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1.
Artigo em Inglês | MEDLINE | ID: mdl-31655297

RESUMO

p-Nitrophenol (PNP) is one type of environmental pollutant, which is difficult to degrade and soluble in water. To investigate the effects of PNP on economically important marine fish species, we subjected Larimichthys crocea juvenile to five different concentrations of PNP for 96 h, and the semi-lethal concentration (LC50) was 6.218 mg/L. Then we collected the liver, kidney, and gill tissues to determine enzyme activity and gene expression levels, and analyzed histological changes. In histological analysis, the gills showed curling of lamella, epithelial lifting and hyperplasia; the parenchymal structure of hepatocytes was significantly damaged, with severe vacuolation and loss of original structure. The renal cells were damaged too, with congestion and renal tubular necrosis. Catalase and superoxide dismutase both showed an up- and down-tendency with the rise of concentration in the three tissues, and GSH-px had similar trend in the kidney, which decreased at 8 mg/L in the liver but showed no significant differences in the gills. Malondialdehyde of three tissues was increased with an increase in PNP concentration. The expression of four detoxification (cyp450, gst, gpx, hsp70) and one immune-related (mhc II) genes was induced at low PNP concentrations but inhibited at high PNP concentrations in the kidney. In liver, cyp450, hsp70 and mhc II showed similar trend but gst and gpx didn't increase at low PNP concentrations. Our results indicate that the fish possesses the ability to detoxify PNP; however, at high concentrations, PNP still causes serious damage to them. Our data not only help in understanding the ability of L. crocea to detoxify PNP but also should serve as a basis for the study of toxic effects of nitrobenzenes on marine fish.

2.
Int Immunopharmacol ; : 105979, 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31771816

RESUMO

Chronic obstructive pulmonary fibrosis (COPD) is a chronic and fatal lung disease with few treatment options. Sodium hydrosulfide (NaHS), a donor of hydrogen sulfide (H2S), was found to alleviate cigarette smoke (CS)-induced emphysema in mice, however, the underlying mechanisms have not yet been clarified. In this study, we investigated its effects on COPD in a CS-induced mouse model in vivo and in cigarette smoke extract (CSE)-stimulated alveolar epithelial A549 cells in vitro. The results showed that NaHS not only relieved emphysema, but also improved pulmonary function in CS-exposed mice. NaHS significantly increased the expressions of tight junction proteins (i.e., ZO-1, Occludin and claudin-1), and reduced apoptosis and secretion of pro-inflammatory cytokines (i.e., TNF-α, IL-6 and IL-1ß) in CS-exposed mouse lungs and CSE-incubated A549 cells, indicating H2S inhibits CS-induced inflammation, injury and apoptosis in alveolar epithelial cells. NaHS also upregulated prolyl hydroxylase (PHD)2, and suppressed hypoxia-inducible factor (HIF)-1α expression in vivo and in vitro, suggesting H2S inhibits CS-induced activation of PHD2/HIF-1α axis. Moreover, NaHS inhibited CS-induced phosphorylation of ERK, JNK and p38 MAPK in vivo and in vitro, and treatment with their inhibitors reversed CSE-induced ZO-1 expression and inflammation in A549 cells. These results suggest that NaHS may prevent emphysema via the suppression of PHD2/HIF-1α/MAPK signaling pathway, and subsequently inhibition of inflammation, epithelial cell injury and apoptosis, and may be a novel strategy for the treatment of COPD.

3.
Opt Express ; 27(6): 8348-8360, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-31052654

RESUMO

The development of a polar-view Kirkpatrick-Baez microscope, fielded in the upper polar zone of the Shenguang-III laser fusion facility, is presented. With this microscope, the resolving power of polar-direction X-ray imaging diagnostics is improved, to the 3 ~5 µm scale. The microscope is designed for implosion asymmetry studies, with response energy points at 1.2 keV, 3.5 keV, and 8 keV. A biperiodic multilayer scheme is adopted to accommodate multiple implosion stages. We present the overall optical system design, target aiming scheme, characteristic composite imaging diagnostic experiments and initial results. The inertial-driven quasi-one-dimensional spherical implosions were observed from orthogonal directions with a convergence ratio of ~14.4. Fine features of the stagnating hot spot core are also resolved.

4.
J Ethnopharmacol ; 237: 307-313, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30910581

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Angong Niuhuang Pill (ANP) is a well-known traditional Chinese patent medicine. This meta-analysis aimed to evaluate the efficacy and safety of ANP as an adjuvant therapy in patients with acute cerebral infarction (ACI) and acute intracerebral hemorrhage (AIH). MATERIALS AND METHODS: We performed a literature search in Embase, Pubmed, Cochrane Library, CNKI, Wanfang, and VIP database from their inceptions to April 2018. Randomized controlled trials evaluating ANP as an adjuvant therapy for acute stroke were selected. Risk ratio (RR) or weighted mean difference (WMD) with their 95% confidence interval (CI) was calculated between with and without ANP therapy. RESULTS: Eighteen trials involving 1,601 patients were identified and analyzed. Meta-analysis showed that ANP plus usual treatment significantly improved the total response rate in patients with ACI (RR 1.27; 95% CI 1.14-1.41) and AIH (RR 1.26; 95% CI 1.14-1.38) compared with the usual treatment alone. Adjuvant treatment with ANP also significantly reduced the neurologic deficit score in patients with ACI (WMD -3.64; 95% CI -4.97 to - 2.31) and AIH (WMD -3.52; 95% CI -5.51 to -1.54). Moreover, ANP significantly improved the Glasgow Coma Scale in patients with ACI (WMD 1.18; 95% CI 0.79-1.56) and AIH (WMD 2.28; 95% CI 1.37-3.19). CONCLUSIONS: Adjuvant treatment with ANP appears to improve the total response rate and neurologic deficit score in patients with ACI and AIH. More well-designed trials are required due to the suboptimal methodological quality of the included trials.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Food Addit Contam Part B Surveill ; 12(2): 90-96, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30632928

RESUMO

The occurrence of free and hidden fumonisins in raw maize and maize-based products from China was investigated. A total of 58 samples were analyzed using high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Among all the samples, 66% were contaminated with free fumonisins above limits of quantitation, and a higher percentage of 86% was found for total fumonisins (free + hidden). The highest contamination levels were observed in dried maize kernels which appeared mouldy, with mean levels of 15,737 and 30,785 µg/kg for free and total fumonisins, respectively. Frozen maize kernels, fresh maize kernels, and maize starch samples exhibited the lowest contamination levels, with no more than 200 µg/kg of total fumonisins. Except for one sample, the concentrations of total fumonisins were greater than those of free fumonisins with all the samples, the ratios of total-to-free fumonisins varied between 1.1 and 5.2, with an average ratio of 2.0.


Assuntos
Contaminação de Alimentos/análise , Fumonisinas/análise , Zea mays/química , China , Alimentos em Conserva/análise , Alimentos Congelados/análise , Humanos , Reprodutibilidade dos Testes , Sementes/química
6.
Fish Shellfish Immunol ; 84: 1170-1179, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30366089

RESUMO

Stress response has negative effect on fish in aquaculture and research, which can be alleviated with anesthetic. To determine the optimal anesthetic, we investigated the physiological response of crucian carp (Carassius auratus) treated with three different anti-stress treatments: MS-222, eugenol and percussive stunning. Stress responses were evaluated by analyzing serum cortisol level and gene expression in blood. We determined the optimal concentrations of MS-222 (100 mg L-1) and eugenol (20 mg L-1) by dose selection. We found that the control group had significantly higher cortisol levels (172.78 ±â€¯19.95 ng mL-1) compared to the MS-222 treated group (46.85 ±â€¯3.22 ng mL-1), the eugenol treated group (72.78 ±â€¯9.07 ng mL-1), and the stunning treatment group (82.78 ±â€¯8.16 ng mL-1). Transcriptome analysis revealed 1572 differentially expressed genes (DEGs), including 155 DEGs related to the stress response, mainly involved in oxidative-stress response, heat shock proteins, and cold shock domain-containing protein. The heat shock protein genes were the primary DEGs in response to stress. RT-qPCR analysis confirmed differential expression of Hsps. We analyzed the function of the DEGs, which were enriched in genes involved in cellular response to stress and antigen processing and presentation. Combining the results from biochemical, transcriptome, and gene expression analysis, our data suggest that eugenol is more effective than MS-222 and percussive stunning in alleviating stress in crucian carp.


Assuntos
Aminobenzoatos/farmacologia , Anestesia/veterinária , Anestésicos/farmacologia , Carpas/fisiologia , Eugenol/farmacologia , Hidrocortisona/sangue , Anestesia/métodos , Animais , Carpas/genética , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica/veterinária , Carpa Dourada/genética , Carpa Dourada/fisiologia , Longevidade/efeitos dos fármacos , Estresse Fisiológico
7.
Exp Physiol ; 103(11): 1532-1542, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30070749

RESUMO

NEW FINDINGS: What is the central question of this study? In this study, by using motor vehicle exhaust (MVE) exposure with or without lipopolysaccharide (LPS) instillation, we established, evaluated and compared MVE, LPS and MVE+LPS treatment-induced chronic obstructive pulmonary disease (COPD) models in mice. What is the main finding and its importance? Our study demonstrated that the combination of chronic exposure to MVE with early LPS instillation can establish a mouse model with some features of COPD, which will allow researchers to investigate the underlying molecular mechanisms linking air pollution and COPD pathogenesis. ABSTRACT: Although it is well established that motor vehicle exhaust (MVE) has a close association with the occurrence and exacerbation of chronic obstructive pulmonary disease (COPD), very little is known about the combined effects of MVE and intermittent or chronic subclinical inflammation on COPD pathogenesis. Therefore, given the crucial role of inflammation in the development of COPD, we wanted to establish an animal model of COPD using both MVE exposure and airway inflammation, which could mimic the clinical pathological changes observed in COPD patients and greatly benefit the study of the molecular mechanisms of COPD. In the present study, we report that mice undergoing chronic exposure to MVE and intratracheal instillation of lipopolysaccharide (LPS) successfully established COPD, as characterized by persistent air flow limitation, airway inflammation, inflammatory cytokine production, emphysema and small airway remodelling. Moreover, the mice showed significant changes in ventricular and vascular pathology, including an increase in right ventricular pressure, right ventricular hypertrophy and remodelling of pulmonary arterial walls. We have thus established a new mouse COPD model by combining chronic MVE exposure with early intratracheal instillation of LPS, which will allow us to study the relationship between air pollution and the development of COPD and to investigate the underlying molecular mechanisms.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Lipopolissacarídeos/efeitos adversos , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Animais , Modelos Animais de Doenças , Camundongos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
8.
Clin Neurol Neurosurg ; 171: 79-84, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29870886

RESUMO

OBJECTIVES: The aim of this study is to investigate the association of HDL-C with CCAS, as well as its intracranial or extracranial location in the Southern Chinese population. PATIENTS AND METHODS: 123 Southern Chinese patients with large-artery atherosclerotic(LAA) ischemic stroke were enrolled for the final analysis. Based on the stenosis severity defined by digital subtraction angiography, the patients were categorized into CCAS and non-CCAS groups. The degree of artery stenosis among patients of CCAS was classified into three grades. CCAS were further categorized into intracranial AS (ICAS), Extracranial AS (ECAS) and combined intra-/extra-cranial AS (IECAS). RESULTS: It was showed that patients with CCAS had a lower HDL-C level compared to NCCAS, and HDL-C levels were correlated to the degree of artery stenosis among CCAS. After adjusting for multiple potential confounders, low HDL-C level remained independently associated with CCAS(adjusted OR = 2.860). Patients with the lowest HDL-C quartile had a significantly increased risk for CCAS(adjusted OR: 5.771), referred to the highest quartile. But HDL-C levels in patients with ICAS, ECAS and IECAS were not significantly different, and there was no significant correlation between HDL-C levels and ICAS. CONCLUSION: Our data indicate that low HDL-C level is associated with CCAS in Southern Chinese patients with LAA ischemic stroke. But the effects of HDL-C on the distribution of CCAS is required to be further explored.


Assuntos
Estenose das Carótidas/etiologia , HDL-Colesterol/sangue , Arteriosclerose Intracraniana/etiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Grupo com Ancestrais do Continente Asiático , Aterosclerose , Constrição Patológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/sangue
9.
Front Mol Neurosci ; 11: 183, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29904342

RESUMO

In developing sensory systems, elaborate morphological connectivity between peripheral cells and first-order central neurons emerges via genetic programming before the onset of sensory activities. However, how the first-order central neurons acquire the capacity to interface with peripheral cells remains elusive. By making patch-clamp recordings from mouse brainstem slices, we found that a subset of neurons in the cochlear nuclei, the first central station to receive peripheral acoustic impulses, exhibits spontaneous firings (SFs) as early as at birth, and the fraction of such neurons increases during the prehearing period. SFs are reduced but not eliminated by a cocktail of blockers for excitatory and inhibitory synaptic inputs, implicating the involvement of intrinsic pacemaker channels. Furthermore, we demonstrate that these intrinsic firings (IFs) are largely driven by hyperpolarization- and cyclic nucleotide-gated channel (HCN) mediated currents (Ih), as evidenced by their attenuation in the presence of HCN blockers or in neurons from HCN1 knockout mice. Interestingly, genetic deletion of HCN1 cannot be fully compensated by other pacemaker conductances and precludes age-dependent up regulation in the fraction of spontaneous active neurons and their firing rate. Surprisingly, neurons with SFs show accelerated development in excitability, spike waveform and firing pattern as well as synaptic pruning towards mature phenotypes compared to those without SFs. Our results imply that SFs of the first-order central neurons may reciprocally promote their wiring and firing with peripheral inputs, potentially enabling the correlated activity and crosstalk between the developing brain and external environment.

10.
Biosci Rep ; 38(1)2018 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-29358309

RESUMO

In peripheral arterial disease (PAD) patients, occlusions in the major arteries that supply the leg makes blood flow dependent on the capacity of neovascularization. There is no current medication that is able to increase neovascularization to the ischemic limb and directly treat the primary problem of PAD. An increasing body of evidence supports the notion that inflammation plays an important role in the vascular remodeling and perfusion recovery after PAD. Interleukins (ILs), a group of proteins produced during inflammation, have been considered to be important for angiogenesis and arteriogenesis after tissue ischemia. This review summarizes the latest clinical and experimental developments of the role of ILs in blood perfusion recovery after PAD.


Assuntos
Inflamação/fisiopatologia , Interleucinas/metabolismo , Isquemia/fisiopatologia , Doença Arterial Periférica/sangue , Artérias/fisiopatologia , Humanos , Inflamação/sangue , Isquemia/sangue , Perna (Membro)/irrigação sanguínea , Perna (Membro)/fisiopatologia , Doença Arterial Periférica/fisiopatologia , Fluxo Sanguíneo Regional/fisiologia , Remodelação Vascular/fisiologia
11.
Mol Genet Genomics ; 293(3): 649-655, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29285564

RESUMO

The polymorphisms of cytokine genes has been reported to modulate the individual's susceptibility to environmental stimuli in COPD development. C-X-C motif chemokine 10 (CXCL10) mediates recruitment inflammatory cells such as monocytes. Therefore, it may play a key role in COPD. Here, a case-control study was conducted to evaluate the association between CXCL10 tag-SNPs and COPD risk. Four tag-SNPs including rs4256246, rs4508917, rs56061981, and rs56316945 were identified based on the linkage disequilibrium (LD) analysis in 30 healthy controls. The associations between these four tag-SNPs and COPD risk were further evaluated in 480 COPD cases and 488 controls. We found that the "T" allele of rs56061981 was significantly associated with reducing risk of COPD, while "G" allele of rs56316945 was significantly associated with increasing risk of COPD. SNP rs56316945 was significantly associated with increasing risk of COPD under different models except recessive model after adjusting the sex, age, pack year, and biomass. SNP rs56061981 was significantly associated with decreasing COPD risk under different models except recessive model after adjusting the sex, age, pack year, and biomass. Stratified analysis of smoking status and biomass with SNPs supported rs56061981 may interact with biomass and smoking thus modulate COPD susceptibility and rs56216945 was apparently associated with the severity of pulmonary function of COPD patients. This study suggests that rs56061981 and rs56216945 in CXCL10 gene promoter contribute COPD susceptibility.


Assuntos
Quimiocina CXCL10/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas
12.
Chem Commun (Camb) ; 53(91): 12329-12332, 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29098224

RESUMO

Reversible conversion of Cu2+ and Cu+ under illumination and with oxidation is demonstrated over CuxO/SrTiO3. Such Cu2+/Cu+ homeostasis together with its photosensitizer function and p-n heterojunction formation has lead to highly active and stable visible photocatalytic performance. This strategy will provide some new insights into the design of highly efficient photocatalysts.

13.
Sci Rep ; 7(1): 7760, 2017 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-28798396

RESUMO

Epimedium brevicornum Maxim has a long history of use in the treatment of estrogen deficiency-related diseases. However, the chemical constituents and mechanism of action of this medicinal plant are not fully understood. In the present study, we isolated four new isoprenylated flavonoid glycosides, as well as 16 known flavonoids (13 isoprenylated flavonoids), from this plant. The chemical structures of the new flavonoid glycosides were elucidated by extensive spectroscopic analysis. The new compounds 1-4 were potent promoters of estrogen biosynthesis in human ovarian granulosa-like KGN cells. ZW1, an isoprenylated flavonoid analogue and a specific inhibitor of phosphodiesterase 5 (PDE5), was synthesized and used to explore the mechanism of the isoprenylated analogues on estrogen biosynthesis. ZW1 treatment increased estrogen production by upregulation of aromatase mRNA and protein expression. ZW1 increased the phosphorylation of cAMP response element-binding protein (CREB). Further study showed that the inhibition of PDE5 by ZW1 increased estrogen biosynthesis partly through suppression of phosphodiesterase 3 (PDE3). Our results suggested that the isoprenylated flavonoids from E. brevicornum may produce beneficial health effects through the promotion of estrogen biosynthesis. PDE5 warrants further investigation as a new therapeutic target for estrogen biosynthesis in the prevention and treatment of estrogen-deficiency related diseases.


Assuntos
Epimedium/química , Estrogênios/biossíntese , Flavonoides/farmacologia , Glicosídeos/farmacologia , Células da Granulosa/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Linhagem Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Feminino , Flavonoides/química , Glicosídeos/química , Células da Granulosa/metabolismo , Humanos , Inibidores de Fosfodiesterase/química , Plantas Medicinais/química
14.
Oncotarget ; 8(69): 113734-113748, 2017 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-29371942

RESUMO

Type I interferons (IFN-α/ß) have broad and potent immunoregulatory and antiproliferative activities, which are negatively regulated by Src homology domain 2 containing tyrosine phosphatase-2 (SHP-2). Inhibition of SHP2 by small molecules may be a new strategy to enhance the effcacy of type I IFNs. Using an in vitro screening assay for new inhibitors of SHP2 phosphatase, we found that quercetin was a potent inhibitor of SHP2. Computational modeling showed that quercetin exhibited an orientation favorable to nucleophilic attack in the phosphatase domain of SHP2. Quercetin enhanced the phosphorylation of signal transducer and activator of transcription proteins 1 (STAT1) and promoted endogenous IFN-α-regulated gene expression. Furthermore, quercetin also sensitized the antiproliferative effect of IFN-α on hepatocellular carcinoma HepG2 and Huh7 cells. The overexpression of SHP2 attenuated the effect of quercetin on IFN-α-stimulated STAT1 phosphorylation and antiproliferative effect, whereas the inhibition of SHP2 promoted the effect of quercetin on IFN-α-induced STAT1 phosphorylation and antiproliferative effect. The results suggested that quercetin potentiated the inhibitory effect of IFN-α on cancer cell proliferation through activation of JAK/STAT pathway signaling by inhibiting SHP2. Quercetin warrants further investigation as a novel therapeutic method to enhance the efficacy of IFN-α/ß.

15.
J Am Chem Soc ; 138(47): 15307-15310, 2016 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-27933926

RESUMO

In spite of widespread interest in rotaxane-based molecular machines and materials, rotaxanes have not been attached covalently to proteins. We describe the near-quantitative aqueous synthesis of [2]rotaxanes based on neutral and charged aqueous hosts-cucurbit[7]uril (CB7) and cyclobis(paraquat-p-phenylene) (CBPQT4+), respectively-using the thiol-ene addition of cysteine and maleimide as a stoppering protocol. After verifying the high efficiency of the reaction using glutathione (GSH) as an oligopeptide stopper, we have employed cytochrome C (CytC) as a protein stopper to produce the first well-characterized protein-rotaxane bioconjugates. We anticipate that this methodology will enable the preparation of novel materials that combine the unique properties of proteins and mechanical bonds.


Assuntos
Citocromos c/química , Glutationa/química , Oligopeptídeos/química , Rotaxanos/síntese química , Água/química , Citocromos c/metabolismo , Estrutura Molecular , Oligopeptídeos/metabolismo , Rotaxanos/química
16.
Bioorg Med Chem Lett ; 26(22): 5497-5500, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27765509

RESUMO

Estrogen biosynthesis is pivotal to many physiological processes of human. Aberrant estrogen level is closely related to a variety of diseases, including breast cancer and osteoporosis. Previously we found that 2-phenylbenzo[b]furan glycosides could promote estrogen biosynthesis. To find high active 2-phenylbenzo[b]furans, fifty-four 2-phenylbenzo[b]furans were prepared via four strategies according to corresponding substrate scopes. Biological evaluation in HEK293A cells showed that some compounds exhibited promotive activity on estrogen biosynthesis. 2-(4-Chlorophenyl)-7-methoxybenzo[b]furan possessed the highest activity with EC50 value of 14.68µM. Furthermore, these compounds did not affect aromatase expression in HEK292A cells, indicating that these 2-phenylbenzo[b]furans might enhance estrogen biosynthesis via directly allosteric regulation of aromatase or indirectly via posttranslational modification.


Assuntos
Derivados de Benzeno/química , Derivados de Benzeno/farmacologia , Estrogênios/agonistas , Estrogênios/metabolismo , Furanos/química , Furanos/farmacologia , Aromatase/metabolismo , Derivados de Benzeno/síntese química , Vias Biossintéticas/efeitos dos fármacos , Furanos/síntese química , Células HEK293 , Humanos
17.
Food Nutr Res ; 60: 31288, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27356910

RESUMO

BACKGROUND: Type I interferons (IFN-α/ß) have broad and potent immunoregulatory and antiproliferative activities. However, it is still known whether the dietary flavonoids exhibit their antiviral and anticancer properties by modulating the function of type I IFNs. OBJECTIVE: This study aimed at determining the role of apigenin, a dietary plant flavonoid abundant in common fruits and vegetables, on the type I IFN-mediated inhibition of cancer cell viability. DESIGN: Inhibitory effect of apigenin on human 26S proteasome, a known negative regulator of type I IFN signaling, was evaluated in vitro. Molecular docking was conducted to know the interaction between apigenin and subunits of 26S proteasome. Effects of apigenin on JAK/STAT pathway, 26S proteasome-mediated interferon receptor stability, and cancer cells viability were also investigated. RESULTS: Apigenin was identified to be a potent inhibitor of human 26S proteasome in a cell-based assay. Apigenin inhibited the chymotrypsin-like, caspase-like, and trypsin-like activities of the human 26S proteasome and increased the ubiquitination of endogenous proteins in cells. Results from computational modeling of the potential interactions of apigenin with the chymotrypsin site (ß5 subunit), caspase site (ß1 subunit), and trypsin site (ß2 subunit) of the proteasome were consistent with the observed proteasome inhibitory activity. Apigenin enhanced the phosphorylation of signal transducer and activator of transcription proteins (STAT1 and STAT2) and promoted the endogenous IFN-α-regulated gene expression. Apigenin inhibited the IFN-α-stimulated ubiquitination and degradation of type I interferon receptor 1 (IFNAR1). Apigenin also sensitized the inhibitory effect of IFN-α on viability of cervical carcinoma HeLa cells. CONCLUSION: These results suggest that apigenin potentiates the inhibitory effect of IFN-α on cancer cell viability by activating JAK/STAT signaling pathway through inhibition of 26S proteasome-mediated IFNAR1 degradation. This may provide a novel mechanism for increasing the efficacy of IFN-α/ß.

18.
J Asian Nat Prod Res ; 18(7): 711-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26982651

RESUMO

One new ursane-type triterpenoid (1), named granditriol, along with 14 known compounds (2-15), was isolated from the organic extracts of Schisandra grandiflora stems. The structure of the new compound was elucidated by extensive spectroscopic methods as 28-norursa-12,17,19,21-tetraen-2α,3α,23-triol. These isolates were evaluated for anti-phytopathogenic fungi activity and cytotoxicity against human cancer cell line (HepG2). Asiatic acid (8) and 2α,3α,19α-trihydroxyurs-12-en-28-oic acid (9) inhibited the growth of two plant pathogens, Alternaria alternata and Alternaria solani. In addition, compounds 12, 15, and 11 displayed notable anti-proliferative activity against HepG2 cells. Compound 1 is the first report of 28-nortriterpenoid from the Schisandraceae family. All these were obtained from this plant for the first time.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Schisandra/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Estrutura Molecular , Caules de Planta/química , Triterpenos/química
19.
Food Chem ; 141(1): 488-94, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23768384

RESUMO

Procyanidin dimers, trimers, and tetramers are absorbable, whereas larger oligomers are not. Procyanidins in cranberries are bioactive components that help prevent chronic diseases; however, 85% of cranberry procyanidins are large oligomers or polymers with a degree of polymerization above four. The objective of this study was to depolymerize cranberry procyanidins, particularly the polymers, into absorbable oligomers. Partially purified cranberry procyanidins (PCP) were obtained using chromatographic methods. The resultant extract contained predominant polymers with a degree of polymerization above ten (77.2% w/w). The extract was depolymerized, using 0.1 or 1M methanolic HCl, with (+)-catechin, (-)-epicatechin, or (-)-epigallocatechin gallate (EGCG) added as chain breakers. Depolymerization converted polymers into A-type and B-type dimers, trimers and tetramers. Use of EGCG as a chain breaker resulted in A- and B-type oligomers with EGCG as a terminal unit, indicating that the added flavan-3-ol attached to the C4 carbocations from procyanidins during depolymerization. The yield of B-type oligomers was higher than that of A-type oligomers. The yield increased when higher amounts of flavan-3-ols were used for depolymerization. EGCG, as a chain breaker, produced fewer procyanidin oligomers than did catechin or epicatechin. This research provided a practical approach that may enhance the bioavailability and bioactivity of procyanidins in cranberries.


Assuntos
Catequina/análogos & derivados , Catequina/química , Extratos Vegetais/química , Proantocianidinas/química , Vaccinium macrocarpon/química , Polimerização
20.
Eur J Med Chem ; 59: 265-73, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23237974

RESUMO

A new dibenzocyclooctene-type lignan, named schisandrin A1 (1), together with nine known lignans (2-10), was isolated from the stems of Schisandra sphenathera. The structure of schisandrin A1, which contains a spirocyclic epoxy unit, was established by means of spectroscopic methods. The absolute configurations of schisandrin A1 (1) and schisantherin A (2) were determined by electronic circular dichroism (CD) and TDDFT calculations, with 2 further confirmed by X-ray crystallographic data. Ten new schisantherin A derivatives (11-20) and 6,7-secoschisantherol A (2b) were synthesized. In addition, natural lignans and semisynthetic schisantherin A derivatives showed the antiproliferative activity on four human cancer cell lines and Id1 (an inhibitor of DNA binding protein) and estrogenic potency. Compounds 5, 7, and 8 exhibited very potent estrogenic activity.


Assuntos
Antineoplásicos , Estrogênios , Lignanas/química , Lignanas/farmacologia , Schisandra/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dicroísmo Circular , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Estrogênios/química , Estrogênios/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Teoria Quântica
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