RESUMO
In order to validate the use of the stem bark of Catalpa ovata G. Don. (Bignoniaceae) as an anti-inflammatory drug in the traditional Korean medicine, we have investigated the effects of the methanol extract of this folk medicine on the productions of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) on RAW 264.7 macrophages activated with the endotoxin lipopolysaccharide. The extract inhibited the productions of TNF-alpha and NO with significant decreases in mRNA levels of TNF-alpha and inducible NO synthase, suggesting that the stem bark of Catalpa ovata may have therapeutic potential in the control of inflammatory disorders.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Bignoniaceae/química , Macrófagos/efeitos dos fármacos , Óxido Nítrico/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Animais , Anti-Inflamatórios não Esteroides/isolamento & purificação , Western Blotting , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Camundongos , Casca de Planta/química , Extratos Vegetais/farmacologia , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
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 RecombinantesRESUMO
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 CultivadasRESUMO
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 fármacosRESUMO
Prunioside A (1) has been isolated from an EtOAc-soluble extract of Spiraea prunifolia var. simpliciflora by a combination of chromatographic techniques. The structure was determined primarily by extensive NMR experiments. Compound 1 is a unique terpene glycoside. Its acetylated derivative (1a) inhibited nitric oxide production in murine macrophage-like RAW 264.7 cells in a dose-dependent manner.
Assuntos
Glicosídeos/isolamento & purificação , Plantas Medicinais/química , Terpenos/isolamento & purificação , Animais , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/metabolismo , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Glicosídeos/química , Glicosídeos/farmacologia , Coreia (Geográfico) , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase Tipo II , Raízes de Plantas/química , Terpenos/química , Terpenos/farmacologiaRESUMO
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 adversosRESUMO
In the present study, we examined the effects of the aqueous extract of Rhodiola sachalinensis root (RSE) on the expression of inducible nitric oxide (NO) synthase (iNOS) gene in RAW264.7 macrophages. RSE synergistically increased NO synthesis in interferon-gamma-primed macrophages. Reverse transcriptase polymerase chain reaction and Northern blotting analysis revealed that RSE may provide a second triggering signal for the synergistic induction of iNOS mRNA expression. Thus, iNOS-mediated NO synthesis in response to RSE may be one mechanism whereby this herbal medicine elicits its therapeutic effects.
Assuntos
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Óxido Nítrico Sintase/efeitos dos fármacos , Extratos Vegetais/farmacologia , Raízes de Plantas , Animais , Células Cultivadas , Indução Enzimática/efeitos dos fármacos , Interferon gama/farmacologia , Macrófagos/enzimologia , Camundongos , Óxido Nítrico Sintase/genética , Extratos Vegetais/isolamento & purificação , RNA Mensageiro/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We have examined the effect of the aqueous extract of Rhodiola sachalinensis root (RSE), a traditional herbal medicine, on nitric oxide (NO) synthesis in murine fetal hepatocytes (BNL CL.2) by measuring the stable end-product nitrite and the mRNA of inducible NO synthase (iNOS). Interferon-gamma (IFN-gamma) by itself failed to induce NO synthesis in BNL CL.2 cells. RSE also did not elicit NO synthesis at concentrations up to 1,000 microg/ml, but dose- and time-dependently induced NO synthesis in the presence of IFN-gamma in BNL CL.2 cells. Whereas RSE or IFN-gamma failed to induce detectable levels of iNOS mRNA, a combination of RSE and IFN-gamma markedly induced iNOS mRNA in BNL CL.2 cells. Thus, we found that RSE triggered IFN-gamma-primed BNL CL.2 cells to synthesize NO by inducing iNOS gene expression. The capability of RSE to induce NO synthesis might be related to the therapeutic efficacy of RSE on the liver diseases.
Assuntos
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hepatócitos/enzimologia , Óxido Nítrico Sintase/biossíntese , Extratos Vegetais/farmacologia , Raízes de Plantas , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Interferon gama/administração & dosagem , Interferon gama/farmacologia , Camundongos , Óxido Nítrico Sintase/administração & dosagem , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , RNA Mensageiro/efeitos dos fármacos , Proteínas Recombinantes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
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 , SementesRESUMO
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 , RatosRESUMO
The effects of aqueous extract of Spiraea prunifolia var. simpliciflora's root, a traditional medicine for the treatment of malaria in Chinese medicine, on the generation of nitric oxide (NO) are investigated in RAW 264.7 cells. NO generation from IFN-gamma primed RAW 264.7 cells is markedly increased by the addition of aqueous extract in a dose-dependent manner. The enhancement of NO generation by the aqueous extract is accompanied by a significantly increased expression of inducible nitric oxide synthase (iNOS). However, the aqueous extract of Spiraea prunifolia var. simpliciflora's root does not affect the viability of RAW 264.7 cells, as assessed by MTT assay. Polymyxin B does not inhibit NO generation by the aqueous extract in IFN-gamma primed RAW 264.7 cells. However, polymyxin B significantly decreases NO generation by lipopolysaccharide (LPS) in IFN-gamma primed RAW 264.7 cells. These data indicate that the signaling pathway of the aqueous extract-induced NO generation is not dependent on PKC. These results strongly support the mechanism by which the aqueous extract may exert anti-malarial effect via direct cytotoxicity of NO as well as NO-mediated modulation of immune functions.
Assuntos
Antimaláricos/farmacologia , Medicina Tradicional Chinesa , Óxido Nítrico/biossíntese , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Macrófagos/metabolismo , Camundongos , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase Tipo II , Extratos Vegetais/farmacologia , Polimixina B/farmacologiaRESUMO
It is well established that nitric oxide (NO) and superoxide radicals play pivotal roles in the pathogenesis of inflammatory diseases and fever. This study is undertaken to address whether the methanol extract of Spiraea prunifolia var. simpliciflora root, a traditional medicine as an antipyretic, modulates the generation of NO and superoxide in IFN-gamma primed or polymyristic acetate (PMA) stimulated RAW 264.7 cells, respectively. The generation of NO as well as the expression of inducible nitric oxide synthase (iNOS) protein from IFN-gamma primed RAW 264.7 cells is markedly decreased by the methanol extract in a dose dependent manner. However, the methanol extract does not affect the viability of RAW 264.7 cells, as assessed by methylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay. In addition, the methanol extract suppresses the generation of superoxide in PMA-stimulated RAW 264.7 cells in a dose and a time dependent manner. Taken together, anti-pyretic effects of Spiraea prunifolia var. simpliciflora root extract could result from direct suppression of NO and decreased superoxide generation.