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1.
Int J Mol Sci ; 25(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38474160

RESUMO

This paper delves into the diverse and significant roles of curcumin, a polyphenolic compound from the Curcuma longa plant, in the context of cancer and inflammatory diseases. Distinguished by its unique molecular structure, curcumin exhibits potent biological activities including anti-inflammatory, antioxidant, and potential anticancer effects. The research comprehensively investigates curcumin's molecular interactions with key proteins involved in cancer progression and the inflammatory response, primarily through molecular docking studies. In cancer, curcumin's effectiveness is determined by examining its interaction with pivotal proteins like CDK2, CK2α, GSK3ß, DYRK2, and EGFR, among others. These interactions suggest curcumin's potential role in impeding cancer cell proliferation and survival. Additionally, the paper highlights curcumin's impact on inflammation by examining its influence on proteins such as COX-2, CRP, PDE4, and MD-2, which are central to the inflammatory pathway. In vitro and clinical studies are extensively reviewed, shedding light on curcumin's binding mechanisms, pharmacological impacts, and therapeutic application in various cancers and inflammatory conditions. These studies are pivotal in understanding curcumin's functionality and its potential as a therapeutic agent. Conclusively, this review emphasizes the therapeutic promise of curcumin in treating a wide range of health issues, attributed to its complex chemistry and broad pharmacological properties. The research points towards curcumin's growing importance as a multi-faceted natural compound in the medical and scientific community.


Assuntos
Curcumina , Neoplasias , Humanos , Curcumina/farmacologia , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Inflamação/tratamento farmacológico , Gerenciamento Clínico
2.
J Med Food ; 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37566462

RESUMO

Regulation of diacylglycerol acyltransferase (DGAT) and pancreatic lipase (PL) activities is important in the treatment of triacylglycerol (TG)-related metabolic diseases. Garcinia mangostana, also known as mangosteen, is a traditional medicine ingredient used in the treatment of inflammation in Southeast Asia. In this study, The ethanolic extract of G. mangostana peel inhibited human recombinant DGAT1 and DGAT2, and PL enzyme activities in vitro. The inhibitory activity of DGAT1 and DGAT2 enzymes of four representative bioactive substances in mangosteen was confirmed. In addition, G. mangostana was confirmed to suppress the serum TG levels in C57 mice by inhibiting the absorption and synthesis of TG in the gastrointestinal tract. Through this study, it was revealed that G. mangostana extract could be useful for the prevention and amelioration of TG-related metabolic diseases such as obesity and fatty liver.

4.
PLoS One ; 14(6): e0218659, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31216334

RESUMO

We studied the effect of derrone (DR), one of the major compounds of unripe fruits of Cudrania tricuspidata, on cancer cell death. DR inhibited cell growth of various cancer cells, and that was partially associated with apoptosis in A549 cells. DR showed the autophagic features, such as the conversion of LC3-I to LC3-II, the formation of autophagosome and the downregulation of SQSTM1/p62 (p62). The treatment of autophagy inhibitor reversed DR-mediated cell death, suggesting that DR induces autophagic cell death. The increase of cytoplasmic Ca2+ and ROS by DR treatment significantly influences the formation of autophagosomes; however, only ROS scavengers significantly rescued the reduced cell viability. Additional results revealed that treatment of DR induces sustained phosphorylation of ERK and the inhibition of ERK phosphorylation using U0126 (ERK inhibitor) markedly attenuated DR-induced cell death. Overall, these results suggest that DR induces autophagic cell death through intracellular ROS and sustained ERK phosphorylation in A549 cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Flavonoides/farmacologia , Moraceae/química , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Morte Celular Autofágica , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fosforilação , Extratos Vegetais/química , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais/efeitos dos fármacos
5.
Artigo em Inglês | MEDLINE | ID: mdl-29507591

RESUMO

Zanthoxylum ailanthoides (ZA) has been used as folk medicines in East Asian and recently reported to have several bioactivity; however, the studies of ZA on the regulation of triacylglycerol (TG) biosynthesis have not been elucidated yet. In this study, we examined whether the methanol extract of ZA (ZA-M) could reduce oleic acid- (OA-) induced intracellular lipid accumulation and confirmed its mode of action in HepG2 cells. ZA-M was shown to promote the phosphorylation of AMPK and its upstream LKB1, followed by reduction of lipogenic gene expressions. As a result, treatment of ZA-M blocked de novo TG biosynthesis and subsequently mitigated intracellular neutral lipid accumulation in HepG2 cells. ZA-M also inhibited OA-induced production of reactive oxygen species (ROS) and TNF-α, suggesting that ZA-M possess the anti-inflammatory feature in fatty acid over accumulated condition. Taken together, these results suggest that ZA-M attenuates OA-induced lipid accumulation and inflammation through the activation of LKB1/AMPK signaling pathway in HepG2 cells.

6.
Biosci Biotechnol Biochem ; 81(12): 2285-2291, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29090619

RESUMO

In the course of screening to find a plant material decreasing the activity of triacylglycerol and cholesterol, we identified Tripterygium regelii (TR). The methanol extract of TR leaves (TR-LM) was shown to reduce the intracellular lipid contents consisting of triacylglycerol (TG) and cholesterol in HepG2 cells. TR-LM also downregulated the mRNA and protein expression of the lipogenic genes such as SREBP-1 and its target enzymes. Consequently, TR-LM reduced the TG biosynthesis in HepG2 cells. In addition, TR-LM decreased SREBP2 and its target enzyme HMG-CoA reductase, which is involved in cholesterol synthesis. In this study, we evaluated that TR-LM attenuated cellular lipid contents through the suppression of de novo TG and cholesterol biosynthesis in HepG2 cells. All these taken together, TR-LM could be beneficial in regulating lipid metabolism and useful preventing the hyperlipidemia and its complications, in that liver is a crucial tissue for the secretion of serum lipids.


Assuntos
Colesterol/biossíntese , Extratos Vegetais/farmacologia , Triglicerídeos/biossíntese , Tripterygium/química , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Metanol/química , Folhas de Planta/química
7.
Planta Med ; 81(3): 228-34, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25671385

RESUMO

Six known triterpenoid compounds, 3-oxoolean-12-en-27-oic acid (1), gypsogenic acid (2), 3α-hydroxyolean-12-en-27-oic acid (3), 3ß-hydroxyolean-12-en-27-oic acid (4), aceriphyllic acid A (5), and oleanolic acid (6), were isolated from the roots of Aceriphyllum rossii. Their chemical structures were determined by comparison with available (1)H-NMR and (13)C-NMR data on known compounds. All the isolated compounds were evaluated for inhibitory activity against human diacylglycerol acyltransferases 1 and 2. Most of the isolates exhibited a better inhibitory activity against diacylglycerol acyltransferase 2 (IC50: 11.6-44.2 µM) than against diacylglycerol acyltransferase 1 (IC50: 22.7-119.5 µM). In particular, compounds 1 and 5 showed strong inhibition efficacy towards diacylglycerol acyltransferases 1 and 2, and appeared to act competitively against oleoyl-CoA in vitro. The results also indicated that both compounds reduced newly synthesized triacylglycerol in HuTu80 and HepG2 cells. Oral administration of compound 1 significantly reduced postprandial triacylglycerol in mice following an oral lipid challenge. In conclusion, the current study indicates that compound 1 suppresses both de novo triacylglycerol biosynthesis and resynthesis through the inhibition of diacylglycerol acyltransferase activity, and therefore may be a useful agent for treating diseases associated with a high triacylglycerol level.


Assuntos
Diacilglicerol O-Aciltransferase/sangue , Inibidores Enzimáticos/farmacologia , Ácido Oleanólico/farmacologia , Extratos Vegetais/farmacologia , Saxifragaceae/química , Triglicerídeos/sangue , Acil Coenzima A/metabolismo , Animais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Células Hep G2 , Humanos , Camundongos , Estrutura Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Extratos Vegetais/química , Raízes de Plantas
8.
Oncol Rep ; 32(1): 373-81, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24859825

RESUMO

Epidemiological studies indicate that components of garlic (Allium sativum) have anti-proliferative effects against various types of cancer. In the present study, we investigated the effect of newly isolated phenylamine derivative N-benzyl-N-methyldecan-1-amine (NBNMA) from garlic cloves on the inhibition of the growth and apoptosis of human leukemia U937 cells and its potential anticancer mechanism. NBNMA exhibited an antiproliferative effect in U937 cells by inducing cell cycle arrest at the G2/M phase and apoptotic cell death. Western blot analyses revealed that NBNMA decreased the expression of the regulator genes of G2/M phase progression, cyclin dependent kinase (Cdk) 2 and Cdc2 and elevated the expression of the Cdk inhibitor p21WAF1/CIP1 in a p53-independent manner. In addition, NBNMA activated caspase-8 and caspase-9, initiator caspases of the extrinsic and intrinsic pathways of apoptosis, respectively, which led to activation of executioner caspase-3 along with degradation of poly(ADP-ribose) polymerase. NBNMA-induced apoptosis was observed in parallel with an increased ratio of pro-apoptotic Bax and Bad/anti-apoptotic Bcl-2 and Bcl-xL, and inhibition of inhibitor of apoptosis protein (IAP) family members XIAP and cIAP-1. Furthermore, NBNMA-treated cells displayed enhanced release of cytochrome c from the mitochondria into the cytosol concomitant with a loss of mitochondrial membrane potential and downregulation of Bid, suggesting that NBNMA-induced apoptosis occurred via the extrinsic and intrinsic apoptotic pathways with a possible link to Bid protein activity between the two pathways. These results indicate that NBNMA has promising potential to become a novel anticancer agent for the treatment of leukemia. We provide new insight into the mechanisms underlying the anticancer effect of NBNMA.


Assuntos
Antineoplásicos/farmacologia , Benzilaminas/farmacologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Alho/química , Leucemia/patologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Benzilaminas/química , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células U937
9.
Neurochem Int ; 67: 39-45, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24486459

RESUMO

α-l-Rhamnopyranosyl-(1→6)-ß-d-glucopyranosyl-3-indolecarbonate (RG3I) is a chemical constituent isolated from the commonly used Asian traditional medicinal plant, Clematis mandshurica; however, no studies have been reported on its anti-inflammatory properties. In the present study, we found that RG3I attenuates the lipopolysaccharide (LPS)-induced DNA-binding activity of nuclear factor-κB (NF-κB) via the dephosphorylation of PI3K/Akt in BV2 microglial cells, leading to a suppression of nitric oxide (NO) and prostaglandin E2 (PGE2) production, along with that of their regulatory genes, inducible NO synthase (iNOS) and cyclooxygenase-2 (Cox-2). Further, the PI3K/Akt inhibitor, LY294002 diminished the expression of LPS-stimulated iNOS and COX-2 genes by suppressing NF-κB activity. Moreover, RG3I significantly inhibited LPS-induced reactive oxygen species (ROS) generation similar to the ROS inhibitors, N-acetylcysteine (NAC) and glutathione (GSH). Notably, NAC and GSH abolished the LPS-induced expression of iNOS and Cox-2 in BV2 microglial cells by inhibiting NF-κB activity. Taken together, our data indicate that RG3I suppresses the production of proinflammatory mediators such as NO and PGE2 as well as their regulatory genes in LPS-stimulated BV2 microglial cells by inhibiting the PI3K/Akt- and ROS-dependent NF-κB signaling pathway, suggesting that RG3I may be a good candidate to regulate LPS-induced inflammatory response.


Assuntos
Anticarcinógenos/farmacologia , Dinoprostona/biossíntese , Dissacarídeos/farmacologia , Indóis/farmacologia , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Óxido Nítrico/biossíntese , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular , Cromatografia por Troca Iônica , Espectroscopia de Ressonância Magnética , Camundongos , Microglia/enzimologia , Microglia/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo
10.
J Med Food ; 16(12): 1108-14, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24283275

RESUMO

Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the first committed step in triacylglycerol (TAG) and phospholipid biosynthesis, and has been considered as one of the drug targets for treating hepatic steatosis, insulin resistance, and other metabolic disorders. The aim of this study was to investigate the GPAT inhibitors from natural products and to evaluate their effects. The methanol extract of Aralia cordata roots showed a strong inhibitory effect on the human GPAT1 activity. A further bioactivity-guided approach led to the isolation of ent-pimara-8(14),15-dien-19-oic acid, (PA), one of the major compounds of A. cordata, which suppressed the GPAT1 activity with IC50 value of 60.5 µM. PA markedly reduced de novo lysophosphatidic acid synthesis through inhibition of GPAT activity and therefore significantly decreased synthesis of TAG in the HepG2 cells. These results suggest that PA as well as A. cordata root extract could be beneficial in controlling lipid metabolism.


Assuntos
Aralia/química , Inibidores Enzimáticos/farmacologia , Glicerol-3-Fosfato O-Aciltransferase/antagonistas & inibidores , Extratos Vegetais/farmacologia , Triglicerídeos/biossíntese , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Inibidores Enzimáticos/química , Glicerol-3-Fosfato O-Aciltransferase/metabolismo , Células Hep G2 , Humanos , Lisofosfolipídeos/biossíntese , Extratos Vegetais/química , Raízes de Plantas/química
11.
Artigo em Inglês | MEDLINE | ID: mdl-19861509

RESUMO

Agaricus blazei is widely accepted as a traditional medicinal mushroom, and it has been known to exhibit immunostimulatory and anti-cancer activity. However, the apoptotic mechanism in cancer cells is poorly understood. In this study, we have investigated whether A. blazei extract (ABE) exerts antiproliferative and apoptotic effects in human leukemic THP-1 cells. We observed that ABE-induced apoptosis is associated with the mitochondrial pathway, which is mediated by reactive oxygen species (ROS) generation and prolonged c-Jun N-terminal kinase (JNK) activation. In addition, the ABE treatment resulted in the accumulation of cytochrome c in the cytoplasm, an increase in caspase activity, and an upregulation of Bax and Bad. With those results in mind, we found that ABE decreases constitutive NF-κB activation and NF-κB-regulated gene products such as IAP-1 and -2. We concluded that ABE induces apoptosis with ROS-dependent JNK activation and constitutive activated NF-κB inhibition in THP-1 cells.

12.
Oncol Rep ; 24(1): 271-6, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20514472

RESUMO

Although pectenotoxin-2 (PTX-2) is known to regulate the actin depolymerization and to induce apoptosis through downregulation of telomerase activity, little is known on its effect on the cell cycle regulation. Therefore, we investigated the effects of PTX-2 on G2/M arrest in human breast cancer cells (MDA-MB-231 and MCF-7). Treatment with PTX-2 significantly suppressed cell proliferation and induced G2/M phase arrest through down-regulation of cyclin B1 and cdc2 expression, but also through phosphorylation of cdc25C. We found increased phosphorylation of ATM and Chk1/2 in a PTX-2 dose-dependent manner. Furthermore, treatment with PTX-2 increased H2O2 generation with correlated G2/M arrest. Our results showed that ATM- and Chk1/2-mediated phosphorylation of cdc25C plays a major role in G2/M arrest, but not in H2O2 generation induced by PTX-2 treatment. We also observed that PTX-2-induced cell cycle arrest was not restricted to p53 status in human breast cancer cells.


Assuntos
Neoplasias da Mama/patologia , Carcinoma/patologia , Ciclo Celular/efeitos dos fármacos , Furanos/farmacologia , Piranos/farmacologia , Fosfatases cdc25/metabolismo , Antineoplásicos/farmacologia , Proteínas Mutadas de Ataxia Telangiectasia , Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/fisiologia , Divisão Celular/efeitos dos fármacos , Quinase 1 do Ponto de Checagem , Quinase do Ponto de Checagem 2 , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/fisiologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Fase G2/efeitos dos fármacos , Humanos , Macrolídeos , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Proteínas Quinases/metabolismo , Proteínas Quinases/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/fisiologia , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/fisiologia , Regulação para Cima/efeitos dos fármacos
13.
J Med Food ; 13(3): 481-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20438329

RESUMO

Up-regulation of telomerase activity is associated with immortalization and unlimited cell division in most cancer cells. Therefore, telomerase represents a particularly attractive target for anticancer therapy. Recent reports have suggested that beta-lapachone (LAPA), the product of the South American Tabebuia avellanedae tree, inhibits growth of tumor cells. However, the underlying relationship between telomerase activity and apoptosis in response to LAPA exposure in leukemia cells remains poorly understood. In this study, we confirmed that LAPA treatment induces direct cytotoxicity in human leukemia cells (U937, K562, HL60, and THP-1) through activation of caspase-3 and subsequent cleavage of poly(ADP-ribose) polymerase. The observed induction of cell death was associated with decreased telomerase activity, which was ascribed to down-regulation of telomerase reverse transcriptase. Additionally, overexpression of anti-apoptotic Bcl-2 could not overcome the induction of apoptosis or the decreased telomerase activity in response to treatment of U937 cells with LAPA. We conclude that LAPA has a direct cytotoxic effect and the loss of telomerase activity in leukemia cells.


Assuntos
Regulação para Baixo , Leucemia/enzimologia , Leucemia/fisiopatologia , Naftoquinonas/farmacologia , Telomerase/metabolismo , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HL-60 , Humanos , Células K562 , Leucemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Tabebuia/química , Células U937
14.
Int Immunopharmacol ; 7(8): 1092-101, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17570326

RESUMO

Bee venom (BV), well known as a traditional Oriental medicine, has been shown to exhibit anti-arthritic and anti-carcinogenic effects. However, the molecular mechanisms responsible for the anti-inflammatory activity of BV have not been elucidated in microglia. In the present study, we investigated the anti-inflammatory effect of BV and its major component, melittin (MEL), on lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results indicate that BV and MEL suppress LPS-induced nitric oxide (NO) and inducible NO synthase (iNOS) expression in a dose-dependent manner, without causing cytotoxicity in BV2 microglia. Moreover, BV and MEL suppressed LPS-induced activation of nuclear factor kappa B (NF-kappaB) by blocking degradation of IkappaBalpha and phosphorylation of c-Jun N-terminal kinase (JNK) and Akt, which resulted in inhibition of iNOS expression. Our data also indicate that BV and MEL exert anti-inflammatory effects by suppressing the transcription of cyclooxygenase (COX)-2 genes and proinflammatory cytokines, such as interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha. BV and MEL also attenuated the production of prostaglandin E(2) (PGE(2)). These results demonstrate that BV and MEL possess a potent suppressive effect on proinflammatory responses of BV2 microglia and suggest that these compounds may offer substantial therapeutic potential for treatment of neurodegenerative diseases that are accompanied by microglial activation.


Assuntos
Venenos de Abelha/farmacologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Meliteno/farmacologia , Microglia/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Venenos de Abelha/química , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Quinase I-kappa B/metabolismo , Immunoblotting , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Meliteno/química , Microglia/citologia , Microglia/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Prolina/análogos & derivados , Prolina/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tiocarbamatos/farmacologia
15.
FEBS Lett ; 580(7): 1883-90, 2006 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-16516891

RESUMO

Epigallocatechin-3-gallate (EGCG), a major form of tea catechin, has anti-allergic properties. To elucidate the anti-allergic mechanisms of EGCG, we investigated its regulation of matrix metalloproteinase (MMP-9) expression in toluene diisocyanate (TDI)-inhalation lung tissues as well as TNF-alpha and Th2 cytokine (IL-5) production in BAL fluid. Compared with untreated asthmatic mice those administrated with EGCG had significantly reduced asthmatic reaction. Also, increased reactive oxygen species (ROS) generation by TDI inhalation was diminished by administration of EGCG in BAL fluid. These results suggest that EGCG regulates inflammatory cell migration possibly by suppressing MMP-9 production and ROS generation, and indicate that EGCG may be useful as an adjuvant therapy for bronchial asthma.


Assuntos
Asma/tratamento farmacológico , Catequina/análogos & derivados , Inflamação/tratamento farmacológico , Sistema Respiratório/patologia , Tolueno 2,4-Di-Isocianato/farmacologia , Animais , Asma/patologia , Líquido da Lavagem Broncoalveolar , Catequina/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/induzido quimicamente , Interleucina-5/biossíntese , Metaloproteinase 9 da Matriz/genética , Camundongos , Espécies Reativas de Oxigênio , Fator de Necrose Tumoral alfa/biossíntese
16.
Biochem Biophys Res Commun ; 313(1): 148-55, 2004 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-14672711

RESUMO

The effects of epigallocatechin-3-gallate (EGCG) on dendritic cells (DC) maturation were investigated. EGCG, in a dose-dependent manner, profoundly inhibited CD80, CD86, and MHC class I and II expression on bone marrow-derived murine myeloid DC. EGCG restored the decreased dextran-FITC uptake and inhibited enhanced IL-12 production by LPS-treated DC. EGCG-treated DC were poor stimulators of nai;ve allogeneic T-cell proliferation and reduced levels of IL-2 production in responding T cells. EGCG-pretreated DC inhibited LPS-induced MAPKs, such as ERK1/2, p38, JNK, and NF-kappaB p65 translocation. Therefore, the molecular mechanisms by which EGCG antagonized LPS-induced DC maturation appeared to involve the inhibition of MAPK and NF-kappaB activation. These novel findings provide new insight into the immunopharmacological role of EGCG and suggest a novel approach to the manipulation of DC for therapeutic application of autoimmune and allergic diseases.


Assuntos
Catequina/análogos & derivados , Catequina/farmacologia , Células Dendríticas/efeitos dos fármacos , Lipopolissacarídeos/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Chá/química , Animais , Antígenos CD/biossíntese , Antígeno B7-1/biossíntese , Antígeno B7-2 , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Células Dendríticas/enzimologia , Células Dendríticas/fisiologia , Relação Dose-Resposta a Droga , Endocitose/efeitos dos fármacos , Endocitose/fisiologia , Expressão Gênica/efeitos dos fármacos , Antígenos de Histocompatibilidade Classe I/biossíntese , Antígenos de Histocompatibilidade Classe II/biossíntese , Interleucina-12/antagonistas & inibidores , Interleucina-12/biossíntese , Lipopolissacarídeos/farmacologia , Masculino , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fenótipo
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