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1.
Cancer Lett ; 174(1): 17-24, 2001 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-11675148

RESUMO

The root of Paeonia suffruticosa ANDREWS is an important Chinese crude drug used in many traditional prescriptions. 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), a major component of this crude drug, was found to exhibit in vitro growth-inhibiting effect on human hepatocellular carcinoma cell line, SK-HEP-1 cells. The growth-inhibitory effect was related to the ability of PGG not only to cause a G(0)/G(1) phase arrest but also to suppress the activation of nuclear factor-kappa B. Neither apoptosis nor necrosis was observed in the cells treated with PGG. These findings suggest that PGG could be a candidate for developing a low-toxic anticancer agent.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/patologia , Taninos Hidrolisáveis , Taninos/farmacologia , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , DNA/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Fase G1/efeitos dos fármacos , Humanos , NF-kappa B/metabolismo , Necrose , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Células Tumorais Cultivadas
2.
Leuk Res ; 25(4): 339-46, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11248331

RESUMO

Water-soluble chitosan oligomer (WSCO) has been reported to have anticancer activity, immuno-enhancing effect and antimicrobial activity. However, other biological activities are unknown. Herein, we have shown that WSCO is able to inhibit proliferation of human leukemia HL-60 cells and induce these cells to differentiate. Treatment with WSCO for 4 days resulted in a concentration-dependent reduction in HL-60 cell growth as measured by cell counting and MTT assay. This effect was accompanied by a marked increase in the proportion of G(0)/G(1) cells as measured by flow cytometry. WSCO also induced differentiation of the cells as measured by phorbol ester-dependent reduction of NBT, morphological changes as examined by Wright-Giemsa staining and expression of CD11b but not of CD14 as analysed by flow cytometry, indicating differentiation of HL-60 cells toward granulocyte-like cells. A combination of low dose of WSCO with all-trans retinoic acid, a differentiating agent toward granulocyte-like cells, exhibited a synergistic effect on the differentiation. In addition, treatment of HL-60 cells with WSCO for 6 or 8 days resulted in the induction of apoptosis as assayed qualitatively by agarose gel electrophoresis and quantitatively by Annexin V technique using flow cytometry. Collectively, there is a potential for WSCO in the treatment of myeloid leukemia.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Quitina/farmacologia , Granulócitos/citologia , Leucemia Promielocítica Aguda/tratamento farmacológico , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Quitina/análogos & derivados , Quitosana , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Células HL-60/efeitos dos fármacos , Células HL-60/patologia , Humanos , Leucemia Promielocítica Aguda/patologia , Tretinoína/farmacologia
3.
Int Immunopharmacol ; 4(3): 377-86, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15037215

RESUMO

We investigated the effects of the gallotannin penta-O-galloyl-beta-d-glucose (PGG) on interleukin (IL)-8 gene expression and nuclear factor (NF)-kappaB activation. PGG inhibited IL-8 production and gene expression in human monocytic U937 cells stimulated with phorbol myristate acetate (PMA), as measured by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction analysis, respectively. PGG also inhibited PMA-mediated NF-kappaB activation, as measured by electromobility shift assay. Furthermore, PGG prevented PMA-mediated degradation of the NF-kappaB inhibitory protein I-kappaBalpha, as measured by Western blot analysis. PGG also inhibited both IL-8 production and NF-kappaB activation in the U937 cells stimulated with tumor necrosis factor-alpha. These results suggest that PGG, a major constituent of the root cortex of Paeonia suffruticosa ANDREWS, can inhibit IL-8 gene expression by a mechanism involving its inhibition of NF-kappaB activation, which is dependent on I-kappaBalpha degradation.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Taninos Hidrolisáveis/farmacologia , Interleucina-8/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Acetato de Tetradecanoilforbol/farmacologia , Transporte Ativo do Núcleo Celular , Western Blotting , Ensaio de Desvio de Mobilidade Eletroforética , Ensaio de Imunoadsorção Enzimática , Regulação da Expressão Gênica , Humanos , Proteínas I-kappa B/metabolismo , Interleucina-8/biossíntese , Interleucina-8/genética , Transporte Proteico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Células U937
4.
J Ethnopharmacol ; 76(1): 59-64, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11378282

RESUMO

The rhizomes of Cyperus rotundus (C. rotundus) have been used in oriental traditional medicines for the treatment of stomach and bowel disorders, and inflammatory diseases. Nitric oxide (NO) and superoxide (O2-) are important mediators in the pathogenesis of inflammatory diseases. This study was undertaken to address whether the metanol (MeOH) extract of rhizomes of C. rotundus could modulate NO and O2- productions by murine macrophage cell line, RAW 264.7 cells. The MeOH extract of rhizomes of C. rotundus showed the inhibition of NO production in a dose-dependent manner by RAW 264.7 cells stimulated with interferon-gamma plus lipopolysaccharide. The inhibition of NO production by the extract was due to the suppression of iNOS protein, as well as iNOS mRNA expression, determined by Western and Northern blotting analyses, respectively. In addition, the MeOH extract suppressed the production of O2- by phorbol ester-stimulated RAW 264.7 cells in dose- and time-dependent manners. Collectively, these results suggest that the MeOH extract of rhizomes of C. rotundus could be developed as anti-inflammatory candidate for the treatment of inflammatory diseases mediated by overproduction of NO and O2-.


Assuntos
Macrófagos/efeitos dos fármacos , Óxido Nítrico/biossíntese , Extratos Vegetais/uso terapêutico , Plantas Medicinais , Superóxidos/metabolismo , Animais , Northern Blotting , Western Blotting , Linhagem Celular , Inflamação/etiologia , Inflamação/prevenção & controle , Coreia (Geográfico) , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/efeitos adversos , Superóxidos/efeitos adversos
5.
Am J Chin Med ; 29(2): 313-20, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11527073

RESUMO

Apoptosis is now widely accepted as playing a role in tumorigenesis. An effective compound which can kill tumors via apoptotic pathway appears to be a relevant strategy to suppress various human tumors. The ethyl acetate extract from the stem bark of Cudrania tricuspidata (EACT) showed dose- and time-dependent cytotoxic effects on human leukemia HL-60 cells. DNA fragmentation and morphological changes, accompanied by condensed and fragmented nuclei, were observed in the cells cultured for 6 hr with EACT. These results suggest that the cytotoxicity of the crude extract from Cudrania tricuspidata against HL-60 cells is due to apoptosis.


Assuntos
Antineoplásicos Fitogênicos/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células HL-60/efeitos dos fármacos , Acetatos/farmacologia , Análise de Variância , DNA de Neoplasias/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/uso terapêutico , Eletroforese em Gel de Ágar , Humanos , Técnicas In Vitro , Casca de Planta , Fatores de Tempo , Células Tumorais Cultivadas/efeitos dos fármacos
7.
Immunopharmacol Immunotoxicol ; 22(3): 545-54, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10946831

RESUMO

Overproduction of nitric oxide (NO) or superoxide (O2-) by activated macrophages is known to be involved in acute or chronic inflammation. The seeds of Job's Tears (Coix lachryma-jobi L. var. ma-yuen) have been used as anti-inflammatory medicine and health food. However, it is still unclear how the seeds show anti-inflammatory properties. Using murine macrophage-like RAW 264.7 cells, we tried to know whether the overproduction of NO and O2 by activated macrophages could be prevented by the methanol (MeOH) extract of the seeds of Job's Tears. RAW 264.7 cells were activated with interferon-gamma plus lipopolysaccharide to produce NO and with pholbol ester to produce O2-. The MeOH extract showed marked inhibition of NO production by activated RAW 264.7 cells in a dose-dependent manner via suppression of inducible NO synthase mRNA expression. The MeOH extract also showed inhibition of O2- production by activated RAW 264.7 cells in dose- and time-dependent manners, possibly by interfering with NADPH oxidase machinery of macrophages. Collectively, these results demonstrate that the MeOH extract of the seeds of Job's Tears shows anti-inflammatory properties which may, in part, involve an inhibition of NO and O2- production by activated macrophages.


Assuntos
Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Óxido Nítrico/biossíntese , Plantas Medicinais , Poaceae , Superóxidos/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular , Ativação de Macrófagos , Macrófagos/imunologia , Camundongos , Extratos Vegetais/farmacologia , Sementes
8.
Gen Pharmacol ; 35(1): 21-8, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11679202

RESUMO

It was found that the production of nitric oxide (NO) by RAW 264.7 macrophages stimulated with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) could be markedly inhibited by the ethyl-acetate-soluble fraction of 80% aqueous methanolic extract of stem barks of Cudrania tricuspidata (EACT). Inhibition of NO production was achieved by reducing inducible nitric oxide synthase (iNOS) expression at protein and mRNA levels and by inactivating nuclear factor-kappa B (NF-kappa B), but not by inhibiting iNOS activity. Thus, further phytochemical and pharmacological studies may lead to isolation and structural identification of an inhibitor of iNOS from C. tricuspidata, which has been used as a traditional medicine for curing inflammation.


Assuntos
Acetatos/farmacologia , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Óxido Nítrico Sintase/genética , Animais , Expressão Gênica/efeitos dos fármacos , Coreia (Geográfico) , Ativação de Macrófagos/efeitos dos fármacos , Modelos Animais , NF-kappa B/metabolismo , Casca de Planta/química , Extratos Vegetais/farmacologia , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos
9.
In Vitr Mol Toxicol ; 14(2): 99-106, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11690563

RESUMO

The mitogen-activated protein kinase (MAPK) family members have been implicated in cell survival. We have previously demonstrated that cytotoxic lectin-II isolated from Korean mistletoe induces apoptotic cell death in the human monoblastic leukemia cell line, U937, via the activation of the stress-activated protein kinases/c-Jun N-terminal kinase (SAPK/JNK). In the present study, the roles of extracellular signal-regulated kinases (ERK1/2) and p38 MAPK in lectin-II-induced apoptosis have been investigated. Treatment of U937 cells with lectin-II resulted in apoptotic DNA fragmentation, which was preceded by the activation of ERK1/2, p38 MAPK and SAPK/JNK. This lectin-II-induced DNA fragmentation was significantly enhanced when ERK1/2 activation was selectively inhibited by PD098059. 12-O-tetradecanoylphorbol-13-acetate, which stimulates ERK activity in U937 cells, markedly reduced lectin-II-induced DNA fragmentation. Inhibition of p38 MAPK activity with p38-specific inhibitor, SB203580, partially inhibited lectin-II-induced DNA fragmentation. These results suggest that ERK1/2 and p38 MAPK may have opposite effects on cell survival in response to cytotoxic mistletoe lectin-II, which may contribute to the modulation of lectin-II-mediated cytotoxic activity.


Assuntos
Apoptose/efeitos dos fármacos , Erva-de-Passarinho , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Preparações de Plantas , Proteínas de Plantas , Transdução de Sinais/fisiologia , Toxinas Biológicas/farmacologia , Apoptose/fisiologia , Fragmentação do DNA/efeitos dos fármacos , Flavonoides/farmacologia , Humanos , Imidazóis/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno , Leucemia Monocítica Aguda/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Piridinas/farmacologia , Proteínas Inativadoras de Ribossomos Tipo 2 , Acetato de Tetradecanoilforbol/farmacologia , Células U937/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno
10.
Immunopharmacol Immunotoxicol ; 23(3): 335-42, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11694025

RESUMO

Inflammation has been known to be associated with excess synthesis of nitric oxide (NO) by inducible NO synthase (iNOS). Retinoids have been reported to have anti-inflammatory activity, but the mechanism by which they can elicit this activity is poorly understood. The effects of retinoids on NO synthesis and iNOS gene expression in murine fibroblast L929 cells were examined. Treatment of the cells with interferon-y resulted in excess NO synthesis and iNOS gene expression. All-trans-retinoic acid significantly inhibited NO synthesis and iNOS gene expression in a dose-dependent manner. Similarly, 9-cis-retinoic acid also inhibited NO synthesis, but retinol did not show any inhibitory effect on NO synthesis. These findings suggest that the modulation of iNOS gene expression is another possible pathway by which retinoids may function as anti-inflammatory agents.


Assuntos
Óxido Nítrico Sintase/genética , Tretinoína/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular , Expressão Gênica/efeitos dos fármacos , Inflamação/enzimologia , Inflamação/genética , Interferon gama/toxicidade , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes
11.
Immunopharmacol Immunotoxicol ; 25(4): 585-94, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14686800

RESUMO

The protective effects of baicalin (BA), a major flavone from Scutellaria radix, on acetaminophen (AP)-induced hepatotoxicity and the possible mechanism(s) of its protective action were investigated in mice. Treatment with BA (300 mg/kg, p.o.) 0.5 h after AP administration significantly prevented an increase in plasma alanine aminotransferase and aspartate aminotransferase activities and AP-induced hepatic necrosis, and also reduced AP-induced mortality from 43% to 0%. In addition, oral treatment with BA significantly prevented AP-induced depletion of glutathione (GSH) contents. However, BA treatment, by itself, did not affect hepatic GSH contents. The effect of BA on the cytochrome P450 2E1 (CYP2E1), the major isozyme involved in AP bioactivation, was investigated. Oral treatment of mice with BA resulted in a significant decrease in AP-induced CYP2E1 activity together with its inhibition of AP-induced CYP2EI expression. These results show that the hepatoprotective effects of BA against AP overdose may be due to its ability to block the bioactivation of AP by inhibiting CYP2E1 expression.


Assuntos
Acetaminofen/toxicidade , Flavonoides/farmacologia , Fígado/efeitos dos fármacos , Fígado/lesões , Fitoterapia , Scutellaria baicalensis , Acetaminofen/farmacocinética , Administração Oral , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Citocromo P-450 CYP2E1/metabolismo , Flavonoides/administração & dosagem , Flavonoides/isolamento & purificação , Glutationa/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Scutellaria baicalensis/química
12.
Immunopharmacol Immunotoxicol ; 26(3): 343-53, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15518169

RESUMO

We studied the effect of mokko lactone (ML) isolated from the roots of Saussurea lappa (Compositae), a plant that is used for medicinal purposes in Korea, on the induction of apoptosis in human leukemia HL-60 cells. ML was cytotoxic to HL-60 cells, and this cytotoxic effect of ML appears to be attributable to its induction of apoptotic cell death, as ML induced nuclear morphologic changes and internucleosomal DNA fragmentation and increased the proportion of Annexin V-positive cells and the activity of caspase-3. Further studies revealed that the induction of apoptosis by ML was associated with the loss of mitochondrial membrane potential. Collectively, our results suggest that apoptosis induced by ML in HL-60 cells was executed by a collapse of mitochondrial membrane potential followed by the activation of caspase-3. This is the first report on the mechanism of apoptosis-inducing effect of ML.


Assuntos
4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Células HL-60/efeitos dos fármacos , Membranas Intracelulares/efeitos dos fármacos , Lactonas/farmacologia , Mitocôndrias/efeitos dos fármacos , Saussurea , Sesquiterpenos/farmacologia , 4-Butirolactona/isolamento & purificação , Caspase 3 , Caspases/análise , Caspases/metabolismo , Fragmentação do DNA , Humanos , Membranas Intracelulares/patologia , Coreia (Geográfico) , Lactonas/isolamento & purificação , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/patologia , Raízes de Plantas/química , Saussurea/química , Sesquiterpenos/isolamento & purificação
13.
Immunopharmacol Immunotoxicol ; 25(3): 295-304, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19180794

RESUMO

The amyloid beta-peptide (Abeta)-induced oxidative stress is a well-established pathway of neuronal cell death in Alzheimer's disease (AD). Salidroside, one of the major compounds from the roots of Rhodiola species (Crassulaceae), was investigated in vitro for its cytoprotection against Abeta-induced toxicity on rat neuronal PCl2 cells. Salidroside significantly reduced Abeta-induced cytotoxicity in a dose-dependent manner. Salidroside also reduced Abeta-mediated intracellular accumulation of reactive oxygen species and malondialdehyde (MDA), a product of lipid peroxides, by preventing Abeta-induced decline of antioxidant enzyme activities. These results suggest that salidroside protects neuronal PC12 cells from Abeta-induced cytotoxicity via its antioxidant pathway.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Antioxidantes/farmacologia , Citoproteção , Glucosídeos/farmacologia , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Rhodiola , Animais , Morte Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glucosídeos/isolamento & purificação , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Células PC12 , Fenóis/isolamento & purificação , Raízes de Plantas , Ratos , Espécies Reativas de Oxigênio/metabolismo , Rhodiola/química
14.
Immunopharmacol Immunotoxicol ; 24(1): 31-41, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12022443

RESUMO

Expression of alkaline phosphatase(ALP)activity represents a key event during the differentiation processes of osteoblasts, and the level of ALP activity has been routinely used as a relative measure of differentiation stages of osteoblasts. In human osteoblasts, we showed that vitamin D3 analogue, 1,25(OH)2D3, had a stimulatory effect on ALP activity after 3 days, compared with control. The treatment of PD098059, an ERK MAP Kinase inhibitor, had a reducing effect on ALP activity, a differentiation marker in 1,25(OH)2D3-treated primary human osteoblasts. However, SB203580, a potent p38 MAP Kinase inhibitor, had no effect on the differentiation in this system. This indicates that ERK, not p38, is directly related to 1,25(OH)2D3-stimulated ALP activity in primary human osteoblasts. These results also show that the vitamin D3 analogue stimulates ERK1 activation in primary human osteoblasts. This finding provides one of signaling pathways for differentiation in primary human osteoblasts.


Assuntos
Calcitriol/farmacologia , Agonistas dos Canais de Cálcio/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Osteoblastos/enzimologia , Fosfatase Alcalina/metabolismo , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Humanos , Imidazóis/farmacologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/imunologia , Osteoblastos/citologia , Testes de Precipitina , Piridinas/farmacologia
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