of key targets with kaempferol; In cell experiment, oleic acid induced steatosis in HepG2 cells, which was intervened by kaempferol, the level of triglyceride (TG) was detected, the lipid deposition was observed by oil red O staining, and the protein expression was detected by Western blot. RESULTS: The results showed that there are 33 common targets for kaempferol and MAFLD. The biological process of GO is related to the regulation of protein kinase B, cell apoptosis, inflammatory factors, lipoxygenase, etc. Its action pathway is related to the phosphatidylinositol-3-kinase and protein kinase B (PI3K-AKT) signaling pathway, hypoxia-inducible factor 1 signaling pathway, forkhead box protein O signaling pathway, AMP-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, etc., the key targets are protein kinase B (AKT1), pros-taglandin G/H synthase 2, matrix metalloproteinase-9, epidermal growth factor receptor, and the molecular docking of kaempferol with the four key targets shows good binding properties. Cell experiments show that kaempferol can reduce cell TG levels, reduce lipid deposition, increase the expression of PI3K, AKT, and beclin-1, and reduce the expression of caspase-3 and nuclear factor-kappa B. Kaempferol can treat MAFLD by regulating the PI3K-AKT signaling pathway to regulate cell autophagy, apoptosis, and inflammation. CONCLUSIONS: This study shows that kaempferol can regulate lipid metabolism, reduce apoptosis, regulate inflammation and autophagy in the fatty liver cell model. It reveals the therapeutic mechanism of kaempferol on MAFLD and provides a natural product candidate for the treatment of MAFLD.


Assuntos
Medicamentos de Ervas Chinesas , Hepatopatias , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Lipídeos , Hepatopatias/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
9.
Medicine (Baltimore) ; 101(36): e30411, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086754

RESUMO

BACKGROUND: The aim of this study was to shed light on the active ingredients and potential targets of Cassia Seed about anti-atherosclerosis based on network pharmacology. METHODS: The active ingredients and potential targets of Cassia Seed were obtained from traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction database. Then, atherosclerosis-related targets were screened via GeneCards, online mendelian inheritance in man, therapeutic target database and DrugBank database. The common targets and protein-protein interaction (PPI) network was later identified and built. Furthermore, we used the database for annotation, visualization and integrated discovery (DAVID) database server to accomplish the enrichment analysis. The compounds-targets-pathways network was ultimately constructed by Cytoscape. RESULTS: A total of 14 active ingredients and 475 related targets were sifted from Cassia Seed. Among 574 potential atherosclerotic targets, there were 99 targets overlapped with those of Cassia Seed. Topological analysis with Cytoscape revealed that proto-oncogene tyrosine-protein kinase proto-oncogene tyrosine-protein kinase Src, transcription factor AP-1 (JUN), mitogen-activated protein kinase 8 (MAPK8), mitogen-activated protein kinase 14 (MAPK14) and catenin beta-1 were considered as the hub gene. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis suggested that the Cassia Seed had the potential to influence varieties of biological processes and pathways, including positive regulation of smooth muscle cell proliferation, inflammatory response, tumor necrosis factor (TNF) signaling pathway, vascular endothelial growth factor (VEGF) signaling pathway and arachidonic acid (ARA) metabolism. CONCLUSION: Taken together, our findings support that anti-atherosclerosis effects of Cassia Seed are characterized by multi-component, multi-target and multi-path mechanism of action.


Assuntos
Cassia , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Proteínas Quinases Ativadas por Mitógeno , Farmacologia em Rede , Sementes , Tirosina , Fator A de Crescimento do Endotélio Vascular
10.
Endokrynol Pol ; 73(4): 725-735, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059165

RESUMO

INTRODUCTION: Yerba mate is widely consumed in South American countries and is gaining popularity around the world. Long-term consumption of yerba mate has been proven to have health-care functions and therapeutic effects on many diseases; however, its underlying mechanism has not been clearly elucidated. In this research, we explored the pharmacological mechanism of yerba mate through a network pharmacological approach. MATERIAL AND METHODS: The bioactive components of yerba mate were screened from published literature and the Traditional Chinese Medicine System Pharmacology Database (TCMSP), and the targets and related diseases were retrieved by TCMSP. Furthermore, the component-target-disease network an protein-protein interaction (PPI) network were constructed, and combined with gene ontology (GO) functional analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis to explore the pharmacological mechanism of yerba mate. RESULTS: As a result, 16 bioactive components of yerba mate were identified, which acted on 229 targets in total. Yerba mate can be used to treat 305 diseases, such as breast cancer, asthma, Alzheimer's disease, osteoarthritis, diabetes mellitus, atherosclerosis, and obesity. Protein kinase B (AKT1), signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase 1 (MAPK1), transcription factor AP-1 (JUN), cellular tumour antigen (p53) TP53, tumour necrosis factor (TNF), transcription factor p65 (RELA), interleukin-6 (IL6), amyloid-beta precursor protein (APP), and vascular endothelial growth factor A (VEGFA) were identified as the key targets of yerba mate playing pharmacological roles. The signalling pathways identified by KEGG pathway enrichment analysis that were most closely related to the effects of yerba mate included pathways in cancer, fluid shear stress and atherosclerosis, and human cytomegalovirus infection. CONCLUSION: the results of our study preliminarily verify the basic pharmacological action and possible mechanism of yerba mate and provide a reference for the further development of its medicinal value.


Assuntos
Aterosclerose , Ilex paraguariensis , Neoplasias , Humanos , Farmacologia em Rede , Fator A de Crescimento do Endotélio Vascular
11.
Oxid Med Cell Longev ; 2022: 2896049, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36062197

RESUMO

Background: Compound fuling granule (CFG) is a traditional Chinese medicine formula that is used for more than twenty years to treat ovarian cancer (OC) in China. However, the underlying processes have yet to be completely understood. This research is aimed at uncovering its molecular mechanism and identifying possible therapeutic targets. Methods: Significant genes were collected from Therapeutic Target Database and Database of Gene-Disease Associations. The components of CFG were analyzed by LC-MS/MS, and the active components of CFG were screened according to their oral bioavailability and drug-likeness index. The validated targets were extracted from PharmMapper and PubChem databases. Venn diagram and STRING website diagrams were used to identify intersection targets, and a protein-protein interaction network was prepared using STRING. The ingredient-target network was established using Cytoscape. Molecular docking was performed to visualize the molecule-protein interactions using PyMOL 2.3. Enrichment and pathway analyses were performed using FunRich software and Reactome pathway, respectively. Experimental validations, including CCK-8 assay, wound-scratch assay, flow cytometry, western blot assay, histopathological examination, and immunohistochemistry, were conducted to verify the effects of CFG on OC cells. Results: A total of 56 bioactive ingredients of CFG and 185 CFG-OC-related targets were screened by network pharmacology analysis. The potential therapeutic targets included moesin, glutathione S-transferase kappa 1, ribonuclease III (DICER1), mucin1 (MUC1), cyclin-dependent kinase 2 (CDK2), E1A binding protein p300, and transcription activator BRG1. Reactome analysis showed 51 signaling pathways (P < 0.05), and FunRich revealed 44 signaling pathways that might play an important role in CFG against OC. Molecular docking of CDK2 and five active compounds (baicalin, ignavine, lactiflorin, neokadsuranic acid B, and deoxyaconitine) showed that baicalin had the highest affinity to CDK2. Experimental approaches confirmed that CFG could apparently inhibit OC cell proliferation and migration in vitro; increase apoptosis; decrease the protein expression of MUC1, DICER1, and CDK2; and suppress the progression and distant metastasis of OC in vivo. DICER1, a tumor suppressor, is essential for microRNA synthesis. Our findings suggest that CFG may impair the production of miRNAs in OC cells. Conclusion: Based on network pharmacology, molecular docking, and experimental validation, the potential mechanism underlying the function of CFG in OC was explored, which supplies the theoretical groundwork for additional pharmacological investigation.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias Ovarianas , Wolfiporia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Cromatografia Líquida , RNA Helicases DEAD-box , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Neoplasias Ovarianas/tratamento farmacológico , Ribonuclease III , Espectrometria de Massas em Tandem
12.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 38(3): 273-278, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36062799

RESUMO

Objective: By means of network pharmacology, potential targets and molecular pathways of QiZhenYuanDan in the treatment of atherosclerosis (AS) were studied. Methods: TCMSP database was used to obtain the main active components and target information of Astragali Radix, Fructus Ligustri Lucidi, Corydalis Rhizoma and Salvia Miltiorrhiza in QiZhenYuanDan. Disease targets were retrieved by OMIM and other databases. Molecular networks were constructed using Cytoscape. STRING database was searched and PPI network diagram was drawn to obtain the key targets of QiZhenYuanDan in the treatment of AS; and the targets were uploaded to Metascape data platform for GO and KEGG analysis. Results: There were 118 targets of intersection between QiZhenYuanDan and AS, which were used as the predicted targets of QiZhenYuanDan on AS. GO analysis showed that the biological functions of QiZhenYuanDan in the treatment of AS targets mainly involved biological processes, such as the cytokine-mediated signaling pathway, cytokine receptor binding. KEGG pathway was mainly enriched in 155 signaling pathways, including PI3K-Akt, HIF-1, NF-κB signal pathway and inflammatory bowel disease pathway. Conclusion: Based on the result of network pharmacology study, the mechanisms of Qizhenyuandan for AS treatment was preliminarily revealed. The active ingredients such as quercetin and kaempferol act on targets such as IL-6 and PI3K-Akt, and exert anti-AS effects by inhibiting apoptosis, oxidative stress, as well as inflammatory responses. Our result indicates that QiZhenYuanDan exhibits anti-AS effect via a multi-component, multi-target and multi-route synergistic process.


Assuntos
Aterosclerose , Medicamentos de Ervas Chinesas , Aterosclerose/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt
13.
Biomed Res Int ; 2022: 3008842, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046463

RESUMO

Background: Kangai injection is a traditional Chinese medicine (TCM) mixed by extracts from astragalus, ginseng, and kurorinone with modern technology. It is a commonly used antitumor injection in China, but the mechanism of Kangai injection in the treatment of colorectal cancer (CRC) is still unclear. The purpose of this study is to explore the mechanism of Kangai injection against CRC using network pharmacology and molecular docking technology. Methods: Targets of Kangai injection in CRC were predicted by SwissTargetPrediction and DisGeNET databases. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed by using the DAVID database. A component-disease-target gene-pathway network was constructed by Cytoscape 3.8.0 software. Results: 114 overlapping targets of Kangai injection and CRC were used to construct a PPI network, and the top 10 hub targets of Kangai injection were rated from high to low as TP53, VEGFA, EGFR, TNF, ESR1, STAT3, HSP90AA1, HDAC1, AR, and MMP9. The ingredient-target-disease interactive network was constructed, which included 22 compounds and 114 overlapping targets with 161 nodes and 707 edges. Entries of enrichment analysis were obtained based on P value (<0.05), which included 19 of GO-MF, 217 of GO-BP, 8 of GO-CC, and 13 KEGG. Molecular docking analysis showed that Kangai injection strongly interacted with top 10 hub target proteins. Conclusion: Network pharmacology intuitively showed the multicomponent, multiple targets, and multiple pathways of Kangai injection in the treatment of CRC. The molecular docking experiment verified that compounds of Kangai injection had good binding ability with top 10 hub target proteins as well.


Assuntos
Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , Mapas de Interação de Proteínas/genética
14.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4454-4461, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046875

RESUMO

This study aimed to further explore the relevant mechanism of action by network pharmacology integrated with animal experimental verification based on previous proven effective treatment of vertebral artery type of cervical spondylosis(CSA) by Panlongqi Tablets. Bionetwork analysis was performed to establish drug-disease interaction network, and it was found that the key candidate targets of Panlongqi Tablets were enriched in multiple signaling pathways related to CSA pathological links, among which phosphatidylinositol 3-kinase(PI3 K)/serine-threonine kinase(AKT/PKB) signaling pathway was the most significant. Further, mixed modeling method was used to build the CSA rat model, and the rats were divided into normal, model, Panlongqi Tablets low-, medium-and high-dose(0.16, 0.32, 0.64 g·kg~(-1)) and Jingfukang Granules(positive drug, 1.35 g·kg~(-1)) groups. After successful modeling, the rats were administered for 8 consecutive weeks. Pathological changes of rat cervical muscle tissues were detected by hematoxylin-eosin(HE) staining, and the content of interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), vascular endothelial cell growth factor(VEGF) and chemokine(C-C motif) ligand 2(CCL2) in rat serum and/or cervical tissues was determined by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to detect the protein expression levels of chemokine(C-C motif) receptor 2(CCR2), PI3 K, AKT, phosphorylated AKT(p-AKT), I-kappa-B-kinase beta(IKK-beta/IKKß), nuclear factor kappa B(NF-κB P65) and phosphorylated nuclear factor kappa B(NF-κB p-P65) in rat cervical tissues, and positive expression of p-NF-κB P65 in rat cervical muscle tissues was detected by immunofluorescence. The results showed that Panlongqi Tablets at different doses improved the degree of muscle fibrosis and inflammation in cervical muscle tissues of CSA rats, and reduced the content of inflammatory factors IL-1ß, TNF-α, VEGF, CCL2 and CCR2 in serum and/or cervical tissues. The protein expression levels of PI3 K, p-AKT, IKKß and p-NF-κB P65 as well as the nuclear entry of p-NF-κB P65 in cervical tissues were down-regulated. These findings suggest that Panlongqi Tablets can significantly inhibit the inflammatory response of CSA rats, and the mechanism of action may be related to the down-regulation of the activation of PI3 K/AKT signaling pathway.


Assuntos
NF-kappa B , Espondilose , Animais , Medicamentos de Ervas Chinesas , Quinase I-kappa B/metabolismo , Quinase I-kappa B/farmacologia , NF-kappa B/metabolismo , Farmacologia em Rede , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais , Espondilose/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Artéria Vertebral/metabolismo
15.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4164-4176, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046907

RESUMO

The present study explored the material basis and underlying mechanism of Wumei Pills in the treatment of ulcerative colitis(UC), diabetic enteropathy(DE), and irritable bowel syndrome(IBS) based on network pharmacology and molecular docking.The active components and targets of Wumei Pills were obtained and screened out from TCMSP, and the target names were standardized by UniProt.The related targets of UC, DE, and IBS were searched from GeneCards, DisGeNET, DrugBank, and OMIM.The Venn dia-gram was constructed using the Venny 2.1 online analysis tool to obtain the common targets of the drug and diseases.The "drug-active ingredient-target" network was constructed by Cytoscape 3.7.2.Gene Ontology(GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of common targets were carried out by DAVID.The main active components and targets were docked by AutoDock.The therapeutic mechanism of Wumei Pills was presumedly related to the regulation of the cancer pathway, TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, NF-κB signaling pathway, Toll-like receptor signaling pathway, JAK-STAT signaling pathway, etc.The results of molecular docking showed that the main active components could bind to the core targets, possessing stable conformation.The therapeutic effects of Wumei Pills against three diseases involved a variety of compounds such as flavonoids, sterols, and alkaloids in the prescriptions, which acted on key targets through multiple organs and participated in multiple signaling pathways such as apoptosis and immune inflammation, thereby exerting the therapeutic action on different diseases with the same method.This study explained the underlying mechanism of Wumei Pills in "treating different diseases with same method", and is expected to provide a theoretical basis for further understanding the mechanism of Wumei Pills and exploring the new clinical application.


Assuntos
Medicamentos de Ervas Chinesas , Síndrome do Intestino Irritável , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Síndrome do Intestino Irritável/tratamento farmacológico , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede
16.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4190-4201, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046910

RESUMO

The chemical components in rats after oral administration of the water extract of Chrysanthemum morifolium cv. Fubaiju(CMF) were analyzed by UPLC-Q-TOF-MS/MS technique. Forty-four compounds were identified from the water extract of CMF and 11 components were identified from the rat serum. A total of 264 potential anti-inflammatory targets were identified by network pharmacology based on serum components. The "component-target" network and protein-protein interaction(PPI) network were constructed, and GO function enrichment and KEGG pathway enrichment analyses were performed. The molecular docking was carried out to validate the results of network pharmacology. The results showed that CMF might act on AKT1, TNF, TP53, IL6, INS, and other core targets through apigenin, luteolin, acacetin, diosmetin, 3,4-O-dicaffeoylquinic acid, and other active components, and exert anti-inflammatory effects by regulating PI3 K-AKT signaling pathway, FoxO signaling pathway, cAMP signaling pathway, Ras signaling pathway, and other pathways. The pharmacodynamic materials basis of CMF was identified by UPLC-Q-TOF-MS/MS technology, and the core anti-inflammatory targets and the underlying mechanism of action were analyzed by network pharmacology and molecular docking, which provided a reference for comprehensively clarifying the pharmacodynamic materials basis and quality control of CMF.


Assuntos
Chrysanthemum , Medicamentos de Ervas Chinesas , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/química , Simulação de Acoplamento Molecular , Farmacologia em Rede , Ratos , Espectrometria de Massas em Tandem/métodos , Água
17.
Pharm Biol ; 60(1): 1819-1838, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36124995

RESUMO

CONTEXT: Shen-Shi-Jiang-Zhuo formula (SSJZF) exhibits a definite curative effect in the clinical treatment of non-alcoholic fatty liver disease (NAFLD). OBJECTIVE: To explore the therapeutic effect and mechanism of SSJZF on NAFLD. MATERIALS AND METHODS: Sprague Dawley rats were randomly divided into control, NAFLD, positive drug (12 mg/kg/day), SSJZF high-dose (200 mg/kg/day), SSJZF middle-dose (100 mg/kg/day), and SSJZF low-dose (50 mg/kg/day) groups. After daily intragastric administration of NAFLD rats for 8 weeks, lipid metabolism and hepatic fibrosis were evaluated by biochemical indices and histopathology. Then we uncovered the main active compounds and mechanism of SSJZF against NAFLD by integrating RNA-sequencing and network pharmacology, and PI3K/AKT pathway activity was verified by western blot. RESULTS: High dose SSJZF had the best inhibitory effect on hepatic lipid accumulation and fibrosis in rats with NAFLD, which significantly down-regulated total triglycerides (58%), cholesterol (62%), aspartate aminotransferase (57%), alanine aminotransferase (41%) andγ-glutamyl transpeptidase (36%), as well as the expression of ACC (5.3-fold), FAS (12.1-fold), SREBP1C (2.3-fold), and CD36 (4.4-fold), and significantly reduced collagen deposition (67%). Then we identified 23 compounds of SSJZF that acted on 25 key therapeutic targets of NAFLD by integrating RNA-sequencing and network pharmacology. Finally, we also confirmed that high dose SSJZF increased p-PI3K/PI3K (1.6-fold) and p-AKT/AKT (1.6-fold) in NAFLD rats. DISCUSSION AND CONCLUSION: We found for first time that SSJZF improved NAFLD in rats by activating the PI3K/Akt pathway. These findings provide scientific support for SSJZF in the clinical treatment of NAFLD and contribute to the development of new NAFLD drugs.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Alanina Transaminase , Animais , Aspartato Aminotransferases , Colesterol , Dieta Hiperlipídica , Farmacologia em Rede , Hepatopatia Gordurosa não Alcoólica/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA/uso terapêutico , Ratos , Ratos Sprague-Dawley , Triglicerídeos , gama-Glutamiltransferase/uso terapêutico
18.
Pharm Biol ; 60(1): 1751-1761, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36102631

RESUMO

CONTEXT: Ursolic acid (UA) and acteoside (ATS) are important active components that have been used to treat Alzheimer's disease (AD) because of their neuroprotective effects, but the exact mechanism is still unclear. OBJECTIVE: Network pharmacology was used to explore the mechanism of UA + ATS in treating AD, and cell experiments were used to verify the mechanism. MATERIALS AND METHODS: UA + ATS targets and AD-related genes were retrieved from TCMSP, STITCH, SwissTargetPrediction, GeneCards, DisGeNET and GEO. Key targets were obtained by constructing protein interaction network through STRING. The neuroprotective effects of UA + ATS were verified in H2O2-treated PC12 cells. The subsequent experiments were divided into Normal, Model (H2O2 pre-treatment for 4 h), Control (H2O2+ solvent pre-treatment), UA (5 µM), ATS (40 µM), UA (5 µM) + ATS (40 µM). Then apoptosis, mitochondrial membrane potential, caspase-3 activity, ATG5, Beclin-1 protein expression and Akt, mTOR phosphorylation levels were detected. RESULTS: The key targets of UA + ATS-AD network were mainly enriched in Akt/mTOR pathway. Cell experiments showed that UA (ED50: 5 µM) + ATS (ED50: 40 µM) could protect H2O2-induced (IC50: 250 µM) nerve damage by enhancing cells viability, combating apoptosis, restoring MMP, reducing the activation of caspase-3, lessening the phosphorylation of Akt and mTOR, and increasing the expression of ATG5 and Beclin-1. CONCLUSIONS: ATS and UA regulates multiple targets, bioprocesses and signal pathways against AD pathogenesis. ATS and UA synergistically protects H2O2-induced neurotrosis by regulation of AKT/mTOR signalling.


Assuntos
Fármacos Neuroprotetores , Proteínas Proto-Oncogênicas c-akt , Animais , Caspase 3/metabolismo , Glucosídeos , Peróxido de Hidrogênio/toxicidade , Farmacologia em Rede , Fármacos Neuroprotetores/farmacologia , Ácido Oleanólico/análogos & derivados , Células PC12 , Polifenóis , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
19.
J Ethnopharmacol ; 298: 115679, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36058481

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shi Wei Ru Xiang powder (SWR) is a traditional Tibetan medicinal formula with the effect of dispelling dampness and dispersing cold. In clinical practice, SWR is generally used for the treatment of hyperuricemia (HUA). However, its exact pharmacological mechanism remains unclear. AIMS OF THE STUDY: To preliminarily elucidate the regulatory effects and possible mechanisms of SWR on hyperuricemia using network pharmacology and experimental validation. MATERIALS AND METHODS: A mouse model of hyperuricemia was used to evaluate the alleviating effect of SWR on hyperuricemia. The major components of SWR were acquired by UPLC-Q/TOF-MS. The potential molecular targets and associated signaling pathways were predicted through network pharmacology. The mechanism of action of SWR in ameliorating hyperuricemia was further investigated by pharmacological evaluation. RESULTS: Mice with hyperuricemia and renal dysfunction were ameliorated by SWR. The 36 components of SWR included phenolic acids, terpenoids, alkaloids and flavonoids were identified. Network pharmacological analysis showed the involvement of the above compounds, and 115 targets were involved to treat hyperuricemia, involving multiple biological processes and different signaling pathways. Pharmacological experiments validated that SWR ameliorated hyperuricemic nephropathy in mice by modulating the mitogen-activated protein kinase (MAPK) signaling pathway, nuclear factor kappaB (NF-κB) signaling pathway and NOD-like receptor signaling pathway. CONCLUSION: MAPK signaling pathway, NF-κB signaling pathway and NOD-like receptor signaling pathway play important roles in the therapeutic effects of SWR on hyperuricemia.


Assuntos
Medicamentos de Ervas Chinesas , Hiperuricemia , Animais , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Medicina Tradicional Tibetana , Camundongos , NF-kappa B , Proteínas NLR , Farmacologia em Rede , Pós/uso terapêutico
20.
J Ethnopharmacol ; 299: 115676, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36057408

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shenkangning (SKN), a Chinese patent medicine composed by eight Chinese medicinal herbs, is commonly applied to treat chronic glomerulonephritis (CGN) in clinic. However, its mechanism is still not clear now. AIM OF THE STUDY: This study is designed to evaluate the SKN-provided alleviation on adriamycin (ADR)-induced nephropathy, to reveal its mechanism by integrating network pharmacology analysis and experimental evidences, and to further find the main drug that makes a major contribution to its efficacy. MATERIALS AND METHODS: ADR was intravenously injected to mice to induce focal segmental glomerulosclerosis (FSGS). Renal histological evaluation was conducted. The level of urinary protein, and serum amounts of creatinine, urea nitrogen (BUN) and albumin were detected. The potential mechanisms were predicted by network pharmacology analysis and further validated by Real-time polymerase chain reaction (RT-PCR), Western-blot and enzyme-linked immunosorbent assay (ELISA). RESULTS: SKN (1, 10 g/kg) improved ADR-induced nephropathy in mice. Network pharmacology results predicted that inflammation and oxidative stress were crucially involved in the SKN-provided amelioration on nephropathy. SKN reduced the activation of nuclear factor-κB (NF-κB) and the expression of some pro-inflammatory cytokines, and increased the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the expression of its downstream genes in ADR-induced nephropathy in mice. Furthermore, SKN also restored the reduced expression of both podocin and synaptopodin, which are podocyte-associated proteins. Further results showed that the toxic drug Danfupian (DFP) had no contribution to the SKN-provided alleviation on ADR-induced nephropathy in mice. After integrating the results from evaluating anti-inflammation, anti-oxidant and anti-injury of podocytes in vitro and from comparing the activity of the whole SKN and SKN without Astragali Radix (Huangqi, HQ) in vivo, we found that HQ played a crucial contribution to the SKN-provided amelioration on ADR-induced nephropathy in mice. CONCLUSION: SKN improved ADR-induced nephropathy through suppressing renal inflammation and oxidative stress injury via abrogating NF-κB activation and activating Nrf2 signaling pathway. HQ played a main contribution to the SKN-provided amelioration on ADR-induced nephropathy.


Assuntos
Glomerulosclerose Segmentar e Focal , Nefropatias , Albuminas/efeitos adversos , Animais , Antioxidantes/uso terapêutico , Creatinina , Citocinas , Doxorrubicina/uso terapêutico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Isoflurofato/efeitos adversos , Nefropatias/induzido quimicamente , Camundongos , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/metabolismo , Farmacologia em Rede , Nitrogênio/efeitos adversos , Medicamentos sem Prescrição/efeitos adversos , Ureia
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