Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 50
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Med Food ; 22(5): 508-520, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31084540

RESUMO

In this study, we investigated the antioxidant and protective effect of Lindera glauca stem (LGS) extracts against oxidative stress. We compared antioxidant properties of water extract (LGSW) with ethanol extract (LGSE) by determining the contents responsible for antioxidant activities such as polyphenols and flavonoids. Antioxidant properties were also determined by 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity and ferric reducing antioxidant power (FRAP). Lipid peroxidation was estimated using ferric thiocyanate (FTC) and thiobarbituric acid (TBA) method. Both LGSW and LGSE strongly inhibited lipid peroxidation. Especially, LGSE showed a protective effect through increasing cell viability, decreasing intracellular reactive oxygen species (ROS) against tert-butyl hydroperoxide-induced oxidative stress in Chang cells. Furthermore, LGSE increased antioxidant related enzyme activities such as catalase, glutathione S-transferase, glutathione peroxidase, and superoxide dismutase gene expression against oxidative stress in a zebrafish model. Our findings suggest that LGSE could be useful for developing potential therapeutic agents with protective effects against oxidative stress.


Assuntos
Lindera/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/química , terc-Butil Hidroperóxido/farmacologia , Catalase/metabolismo , Linhagem Celular , Glutationa Peroxidase/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Extratos Vegetais/química , Caules de Planta/química , Polifenóis/química , Polifenóis/farmacologia , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , terc-Butil Hidroperóxido/química
2.
Biomed Res Int ; 2019: 5073085, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30911544

RESUMO

The aim of the present study was to investigate the antiosteoclastogenic effects of black rice (Oryza sativa L.) fermented with Lactobacillus casei (LAB) in RANKL-induced RAW macrophage cells and its antiosteoporosis activity against ovariectomy-induced osteoporosis in rats. LAB extract (LABE) treatment attenuated receptor activator of nuclear factor-kappa B (NF-κB) ligand-induced osteoclastic differentiation in RAW cells by inhibiting intercellular reactive oxygen species generation and downregulating the activation of mitogen-activated protein kinases and NF-κB, leading to the downregulation of c-Fos and expression of nuclear factor of activated T cells c1. This consequently suppressed the expression of osteoclast-specific genes including those for cathepsin K, tartrate-resistant acid phosphatase, calcitonin receptor, and integrin ß3. Oral administration of LABE protected against ovariectomy-induced bone loss by significantly inhibiting bone architecture alterations and improving serum bone turnover markers in ovariectomized rats. The findings suggest that the antiosteoporotic activity of LABE may be derived from its antiosteoclastic and anti-bone-resorptive activities. LABE has potential as a promising functional material or substrate to prepare protective agents for osteoporosis and osteoclast-mediated bone diseases.


Assuntos
Lactobacillus casei , Oryza , Osteoclastos/metabolismo , Osteoporose , Animais , Feminino , Camundongos , Osteoclastos/patologia , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/patologia , Ovariectomia , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley
3.
World J Gastroenterol ; 24(25): 2673-2685, 2018 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-29991873

RESUMO

Inflammatory bowel disease (IBD) is a serious health concern among western societies. The disease is also on the rise in some East Asian countries and in Australia. Health professionals and dietitians around the world are facing an unprecedented challenge to prevent and control the increasing prevalence of IBD. The current therapeutic strategy that includes drugs and biological treatments is inefficient and are associated with adverse health consequences. In this context, the use of natural products is gaining worldwide attention. In vivo studies and clinical evidence suggest that well-planned dietary regimens with specific nutrients can alleviate gastrointestinal inflammation by modulating inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin 1 (IL-1), IL-6, IL-1ß, and IL-10. Alternatively, the avoidance of high-fat and high-carbohydrate diets is regarded as an effective tool to eliminate the causes of IBD. Many functional foods and bioactive components have received attention for showing strong therapeutic effects against IBD. Both animal and human studies suggest that bioactive functional foods can ameliorate IBD by downregulating the pro-inflammatory signaling pathways, such as nuclear factor κB, STAT1, STAT6, and pro-inflammatory cytokines, including IL-1ß, IL-4, IL-6, COX-2, TNF-α, and interferon γ. Therefore, functional foods and diets have the potential to alleviate IBD by modulating the underlying pathogenic mechanisms. Future comprehensive studies are needed to corroborate the potential roles of functional foods and diets in the prevention and control of IBD.


Assuntos
Terapias Complementares/métodos , Dietoterapia/tendências , Suplementos Nutricionais , Alimento Funcional , Doenças Inflamatórias Intestinais/terapia , Animais , Produtos Biológicos/uso terapêutico , Terapias Complementares/tendências , Citocinas/metabolismo , Dietoterapia/métodos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Mediadores da Inflamação/metabolismo , Doenças Inflamatórias Intestinais/etiologia , Resultado do Tratamento
4.
Molecules ; 23(3)2018 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-29518052

RESUMO

This study aimed to determine the anti-osteoclastogenic effects of extracts from Aronia melanocarpa 'Viking' (AM) and identify the underlying mechanisms in vitro. Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW 264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL) were also investigated. RANKL triggers many transcription factors through the activation of mitogen-activated protein kinase (MAPK) and ROS, leading to the induction of osteoclast-specific genes. The extracts significantly suppressed RANKL-induced activation of MAPKs, such as extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38 and consequently led to the downregulation of c-Fos and nuclear factor of activated T cells 1 (NFATc1) protein expression which ultimately suppress the activation of the osteoclast-specific genes, cathepsin K, TRAP, calcitonin receptor and integrin ß3. In conclusion, our findings suggest that AM extracts inhibited RANKL-induced osteoclast differentiation by downregulating ROS generation and inactivating JNK/ERK/p38, nuclear factor kappa B (NF-κB)-mediated c-Fos and NFATc1 signaling pathway.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Photinia/química , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ligante RANK/metabolismo , Animais , Antocianinas/química , Antioxidantes/química , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Flavonoides , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Fenóis , Compostos Fitoquímicos/química , Extratos Vegetais/química , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
5.
J Agric Food Chem ; 66(1): 99-107, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-29260547

RESUMO

The present study aimed to evaluate the preventive effects of highbush blueberry (Vaccinium corymbosum L.) vinegar (BV) on cognitive functions in a scopolamine (Sco)-induced amnesia model in mice. In this study, Sco (1 mg/kg, intraperitoneal injection) was used to induce amnesia. ICR mice were orally administered donepezil (5 mg/kg), blueberry extract (120 mg/kg), and BV (120 mg/kg) for 7 days. After inducing cognitive impairment by Sco, a behavioral assessment using behavior tests (i.e., Y-maze and passive avoidance tests) was performed. The BV group showed significantly restored cognitive function in the behavioral tests. BV facilitated cholinergic activity by inhibiting acetylcholinesterase activity, and enhanced antioxidant enzyme activity. Furthermore, BV was found to be rehabilitated in the cornu ammonis 1 neurons of hippocampus. In our study, we demonstrated that the memory protection conferred by BV was linked to activation of brain-derived neurotrophic factor (BDNF)/cAMP response element binding protein (CREB)/serine-threonine kinase (AKT) signaling.


Assuntos
Amnésia/tratamento farmacológico , Mirtilos Azuis (Planta)/química , Cognição/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Acetilcolina/metabolismo , Acetilcolinesterase/metabolismo , Amnésia/induzido quimicamente , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Aprendizagem em Labirinto , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Escopolamina/toxicidade
6.
Int J Mol Sci ; 18(9)2017 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-28880216

RESUMO

N-acetyltransferase 10 (NAT10) has been considered a target for the treatment of human diseases such as cancer and laminopathies; however, its functional role in the biology of melanocytes is questionable. Using a small molecule or small interfering RNA targeting NAT10, we examined the effect of NAT10 inhibition on melanogenesis and melanoma growth in human and mouse melanoma cells. Genetic silencing or chemical inhibition of NAT10 resulted in diminished melanin synthesis through the suppression of melanogenesis-stimulating genes such as those encoding dopachrome tautomerase (DCT) and tyrosinase in B16F10 melanoma cells. In addition, NAT10 inhibition significantly increased cell cycle arrest in S-phase, thereby suppressing the growth and proliferation of malignant melanoma cells in vitro and in vivo. These results demonstrate the potential role of NAT10 in melanogenesis and melanoma growth through the regulation of microphthalmia-associated transcription factor (MITF) expression and provide a promising strategy for the treatment of various skin diseases (melanoma) and pigmentation disorders (chloasma and freckles).


Assuntos
Hidrazonas/farmacologia , Melanoma/metabolismo , Fator de Transcrição Associado à Microftalmia/metabolismo , Acetiltransferase N-Terminal A/metabolismo , Tiazóis/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Melaninas/metabolismo , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Fator de Transcrição Associado à Microftalmia/genética , Acetiltransferase N-Terminal A/genética
7.
Int J Mol Sci ; 18(3)2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28257048

RESUMO

Recent studies have shown that vanillin has anti-cancer, anti-mutagenic, and anti-metastatic activity; however, the precise molecular mechanism whereby vanillin inhibits metastasis and cancer progression is not fully elucidated. In this study, we examined whether vanillin has anti-cancer and anti-metastatic activities via inhibition of hypoxia-inducible factor-1α (HIF-1α) in A2058 and A375 human malignant melanoma cells. Immunoblotting and quantitative real time (RT)-PCR analysis revealed that vanillin down-regulates HIF-1α protein accumulation and the transcripts of HIF-1α target genes related to cancer metastasis including fibronectin 1 (FN1), lysyl oxidase-like 2 (LOXL2), and urokinase plasminogen activator receptor (uPAR). It was also found that vanillin significantly suppresses HIF-1α mRNA expression and de novo HIF-1α protein synthesis. To understand the suppressive mechanism of vanillin on HIF-1α expression, chromatin immunoprecipitation was performed. Consequently, it was found that vanillin causes inhibition of promoter occupancy by signal transducer and activator of transcription 3 (STAT3), but not nuclear factor-κB (NF-κB), on HIF1A. Furthermore, an in vitro migration assay revealed that the motility of melanoma cells stimulated by hypoxia was attenuated by vanillin treatment. In conclusion, we demonstrate that vanillin might be a potential anti-metastatic agent that suppresses metastatic gene expression and migration activity under hypoxia via the STAT3-HIF-1α signaling pathway.


Assuntos
Benzaldeídos/farmacologia , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Melanoma/genética , Melanoma/metabolismo , Fator de Transcrição STAT3/metabolismo , Linhagem Celular Tumoral , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ativação Transcricional
8.
J Nutr Biochem ; 28: 103-13, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26878787

RESUMO

Inflammatory bowel disease (IBD) is an inflammatory disorder caused by hyperactivation of effector immune cells that produce high levels of proinflammatory cytokines. The aims of our study were to determine whether orally administered blueberry extract (BE) could attenuate or prevent the development of experimental colitis in mice and to elucidate the mechanism of action. Female Balb/C mice (n=7) were randomized into groups differing in treatment conditions (prevention and treatment) and dose of BE (50 mg/kg body weight). Acute ulcerative colitis was induced by oral administration of 3% dextran sodium sulfate for 7 days in drinking water. Colonic mucosal injury was assessed by clinical, macroscopic, biochemical and histopathological examinations. BE significantly decreased disease activity index and improved the macroscopic and histological score of colons when compared to the colitis group (P<.05). BE markedly attenuated myeloperoxidase accumulation (colitis group 54.97±2.78 nmol/mg, treatment group 30.78±1.33 nmol/mg) and malondialdehyde in colon and prostaglandin E2 level in serum while increasing the levels of superoxide dismutase and catalase (colitis group 11.94±1.16 U/ml, BE treatment group 16.49±0.39 U/ml) compared with the colitis group (P<.05). mRNA levels of the cyclooxygenase (COX)-2, interferon-γ, interleukin (IL)-1ß and inducible nitric oxide synthase cytokines were determined by reverse transcriptase polymerase chain reaction. Immunohistochemical analysis showed that BE attenuates the expression of COX-2 and IL-1ß in colonic tissue. Moreover, BE reduced the nuclear translocation of nuclear transcription factor kappa B (NF-κB) by immunofluorescence analysis. Thus, the anti-inflammatory effect of BE at colorectal sites is a result of a number of mechanisms: antioxidation, down-regulation of the expression of inflammatory mediators and inhibition of the nuclear translocation of NF-κB.


Assuntos
Antioxidantes/metabolismo , Mirtilos Azuis (Planta)/química , Colite Ulcerativa/prevenção & controle , Sulfato de Dextrana/toxicidade , Mediadores da Inflamação/metabolismo , Extratos Vegetais/uso terapêutico , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Feminino , Camundongos
9.
Sci Rep ; 6: 18928, 2016 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-26740011

RESUMO

Prolyl hydroxylase domain protein 2 (PHD2) belongs to an evolutionarily conserved superfamily of 2-oxoglutarate and Fe(II)-dependent dioxygenases that mediates homeostatic responses to oxygen deprivation by mediating hypoxia-inducible factor-1α (HIF-1α) hydroxylation and degradation. Although oxidative stress contributes to the inactivation of PHD2, the precise molecular mechanism of PHD2 inactivation independent of the levels of co-factors is not understood. Here, we identified disulfide bond-mediated PHD2 homo-dimer formation in response to oxidative stress caused by oxidizing agents and oncogenic H-ras(V12) signalling. Cysteine residues in the double-stranded ß-helix fold that constitutes the catalytic site of PHD isoforms appeared responsible for the oxidative dimerization. Furthermore, we demonstrated that disulfide bond-mediated PHD2 dimerization is associated with the stabilization and activation of HIF-1α under oxidative stress. Oncogenic H-ras(V12) signalling facilitates the accumulation of HIF-1α in the nucleus and promotes aerobic glycolysis and lactate production. Moreover, oncogenic H-ras(V12) does not trigger aerobic glycolysis in antioxidant-treated or PHD2 knocked-down cells, suggesting the participation of the ROS-mediated PHD2 inactivation in the oncogenic H-ras(V12)-mediated metabolic reprogramming. We provide here a better understanding of the mechanism by which disulfide bond-mediated PHD2 dimerization and inactivation result in the activation of HIF-1α and aerobic glycolysis in response to oxidative stress.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Estresse Oxidativo , Sequência de Aminoácidos , Linhagem Celular Tumoral , Cistina/metabolismo , Glicólise , Humanos , Oxirredução , Multimerização Proteica , Estabilidade Proteica , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
10.
Int J Oncol ; 48(1): 399-408, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26573871

RESUMO

Recent studies have shown anticancer activity of apigenin by suppressing glucose transporter 1 (GLUT1) expression in cultured cancer cells; however, it is not clear whether apigenin can suppress glucose metabolism in lung cancer cells or sensitize them to inhibition of glutamine utilization-mediated apoptosis through metabolic and oxidative stress. We show that apigenin significantly decreases GLUT1 expression in mice. Furthermore, we demonstrate that apigenin induces growth retardation and apoptosis through metabolic and oxidative stress caused by suppression of glucose utilization in lung cancer cells. The underlying mechanisms were defined that the anticancer effects of apigenin were reversed by ectopic GLUT1 overexpression and galactose supplementation, through activation of pentose phosphate pathway-mediated NADPH generation. Importantly, we showed that severe metabolic stress using a glutaminase inhibitor, compound 968, was involved in the mechanism of sensitization by apigenin. Taken together, the combination of apigenin with inhibitors of glutamine metabolism may provide a promising therapeutic strategy for cancer treatment.


Assuntos
Apoptose/efeitos dos fármacos , Transportador de Glucose Tipo 1/biossíntese , Neoplasias Pulmonares/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Apigenina/administração & dosagem , Benzofenantridinas/administração & dosagem , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 1/antagonistas & inibidores , Transportador de Glucose Tipo 1/genética , Glutamina/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , NADP/metabolismo , Espécies Reativas de Oxigênio/metabolismo
11.
Molecules ; 20(12): 21157-66, 2015 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-26633318

RESUMO

Apigenin, a nonmutagenic flavonoid, has been found to have antitumor properties and is therefore particularly relevant for the development of chemotherapeutic agents for cancers. In this study, time- and dose-dependent cell viability and cytotoxicity were assessed to determine the effects of apigenin on A2058 and A375 melanoma cells. Melanoma cells were pretreated with different concentrations of apigenin and analyzed for morphological changes, anoikis induction, cell migration, and levels of proteins associated with apoptosis. Apigenin reduced integrin protein levels and inhibited the phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK1/2), which induce anoikis in human cutaneous melanoma cells. Apigenin exhibited dose-dependent inhibition of melanoma cell migration, unlike untreated controls. Furthermore, apigenin treatment increased apoptotic factors such as caspase-3 and cleaved poly(ADP-ribose) polymerase in a dose-dependent manner, demonstrating the metastasis of melanoma cells. Our results provide a new insight into the mechanisms by which apigenin prevents melanoma metastasis by sensitizing anoikis induced by the loss of integrin proteins in the FAK/ERK1/2 signaling pathway. These findings elucidate the related mechanisms and suggest the potential of apigenin in developing clinical treatment strategies against malignant melanoma.


Assuntos
Anoikis/efeitos dos fármacos , Apigenina/farmacologia , Movimento Celular/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/antagonistas & inibidores , Integrinas/antagonistas & inibidores , Melanoma/patologia , Apoptose/efeitos dos fármacos , Western Blotting , Proliferação de Células/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/genética , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Integrinas/genética , Integrinas/metabolismo , Melanoma/tratamento farmacológico , Melanoma/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
12.
J Nanosci Nanotechnol ; 15(11): 8870-5, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26726609

RESUMO

The effects of compact TiO2 overlayers, deposited on TiO2 photoelectrodes through the hydrolysis of TiCl4, on the overall performance of dye-sensitized solar cells (DSSCs) were investigated. A thermal treatment at high-enough temperature was required for a more effective and higher dye-loading of the compact TiO2 overlayers. This led to improvements in the crystallinity and porosity of the layer, which contributed to higher power conversion efficiencies (PCE) of DSSCs compared with the electrodes prepared at relatively lower temperatures. Moreover, the existence of an additional secondary overlayer led to an increase in the net PCE of the cells by increasing the amount of dye-loading, even though this layer itself, in the absence of a first overlayer formed under high thermal treatment, did not enhance cell efficiency, because of the higher charge transport resistance over the layers and an increase in surface states.

13.
Phytochemistry ; 114: 125-36, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25457483

RESUMO

Ganoderma lucidum is a popular medicinal mushroom with anti-inflammatory potential. In the present study, the aim was to determine the anti-inflammatory effect and mode of action of G. lucidum grown on germinated brown rice (GLBR) in a mouse model of colitis. It was shown that GLBR suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated macrophages and decreased the expression of COX-2, TNF-α, iNOS, IL-1ß, IL-6, and IL-10 mRNAs. GLBR also inhibited activation of p38, ERK, JNK, MAPKs, and nuclear factor kappa-B (NF-κB). In a mouse model of colitis, colonic mucosal injury was evaluated using macroscopic, biochemical, and histopathological testing. Disease activity index (DAI), macroscopic score, and histological score significantly decreased upon GLBR treatment. Moreover, immunofluorescence studies indicated that DSS activates nuclear translocation of NF-κB in colon tissue, which is attenuated by GLBR extract. These findings suggest that GLBR is protective against colitis via inhibition of MAPK phosphorylation and NF-κB activation.


Assuntos
Anti-Inflamatórios/farmacologia , Oryza/microbiologia , Reishi/química , Animais , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Interleucina-10 , Interleucina-1beta/imunologia , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Biochem Biophys Res Commun ; 452(4): 1016-21, 2014 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-25234597

RESUMO

It is becoming clear that PRMT5 plays essential roles in cell cycle progression, survival, and responses to external stresses. However, the precise mechanisms underlying such roles of PRMT5 have not been clearly understood. Previously, we have demonstrated that PRMT5 participates in cellular adaptation to hypoxia by ensuring 5'-cap dependent translation of HIF-1α. Given that c-Myc and cyclin D1 expressions are also tightly regulated in 5'-cap dependent manner, we here tested the possibility that PRMT5 promotes cell proliferation by increasing de novo syntheses of the oncoproteins. c-Myc and cyclin D1 were found to be noticeably downregulated by PRMT5 knock-down. A RNA immunoprecipitation analysis, which can identify RNA-protein interactions, showed that PRMT5 is required for the interaction among eIF4E and 5'-UTRs of HIF-1α, c-Myc and cyclin D1 mRNAs. In addition, PRMT5 knock-down inhibited cell proliferation by inducing cell cycle arrest at the G1 phase. More importantly, ectopic expression of eIF4E significantly rescued the cell cycle progression and cell proliferation even in PRMT5-deficeint condition. Based on these results, we propose that PRMT5 determines cell fate by regulating 5'-cap dependent translation of proteins essential for proliferation and survival.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Biossíntese de Proteínas , Proteína-Arginina N-Metiltransferases/metabolismo , Linhagem Celular Tumoral , Humanos
15.
Anticancer Res ; 34(8): 4087-93, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25075033

RESUMO

Few studies have been performed on the anticancer activity of hispidin, a phenolic compound produced from the medicinal mushroom Phellinus linteus. Herein, we studied hispidin-induced apoptosis, which is associated with the generation of reactive oxygen species (ROS) in colon cancer cells. Hispidin was found to reduce cell viability both in mouse and human colon cancer cells. Apoptotic cell morphological changes were observed by microscopy, and apoptosis was assessed in hispidin-treated cells using a biochemical method. The results showed accumulation of the sub-G1 cell population and increase in early apoptosis in a dose-dependent manner. In addition, hispidin induced apoptosis through up-regulation of both intrinsic and extrinsic apoptotic pathways. Although the molecular mechanism underlying hispidin-induced apoptosis is known to involve the generation of ROS, however hispidin did not show any apoptosis in the pre-treatment with a ROS scavenger, N-acetyl-L-cysteine. In conclusion, hispidin induces both intrinsic and extrinsic apoptotic pathways mediated by ROS in colon cancer cells, thereby suggesting that hispidin could be a promising new anticancer agent.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Pironas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Acetilcisteína/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Citometria de Fluxo , Humanos
16.
Molecules ; 19(7): 9403-18, 2014 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-24995924

RESUMO

We aimed to investigate the antioxidant and acetylcholinesterase inhibitory activities of the anthocyanin rich extract of grape skin. Grape skin anthocyanin (GSA) neutralized free radicals in different test systems, such as 2,-2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, to form complexes with Fe2+ preventing 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced erythrocyte hemolysis and oxidative DNA damage. Moreover, GSA decreased reactive oxygen species (ROS) generation in isolated mitochondria thus inhibiting 2',-7'-dichlorofluorescin (DCFH) oxidation. In an in vivo study, female BALB/c mice were administered GSA, at 12.5, 25, and 50 mg per kg per day orally for 30 consecutive days. Herein, we demonstrate that GSA administration significantly elevated the level of antioxidant enzymes in mice sera, livers, and brains. Furthermore, GSA inhibited acetylcholinesterase (AChE) in the in vitro assay with an IC50 value of 363.61 µg/mL. Therefore, GSA could be an excellent source of antioxidants and its inhibition of cholinesterase is of interest with regard to neurodegenerative disorders such as Alzheimer's disease.


Assuntos
Acetilcolinesterase/química , Inibidores da Colinesterase/farmacologia , Depuradores de Radicais Livres/farmacologia , Extratos Vegetais/farmacologia , Vitis/química , Animais , Benzotiazóis/química , Compostos de Bifenilo/química , Inibidores da Colinesterase/química , Dano ao DNA , Avaliação Pré-Clínica de Medicamentos , Eritrócitos/efeitos dos fármacos , Eritrócitos/fisiologia , Feminino , Depuradores de Radicais Livres/química , Frutas/química , Hemólise , Concentração Inibidora 50 , Camundongos Endogâmicos BALB C , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Oxirredução , Estresse Oxidativo , Picratos/química , Extratos Vegetais/química , Ácidos Sulfônicos/química
17.
Molecules ; 18(8): 9293-304, 2013 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-23917116

RESUMO

Inonotus obliquus (IO) is parasitic mushroom that grows on birch and other trees in Russia, Korea, Europe and United States. However, IO is not readily available for consumption due to its high cost and difficult growth. In this regard, IO was inoculated on germinated brown rice (GBR) in the present study and the antioxidant and anti-inflammatory activities of the IO grown on germinated brown rice (IOGBR) extracts were evaluated extensively and compared with those for IO and GBR. IOGBR showed highest antioxidant activities with scavenging total intracellular ROS and MDA levels as well as increasing the antioxidant enzymes activity in the H2O2-stimulated mice liver. It also exhibited best inflammatory activities by suppressing the proinflammatory mediators such as NO, PGE2, iNOS, COX-2, TNF-α, IL-1ß, and IL-6 in an LPS-stimulated RAW 264.7 cell line. This study provides a comparative approach to find out an excellent natural source of antioxidants and anti-inflammatory agent as a dietary supplement.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Oryza/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Basidiomycota/química , Basidiomycota/crescimento & desenvolvimento , Suplementos Nutricionais , Germinação/fisiologia , Peróxido de Hidrogênio/toxicidade , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos , Oryza/crescimento & desenvolvimento , Extratos Vegetais/química
18.
Food Chem Toxicol ; 60: 439-47, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23941773

RESUMO

Cordycepin is known to have many pharmacological effects such as anti-tumorigenic, anti-inflammatory and anti-angiogenic activity. However, cordycepin induced apoptosis through the DR3 pathway in human colon cancer cells has not been studied. The effect of cordycepin on anti-proliferation was investigated in this study. Cordycepin significantly inhibited cell viability in a dose and time-dependent manner. Cordycepin increased sub G1 and G2/M phase arrest on HT-29 cells at the concentration of 100 µM, whereas cordycepin at 200 µM and 400 µM increased G1 phase arrest. Cordycepin induced apoptosis in HT-29 cells in a dose-dependent manner as detected by Hoechst and Annexin V-FITC staining. Intracellular ROS levels were higher in cordycepin treated cells as compared to control cells. The protein related to apoptosis was determined by antibody array. p53 and Bax expression increased treatment with cordycepin for 18 h. DR3, caspase-8, caspase-1, cleaved caspase-3 and cleaved PARP expression increased. These finding suggest that the cordycepin induces apoptosis through the DR3 pathway in human colon cancer HT-29. These findings suggest that cordycepin should be evaluated further as a therapeutic agent in human colon cancer.


Assuntos
Antineoplásicos/farmacologia , Desoxiadenosinas/farmacologia , Membro 25 de Receptores de Fatores de Necrose Tumoral/metabolismo , Transdução de Sinais , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Fase G1/efeitos dos fármacos , Células HT29 , Humanos , Espécies Reativas de Oxigênio , Membro 25 de Receptores de Fatores de Necrose Tumoral/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
19.
Molecules ; 18(6): 7253-70, 2013 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-23783459

RESUMO

Accumulating epidemiological and clinical study indicates that inflammation is a significant risk factor to develop various human diseases such as inflammatory bowel disease (IBD), chronic asthma, rheumatoid arthritis, multiple sclerosis, and psoriasis. Suppressing inflammation is therefore important to control or prevent various diseases. Among them, IBD is one of the major problems affecting people worldwide. IBD affects at least one in a thousand persons in many Western countries. Various natural products have been shown to safely suppress pro-inflammatory pathway and control IBD. In vivo and/or in vitro studies indicate that anti-IBD effects of natural products occur by inhibition of the expression of pro-inflammatory cytokines (for example, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule expression and pro-inflammatory mediators (such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2), master transcription factors (such as nuclear factor-κB (NF-κB)), reactive oxygen species (ROS) and by improving the antioxidant activity. In this review, we summarize recent research focused on IBD and the effects that natural products have on IBD factors.


Assuntos
Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/etiologia , Animais , Anti-Inflamatórios/farmacologia , Produtos Biológicos/farmacologia , Humanos , Resultado do Tratamento
20.
Molecules ; 18(6): 6663-78, 2013 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-23749158

RESUMO

In this study, the acetylcholinesterase inhibition and in vitro and in vivo antioxidant activities of Ganoderma lucidum grown on germinated brown rice (GLBR) were evaluated. In antioxidant assays in vitro, GLBR was found to have strong metal chelating activity, DPPH, ABTS, hydroxyl and superoxide radical scavenging activity. Cell-based antioxidant methods were used, including lipid peroxidation on brain homogenate and AAPH-induced erythrocyte haemolysis. In antioxidant assays in vivo, mice were administered with GLBR and this significantly enhanced the activities of antioxidant enzymes in the mice sera, livers and brains. The amount of total phenolic and flavonoid compounds were 43.14 mg GAE/g and 13.36 mg CE/g dry mass, respectively. GLBR also exhibited acetylcholinesterase inhibitory activity. In addition, HPLC analyses of GLBR extract revealed the presence of different phenolic compounds. These findings demonstrate the remarkable potential of GLBR extract as valuable source of antioxidants which exhibit interesting acetylcholinesterase inhibitory activity.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Oryza/microbiologia , Reishi/química , Acetilcolinesterase/metabolismo , Animais , Ácido Ascórbico/química , Carotenoides/química , Catalase/metabolismo , Quelantes/química , Quelantes/farmacologia , Eritrócitos/efeitos dos fármacos , Feminino , Flavonoides/química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Glutationa/metabolismo , Hemólise/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Licopeno , Camundongos , Oxirredução/efeitos dos fármacos , Fenóis/química , Extratos Vegetais/química , Reishi/crescimento & desenvolvimento , Superóxido Dismutase/metabolismo , beta Caroteno/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA