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1.
Nat Prod Res ; 34(2): 225-232, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30580619

RESUMO

One new aryldihydronaphthalene-type lignan (1) together with eight known lignans (2-4, 7-11) as well as two caffeic-acid dimers (5, 6) were isolated from an ethanol extract of the whole plant of Corispermum mongolicum Iljin (Chenopodiaceae). The chemical structures of these compounds were determined from 1D and 2D NMR and HR-ESI-MS spectra, and results were compared with data from the literature. This study is the first demonstration of nine compounds (2 and 4-11) isolated from the Chenopodiaceae family, with one of these (3) from the genus Corispermum. Anti-inflammatory effects of the isolated compounds were evaluated in terms of inhibition of production of nitric oxide, tumour necrosis factor-α, and interleukin-6 in lipopolysaccharide-induced RAW 264.7 cells.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31015848

RESUMO

Mongolian medicine RuXian-I is composed of 30 Mongolian herbs, which is a traditional Mongolian recipe for clinical treatment of breast "Qi Su Bu Ri Le Du Sen" disease (hyperplasia of mammary glands, HMG). Based on the previous study, this dissertation further explores the therapeutic mechanism of RuXian-I on estrogen-induced HMG in rats. RuXian-I had no effect on the body weight and food intake of HMG rats and had no toxic effects on the five organs (heart, lung, spleen, and kidney). RuXian-I reduced the diameter and height of nipple, organ index, and pathological changes and alleviated the sex hormone levels oh HMG; RuXian-I reduced the upregulation of TCTP, Mcl-1, and Bcl-xL in breast tissue of mammary gland hyperplasia and increased the downregulation of p53, Bax, caspase-9, and caspase-3 protein. RuXian-I has an effective therapeutic activity on HMG rats, and its possible therapeutic mechanism is closely related to antiapoptosis protein TCTP-regulated apoptosis.

3.
Nat Prod Res ; 33(2): 226-232, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29468903

RESUMO

A new benzofuran, methyl (2S,2″S,3'E)-[2-(1″-acetoxypropan-2-yl)-2,3-dihydrobenzofuran-5-yl]acrylate (1), and 13 known compounds (2-14) were isolated from an ethanol extract of Artemisia halodendron Turcz. ex Bess. The chemical structures of these compounds were determined by 1D and 2D NMR (1H-1H COSY, HMBC, HMQC and NOESY) and HR-ESI-MS spectra, and results were compared with data from the literature. The effects of compounds 1-14 were measured on NF-κB activation, with compounds 2 and 3 exhibiting inhibitory activities against TNF-α-induced NF-κB reporter gene expression in HeLa cells from 10 to 100 µM.


Assuntos
Artemisia/química , Benzofuranos/isolamento & purificação , Benzofuranos/farmacologia , Etanol , Células HeLa/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia
4.
Nat Prod Res ; 33(20): 3021-3024, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30580580

RESUMO

A new flavanone glycoside, (2S)-dihydrooroxylin A 7-O-[ß-D-apiosyl(1→2)]-ß-D-glucoside (1), and four known compounds (2-5) were isolated from Tournefortia sibirica L. The chemical structures of these compounds were determined by 1 D and 2 D NMR and HR-ESI-MS spectra, and results were compared with data from the literature. These five compounds (1-5) were isolated from the family Boraginaceae for the first time. Anti-inflammatory effects of compounds (1-5) were evaluated in terms of inhibition of production of NO, TNF-α, and IL-6 in LPS-induced RAW 264.7 cells.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Boraginaceae/química , Flavanonas/isolamento & purificação , Glicosídeos/isolamento & purificação , Animais , Anti-Inflamatórios/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Glicosídeos/química , Interleucina-6/antagonistas & inibidores , Interleucina-6/biossíntese , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Extratos Vegetais/química , Células RAW 264.7 , Análise Espectral , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese
5.
Cell Physiol Biochem ; 51(3): 1399-1409, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30485839

RESUMO

BACKGROUND/AIMS: Temporal lobe epilepsy (TLE) is the most common form of adult localization-related epilepsy that is accompanied by progressive etiopathology and high incidences of drug resistance. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression, however, the expression profile and clinical significance of circRNAs in TLE remains unknown. METHODS: Circular RNA microarray was conducted to identify TLE-related circRNAs. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in TLE in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in TLE cell. RESULTS: 586 differentially expressed circRNAs were identified between TLE and the control tissues. The expression of circRNA-0067835 was significantly down-regulated in tissues and plasma from TLE patients. Lower circRNA-0067835 correlated to increased seizure frequency, HS, and higher Engel's score. Overexpression of circRNA-0067835 observably decreased SH-SY5Y cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. CONCLUSION: Our experiments showed that circRNA-0067835 regulated refractory epilepsy progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with TLE.


Assuntos
Epilepsia do Lobo Temporal/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , MicroRNAs/genética , RNA/genética , Linhagem Celular , Proliferação de Células , Epilepsia do Lobo Temporal/patologia , Proteína Forkhead Box O3/genética , Humanos
6.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(1): 16-18, 2018 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926652

RESUMO

OBJECTIVE: To investigate the effects of total flavonids of astragalus(TFA) on arrhythmia, endoplasmic reticulum stress and connexcin in mice with viral myocarditis and to clarify the mechanisms of TFA against viral myocarditis complicated with arrhythmia. METHODS: Thirty-six male Balb/c mice were randomly divided into control group, viral myocarditis group and total flavonoids group (n=12). The mice of viral myocarditis were intraperitonealy injected with 0.1 ml/day 10-950 TCID CVB3 for 3 days. The mice of TFA group were intraperitoneal injected with 0.1 ml/day 10-950 TCID CVB3 for 3 days and treated with 0.1ml, 20 mg/L TFA by tail vein injection. At the end of the experiment, arrhythmia was detected by electrocardiogram, the heart of mice were stained by HE, the expressions of glucose-regulated protein 78(GRP78), endoplasmic reticulum stress signaling pathway factor activating transcription factor 4(ATF4) and connexcin 43(Cx43) were detected by Western blot. RESULTS: The expressions of GRP78 and ATF4 were increased and the expression of Cx43 was decreased in viral myocarditis, while TFA inhibited these effect of viral myocarditis in heart of mice. CONCLUSIONS: The antiarrhythmic effect of TFA may be related to the alleviation of endoplasmic reticulum stress and the increase of Cx43 expression.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Astrágalo (Planta)/química , Infecções por Coxsackievirus/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Flavonoides/farmacologia , Miocardite/tratamento farmacológico , Fator 4 Ativador da Transcrição/metabolismo , Animais , Conexina 43/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Proteínas de Choque Térmico/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Miocardite/virologia , Miocárdio
7.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(2): 159-163, 2018 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926682

RESUMO

OBJECTIVES: To investigate the effect of Astragalus injection on cardiomyocyte apoptosis, endoplasmic reticulum stress and connexin protein in cardiomyopathy rats induced by adriamycin. METHODS: Thirty-six male Wister rats were randomly divided into control group (n=12), adriamycin(ADR) group (n=12) and Astragalus group (n=12). The normal saline (10 ml/kg body weight) was injected intraperitoneally in control group rats, ADR (2 mg/kg body weight) was injected intraperitoneally in ADR group rats, ADR (10 ml/kg body weight) and Astragalus injection (10 ml/kg body weight) were injected intraperitoneally in rats of astragalus group, one time a week, totle 3 times. By the end of the 7th week, the left ventricular end-diastolic diameter(LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Then the rats in the three groups were sacrificed and the left ventricle section was stained by HE, Masson, uranyl acetate/lead citrate respectively, the cardiomyopathy and ultrastructural changes were observed under light microscope and transmission electron microscope. The apoptosis of rat cardiomyocyte were analyzed by TUNEL. The expression of connexin Cx43 and p-Cx43 was detected by immunohistochemistry. The expression of glucose-regulated protein 78 (Grp78),activating transcription factor 4 (ATF-4) and C/EBP homologous protein (CHOP) were detected by real time PCR. RESULTS: Compared with control group, LVEDD, LVESD increased and LVEF decreased, myocardial fibers were disordered and edematous, infiltrated by lymphocytes, the mitochondria were destroyed and vacuolized, and the number of cardiomyocyte apoptosis was increased(P<0.01) in ADR group. The expression of Grp78, ATF-4, CHOP and p-Cx43 were increased, and the expression of Cx43 was decreased in ADR group. However, compared with ADR group, LVEDD, LVESD decreased and LVEF increased, the cardiomyopathy and ultrastructural changes were significantly improved, the number of cardiomyocyte apoptosis was significantly decreased (P<0. 01); the expression of Grp78, ATF-4, CHOP and p-Cx43 decreased (P<0.01); the expression of Cx43 increased in Astragalus group (P<0.01). CONCLUSIONS: Astragalus injection may effectively improve the myocardial damage induced by adriamycin, its mechanism may be related to the inhibition of endoplasmic reticulum stress (ERS) and the decrease of phosphorylation of CX43 in cardiomyopathy rats induced by adriamycin.


Assuntos
Apoptose , Astrágalo (Planta)/química , Cardiomiopatias/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Animais , Cardiomiopatias/induzido quimicamente , Doxorrubicina/efeitos adversos , Masculino , Miócitos Cardíacos/citologia , Distribuição Aleatória , Ratos , Ratos Wistar
8.
Oncotarget ; 9(9): 8542-8547, 2018 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-29492215

RESUMO

Mesial temporal lobe epilepsy (mTLE), the most common type of temporal lobe epilepsy (TLE), is particularly relevant due to its high frequency of therapeutic resistance of anti-epileptic therapies. MicroRNAs (miRNAs) have been shown to be dysregulated in epilepsy and neurodegenerative diseases, and we hypothesized that miRNAs could be involved in the pathogenesis of MTLE. The present study aimed to explore the expression and functions of miRNA-153 in mTLE. The expression levels of miRNA-153 in refractory TLE patients were evaluated. The bioinformatics analysis showed that the potential target genes of miR-153 were involved in biological processes, molecular functions, and cellular components. miRNA-153 is significantly dysregulated in temporal cortex and plasma of mTLE patients. We identify HIF-1α as a direct target of miRNA-153, and luciferase reporter assays demonstrated that miR-153 could regulate the HIF-1αexpression via 3'-UTR pairing. These data suggest that miR-153 might represent a useful biomarker and treatment target for patients with mTLE.

9.
Acta Cardiol Sin ; 34(1): 77-86, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29375227

RESUMO

Background: Micro-RNAs (miRNAs) are small non-coding RNAs that modulate many target genes. Viral myocarditis is common cardiomyopathy, however, there is an absence of effective therapeutic strategies for viral myocarditis (VMC). The purpose of this research was to characterize changes in miRNAs expression in VMC mice. Methods: Atrial myocytes were infected coxsackievirus B3 and miRNAs microarray was performed. miRNAs target predicted and the bioinformatics analysis was carried out by gene ontology (GO) and KEGG pathway analysis. To validate the results, Difference miRNAs were identified in heart of mice by real-time polymerase chain reaction (PCR). Results: We identified 94 miRNAs that were differentially expressed (27 were up-regulated and 67 were down-regulated by at least 2.0-fold). Real time PCR analysis has confirmed that the expression levels of 7 miRNAs up-regulated, 18 miRNAs down-regulated. They were mainly involved in protein binding, small GTPase mediated signal transduction, protein phosphorylation by GO. Pathway analysis showed that a significant enrichment in several pathways related to cAMP signaling pathway, AMPK signaling pathway, RAS signaling pathway, Rap1 signaling pathway, ErbB signaling pathway, Oxytocin signaling pathway. Conclusions: Our results provide a better understanding of the mechanisms of viral myocarditis pathophysiology.

10.
Med Mol Morphol ; 51(2): 96-101, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29282541

RESUMO

Inhibiting endoplasmic reticulum stress (ERS)-induced apoptosis may be a new therapeutic target in cardiovascular diseases. Creatine phosphate disodium salt (CP) has been reported to have cardiovascular protective effect, but its effects on ERS are unknown. The aim of this study was to identify the mechanism by which CP exerts its cardioprotection in doxorubicin (Dox)-induced cardiomyocytes injury. In our study, neonatal rats cardiomyocytes (NRC) was randomly divided into control group, model group, and treatment group. The cell viability and apoptosis were detected. grp78, grp94, and calumenin of the each group were monitored. To investigate the role of calumenin, Dox-induced ERS was compared in control and down-regulated calumenin cardiomyocytes. Our results showed that CP decreased Dox-induced apoptosis and relieved ERS. We found calumenin increased in Dox-induced apoptosis with CP. ERS effector C/EBP homologous protein was down-regulated by CP and it was influenced by calumenin. CP could protect NRC by inhibiting ERS, this mechanisms may be associated with its increasing of calumenin.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Cardiotoxicidade/prevenção & controle , Doxorrubicina/efeitos adversos , Miócitos Cardíacos/efeitos dos fármacos , Fosfocreatina/farmacologia , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/genética , Cardiotônicos/farmacologia , Cardiotoxicidade/etiologia , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas de Choque Térmico/genética , Miócitos Cardíacos/patologia , Ratos , Fator de Transcrição CHOP/metabolismo
11.
Pharmacogn Mag ; 13(51): 517-522, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28839382

RESUMO

BACKGROUND: Sugemule-3 (SD) is a traditional Chinese medicine with protective effect of myocardium. However, the underlying mechanisms of the effect had not been elucidated. MATERIALS AND METHODS: In the present study, the serum of SD was prepared. A model of ß-adrenergic agonist isoprenaline (ISO)-induced H9c2 cardiomyocytes injury was established in vitro. The changes in cell viability were examined to determine the available concentration of ISO and serum of SD. ELISA, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and flow cytometry were used to detect the effect of serum of SD on oxidative stress and apoptosis. The expression levels of the mitochondria-dependent apoptotic pathway and mitogen-activated protein kinase signalling-related proteins were analyzed. RESULTS: Incubation with different dose of ISO (0.015, 0.01, 0.005, and 0.0025 mol/L) for 24 h caused dose-dependent loss of cell viability and 0.01 mol/L of ISO approximately reduced the cell viability to 50%. Pretreatment with 50 µ mol/L serum of SD effectively decreased the levels of ISO-induced cell toxicity. Serum of SD relived ISO-induced oxidative stress and apoptosis in H9c2 cardiomyocytes. A further mechanism study indicated that serum of SD inhibited the mitochondria-dependent apoptotic pathways and regulated the expression levels of Bcl-2 family. ISO activated ERK and P38, whereas serum of SD inhibited their activation. CONCLUSION: Serum of SD inhibits the ISO-induced activation of the mitochondria-dependent apoptotic pathway, oxidative stress, and ERK, P38 inactivation. Serum of SD is used for the treatment of ISO-induced cardiomyopathy. SUMMARY: The serum of SD pretreatment significantly ameliorated ISO-induced H9c2 cardiomyocytes injuries.The protective effect related with apoptosis and oxidative stressInhibition of MAPK pathway was involed in serum of SD induced cardioprotection.The serum of SD is used for the treatment of ISO-induced cardiomyopathy. Abbreviations used: ELISA: Enzyme-linked Immunosorbent Assay; TUNEL: TdT-mediated dUTP nick end labeling; MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, DMSO: dimethyl sulfoxide; MDA: Malondialdehyde; SOD: Superoxide Dismutase; GSH-Px: Glutathione peroxidase.

12.
Heart Vessels ; 32(2): 208-215, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27639990

RESUMO

Atrial fibrillation (AF) is a complex disease with multiple inter-relating causes culminating in rapid atrial activation and atrial structural remodeling. The contribution of endoplasmic reticulum and mitochondria stress to AF has been highlighted. As the class III antiarrhythmic agent, ibutilide are widely used to AF. This study was designed to explore whether ibutilide could treat AF by inhibiting endoplasmic reticulum stress pathways and mitochondria stress. The neonatal rat cardiomyocytes were isolated and exposed to H2O2, ibutilide was add to the culture medium 12 h. Then the cell viability, oxidative stress levels and apoptotic rate were analyzed. In addition, endoplasmic reticulum stress related protein (GRP78, GRP94, CHOP), mitochondria-dependent protein (Bax, Bcl-2) and caspase-3/9/12 were identified by real-time PCR and western blot analysis. In our results, remarkable decreased cell viability and oxidative stress levels were detected in cardiomyocytes after treating with H2O2. The apoptotic rate and the expression of proteins involved in mitochondrial stress and endoplasmic reticulum stress pathways increased. While ibutilide significantly inhibited these changes. These data suggested that ibutilide serves a protective role against H2O2-induced apoptosis of neonatal rat cardiomyocytes, and the mechanism is related to suppression of mitochondrial stress and endoplasmic reticulum stress.


Assuntos
Retículo Endoplasmático/metabolismo , Mitocôndrias/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Oxidantes/toxicidade , Substâncias Protetoras/farmacologia , Sulfonamidas/farmacologia , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Ratos
14.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 33(4): 304-307, 2017 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926634

RESUMO

OBJECTIVE: To investigate the effects of silencing miRNA378* on apoptosis, endoplasmic reticulum stress and calumenin of cardiomyocyte with coxsackie virus B3 (CVB3) infection. METHODS: Primary cultured suckling mouse myocardium were divided into control group (normal cell), coxsackie virus infection group (normal cell and coxsackie virus B3), miRNA378* control group (normal cell +coxsackie virus B3+miRNA378* empty plasmid), miRNA378* silencing plasmid group(normal cells + coxsackie virus B3 + miRNA378* silencing plasmid). Four groups of cells were transfected, infected and treated in CO2 incubator at 37℃. The α-SMA protein, cell apoptosis rate, calumenin, glucose regulated protein 78 (GRP78), activation transcription factor 6(ATF6) and transcription factors c/ebp homologue protein (CHOP) in endoplasmic reticulum were analyzed. RESULTS: By detecting α-SMA protein, the isolated suckling mouse ventricular myocardium were confirmed. TUNEL detection of different groups of ventricular cell apoptosis found that coxsackie virus group of ventricular myocytes apoptosis was significant. Compared with the coxsackie virus infection group of myocardial cells, miRNA378* silencing plasmid expression of cardiomyocyte apoptosis cells significantly reduced(P<0.01). The expressions of GRP78, ATF6 and CHOP were increased compared with those infected by Coxsackie virus infection (P<0.01), while the expressions of calumenin were decreased (P<0.01). CONCLUSIONS: CVB3 infected myocardial cells effected miRNA378* expression. It can trigger endoplasmic reticulum stress and activates signaling pathway factor and increase myocardial cell apoptosis.>.


Assuntos
Apoptose , Proteínas de Ligação ao Cálcio/metabolismo , Infecções por Coxsackievirus/metabolismo , Estresse do Retículo Endoplasmático , MicroRNAs/genética , Miócitos Cardíacos/metabolismo , Actinas/metabolismo , Fator 6 Ativador da Transcrição/metabolismo , Animais , Animais Recém-Nascidos , Células Cultivadas , Proteínas de Choque Térmico/metabolismo , Camundongos , Miocárdio , Miócitos Cardíacos/virologia , Cultura Primária de Células , Transdução de Sinais , Fator de Transcrição CHOP/metabolismo
15.
Bioorg Med Chem Lett ; 26(6): 1576-1579, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26876930

RESUMO

The transcription factor nuclear factor-κB (NF-κB) controls many physiological processes including inflammation, immunity, and apoptosis. In this study, a novel series of 6-phenoxy-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide derivatives were synthesized as potent anti-inflammatory agents, which acted on tumor necrosis factor (TNF-α) as inhibitors of NF-κB activation. We showed that compounds 6h (6-(2,4-dichlorophenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide) and 6i (6-(3-tolyloxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide) showed more prominent anti-inflammatory activity than other compounds, with similar activities as the reference drug dihydrotanshinone; compound 6i showed the lowest cellular toxicity among the tested compounds. In vivo evaluation of the anti-inflammatory activity showed that compound 6i exhibited excellent anti-inflammatory activity with 58.19% inhibition at 50mg/kg intraperitoneal (i.p.), with equal efficacy as the positive control indomethacin (100mg/kg i.p.; 59.21% inhibition).


Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Ftalazinas/síntese química , Ftalazinas/farmacologia , Triazóis/síntese química , Triazóis/farmacologia , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/tratamento farmacológico , Células HeLa , Humanos , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , NF-kappa B/metabolismo , Ftalazinas/administração & dosagem , Ftalazinas/química , Relação Estrutura-Atividade , Triazóis/administração & dosagem , Triazóis/química , Fator de Necrose Tumoral alfa/metabolismo , Xilenos
16.
Molecules ; 20(11): 20741-76, 2015 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-26610448

RESUMO

Epilepsy affects about 1% of the world's population. Due to the fact all antiepileptic drugs (AEDs) have some undesirable side effects and about 30% of epileptic patients are not seizure-free with the existing AEDs, there is still an urgent need for the development of more effective and safer AEDs. Based on our research work on antiepileptic compounds and other references in recent years, this review covers the reported work on antiepileptic compounds which are classified according to their structures. This review summarized 244 significant anticonvulsant compounds which are classified by functional groups according to the animal model data, although there are some limitations in the data. This review highlights the properties of new compounds endowed with promising antiepileptic properties, which may be proven to be more effective and selective, and possibly free of unwanted side effects. The reviewed compounds represent an interesting possibility to overcome refractory seizures and to reduce the percentage of patients with a poor response to drug therapy.


Assuntos
Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Descoberta de Drogas , Epilepsia , Pesquisa , Animais , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Humanos , Relação Estrutura-Atividade
17.
Molecules ; 20(4): 5528-53, 2015 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-25826789

RESUMO

Tetrazoles represent a class of five-membered heterocyclic compounds with polynitrogen electron-rich planar structural features. This special structure makes tetrazole derivatives useful drugs, explosives, and other functional materials with a wide range of applications in many fields of medicine, agriculture, material science, etc. Based on our research works on azoles and other references in recent years, this review covers reported work on the synthesis and biological activities of tetrazole derivatives.


Assuntos
Tetrazóis/síntese química , Tetrazóis/farmacologia , Analgésicos/síntese química , Analgésicos/química , Analgésicos/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anticonvulsivantes/síntese química , Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Anti-Hipertensivos/síntese química , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Estrutura Molecular , Tetrazóis/química
18.
Med Chem ; 11(6): 595-601, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25770755

RESUMO

Aim to find new compounds with stronger anticonvulsant activity and lower neurotoxicity, a novel series of 6-substituted-pyrido[3,2-d]pyridazine derivatives was synthesized using furo[3,4-b]pyridine-5,7-dione as the starting material. We evaluated their anticonvulsant activity and neurotoxicity using by maximal electroshock (MES) and rotarod neurotoxicity (TOX) tests. The results showed that N-m-chlorophenyl-[1,2,4]triazolo- [4,3-b]-pyrido[3,2- d]pyridazin-6-amine (3) was the most potent anticonvulsant, with ED50 value of 13.6 mg/kg and protective index ( PI = TD50/ED50) values of 7.2 in the MES test. Compound N-m-chlorophenyltetriazolo[5,1-b]-pyrido[3,2-d]pyridazin-6-amine (19), exhibited significant anticonvulsant activity in maximal electroshock test with PI value of 13.4, which was safer than marketed drug carbamazepine.


Assuntos
Anticonvulsivantes/síntese química , Anticonvulsivantes/farmacologia , Desenho de Drogas , Movimento/efeitos dos fármacos , Piridazinas/farmacologia , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/química , Relação Dose-Resposta a Droga , Eletrochoque , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Piridazinas/síntese química , Piridazinas/química
19.
Molecules ; 19(11): 18090-101, 2014 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-25379645

RESUMO

VirG is outer membrane protein of Shigella and affects the spread of Shigella. Recently it has been reported that apyrase influences the location of VirG, although the underlying mechanism remains poorly understood. The site of interaction between apyrase and VirG is the focus of our research. First we constructed recombinant plasmid pHIS-phoN2 and pS-(v1-1102, v53-758, v759-1102, v53-319, v320-507, v507-758) by denaturation-renaturation, the phoN2:kan mutant of Shigella flexneri 5a M90T by a modified version of the lambda red recombination protocol originally described by Datsenko and Wanner and the complemented strain M90TΔphoN2/pET24a(PhisphoN2). Second, the recombinant plasmid pHIS-phoN2 and the pS-(v1-1102, v53-758, v759-1102, v53-319, v320-507, v507-758) were transformed into E. coli BL21 (DE3) and induced to express the fusion proteins. Third, the fusion proteins were purified and the interaction of VirG and apyrase was identified by pull-down. Fourth, VirG was divided and the interaction site of apyrase and VirG was determined. Finally, how apyrase affects the function of VirG was analyzed by immunofluorescence. Accordingly, the results provided the data supporting the fact that apyrase combines with the α-domain of VirG to influence the function of VirG.


Assuntos
Apirase/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Shigella flexneri/metabolismo , Fatores de Transcrição/metabolismo , Apirase/genética , Proteínas de Bactérias/genética , Proteínas de Ligação a DNA/genética , Ligação Proteica , Estrutura Terciária de Proteína , Shigella flexneri/genética , Fatores de Transcrição/genética
20.
Molecules ; 19(10): 16179-89, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25310147

RESUMO

The aim of this work was to develop a new method for constructing vectors, named ligation-independent cloning (LIC) method. We constructed the S label expression vector and recombinant pET32a (+) S-phoN2 by LIC. The recombinant proteins were expressed in E. coli at a high level, and then the specificity of the recombinant proteins was identified by western blot. The target band was detected by S monoclonal antibody and Apyrase polyclonal antibodies but not Trx monoclonal antibody and HIS monoclonal antibody. Finally, we obtained protein Apyrase in E. coli (BL21), with a protein-only expression S tag. Collectively, our results demonstrated that LIC is effective for the construction of new vectors and recombinant plasmids. Free from the limitations of restriction enzyme sites and with a higher positive rate, LIC processes should find broad applications in molecular biology research.


Assuntos
Clonagem Molecular/métodos , Expressão Gênica , Vetores Genéticos/genética , Proteínas Recombinantes/genética
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