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1.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3016-3023, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467691

RESUMO

The acupoint application of Euodiae Fructus at Yongquan(KI1) can significantly improve the sleep quality of patients with insomnia with berberine as the main effective component for the efficacy. Nineteen active compounds and 203 drug targets were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). After comparison with GeneCards and Online Mendelian Inheritance in Man(OMIM), 24 common genes of diseases and drugs were obtained. STRING 11.0 was used to construct a protein-protein interaction(PPI) network of the overlapping genes, and Matthews correlation coefficient(MCC) was employed to screen the core genes, which were then subjected to enrichment analysis with gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG). The results revealed that the main compounds of Euodiae Fructus, such as berberine and rutaecarpine, participated in the biological processes(such as neurotransmitter receptor activity) by regulating C-reactive protein(CRP), estrogen receptor 1(ESR1), 5-hydroxytryptamine(5-HT) receptor, and interleukin-6(IL-6) to exert sedative, anxiolytic, and antidepressant effects. Sixty 4-week-old SPF mice were randomly divided into a control group, a model group, a positive drug(diazepam tablets) group, and low-, medium-, and high-dose berberine groups. Medication with corresponding drugs was performed for one week. The results demonstrated that berberine was potent in reducing the activities and standing times of mice, down-regulating the levels of CRP and IL-6 mRNA in the hypothalamus, and up-regulating the expression of 5-HT(P<0.01); however, no significant effect on ESR1 was observed. The network of Euodiae Fructus in treating insomnia was constructed by network pharmacology and verified by tests. The findings indicated that the therapeutic efficacy of Euodiae Fructus in treating insomnia was achieved by participating in multiple biological processes, such as neurotransmitter receptor activity, which provided a scientific basis for its clinical application.


Assuntos
Medicamentos de Ervas Chinesas , Distúrbios do Início e da Manutenção do Sono , Animais , Bases de Dados Genéticas , Medicamentos de Ervas Chinesas/farmacologia , Ontologia Genética , Humanos , Medicina Tradicional Chinesa , Camundongos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/genética
2.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3058-3065, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467696

RESUMO

In this study, the compound search was completed through SciFinder and CNKI databases, and the drug-like properties were screened in FAFdrugs4 and SEA Search Server databases. In addition, based on the target sets related to acute myocardial ischemia(AMI) searched in disease target databases such as OMIM database, GeneCards database and DrugBank, a network diagram of chemical component-target-pathway-disease was established via Cytoscape to predict the potential active components of Corydalis Herba, a traditional Tibetan herbal medicine which derived from the aerial parts of Corydalis hendersonii and C. mucronifera against AMI. A protein-protein interaction(PPI) network was constructed through the STRING database and the core targets in the network were predicted. And the enrichment analyses of core targets were completed by DAVID database and R software. Furthermore, a molecular docking method was used to verify the binding of the components with core targets using softwares such as Autodock Vina. The present results showed that there were 60 compounds related to AMI in Corydalis Herba, involving 73 potential targets. The GO functional enrichment analysis obtained 282 biological processes(BP), 49 cell components(CC) and 78 molecular functions(MF). KEGG was enriched into 85 pathways, including alcoholism pathway, endocrine resistance pathway, calcium signaling pathway, cAMP signaling pathway, vascular endothelial growth factor signaling pathway and adrenergic signaling transduction pathway of myocardial cells. The results of network topology analysis showed that the key components of anti-AMI of Corydalis Herba might be tetrahydropalmatine, etrahydrocolumbamine, N-trans-feruloyloctopamine, N-cis-p-coumaroyloctopamine, N-trans-p-coumaroylnoradrenline and N-trans-p-coumaroyloctopamine, and their core targets might be CDH23, SCN4 B and NFASC. The results of molecular docking showed that the key components of Corydalis Herba had stable binding activity with the core targets. This study provides reference for further elucidation of the pharmacological effects of Corydalis Herba against AMI, subsequent clinical application, and development.


Assuntos
Corydalis , Medicamentos de Ervas Chinesas , Isquemia Miocárdica , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Tibetana , Simulação de Acoplamento Molecular , Isquemia Miocárdica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular
3.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4061-4068, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467715

RESUMO

Reverse prediction and molecular docking techniques were employed to evaluate the feasibility of reniformin A(RA) as an anti-tumor leading compound. Based on the reverse prediction, network pharmacology was used to construct a "disease-compound-target-pathway" network. Thirty-nine tumor-related targets of RA were predicted, which participated in the regulation of multiple cellular activities such as apoptosis, cell cycle, and tumor metastasis, and regulated estrogen signal transduction and inflammatory response. Discovery Studio 2020 was adopted for molecular docking and toxicity prediction(TOPKAT). As revealed by the results, the binding affinity of RA with the tumor-related targets ABL1, ESR1, SRC and BCL-XL was stronger than that of oridonin(OD), while its mutagenicity, rodent carcinogenesis, and oral LD_(50) in rats were all inferior to that of OD. Furthermore, in vitro experiments were performed to confirm the anti-tumor activity of RA, and the mechanism was preliminarily discussed. The results demonstrated that RA was superior to OD in cytotoxicity, inhibition of cell colony formation, and induction of apoptosis. RA, possessing potent anti-tumor activity, is expected to be a new anti-tumor leading compound.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias , Animais , Medicamentos de Ervas Chinesas/farmacologia , Chumbo , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/genética , Ratos , Transdução de Sinais
4.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4157-4166, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467728

RESUMO

This article aims to establish the fingerprints, determine the hemostatic pharmacodynamic indicators, and explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in 12 different specifications. Firstly, HPLC and liquid chromatography-mass spectrometry(LC-MS) were employed to establish the fingerprints of Notoginseng Radix et Rhizoma. The rat plasma recalcification experiment and the rat gastric bleeding experiment were conducted to determine the pharmacodynamic indicators, including plasma recalcification time(PRT), thrombin time(TT), prothrombin time(PT), and activated partial thromboplastin time(APTT). Afterwards, the partial least squares method was employed to explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in different specifications. Twenty-six common peaks were detected in the HPLC fingerprints of different specifications of Notoginseng Radix et Rhizoma, and 11 out of the 26 common peaks represented saponins. The content of dencichine was determined by LC-MS. The rat experiments showed that the pharmacodynamic indicators were significantly different among different specifications of Notoginseng Radix et Rhizoma. The spectrum-effect relationship was explored between 27 common components and pharmacodynamic indicators. Among them, 16 components had positive effects on the pharmacodynamic indicators of Notoginseng Radix et Rhizoma, and 11 exerted negative effects. This study provides a basis for the precision medication and quality control of Notoginseng Radix et Rhizoma.


Assuntos
Medicamentos de Ervas Chinesas , Hemostáticos , Saponinas , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacologia , Controle de Qualidade , Ratos , Rizoma
5.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4201-4207, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467733

RESUMO

The present study aims to investigate the effects of the main components(aesculin, berberine hydrochloride, and anemoside B4) in the butyl alcohol extract of Baitouweng Decoction(BAEB) on the chemotaxis of neutrophils induced by dimethyl sulfoxide(DMSO). HL60 cells were cultivated in RPMI-1640 complete medium, and transferred into a 6-well plate(2 × 10~5 per mL) with 4 mL in each well, followed by incubation with DMSO at 1.3% for five days. The morphologic changes of cells were observed under an inverted microscope. The CD11 b expression after DMSO induction was analyzed by flow cytometry. The effects of aesculin, berberine hydrochloride, and anemoside B4 on the cell proliferation and migration were detected by CCK8 assay and Transwell assay, respectively. The effects of the main components on the production and polarization of F-actin protein were also examined by flow cytometry and laser confocal microscopy. PI3 K/Akt signaling pathway was checked by Western blot. As revealed by the results, neutrophil-like HL60 cells were observed after DMSO induction. The CD11 b expression in these cells increased significantly as indicated by the flow cytometry. Additionally, 100 µg·mL~(-1) aesculin, 8 µg·mL~(-1) berberine hydrochloride, and 80 µg·mL~(-1) anemoside B4 were potent in inhibiting the migration of neutrophils and reducing F-actin expression. Berberine hydrochloride was verified to be capable of diminishing phosphorylated PI3 K/Akt protein expression. The findings indicate that aesculin, anemoside B4, and especially berberine hydrochloride in the BAEB can inhibit the chemotaxis of neutrophils, which is possibly achieved by the inhibition of F-actin and PI3 K/Akt signaling pathway.


Assuntos
Berberina , Medicamentos de Ervas Chinesas , 1-Butanol , Berberina/farmacologia , Quimiotaxia , Medicamentos de Ervas Chinesas/farmacologia , Neutrófilos
6.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4230-4237, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467737

RESUMO

This study aimed to explore the mechanism of Xiaoyao San(XYS) in the treatment of three diseases of liver depression and spleen deficiency, ie, depression, breast hyperplasia, and functional dyspepsia, and to provide a theoretical basis for the interpretation of the scientific connotation of "treating different diseases with the same method" of traditional Chinese medicines. Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) was used to screen the active components of XYS which underwent principal component analysis(PCA) with the available drugs for these three diseases to determine the corresponding biological activities. The targets of XYS on depression, breast hyperplasia, and functional dyspepsia were obtained from GeneCards, TTD, CTD, and DrugBank databases. Cytoscape was used to plot the "individual herbal medicine-active components-potential targets" network. The resulting key targets were subjected to Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis and gene ontology(GO) enrichment analysis. A total of 121 active components of XYS and 38 common targets in the treatment of depression, breast hyperplasia, and functional dyspepsia were collected. The key biological pathways were identified, including advanced glycation and products(AGEs)-receptor for advanced glycation and products(RAGE) signaling pathway in diabetic complications, HIF-1 signaling pathway, and cancer-related pathways. The key targets of XYS in the treatment of depression, breast hyperplasia, and functional dyspepsia included IL6, IL4, and TNF, and the key components were kaempferol, quercetin, aloe-emodin, etc. As revealed by the molecular docking, a strong affinity was observed between the key components and the key targets, which confirmed the results. The therapeutic efficacy of XYS in the treatment of diseases of liver depression and spleen deficiency was presumedly achieved by reducing the inflammatory reactions. The current findings are expected to provide novel research ideas and approaches to classify the scientific connotation of "treating different diseases with the same method" of Chinese medicines, as well as a theoretical basis for understanding the mechanism of XYS and exploring its clinical applications.


Assuntos
Medicamentos de Ervas Chinesas , Dispepsia , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Dispepsia/tratamento farmacológico , Humanos , Hiperplasia/tratamento farmacológico , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular
7.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3949-3959, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472272

RESUMO

Qishen Yiqi Dripping Pills(QSYQ) are used clinically to treat various myocardial ischemic diseases, such as angina pectoris, myocardial infarction, and heart failure; however, the molecular mechanism of QSYQ remains unclear, and the scientific connotation of traditional Chinese medicine(TCM) compatibility has not been systematically explained. The present study attempted to screen the critical pathway of QSYQ in the treatment of myocardial ischemia by network pharmacology and verify the therapeutic efficacy with the oxygen-glucose deprivation(OGD) model, in order to reveal the molecular mechanism of QSYQ based on the critical pathway. The key targets of QSYQ were determined by active ingredient identification and target prediction, and underwent pathway enrichment analysis and functional annotation with David database to reveal the biological role and the critical pathway of QSYQ. Cell counting Kit-8(CCK-8), lactate dehydrogenase(LDH), and Western blot tests were launched on high-content active ingredients with OGD cell model to reveal the molecular mechanism of QSYQ based on the critical pathway. The results of network pharmacology indicated that QSYQ, containing 18 active ingredients and 82 key targets, could protect cardiomyocytes by regulating biological functions, such as nitric oxide biosynthesis, apoptosis, inflammation, and angiogenesis, through TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, etc. HIF-1 signaling pathway was the critical pathway. As revealed by CCK-8 and LDH tests, astragaloside Ⅳ, salvianic acid A, and ginsenoside Rg_1 in QSYQ could enhance cell viability and reduce LDH in the cell supernatant in a concentration-dependent manner(P<0.05). As demonstrated by the Western blot test, astragaloside Ⅳ significantly down-regulated the protein expression of serine/threonine-protein kinase(Akt1) and hypoxia-inducible factor 1α(HIF-1α) in the HIF-1 signaling pathway, and up-regulated the protein expression of vascular endothelial growth factor A(VEGFA). Salvianic acid A significantly down-regulated the protein expression of upstream phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA) and downstream HIF-1α of Akt1. Ginsenoside Rg_1 significantly down-regulated the expression of HIF-1α protein and up-regulated the expression of VEGFA. The therapeutic efficacy of QSYQ on myocardial ischemia was achieved by multiple targets and multiple pathways, with the HIF-1 signaling pathway serving as the critical one. The active ingredients of QSYQ could protect cardiomyocytes synergistically by regulating the targets in the HIF-1 signaling pathway to inhibit its expression.


Assuntos
Medicamentos de Ervas Chinesas , Isquemia Miocárdica , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/genética , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular
8.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3970-3979, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472274

RESUMO

The traditional Chinese medicines(TCM) for activating blood circulation and the TCM for regulating Qi are often used in combination in clinical practice. However, their mechanisms are still unclear. The activity spectrum of targets can fuse the active components, targets and intensity of action, which provides support for the discussion of efficacy targets. The chemical components of common TCM sets for activating blood circulation and regulating Qi, as well as the negative sets not for activating blood circulation and re-gulating Qi were obtained from the database of TCM. By the similarity analysis of chemical components in TCM for activating blood circulation and DrugBank database, the predicted targets of chemical components in TCM for activating blood circulation were obtained, and the similarity value of the two was taken as the activity value of the active components and predicted targets. Then, the component-target activity value was weighted. The activity values of herb acting on the same target were fused to construct activity spectra of targets of the herbs for activating blood circulation, herbs for regulating Qi and negative herbs. The targets whose activity values of activating blood circulation and regulating Qi were higher than those of negative herbs were selected as potential targets of efficacy. Protein-protein interaction networks were constructed for topological, GO and KEGG enrichment analysis to determine the key targets of efficacy of activating blood circulation and regulating Qi. The component-target activity information collected from DrugBank database contained 4 499 compounds, 627 targets and 11 295 action relationships. The activating blood function protein-protein interaction network contained 206 nodes and 1 728 edges, while the regulating Qi function protein-protein interaction network contained 230 nodes and 986 edges. The enrichment analysis of topology, GO and KEGG showed that TCM for activating blood circulation mainly exerted its anti-inflammatory, neuroprotective and angiogenic effects on signaling cascade pathway mediated by VEGF/VEGFR2, ERK signaling pathway, calcium signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 3(MAPK3), proto-oncogene tyrosine-protein kinase Src(SRC), mitogen activated protein kinases 1(MAPK1), epidermal growth factor receptor(EGFR), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform(PIK3 CA), peroxisome proliferators-activated receptor gamma(PPARG), nitric oxide synthase 3(NOS3), prostaglandin G/H synthetase 2(PTGS2), matrix metalloproteinase-9(MMP9), and vascular endothelial growth factor A(VEGFA). TCM for regulating Qi mainly exerted anti-inflammatory and neuroprotective effects by acting on MAPK signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 8(MAPK8), SRC, mitogen activated protein kinases 14(MAPK14), and RAC-alpha serine/threonine-protein kinase(AKT1), mitogen activated protein kinases 3(MAPK3). Based on the activity spectrum of targets, the targets of the TCM for activating blood and the targets of the TCM for regulating Qi were analyzed to provide reference for the study of efficacy targets of TCM, and also provide some scientific basis for clinical application.


Assuntos
Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Mapas de Interação de Proteínas , Qi , Fator A de Crescimento do Endotélio Vascular
9.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360840

RESUMO

Obesity is characterized as a chronic, low-grade inflammation state accompanied by the infiltration of immune cells into adipose tissue and higher levels of inflammatory cytokines and chemokines. This study aimed to investigate the mechanisms and effects of Coptidis Rhizoma (CR) on obesity and its associated inflammation. First, we applied a network pharmacology strategy to search the target genes and pathways regulated by CR in obesity. Next, we performed in vivo experiments to confirm the antiobesity and anti-inflammatory effects of CR. Mice were assigned to five groups: normal chow (NC), control (high-fat diet (HFD)), HFD + CR 200 mg/kg, HFD + CR 400 mg/kg, and HFD + metformin 200 mg/kg. After 16 weeks of the experimental period, CR administration significantly reduced the weight of the body, epididymal fat, and liver; it also decreased insulin resistance, as well as the area under the curve of glucose in the oral glucose tolerance test and triglyceride in the oral fat tolerance test. We observed a decrease in adipose tissue macrophages (ATMs) and inflammatory M1 ATMs, as well as an increase in anti-inflammatory M2 ATMs. Gene expression levels of inflammatory cytokines and chemokines, including tumor necrosis factor-α, F4/80, and C-C motif chemokine (CCL)-2, CCL4, and CCL5, were suppressed in adipose tissue in the CR groups than levels in the control group. Additionally, histological analyses suggested decreased fat accumulation in the epididymal fat pad and liver in the CR groups than that in the control group. Taken together, these results suggest that CR has a therapeutic effect on obesity-induced inflammation, and it functions through the inhibition of macrophage-mediated inflammation in adipose tissue.


Assuntos
Citocinas/genética , Medicamentos de Ervas Chinesas/farmacologia , Inflamação/tratamento farmacológico , Macrófagos/metabolismo , Obesidade/complicações , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Simulação por Computador , Dieta Hiperlipídica , Regulação da Expressão Gênica , Inflamação/etiologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
10.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3422-3428, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396763

RESUMO

The effect of Danhong Injection on the endogenous metabolites of rabbit platelets was analyzed by the liquid chromatography-mass spectrometry( LC-MS) based metabonomic approach. Anti-platelet aggregation was detected after Danhong Injection treatment and the changes of platelet metabolites were analyzed by metabonomics. Principal component analysis( PCA) and partial least squares discriminant analysis( PLS-DA) were performed to investigate the effect of Danhong Injection on endogenous metabolites of platelets,characterize the biomarkers,and explore the relevant pathways and the underlying mechanism. As demonstrated by the pharmacodynamic results,Danhong Injection of different doses and concentrations antagonized platelet aggregation in a dose-and concentration-dependent manner. In contrast to the control group,25 differential metabolites such as nicotinic acid,nicotinic acid riboside,and hypoxanthine were screened out after platelets were treated by Danhong Injection. These metabolites,serving as important biomarkers,were mainly enriched in the nicotinic acid-niacinamide metabolic pathway and purine metabolic pathway. This study explored the therapeutic mechanism of Danhong Injection from a microscopic perspective by metabonomics,which is expected to provide a new idea for the investigation of platelet-related mechanisms.


Assuntos
Plaquetas , Medicamentos de Ervas Chinesas , Animais , Biomarcadores , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacologia , Metabolômica , Coelhos , Tecnologia
11.
Biomolecules ; 11(7)2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34356672

RESUMO

In the search for new therapeutic strategies to contrast SARS-CoV-2, we here studied the interaction of polydatin (PD) and resveratrol (RESV)-two natural stilbene polyphenols with manifold, well known biological activities-with Spike, the viral protein essential for virus entry into host cells, and ACE2, the angiotensin-converting enzyme present on the surface of multiple cell types (including respiratory epithelial cells) which is the main host receptor for Spike binding. Molecular Docking simulations evidenced that both compounds can bind Spike, ACE2 and the ACE2:Spike complex with good affinity, although the interaction of PD appears stronger than that of RESV on all the investigated targets. Preliminary biochemical assays revealed a significant inhibitory activity of the ACE2:Spike recognition with a dose-response effect only in the case of PD.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/tratamento farmacológico , Glucosídeos/farmacologia , Resveratrol/farmacologia , SARS-CoV-2/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/metabolismo , Estilbenos/farmacologia , COVID-19/metabolismo , Descoberta de Drogas , Medicamentos de Ervas Chinesas/farmacologia , Inibidores Enzimáticos/farmacologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica/efeitos dos fármacos , SARS-CoV-2/metabolismo
12.
FASEB J ; 35(9): e21870, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34436790

RESUMO

COVID-19 is often characterized by dysregulated inflammatory and immune responses. It has been shown that the Traditional Chinese Medicine formulation Qing-Fei-Pai-Du decoction (QFPDD) is effective in the treatment of the disease, especially for patients in the early stage. Our network pharmacology analyses indicated that many inflammation and immune-related molecules were the targets of the active components of QFPDD, which propelled us to examine the effects of the decoction on inflammation. We found in the present study that QFPDD effectively alleviated dextran sulfate sodium-induced intestinal inflammation in mice. It inhibited the production of pro-inflammatory cytokines IL-6 and TNFα, and promoted the expression of anti-inflammatory cytokine IL-10 by macrophagic cells. Further investigations found that QFPDD and one of its active components wogonoside markedly reduced LPS-stimulated phosphorylation of transcription factor ATF2, an important regulator of multiple cytokines expression. Our data revealed that both QFPDD and wogonoside decreased the half-life of ATF2 and promoted its proteasomal degradation. Of note, QFPDD and wogonoside down-regulated deubiquitinating enzyme USP14 along with inducing ATF2 degradation. Inhibition of USP14 with the small molecular inhibitor IU1 also led to the decrease of ATF2 in the cells, indicating that QFPDD and wogonoside may act through regulating USP14 to promote ATF2 degradation. To further assess the importance of ubiquitination in regulating ATF2, we generated mice that were intestinal-specific KLHL5 deficiency, a CUL3-interacting protein participating in substrate recognition of E3s. In these mice, QFPDD mitigated inflammatory reaction in the spleen, but not intestinal inflammation, suggesting CUL3-KLHL5 may function as an E3 for ATF2 degradation.


Assuntos
Fator 2 Ativador da Transcrição/metabolismo , Regulação para Baixo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Flavanonas/farmacologia , Glucosídeos/farmacologia , Inflamação/tratamento farmacológico , Proteólise/efeitos dos fármacos , Ubiquitina Tiolesterase/deficiência , Animais , Linhagem Celular , Colite/induzido quimicamente , Colite/tratamento farmacológico , Proteínas Culina/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/farmacologia , Sulfato de Dextrana/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Flavanonas/uso terapêutico , Glucosídeos/uso terapêutico , Inflamação/induzido quimicamente , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Pirróis/farmacologia , Pirrolidinas/farmacologia , Ubiquitina Tiolesterase/antagonistas & inibidores , Ubiquitinação
13.
Medicine (Baltimore) ; 100(32): e26865, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397898

RESUMO

BACKGROUND: The incidence of insomnia is very high and seriously affects the lives of its patients. Long-term insomnia can induce other diseases and even cause sudden death. Tian Meng oral liquid is a type of Chinese patent medicine that has been used in the clinical treatment of insomnia and has certain clinical effects. However, its wide application is limited by the lack of evidence-based medical evaluation. METHODS: Using retrieval strategies, randomized controlled trials on Tian Meng oral liquid for insomnia were obtained from China National Knowledge Infrastructure, WanFang, Chinese Scientific Journals Database PubMed, Embase, and Cochrane Library, regardless of publication date or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the studies. The meta-analysis was performed using RevMan 5.3 and STATA 14.2 software. Ultimately, the evidentiary grade for the results will be evaluated. RESULTS: This study aims to evaluate the efficacy and safety of Tian Meng oral liquid in the treatment of insomnia and to provide a more reasonable option for clinical medication. CONCLUSION: Our findings will provide a strong basis for the effectiveness and safety of Tian Meng oral liquid in the treatment of insomnia.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Distúrbios do Início e da Manutenção do Sono/terapia , Humanos , Medicina Tradicional Chinesa/métodos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
14.
Sci Rep ; 11(1): 16307, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381116

RESUMO

Structure-based drug design targeting the SARS-CoV-2 virus has been greatly facilitated by available virus-related protein structures. However, there is an urgent need for effective, safe small-molecule drugs to control the spread of the virus and variants. While many efforts are devoted to searching for compounds that selectively target individual proteins, we investigated the potential interactions between eight proteins related to SARS-CoV-2 and more than 600 compounds from a traditional Chinese medicine which has proven effective at treating the viral infection. Our original ensemble docking and cooperative docking approaches, followed by a total of over 16-micorsecond molecular simulations, have identified at least 9 compounds that may generally bind to key SARS-CoV-2 proteins. Further, we found evidence that some of these compounds can simultaneously bind to the same target, potentially leading to cooperative inhibition to SARS-CoV-2 proteins like the Spike protein and the RNA-dependent RNA polymerase. These results not only present a useful computational methodology to systematically assess the anti-viral potential of small molecules, but also point out a new avenue to seek cooperative compounds toward cocktail therapeutics to target more SARS-CoV-2-related proteins.


Assuntos
Antivirais/farmacologia , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , SARS-CoV-2/efeitos dos fármacos , Proteínas Virais/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Antivirais/química , Antivirais/metabolismo , Gatos , Biologia Computacional , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Flavonoides/metabolismo , Humanos , Simulação de Dinâmica Molecular , Ligação Proteica , RNA Polimerase Dependente de RNA/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Relação Estrutura-Atividade
15.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445585

RESUMO

Head and neck squamous cell carcinomas (HNSCCs) are the most common cancers of the head and neck, and their prevalence is rapidly increasing. HNSCCs present a clinical challenge because of their high recurrence rate, therapeutic resistance to radiation and chemotherapy drugs, and adverse effects. Hence, traditional Chinese herbal treatment may be advantageous to therapeutic strategies for HNSCCs. Danshen (Salvia miltiorrhiza), a well-known Chinese herb, has been extensively applied in treatments for various diseases, including cancer, because of its high degree of safety and low rate of adverse effects despite its unclear mechanism. Thus, we aimed to explore the possible anticancer effects and mechanisms of dihydroisotanshinone I (DT), a compound in danshen (extract from danshen), on HNSCCs. Three HNSCCs cell lines were used for in vitro studies, and a Detroit 562 xenograft mouse model was chosen for in vivo studies. Our in vitro results showed that DT could initiate apoptosis, resulting in cell death, and the p38 signaling partially regulated DT-initiated cell apoptosis in the Detroit 562 model. In the xenograft mouse model, DT reduced tumor size with no obvious adverse effect of hepatotoxicity. The present study suggests that DT is a promising novel candidate for anti-HNSCCs therapy.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Fenantrenos/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Animais , Apoptose , Proliferação de Células , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(3): 318-323, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34374247

RESUMO

Objective: To investigate the molecular protective mechanisms of Huangqi decoction inhibiting the apoptosis of renal cells in the 12C6+ radiation brain model rats. Methods: Fifty Wistar rats were randomly divided into five groups: normal control group, radiation alone model group, Huangqi decoction (high-dose, middle-dose and low-dose ) groups. The normal control group and the radiation alone group were treated with saline10 ml/(kg·d) by gavage, the Huangqi decoction treatment groups were treated with Huangqi decoction at the doses of 4.5, 9 and 18 g/(kg·d) by gavage respectively. After 7 d, except mice in normal control group, the brain of the rats in radiation alone model group, high-dose, middle-dose and low-dose Huangqi decoction group were radiated by 4 Gy 12C6+ ion once. The rats were killed by the femoral artery after irradiation 7 d. The pathomorphism changes of renal tissue were observed by HE, the IL-6 level in serum was detected by ELISA, the gene expressions of Bcl-2, Bax and caspase-3 in renal tissue were assessed by RT-PCR, and the protein expressions of Bcl-2, Bax, caspase-3 and NF-κB in renal tissue were analyzed by immunehistochemical staining. Results: Compared with normal control group, the body weight and kidney index were decreased significantly, the expression of Bcl-2 in renal tissue was decreased significantly, the serum content of IL-6 was increased obviously, and the expressions of Bax, caspase-3 and NF-κB in renal tissue were increased significantly in the radiation alone model group (P<0.01). The mesangial cells proliferated obviously, interstitial vessels of renal tubules were dilated and congested obviously, the lumen of renal tubules was narrow and irregular in the radiation alone model group. As compared with the radiation alone model group, the body weight and the kidney index were increased obviously in high-dose Huangqi decoction group, the gene and protein expressions of Bcl-2 in renal tissue were increased significantly in Huangqi decoction intervention group(P<0.05 or P<0.01). whereas, the protein expressions of Bax and caspase-3 in renal tissue were decreased significantly in middle-dose and high-dose Huangqi decoction group, the serum content of IL-6 was decreased obviously, the gene expressions of Bax and caspase-3 in renal tissue were decreased significantly and the protein expression of NF-κB in renal tissue was decreased significantly in Huangqi decoction intervention group(P<0.05 or P<0.01). The proliferation of mesangial cells was improved and the contour of renal tubules was clear in high-dose huangqi decoction group. Conclusion: High-dose of huangqi decoction has protective effect on kidney in rats induced by 12C6+ radiation brain, the mechanism may be related to the regulation of Bcl-2/NF-κB signal pathway.


Assuntos
Medicamentos de Ervas Chinesas , Animais , Apoptose , Medicamentos de Ervas Chinesas/farmacologia , Rim , Camundongos , Ratos , Ratos Wistar
17.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3455-3464, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34402267

RESUMO

Chinese materia medica( CMM) serves as an important cornerstone for the development of traditional Chinese medicine( TCM) culture and industry due to its unique ecological,medical,economic,scientific and technological,and cultural values. The supply shortage and unstable quality of some CMM resources have hindered the development of TCM. Ensuring the sustainable use of CMM resources has become essential for the development of TCM in China. Enriching CMM resources is the key to ensuring the sustainable utilization of TCM resources in China,which can be achieved via expanding the medicinal parts,developing the substitutes,seeking for analogues,exploring the ethnic and folk medicines,or introducing foreign medicinal materials. CMM efficacy or function positioning plays a very important role in the transformation of new CMM resources. The strategies and methods for efficacy or function positioning of new CMM resources,including analogy,plant genetic relationship exploration,medicinal property deduction,ethnobotanical investigation,text mining,network pharmacology,and structure-activity relationship exploration,were systematically proposed in this study based on CMM theory,textual research,and modern methodologies. This paper is expected to provide a theoretical reference for the continuous enrichment and development of CMM resources and the high-quality development of TCM culture and industry.


Assuntos
Medicamentos de Ervas Chinesas , Materia Medica , China , Mineração de Dados , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional Chinesa
18.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3625-3632, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34402286

RESUMO

In this paper,metabolomics and network pharmacology were used to investigate the bioactive components of Harrisonia perforata and their possible mechanisms of action. Metabolites in the flowers,fruits,branches,leaves and stalks of H. perforata were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Meanwhile,multiple statistical analysis methods including principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA)were applied to screen and identify differential compounds. With metabolomics method,9 differential compounds were preliminarily identified from leaves and other non-traditional medicinal parts. Subsequently,these compounds were explored by using network pharmacology. With gastrointestinal absorption and drug-likeness as limiting conditions,they were imported into the Swiss ADME,from which 7 compounds with potential medicinal activity were obtained. Then,their targets were predicted by PharmMapper,with Human Protein Targets Only and Normalized Fit Score>0. 9 set as limiting conditions,and 60 standardized potential targets were identified with Uniprot. KEGG( Kyoto encyclopedia of genes and genomes) pathway data was obtained using metascape and the " potential active ingredients-target-pathway" network was constructed with Cytoscape 3. 7. 2. The enrichment analysis of KEGG demonstrated that the 60 targets were enriched in 78 signaling pathways( min overlap: 3,P value cutoff: 0. 01,min enrichment: 1. 5),many of which are related to anti-bacteria,anti-inflammation and anti-virus,such as IL-17 signaling pathway,RIG-I-like receptor signaling pathway and NOD-like receptor signaling pathway. Finally,depending on the clinical activity of H. perforata,the relevant signaling pathways were analyzed through experimental data and literature. Dehydroconiferyl alcohol was reported to have the anti-inflammatory effect and perforamone D to possess the antimycobacterial activity. The KEGG pathway enrichment analysis showed that dehydroconiferyl alcohol could act on the Alzheimer's disease( AD) signaling pathway by targeting CDK5 R1 and BACE1. ACh E inhibitor is the most promising drug to treat AD,while dehydroconiferyl alcohol has been proved to inhibit ACh E according to literature. The experimental results revealed that the extract of leaves of H. perforata can effectively inhibit the growth of Staphylococcus aureus. These are consistent with the enrichment analysis results of KEGG. This study explored the bioactive components and pharmacodynamics of the leaves of the H. perforata,laying a theoretical foundation for its in-depth development and rational application.


Assuntos
Medicamentos de Ervas Chinesas , Simaroubaceae , Secretases da Proteína Precursora do Amiloide , Ácido Aspártico Endopeptidases , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Metabolômica
19.
Zhongguo Zhong Yao Za Zhi ; 46(11): 2677-2685, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34296563

RESUMO

Danggui Buxue Decoction is a classic prescription of Qi and blood tonification, which is mainly applied in treating fatigue, internal damage Qi weakness, blood deficiency, and outward going of floating Yang. Modern pharmacology shows that it can promote hematopoiesis, regulate immunity, and protect heart and cerebral vessels. The prescription, often used for the treatment of anemia and other diseases in clinic, is composed of Astragali Radix and Angelicae Sinensis Radix at a dosage ratio of 5∶1. It is a modern compound prescription for invigorating Qi and generating blood. Based on the review of the chemical constituents, pharmacological effects, and clinical applications of Danggui Buxue Decoction, its Q-marker was predicted and analyzed according to the "five principles" of Chinese medicine Q-marker--quality transmissibility and traceability, ingredient specificity, component validity, component measurabi-lity, and formula compatibility environment. The results suggested that calycosin, calycosin-7-O-ß-D-glucoside, formononetin, ononin, astragaloside A, ferulic acid, and ligustilide could be used as Q-markers of Danggui Buxue Decoction, which provides reference for establishing the quality system of Danggui Buxue Decoction.


Assuntos
Astrágalo (Planta) , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/farmacologia , Raízes de Plantas
20.
J Pharm Biomed Anal ; 204: 114267, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34303214

RESUMO

As a kind of commonly used Traditional Chinese Medicine in clinical, Spatholobi Caulis (SPC) contains a wide variety of bioactive compounds, including protocatechuate (1), nicotinic acid (2), p-hydroxybenzoic acid (3), salicylic acid (4), 6,9-dihydroxy megastigma-4,7-dien-3-one (5), 8,9-dihydroxy megastigma-4,6-dien-3-one (6), daidzin (7), genistin (8), isolariciresinol (9), ononin (10), 4',8-dimethoxy-7-O-ß-d-glucopyranosyl isoflavone (11), 3'-methoxydaidzein (12), odoratin (13), spasuberol A (14), (+)-pinoresinol (15), 4-hydroxy-3-methoxy cinnamic acid methyl ester (16), (+)-epipinoresinol (17), calycosin (18), 8-O-methylretusin (19), formononetin sodium (20), formononetin (21), biochanin A (22), butesuperin A (23), homovanillyl-4-oxo-nonanoate (24) and (6aR,11aR)-maackiain (25). The pharmacokinetic characteristics of these twenty-five compounds in rat plasma were quantitatively and simultaneously studied using a fast, sensitive and precise ultra fast liquid chromatography combined with electrospray ionization triple quadrupole tandem mass spectrometry (UFLC-MS/MS) method after oral administration of aqueous extract of SPC to rats. The mobile phase consists of acetonitrile and 0.5 mM ammonium acetate in water, and these compounds were well separated at a gradient elution program with flow rate of 0.35 mL/min. Carbamazepine was employed as the internal standard (IS) and all samples were precipitated with MeOH-ACN (2:1, v/v). The analytical method has been proved to be good linearity (R2 ≥ 0.9957), precise, accurate, stable, recovery and matrix effect, which applicated becomingly to study the pharmacokinetic processes of these compounds in rat plasma. In addition, these twenty-five compounds exhibited anti-inflammatory activity on the inflammatory model of NO over production in RAW264.7 cells stimulated by lipopolysaccharide (LPS). Isoflavones, especially compounds 20-22 (The IC50 of which were 22.75 µM, 21.11 µM and 48.29 µM, respectively.) might be the important constituents for anti-inflammatory activity of SPC. This study provides reference values for the clinical application, in-depth study on new dosage forms and pharmacological activities of SPC.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Animais , Anti-Inflamatórios/farmacologia , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Medicamentos de Ervas Chinesas/farmacologia , Ratos , Reprodutibilidade dos Testes
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