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1.
In Vitro Cell Dev Biol Anim ; 55(5): 355-367, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30993557

RESUMO

N-terminal acetylation (Nt-acetylation) refers to the acetylation of the free α-amino group at the N-terminus of a polypeptide. While the effects of Nt-acetylation are multifaceted, its most known function is in the acetylation-dependent N-end rule protein degradation pathway (Ac/N-end rule pathway), where Nt-acetylation is recognized as a degron by designated E3 ligases, eventually leading to target degradation by the ubiquitin-proteasome system. Naa10 is the catalytic subunit of the major Nt-acetylation enzyme NatA, which Nt-acetylates proteins whose second amino acid has a small side chain. In humans, NAA10 is the responsible mutated gene in Ogden syndrome and is thought to play important roles in development. However, it is unclear how the Ac/N-end rule pathway affects the differentiation ability of mouse embryonic stem cells (mESCs). We hypothesized that the balance of pluripotency factors may be maintained by the Ac/N-end rule pathway. Thus, we established Naa10 knockout mESCs to test this hypothesis. We found that Naa10 deficiency attenuated differentiation towards the epiblast lineage, deviating towards primitive endoderm. However, this was not caused by disturbing the balance of pluripotency factors, rather by augmenting FGF/MAPK signaling.


Assuntos
Linhagem da Célula/genética , Camadas Germinativas/crescimento & desenvolvimento , Células-Tronco Embrionárias Murinas/metabolismo , Acetiltransferase N-Terminal A/genética , Acetiltransferase N-Terminal E/genética , Acetilação , Animais , Diferenciação Celular/genética , Endoderma/crescimento & desenvolvimento , Endoderma/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Técnicas de Inativação de Genes , Camadas Germinativas/metabolismo , Humanos , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Acetiltransferase N-Terminal A/metabolismo , Acetiltransferase N-Terminal E/metabolismo , Processamento de Proteína Pós-Traducional/genética , Proteólise , Ubiquitina/genética , Ubiquitina-Proteína Ligases/genética
2.
Artigo em Inglês | MEDLINE | ID: mdl-28828029

RESUMO

Red ginseng and its active ingredients have been shown to decrease neuron death after brain ischemia in experimental animals. However, little is known about the effects of orally administered ginseng extract on spinal cord injury. We orally gave red ginseng extract (RGE) to rats with compressed spinal cord injury (SCI). Open-field locomotor scores were measured as indices of motor function. Histopathological changes and cytokine expressions in situ after SCI were evaluated. Compared to vehicle treatment, RGE treatment (350 mg/kg/day) significantly improved locomotor score up to levels close to those pre-SCI, prevented neuron loss, and facilitated the restoration of white matter in the spinal cord at 14 days after SCI. Treatment with RGE caused less aggregation of Iba-1-positive microglia in grey and white matter at 7 days after SCI, upregulated the expression levels of VEGF and Bcl-xL, and reduced IL-1ß and TNFα expressions in the spinal cord at 7 and 14 days after SCI. We concluded that oral administration of RGE facilitates almost complete functional recovery from motor and behavioral abnormalities in rats with SCI and prevents neuron death in situ, possibly through inhibition of inflammation and upregulation of neuroprotective factors in the injured spinal cord.

3.
J Nat Med ; 68(1): 83-94, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23649674

RESUMO

We examined the effects on cell proliferation of 10 methoxyfurocoumarins and 7 dihydrofurocumarins isolated from Umbelliferae medicinal plants, and their mechanisms of action against B16F10 melanoma cells or in melanin-possessing hairless mice implanted with B16F10 melanoma cells, under UVA irradiation. Furocoumarins having a methoxy group, such as bergapten (1), xanthotoxin (2), phellopterin (4), byakangelicin (6), neobyakangelicin (8), isobergapten (9) and sphondin (10), showed anti-proliferative activity and caused G2/M arrest at concentrations of 0.05-15.0 µM. The 7 dihydrofurocoumarins had no effect. UVA plus 1, 2, 4, 6 and sec-O-acetylbyakagelicin (7), having one methoxy group at the C-5 position and a linear-type conformation, reduced tumor growth and final tumor weight in B16F10-bearing mice at 0.5 or 1.0 mg/kg (intraperitoneal injection). UVA plus 1 and 2 increased Chk1 phosphorylation and decreased cdc2 (Thr 161) phosphorylation in the melanoma cells. The anti-tumor actions of UVA plus furocoumarins having a methoxy group might be due to the arrest of the cell cycle at G2/M through an increase in phospho-Chk1 and reduction in phospho-cdc2.


Assuntos
Angelica , Cnidium , Furocumarinas/farmacologia , Melanoma Experimental/tratamento farmacológico , Terapia PUVA , Radiossensibilizantes/farmacologia , Angelica/química , Animais , Proteína Quinase CDC2/metabolismo , Proliferação de Células/efeitos dos fármacos , Quinase 1 do Ponto de Checagem , Cnidium/química , Relação Dose-Resposta a Droga , Frutas , Furocumarinas/isolamento & purificação , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Concentração Inibidora 50 , Masculino , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Camundongos Pelados , Fosforilação , Fitoterapia , Raízes de Plantas , Plantas Medicinais , Proteínas Quinases/metabolismo , Radiossensibilizantes/isolamento & purificação , Sementes , Carga Tumoral/efeitos dos fármacos , Raios Ultravioleta
4.
Photochem Photobiol ; 89(5): 1216-25, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23802687

RESUMO

We examined the effects of six furocoumarins with alkoxy groups at the C-5 or C-8 position isolated from Umbelliferae medicinal plants on cell proliferation, and their mechanisms of action against B16F10 melanoma cells or in melanin-possessing hairless mice implanted with B16F10 cells, under UVA irradiation. Three furocoumarins with an alkoxy group at C-5, isoimperatorin (1), oxypeucedanin (2) and oxypeucedanin hydrate (3), showed antiproliferative activity and caused G2/M arrest at concentrations of 0.1-10.0 µm. Furthermore, three furocoumarins with an alkoxy group at C-8, imperatorin (4), heraclenin (5) and heraclenol (6), inhibited the proliferation of melanoma cells and cell cycle at G2/M at concentrations of 0.1-1.0 µm. UVA plus 1, 2, 3, 4 and 6 reduced tumor growth and final tumor weight in B16F10-bearing mice at a dose of 0.3, 0.5 or 1.0 mg kg(-1) (intraperitoneal injection). UVA plus 1, 3 and 6 increased Chk1 phosphorylation and reduced cdc2 (Thr 161) phosphorylation in melanoma cells. We suggest that the antitumor actions of UVA plus furocoumarins with an alkoxy group at C-5 or C-8 were due to G2/M arrest of the cell cycle by an increase in phosphor-Chk1 and decrease in phospho-cdc2.


Assuntos
Apiaceae/química , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Furocumarinas/farmacologia , Melanoma Experimental/patologia , Plantas Medicinais/química , Raios Ultravioleta , Animais , Furocumarinas/isolamento & purificação , Técnicas In Vitro , Camundongos , Camundongos Pelados
5.
J Cereb Blood Flow Metab ; 32(10): 1897-908, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22739622

RESUMO

The organic cation transporters OCT1, 2, and 3 (SLC22A1-3) have been implicated in the elimination of biogenic amines such as histamine. Among them, OCT3 was identified as an uptake-2 transporter, responsible for clearance of histamine. Because increasing evidence suggests the involvement of histamine in cerebral ischemia, we investigated the effects of targeted disruption of organic cation transporter-3 (Oct3) on the severity of ischemic brain damage. Transient focal ischemia for 1 hour was induced by occlusion of the middle cerebral artery (MCA) of homozygous Oct3-deficient mice and their wild-type (Wt) littermates. Although targeted disruption of Oct3 did not affect physiological parameters after MCA occlusion, this disruption significantly increased histamine content in the ischemic cortex and significantly reduced the infarct volume after cerebral ischemia. Furthermore, targeted disruption of Oct3 prevented the reduction of regulatory T-cell proportion after cerebral ischemia while this disruption did not affect Th1 and Th2 cells proportions after ischemia. Since repeated administration of L-histidine (a precursor of histamine) to Wt mice also showed the same effects, our observations suggested that OCT3 is the molecule responsible for clearance of ischemia-induced histamine in the brain and targeted disruption of Oct3 ameliorated ischemic brain damage through an increase in regulatory T cells.


Assuntos
Encéfalo/patologia , Técnicas de Inativação de Genes , Histamina/imunologia , Infarto da Artéria Cerebral Média/imunologia , Infarto da Artéria Cerebral Média/patologia , Fator 3 de Transcrição de Octâmero/genética , Linfócitos T Reguladores/imunologia , Animais , Astrócitos/imunologia , Encéfalo/irrigação sanguínea , Encéfalo/imunologia , Encéfalo/metabolismo , Células Cultivadas , Citocinas/imunologia , Histidina/administração & dosagem , Histidina/imunologia , Infarto da Artéria Cerebral Média/genética , Lipídeo A/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Knockout , Microglia/imunologia , Óxido Nítrico/imunologia , Fator 3 de Transcrição de Octâmero/imunologia
6.
J Biomed Biotechnol ; 2012: 946242, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22505819

RESUMO

Ginseng roots (Panax ginseng CA Meyer) have been used traditionally for the treatment, especially prevention, of various diseases in China, Korea, and Japan. Both experimental and clinical studies suggest ginseng roots to have pharmacological effects in patients with life-style-related diseases such as non-insulin-dependent diabetic mellitus, atherosclerosis, hyperlipidemia, and hypertension. The topical use of ginseng roots to treat skin complaints including atopic suppurative dermatitis, wounds, and inflammation is also described in ancient Chinese texts; however, there have been relatively few studies in this area. In the present paper, we describe introduce the biological and pharmacological effects of ginsenoside Rb1 isolated from Red ginseng roots on skin damage caused by burn-wounds using male Balb/c mice (in vivo) and by ultraviolet B irradiation using male C57BL/6J and albino hairless (HR-1) mice (in vivo). Furthermore, to clarify the mechanisms behind these pharmacological actions, human primary keratinocytes and the human keratinocyte cell line HaCaT were used in experiments in vitro.


Assuntos
Ginsenosídeos/farmacologia , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Queimaduras/tratamento farmacológico , Linhagem Celular , Células Cultivadas , Quimiocina CCL2/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Ginsenosídeos/uso terapêutico , Humanos , Interleucina-1/metabolismo , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Pelados , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Panax/química , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação , Raios Ultravioleta , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
BMC Neurosci ; 11: 115, 2010 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-20840766

RESUMO

BACKGROUND: Because of the lack of reproducible brainstem ischemia models in rodents, the temporal profile of ischemic lesions in the brainstem after transient brainstem ischemia has not been evaluated intensively. Previously, we produced a reproducible brainstem ischemia model of Mongolian gerbils. Here, we showed the temporal profile of ischemic lesions after transient brainstem ischemia. RESULTS: Brainstem ischemia was produced by occlusion of the bilateral vertebral arteries just before their entry into the transverse foramina of the cervical vertebrae of Mongolian gerbils. Animals were subjected to brainstem ischemia for 15 min, and then reperfused for 0 d (just after ischemia), 1 d, 3 d and 7 d (n = 4 in each group). Sham-operated animals (n = 4) were used as control. After deep anesthesia, the gerbils were perfused with fixative for immunohistochemical investigation. Ischemic lesions were detected by immunostaining for microtubule-associated protein 2 (MAP2). Just after 15-min brainstem ischemia, ischemic lesions were detected in the lateral vestibular nucleus and the ventral part of the spinal trigeminal nucleus, and these ischemic lesions disappeared one day after reperfusion in all animals examined. However, 3 days and 7 days after reperfusion, ischemic lesions appeared again and clusters of ionized calcium-binding adapter molecule-1(IBA-1)-positive cells were detected in the same areas in all animals. CONCLUSION: These results suggest that delayed neuronal cell death took place in the brainstem after transient brainstem ischemia in gerbils.


Assuntos
Tronco Encefálico/patologia , Morte Celular/fisiologia , Ataque Isquêmico Transitório/patologia , Neurônios/patologia , Animais , Temperatura Corporal/fisiologia , Núcleo Coclear/metabolismo , Núcleo Coclear/patologia , Progressão da Doença , Gerbillinae , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Ponte/metabolismo , Ponte/patologia , Núcleos do Trigêmeo/metabolismo , Núcleos do Trigêmeo/patologia , Núcleos Vestibulares/metabolismo , Núcleos Vestibulares/patologia
8.
J Ethnopharmacol ; 132(1): 206-12, 2010 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-20713140

RESUMO

AIM OF THE STUDY: Red Ginseng roots (Panax ginseng C.A. Meyer) have traditionally been thought to have anti-allergic effects, but their influence on food-induced allergic responses is unclear. MATERIALS AND METHODS: This study examined the effects of a Red Ginseng extract on an ova-albumin (OVA)-evoked allergic reaction in mice. RESULTS AND CONCLUSIONS: The orally administered extract significantly inhibited the increase in OVA-specific IgG(1) (Th(2)) levels in OVA-sensitized mice, but had no effect on OVA-specific IgE (Th(2)) levels. The extract prevented a reduction in IL-12 production and the ratio of IFN-γ (Th(1)) to IL-4 (Th(2)) in splenocytes, and enhanced small intestinal CD8-, IFN-γ-, and IgA-positive cell numbers in the OVA-sensitized mice. These findings suggest that Red Ginseng inhibits allergic reactions to food by preventing reductions in the ratio of IFN-γ to IL-4 and in IL-12 production induced by dietary antigens in spleen cells, and/or increasing the expression of CD8 and IFN-γ in the small intestine. It may also protect against sensitization to antigens as an immunomodulator by increasing intestinal IgA secretion without affecting antigen-specific IgE levels. In conclusion, Red Ginseng roots may be a natural preventative of food allergies.


Assuntos
Antialérgicos/uso terapêutico , Hipersensibilidade Alimentar/prevenção & controle , Panax/química , Extratos Vegetais/uso terapêutico , Animais , Antialérgicos/isolamento & purificação , Antialérgicos/farmacologia , Modelos Animais de Doenças , Hipersensibilidade Alimentar/imunologia , Imunoglobulinas/sangue , Interferon gama/imunologia , Interleucina-12/imunologia , Interleucina-4/imunologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Baço/efeitos dos fármacos , Baço/imunologia
9.
Biochem Biophys Res Commun ; 394(3): 843-7, 2010 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-20303333

RESUMO

Although signal transducer and activator of transcription 3 (Stat3) plays crucial roles in the determination of neural stem cell (NSC) fate, Stat3 has multiple roles in NSC function. Moreover, Stat3 plays important roles in neuronal survival and tumorigenesis. To investigate the overall effects of Stat3 on NSC fate, NSC were isolated from Stat3(flox/flox) mouse embryos (E14-15d), in which both Stat3 alleles are flanked by LoxP sites. Isolated NSC was inoculated with an adenovirus vector expressing Cre recombinase (Ad.nCre) or a control adenovirus vector expressing beta-galactosidase (Ad.nLz). Three days later, quantitative real-time PCR (qPCR) analysis revealed that treatment with Ad.nCre eliminated stat3 mRNA expression in NSC. Promoter assay confirmed that overexpression of nCre inhibited transactivation of acute responsive element (APRE) and blocked Stat3 function in NSC. Moreover, Western blot analysis and immunocytochemical analysis revealed that elimination of Stat3 in NSC promoted neurogenesis and inhibited astrogliogenesis. In addition, we investigated the effects of Stat3 elimination in NSC on the mRNA expression of Notch family members and bHLH factors. Consequently, qPCR analysis showed that elimination of Stat3 in NSC promoted neurogenesis and inhibited astrogliogenesis through down-regulation of notch1, notch2 and hes5, but not hes1 mRNA expression.


Assuntos
Astrócitos/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Neurogênese/genética , Neuroglia/fisiologia , Fator de Transcrição STAT3/genética , Células-Tronco/fisiologia , Animais , Astrócitos/citologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Sequências Hélice-Alça-Hélice , Proteínas de Homeodomínio/genética , Integrases/genética , Camundongos , Camundongos Mutantes , Neuroglia/citologia , Receptor Notch1/genética , Receptor Notch2/genética , Proteínas Repressoras/genética , Deleção de Sequência , Células-Tronco/citologia , Fatores de Transcrição HES-1
10.
Br J Nutr ; 103(3): 378-85, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19818196

RESUMO

We investigated the effects of a high-cholesterol (HC) diet administered long term (25 or 55 weeks) on metabolic disorders including hepatic damage in mice. The mice were fed the HC diet (15 % milk fat, 1.5 % cholesterol and 0.1 % cholic acid, w/w) for 25 or 55 weeks. Body and adipose tissue weights were similar to those of mice fed a control diet. Consumption of the HC diet long term resulted in hypercholesterolaemia, hepatic steatosis and gallstones. In addition, focal nodular hyperplasia (FNH) and mild fibrosis of the liver developed in all mice fed the HC diet for 55 weeks. Plasma levels of monocyte chemoattractant protein (MCP)-1 were elevated, and the level of hepatic platelet-derived growth factor (PDGF)-B protein was increased in mice fed the HC diet compared with those fed the control diet. Thus, it seems likely that the liver fibrosis and FNH caused by the long-term consumption of a HC diet may be partly due to an elevation of plasma MCP-1 and hepatic PDGF expression.


Assuntos
Colesterol na Dieta/farmacologia , Fígado Gorduroso/induzido quimicamente , Cálculos Biliares/induzido quimicamente , Cirrose Hepática/induzido quimicamente , Fígado/patologia , Animais , Becaplermina , Peso Corporal/efeitos dos fármacos , Quimiocina CCL2/sangue , Quimiocina CCL2/efeitos dos fármacos , Colesterol/metabolismo , Citocinas/metabolismo , Cálculos Biliares/metabolismo , Teste de Tolerância a Glucose , Lipídeos/fisiologia , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Proto-Oncogênicas c-sis , Valores de Referência
11.
Eur J Pharmacol ; 616(1-3): 281-6, 2009 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-19549519

RESUMO

Oral ulcerative mucositis induced by chemotherapy or radiotherapy has an impact on quality of life, is dose-limiting for chemotherapy, and causes considerable morbidity. The aim of this study was to evaluate the effect of ginsenoside Rb1 on 5-fluorouracil (5-FU)-induced experimental oral mucositis in hamsters. Oral mucositis was induced in hamsters through a combination of 5-FU treatment and mild abrasion of the cheek pouch. Ginsenoside Rb1 isolated from ginseng was contained in chitosan-sodium alginate film (G-Rb1 film). The films were attached to the oral mucosa, and then the healing process was examined by measuring the area of mucositis, myeloperoxidase (MPO) activity and microscopic aspects. Films without ginsenoside Rb1 had no effect on 5-FU-induced oral mucositis in comparison to the control group. However, G-Rb1 films (10(-12) to 10(-4) g/g film) dose-dependently improved recovery from 5-FU-induced damage, and there were significant differences between doses of 10(-6) and 10(-4) g/g film. These results suggest that topical application of films that contain ginsenoside Rb1 has a healing effect on severe oral mucositis induced by chemotherapy.


Assuntos
Adesivos/química , Fluoruracila/efeitos adversos , Ginsenosídeos/administração & dosagem , Ginsenosídeos/farmacologia , Mucosa Bucal/efeitos dos fármacos , Estomatite/induzido quimicamente , Administração Tópica , Alginatos/química , Animais , Antineoplásicos/efeitos adversos , Quitosana/química , Cricetinae , Ginsenosídeos/química , Ginsenosídeos/uso terapêutico , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Mucosa Bucal/metabolismo , Peroxidase/metabolismo , Estomatite/tratamento farmacológico , Estomatite/metabolismo
12.
Brain Res ; 1272: 52-61, 2009 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-19344701

RESUMO

Syntaxin1 and synaptotagmin are located in the pre-synaptic terminals and play central roles in Ca(2+)-triggered neurotransmitter release. Because excessive synaptic transmission has been implicated in neuronal cell death after ischemia, we investigated the effects of cerebral ischemia on the levels of these proteins using a rat permanent focal ischemia model. Western blot analysis revealed that the protein level of syntaxin1 was significantly up-regulated in the ischemic core cortex and peri-ischemic cortex at 1 day after ischemia, while the protein level of synaptotagmin was not. Immunohistochemical analysis revealed that the protein level of syntaxin1 was markedly up-regulated in the ischemic areas where immunoreaction for MAP2 was lost. Furthermore, we showed that resident microglial cells were quite vulnerable to ischemia. Our data provide novel insights into the molecular mechanism of cerebral ischemia at the pre-synaptic terminals.


Assuntos
Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Infarto da Artéria Cerebral Média/patologia , Sintaxina 1/metabolismo , Regulação para Cima/fisiologia , Análise de Variância , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Proteínas dos Microfilamentos , Proteínas Associadas aos Microtúbulos/metabolismo , Ratos , Ratos Endogâmicos SHR , Sinaptotagminas/metabolismo
13.
Eur J Pharmacol ; 602(1): 148-56, 2009 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-19041641

RESUMO

It is well-known that chronic ultraviolet B (UVB) exposure at low-dose causes skin photoaging including increases in skin thickness and wrinkle formation and reduction in skin elasticity. This study examined the effects of total saponins and ginsenoside Rb(1) isolated from Red Ginseng roots on skin thickness, elasticity, and wrinkle formation caused by long-term, low-dose UVB irradiation in hairless mice. The topical application of total ginseng saponins (10 pg or 100 ng/mouse) and ginsenoside Rb(1) (100 fg, 10 pg, or 1 ng/mouse) significantly inhibited increases in skin thickness and wrinkle formation and the reduction in skin elasticity induced by long-term UVB irradiation. Furthermore, we examined the histological effects of total saponins and ginsenoside Rb(1) in the skin of UVB-irradiated hairless mice. The increases in apoptotic, Ki-67-, and 8-hydroxy-2'-deoxyguanosine-positive cells induced by UVB exposure were prevented by the topical application of total saponins and ginsenoside Rb(1). Furthermore, total saponins and ginsenoside Rb(1) prevented the disruption of collagen fibers induced by the long-term UVB irradiation. Ginsenoside Rb(1) (100 fg, 10 pg, and 1 ng/ml) increased the Bcl-2 expression level in UVB-treated human keratinocytes. The protective effect of ginsenoside Rb(1) on UVB-mediated apoptosis may be due to the up-regulation of Bcl-2 expression. These results suggest that the protective effect of ginsenoside Rb(1) on skin photoaging induced by chronic UVB exposure may be due to the increase in collagen synthesis and/or the inhibition of matrix metalloproteinase expression in dermal fibroblasts.


Assuntos
Panax/química , Saponinas/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta , Administração Tópica , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Apoptose/efeitos da radiação , Células Cultivadas , Relação Dose-Resposta a Droga , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Masculino , Metaloendopeptidases/genética , Metaloendopeptidases/metabolismo , Camundongos , Camundongos Pelados , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Saponinas/administração & dosagem , Saponinas/isolamento & purificação
14.
Biorheology ; 45(6): 689-700, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19065015

RESUMO

The extract from Panax ginseng has been reported to improve the microcirculation in various organs. However, the mechanisms underlying this phenomenon are still poorly understood. In the present study, using the rheological properties of erythrocytes as an index, we have screened the components of Panax ginseng extract and identified Rg(2) and Rh(1) as the active ingredients. These two ginsenosides prevented the oxidative stress-induced elevation of erythrocyte suspension viscosity and the impairment of erythrocyte elongation in response to shear stress. Rg(2) and Rh(1) ginsenosides did not have antioxidant activity in an aqueous phase and did not inhibit the peroxidation of membrane lipids, either. However, they inhibited the oxidation-induced decrease of SH-groups in band 3 (anion exchanger-1), one of the important structural proteins of the erythrocyte membrane, but not in other structural proteins: bands 1 and 2 (spectrins), band 4.2 or band 5 (actin). These results suggest that ginsenosides Rg(2) and Rh(1) protect the rheological functions of erythrocytes against oxidative stress by preventing the oxidation of SH-groups in band 3 protein.


Assuntos
Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Membrana Eritrocítica/efeitos dos fármacos , Ginsenosídeos/farmacologia , Panax , Viscosidade Sanguínea/efeitos dos fármacos , Deformação Eritrocítica/efeitos dos fármacos , Humanos , Oxirredução
15.
Phytother Res ; 22(11): 1423-7, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18803235

RESUMO

Red Ginseng (the roots of Panax ginseng C.A. Meyer) is used clinically in China, Korea and Japan for various diseases, including atherosclerosis, hypertension and stress etc. Although Red Ginseng roots have traditionally been thought to have antiageing effects, the basis for this hearsay is unclear. This study examined the effects of Red Ginseng extract on ultraviolet B (UVB)-irradiated skin ageing in mice. Oral administration of Red Ginseng extract (20 or 60 mg/kg, twice daily) prevented UVB-irradiated skin damage (increases of skin thickness and pigmentation, and reduction of skin elasticity). Furthermore, Red Ginseng extract inhibited the increases of epidermis and corium thickness induced by UVB irradiation. Red Ginseng extract inhibited the increase of skin TGF-beta1 content induced by UVB irradiation. These findings suggest that the protective action of Red Ginseng extract against UVB-irradiated skin ageing may be due partly to an inhibition of the increase of skin TGF-beta1 induced by UVB irradiation. In conclusion, the oral administration of Red Ginseng extract may be useful as a health supplement for protection against photoageing.


Assuntos
Panax/química , Extratos Vegetais/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos da radiação , Raios Ultravioleta , Administração Oral , Animais , Elasticidade/efeitos dos fármacos , Elasticidade/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pigmentação/efeitos dos fármacos , Pigmentação/efeitos da radiação , Extratos Vegetais/administração & dosagem , Pele/efeitos dos fármacos , Pele/metabolismo , Envelhecimento da Pele/efeitos da radiação , Fator de Crescimento Transformador beta1/metabolismo
16.
FASEB J ; 22(11): 3866-77, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18685078

RESUMO

The differentiation and proliferation of neural stem cells (NSCs) are regulated by a combination of their intrinsic properties (e.g., transcription factors, epigenetic factors, and microRNA regulation) and cell-extrinsic properties from the microenvironment around NSC (e.g., cytokines, growth factors, and cell-cell contact). Recently, there has been a great interest in clarifying the mechanism of the influence of the microenvironment on NSCs, especially cell-cell contact between NSCs and other types of cells nearby. In this study, we investigated whether microglial (Mi) cells influence the fate of NSCs. Coculture study showed that ramified Mi cells promoted astrogliogenesis and maintenance of NSCs through their paracrine effects. This microglia-induced astrogliogenesis was inhibited by AG490 and by overexpression of the dominant-negative form of Stat3 and SOCS3. Promoter assay revealed transactivation of Stat3 function in NSCs by Mi cells. Gene expression study revealed that mRNA of Notch family members (notch1-3) and sox9 in NSCs was significantly upregulated by Mi cells, and this up-regulation was inhibited by AG490. These results demonstrated that ramified Mi cells promoted astrogliogenesis and maintenance of NSCs by activating Stat3 function and via notch and sox9 signaling pathways.


Assuntos
Astrócitos/metabolismo , Regulação da Expressão Gênica/fisiologia , Microglia/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/fisiologia , Células-Tronco/metabolismo , Animais , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Grupo de Alta Mobilidade/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/fisiologia , Comunicação Parácrina/efeitos dos fármacos , Comunicação Parácrina/fisiologia , Ratos , Receptores Notch/metabolismo , Fatores de Transcrição SOX9 , Transdução de Sinais/efeitos dos fármacos , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Fatores de Transcrição/metabolismo , Tirfostinas/farmacologia
17.
Eur J Pharmacol ; 584(2-3): 415-23, 2008 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-18353310

RESUMO

Some reports published from 1967 to 1999 describe the use of ointments containing high doses (0.1 to 0.2%, w/w) C. asiataica herb extracts to enhance wound repair. Lower doses at which burn wound repair is enhanced by such topical applications have not been established yet. We found that the application of asiaticoside at low doses of 10(-8) to 10(-12)% (w/w) facilitated burn wound repair. To clarify the accelerating mechanisms of asiaticoside on burn wound repair, we examined the effects of asiaticoside on the levels of various cytokines produced at the site of the burn wound. The topical application of a low dose (10 pg, 1 ng, or 100 ng/wound area) of asiaticoside increased monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and interleukin (IL)-1beta levels in burn wound exudates. Asiaticoside (10 pg to 100 ng/ml) enhanced MCP-1 production in HaCaT cells, but it had no direct effect on VEGF production. Furthermore, asiaticoside (10 pg to 100 ng/ml) increased the IL-1beta production in THP-1 macrophages with MCP-1, but it had no effect on IL-1beta production without MCP-1 or with lipopolysaccharide (LPS). These findings suggest that the enhancement of burn wound healing by asiaticoside might be due to the promotion of angiogenesis during skin wound repair as a result of the stimulation of VEGF production caused by the increase in MCP-1 expression in keratinocytes and the increase in IL-1beta expression in macrophages induced cooperatively by asiaticoside plus MCP-1.


Assuntos
Queimaduras/tratamento farmacológico , Citocinas/metabolismo , Fármacos Dermatológicos/farmacologia , Triterpenos/farmacologia , Cicatrização/efeitos dos fármacos , Administração Cutânea , Animais , Queimaduras/imunologia , Queimaduras/metabolismo , Queimaduras/fisiopatologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Centella , Quimiocina CCL2/metabolismo , Fármacos Dermatológicos/uso terapêutico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Exsudatos e Transudatos/efeitos dos fármacos , Exsudatos e Transudatos/metabolismo , Humanos , Interleucina-1beta/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Fisiológica/efeitos dos fármacos , Extratos Vegetais , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Triterpenos/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/imunologia
18.
J Ethnopharmacol ; 117(2): 278-84, 2008 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-18329832

RESUMO

AIM OF THE STUDY: We reported recently that the facilitating effects of ginsenosid Rb(1) on burn wound-healing might be due to the promotion of angiogenesis. Increased histamine, substance P (SP), and monocyte chemoattractant protein (MCP)-1 levels caused inflammation, and pain following severe burn wound injury. MATERIALS AND METHODS: We examined the effects of ginsenoside Rb1 on the histamine, SP, and MCP-1 levels in burn wound tissue during burn wound repair. RESULTS AND CONCLUSIONS: Ginsenoside Rb1 (1 ng/wound) and basic fibroblast growth factor (bFGF) (2.5 microg/wound) significantly increased the levels of MCP-1 on day 1 compared to the MCP-1 level in vehicle-treated mice. Histamine production of the burn wound area on day 7 was increased by topical application of ginsenoside Rb1 (100 fg-1 ng/wound) and bFGF. The number of mast cells migrating to the burn wound area was also increased by ginsenoside Rb1. Conversely, the increased SP production was reduced by ginsenoside Rb1. This finding suggests that the pain induction by burn injury may be reduced by ginsenoside Rb1. The facilitating actions of ginsenoside Rb1 on burn wound healing may be due to the increase in histamine production via the increase in mast cell migration to the burn wound area induced by the rapid elevation of MCP-1.


Assuntos
Queimaduras/metabolismo , Quimiocina CCL2/metabolismo , Ginsenosídeos/farmacologia , Histamina/metabolismo , Substância P/metabolismo , Cicatrização/efeitos dos fármacos , Animais , Contagem de Células , Ginsenosídeos/química , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Pele/patologia
19.
J Pharm Pharmacol ; 59(8): 1137-44, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17725857

RESUMO

It is well known that different stress paradigms are able to rapidly induce corticosterone production and immune function through the activation of the hypothalamic-pituitary-adrenal axis. It has been reported that glucocorticoids suppress natural killer (NK) activity and interleukin (IL)-1 production and, on the other hand, that IL-1 and IL-6 stimulate the release of corticotrophin-releasing-hormone from the rat hypothalamus. Moreover, it has been reported that IL-12 plays a central role in the initiation of cell-mediated immunity, directly and via its induction of interferon (IFN)-gamma and activation of NK cells. In this study, we examined the effects of water-soluble low-molecular-weight beta-glucan isolated from Aureobasidium pullulans 1A1 strain on the corticosterone levels and immune function, such as NK activity and IL-6 and IL-12 production, using a restraint stress-induced mouse model. The water-soluble low-molecular-weight beta-glucan at a dose of 50 or 100 mg kg(-1) inhibited the increases in the blood corticosterone level and the reduction of NK activity induced by restraint stress. Furthermore, the water-soluble low-molecular-weight beta-glucan (100 mg kg(-1)) prevented the reduction of IL-6 and IL-12 production by splenocytes caused by restraint stress. These findings suggest that the inhibitory actions of water-soluble low-molecular-weight beta-glucan on the increase in corticosterone level and reduction of NK activity induced by restraint stress may be associated with the abrogation of the IL-6 and IL-12 reduction caused by the stress. Thus, water-soluble low-molecularweight beta-glucan may be an effective dietary supplement for the prevention of stress.


Assuntos
Ascomicetos/química , Glucanos/farmacologia , Estresse Psicológico/tratamento farmacológico , Animais , Corticosterona/sangue , Relação Dose-Resposta a Droga , Glucanos/administração & dosagem , Glucanos/isolamento & purificação , Interleucina-12/biossíntese , Interleucina-6/biossíntese , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Tamanho do Órgão/efeitos dos fármacos , Restrição Física , Baço/citologia , Estresse Psicológico/sangue , Estresse Psicológico/imunologia
20.
J Neurotrauma ; 24(6): 1037-54, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17600519

RESUMO

Red ginseng root (Panax Ginseng CA Meyer) has been used clinically by many Asian people for thousands of years without any detrimental effects. One of the major components of Red ginseng root is ginsenoside Rb(1) (gRb1). Previously, we showed that intravenous infusion of gRb1 ameliorated ischemic brain damage through upregulation of an anti-apoptotic factor, Bcl-x(L) and that topical application of gRb1 to burn wound lesion facilitated wound healing through upregulation of vascular endothelial growth factor (VEGF). In the present study, we produced dihydroginsenoside Rb1 (dgRb1), a stable chemical derivative of gRb1, and showed that intravenous infusion of dgRb1 improved spinal cord injury (SCI) as well as ischemic brain damage. As we expected, the effective dose of dgRb1 was ten times lower than that of gRb1. Intravenous infusion of dgRb1 at this effective dose did not affect brain temperature, blood pressure or cerebral blood flow, suggesting that dgRb1 rescued damaged neurons without affecting systemic parameters. In subsequent in vitro studies that focused on dgRb1-induced expression of gene products responsible for neuronal death or survival, we showed that dgRb1 could upregulate the expression of not only Bcl-x(L), but also a potent angiogenic and neurotrophic factor, VEGF. We also showed that dgRb1-induced expression of bcl-x(L) and VEGF mRNA was HRE (hypoxia response element) and STRE (signal transducers and activators of transcription 5 (Stat5) response element) dependent, respectively.


Assuntos
Infarto Encefálico/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Ginsenosídeos/farmacologia , Compressão da Medula Espinal/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/genética , Proteína bcl-X/genética , Animais , Infarto Encefálico/fisiopatologia , Infarto Encefálico/prevenção & controle , Isquemia Encefálica/genética , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ginsenosídeos/síntese química , Ginsenosídeos/uso terapêutico , Infusões Intravenosas , Masculino , Estrutura Molecular , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Fator de Transcrição STAT5/metabolismo , Compressão da Medula Espinal/genética , Compressão da Medula Espinal/fisiopatologia , Resultado do Tratamento , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia
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