RESUMO
A new 7,20-epoxy kaurane diterpenoid, 15-acetyldemethylkamebacetal A (1) and six known kaurane diterpenoids (2-7) were isolated from the aerial parts of Isodon inflexus in nuclear transcription factor-κB (NF-κB)-dependent reporter gene assay-guided fractionation. Their chemical structures were determined on the basis of extensive spectroscopic analysis (UV, IR, MS, 1D- and 2D-NMR) and comparison with literature data. The isolated compounds were evaluated for their inhibitory effects on TNF-α-induced NF-κB activation, and all compounds exhibited NF-κB inhibitory activities with IC50 values ranging from 1.91 to 20.15 µM.
Assuntos
Diterpenos do Tipo Caurano/análise , Isodon/química , Genes Reporter/genética , Células HeLa , Humanos , Espectroscopia de Ressonância Magnética , NF-kappa B/efeitos dos fármacos , NF-kappa B/genética , Extratos Vegetais/análise , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Bronchial asthma is characterized by chronic lung inflammation, airway hyperresponsiveness (AHR), and airway remodeling. Astilbic acid, extracted from the medicinal herb Astilbe chinensis, is used as a headache remedy in traditional medicine and has anti-pyretic and analgesic effects. However, the effect of astilbic acid on asthma remains to be established. In the present study, we therefore examined the effect of astilbic acid in a mouse model in which asthma was established by sensitization and challenge with ovalbumin (OVA). Astilbic acid inhibited OVA-induced AHR to inhaled methacholine and significantly suppressed the levels of T-helper 2-type cytokines (including IL [interleukin]-4, IL-5, and IL-13) and inflammatory cells (including eosinophils) in bronchoalveolar lavage (BAL) fluid. Histochemical analysis revealed reduced goblet cell hyperplasia and mucus production, as well as attenuated eosinophil-rich leukocyte infiltration, in the astilbic acid-treated group, compared with OVA-challenged mice. Moreover, the compound significantly inhibited synthesis of IL-4-, IL-5-, IL-13-, IL-17-, and eotaxin-encoding mRNA following asthma induction in lung tissue, in addition to suppressing the immunoglobulin E (IgE) response to asthma in both BAL fluid and serum. Our results indicate that astilbic acid has great potential as a therapeutic candidate for the treatment of asthma.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Asma/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Sistema Respiratório/imunologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/isolamento & purificação , Asma/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Ácido Oleanólico/administração & dosagem , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/uso terapêutico , Sistema Respiratório/efeitos dos fármacos , Saxifragaceae/química , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologiaRESUMO
The hepatoprotective effects of sarmentosin-containing extracts of Sedum sarmentosum (SS) in D-galactosamine (D-GalN) / lipopolysaccharide (LPS)-induced fulminant hepatic failure mouse model. Pretreatment with SS markedly protected mice from lethal liver injury, which has known to be associated with an abrupt elevation of serum tumor necrosis factor (TNF)-α level. Indeed, SS significantly blocked the elevation of TNF-α and alanine aminotransferase and aspartate aminotransferase as well. SS also remarkably reduced number of apoptotic hepatocytes and DNA fragmentation in the liver, which correlated with blockade of caspase-3 activation. In addition, SS suppressed the increased expression of toll-like receptor 4 (TLR4). The activation of c-Jun NH(2)-terminal kinase, extracellular signal-regulated kinase, and p38 induced by D-GalN/LPS was also significantly suppressed by SS treatment. Furthermore, SS significantly inhibited the activation of nuclear factor-κB. In RAW 264.7 cells stimulated with LPS, TNF-α release and TLR4 expression was suppressed by SS pretreatment, which was in line with in vivo results. These findings suggested that SS prevents D-GalN/LPS-induced fulminant hepatic failure, and this protection is likely associated with its anti-apoptotic activity and the down-regulation of mitogen activated protein kinase activity associated at least in part with suppressing the transcription of LPS receptors.
Assuntos
Glucose/análogos & derivados , Falência Hepática Aguda/prevenção & controle , Nitrilas/farmacologia , Extratos Vegetais/farmacologia , Sedum/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Caspase 3/metabolismo , Fragmentação do DNA , Modelos Animais de Doenças , Regulação para Baixo , Galactosamina , Glucose/farmacologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Lipopolissacarídeos , Fígado/metabolismo , Fígado/patologia , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
Acanthoic acid (AA) is a pimaradiene diterpene isolated from Acanthopanax koreanum. We examined the effect of AA in dextran sulfate sodium (DSS)-induced colitis. AA (100 mg/kg or 300 mg/kg) was administered p.o. daily for 7 days. AA significantly inhibited Disease Activity Index, histological score, and myeloperoxidase activity. Furthermore, AA markedly suppressed the protein expression of TNF-alpha, COX-2, NF-kappaB and chymase as well as the mRNA expression of TNF-alpha and COX-2. These results suggest that AA exerts beneficial effects in experimental colitis, and therefore we propose that this compound may have therapeutic implications for ulcerative colitis.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Diterpenos/química , Diterpenos/uso terapêutico , Eleutherococcus/química , Animais , Western Blotting , Peso Corporal/efeitos dos fármacos , Quimases/biossíntese , Colite Ulcerativa/patologia , Colo/patologia , Ciclo-Oxigenase 2/biossíntese , Diarreia/tratamento farmacológico , Diarreia/etiologia , Feminino , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/biossíntese , Peroxidase/metabolismo , Raízes de Plantas/química , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Six new triterpenoids (1-6) with a carboxylic acid functionality at C-27 were isolated from the rhizomes of a Korean native perennial herb, Astilbe chinensis, along with nine known triterpenoids. The structures of 1-6 were elucidated on the basis of spectroscopic data interpretation. All compounds isolated were evaluated for cytotoxic effects against a small panel of human cancer lines.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Plantas Medicinais/química , Saxifragaceae/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Coreia (Geográfico) , Estrutura Molecular , Rizoma/química , Triterpenos/químicaRESUMO
The hexane-soluble fraction of the roots of Aceriphyllum rossii was used to isolate seven new oleanane-type triterpenoids, aceriphyllic acids C-I (1-7), together with seven known triterpenoids. The structures of aceriphyllic acids C-I were determined as 3alpha-hydroxyolean-12-en-23,29-dioic acid (1), 3beta-hydroxyolean-12-en-23,29-dioic acid (2), 3beta,23-dihydroxyolean-12-en-29-oic acid (3), 3alpha-O-acetylolean-12-en-23,27-dioic acid (4), 3alpha-O-caffeoylolean-12-en-27-oic acid (5), 3alpha-O-acetylolean-12-en-23,29-dioic acid (6), and 3alpha-hydroxyolean-12-en-23-al-27-oic acid (7) by spectroscopic analyses. In the evaluation of the in vitro cytotoxicity of these compounds against the MCF-7 and LLC cancer cell lines, compounds 10 and 13 exhibited cytotoxic activity against the LLC cancer cell line with IC(50) values of 7.63 and 6.56 microM, respectively.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Plantas Medicinais/química , Saxifragaceae/química , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Coreia (Geográfico) , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Ácido Oleanólico/química , Raízes de Plantas/químicaRESUMO
Bisacurone, one of the active compounds of the traditionally used indigenous herb Curcuma longa Linne (Zingiberaceae), has anti-oxidant, anti-inflammatory, and anti-metastatic activities. We studied how the level of vascular cell adhesion molecule-1 (VCAM-1), one of the key molecules in the development of atherosclerosis as well as carcinogenesis and metastasis, might be affected by bisacurone in tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVECs). Bisacurone dose-dependently inhibited TNF-alpha-mediated expression of VCAM-1. It showed significant suppressive effect on ROS generation in response to TNF-alpha stimulation and it blocked nuclear factor-kappa B (NF-kappaB) p65 translocation into the nucleus and phosphorylation of inhibitory factor kappaBalpha (IkappaBalpha). It also inhibited phosphorylation of Akt and PKC, which are upstream in the regulation of VCAM-1 by TNF-alpha. Furthermore, bisacurone decreased U937 monocyte and human oral cancer cell (Hep-2, QLL-I, SCC-15) adhesion to HUVECs stimulated by TNF-alpha, suggesting that it may inhibit the binding of these cells by regulating the expression of critical adhesion molecules by TNF-alpha. Thus, bisacurone may be beneficial in the treatment of inflammatory diseases, such as atherosclerosis, where inflammatory monocytes are involved in their pathology, and, moreover, in the development of tumors.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Cicloexanóis/farmacologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Inflamação/metabolismo , Inflamação/patologia , Monócitos/efeitos dos fármacos , Sesquiterpenos/farmacologia , Molécula 1 de Adesão de Célula Vascular/biossíntese , Western Blotting , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/biossíntese , MAP Quinases Reguladas por Sinal Extracelular/genética , Genes Reporter , Humanos , Luciferases/genética , Proteína Oncogênica v-akt/biossíntese , Proteína Oncogênica v-akt/genética , Oxidantes/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plasmídeos/genética , Proteína Quinase C/biossíntese , Proteína Quinase C/genética , Transfecção , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Six diarylheptanoids (1-6) from the stem bark of Alnus hirsuta were investigated for their inhibitory activity against LPS-induced NF-kB activation and NO and TNF-alpha production. Among them, compounds 2, 3, and 6 displayed inhibitory activity against NF-kB activation and NO and TNF-alpha production with IC50 values of 9.2-9.9 microM, 18.2-19.3 microM, and 22.3-23.7 microM, respectively, in RAW264.7 cells. Three active compounds had no significant cytotoxicity in RAW264.7 cells at their effective concentrations. This is the first report of NF-kB-inhibitory activity of these compounds and supports the pharmacological use of A. hirsuta, which has been employed as a herbal medicine for the treatment of inflammatory diseases.
Assuntos
Alnus/química , Diarileptanoides/farmacologia , NF-kappa B/antagonistas & inibidores , Óxido Nítrico/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Linhagem Celular , Diarileptanoides/química , Diarileptanoides/isolamento & purificação , Concentração Inibidora 50 , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Metanol/química , Camundongos , Estrutura Molecular , Óxido Nítrico/análise , Óxido Nítrico/biossíntese , Casca de Planta/química , Extratos Vegetais/química , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/biossínteseRESUMO
The unripe fruit of Evodia rutaecarpa (JUSS) BENTH (ER, Family Rutaceae) has been used frequently as a traditional medicine against inflammatory diseases in Korea, China and Japan. To evaluate antiallergic effect of ER, we isolated its main constituents, evodiamine and rutaecarpine, and evaluated in vivo their inhibitory effects against passive cutaneous anaphylaxis (PCA) reaction induced by IgE-antigen complex and scratching behaviors by compound 48/80. ER and its constituents, evodiamine and rutaecarpine, potently inhibited PCA reaction and scratching behaviors in mice, although ER weakly inhibited scratching behaviors. Evodiamine and rutaecarpine inhibited TNF-alpha and IL-4 protein expression in RBL-2H3 cells induced by IgE-antigen complex, although these did not inhibit degranulation of RBL-2H3 cells induced by IgE-antigen complex and rat peritoneal mast cells induced by compound 48/80. These findings suggest that ER and its constituents, evodiamine and rutaecarpine, may be effective for IgE-induced allergic diseases such as atopic dermatitis and rhinitis.
Assuntos
Alcaloides/farmacologia , Antialérgicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Evodia , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Extratos Vegetais/farmacologia , Prurido/prevenção & controle , Quinazolinas/farmacologia , Alcaloides/isolamento & purificação , Alcaloides/uso terapêutico , Animais , Antialérgicos/isolamento & purificação , Antialérgicos/uso terapêutico , Degranulação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Frutas , Alcaloides Indólicos , Interleucina-4/metabolismo , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Prurido/induzido quimicamente , Quinazolinas/isolamento & purificação , Quinazolinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , p-Metoxi-N-metilfenetilaminaRESUMO
A bioassay-guided phytochemical investigation on the methanol extract of Boehmeria pannosa, using a HIF-1-mediated reporter gene assay, led to the isolation of two phenanthroquinolizidine alkaloids, (-)-cryptopleurine (1) and (-)-(15R)-hydroxycryptopleurine (2). The structure of the new compound 2 was determined by spectroscopic methods. Compounds 1 and 2 potently inhibited the hypoxia-induced expression of a reporter gene under the control of a hypoxia response element (HRE) with IC(50) values of 8.7 and 48.1 nM, respectively. Furthermore, 1 and 2 suppressed the accumulation of HIF-1alpha protein in a dose-dependent manner, but not the HIF-1beta protein and inhibited expression of vascular endothelial growth factor (VEGF) by hypoxia.
Assuntos
Alcaloides/isolamento & purificação , Boehmeria/química , Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Plantas Medicinais/química , Neoplasias Gástricas/metabolismo , Alcaloides/química , Alcaloides/farmacologia , Relação Dose-Resposta a Droga , Humanos , Hipóxia/metabolismo , Concentração Inibidora 50 , Coreia (Geográfico) , Raízes de Plantas/química , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
The fruits of Evodia rutaecarpa Benth (Rutaceae) has long been used for inflammatory disorders and some anti-inflammatory actions of its constituents such as dehydroevodiamine, evodiamine and rutaecarpine were previously reported. Since the pharmacological data is not sufficient to clearly establish the scientific rationale of anti-inflammatory medicinal use of this plant material and the search for its active principles is limited so far, three major constituents (evodiamine, rutaecarpine, goshuyuamide II) were evaluated for their anti-inflammatory cellular action mechanisms in the present study. From the results, evodiamine and rutaecarpine were found to strongly inhibit prostaglandin E2 synthesis from lipopolysaccharide-treated RAW 264.7 cells at 1-10 microM. Evodiamine inhibited cyclooxygenase-2 induction and NF-kappaB activation, while rutaecarpine did not. On the other hand, goshuyuamide II inhibited 5-lipoxygenase from RBL-1 cells (IC50 = 6.6 microM), resulting in the reduced synthesis of leukotrienes. However, these three compounds were not inhibitory against inducible nitric oxide synthase-mediated nitric oxide production from RAW cells up to 50 micorM. These pharmacological properties may provide the additional scientific rationale for anti-inflammatory use of the fruits of E. rutaecarpa.
Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Evodia , Macrófagos/efeitos dos fármacos , Alcaloides/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Araquidonato 5-Lipoxigenase/metabolismo , Calcimicina , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Inibidores de Ciclo-Oxigenase 2/farmacologia , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Evodia/química , Frutas/química , Alcaloides Indólicos , Leucotrieno C4/metabolismo , Lipopolissacarídeos , Inibidores de Lipoxigenase/isolamento & purificação , Inibidores de Lipoxigenase/farmacologia , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Quinazolinas/isolamento & purificação , Quinazolinas/farmacologiaRESUMO
Acanthoic acid (AA) is a pimaradiene diterpene isolated from the Korean medicinal plant, Acanthopanax koreanum (Araliaceae). In the present study, we examined whether AA has the inhibitory effect on the production of inflammatory mediators and activating signals induced in trypsin-treated human leukemic mast cell-1 (HMC-1). HMC-1 cells were stimulated with trypsin (100 nM) in the presence or absence of AA (1, 10, and 100 microg/ml). We assessed the production of TNF-alpha and tryptase by enzyme-linked immunosorbent assay (ELISA) or reverse transcription-PCR, ERK activation by Western blot, and NF-kappaB activation by gel shift assay. AA (10 and 100 microg/ml) significantly inhibited production of both TNF-alpha and tryptase in a dose-dependent manner in trypsin-stimulated HMC-1. Furthermore, AA inhibited ERK phosphorylation and NF-kappaB activation induced by trypsin treatment without blocking of trypsin activity even with 100 microg/ml. These results suggest that AA may inhibit the production of inflammatory mediators through inhibition of ERK phosphorylation and NF-kappaB activation pathway in human mast cells. It supports the evidence that AA may be used to blocks the development of inflammation caused from mast cells.
Assuntos
Diterpenos/farmacologia , Mastócitos/efeitos dos fármacos , Inibidores da Tripsina/farmacologia , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , NF-kappa B/metabolismo , Fosforilação , RNA Mensageiro/análise , Triptases/genética , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
A new polyacetylene, gymnasterkoreayne G (1) and seven known (2--8) constituents were isolated from the leaves of Gymnaster koraiensis. Base on extensive 1D and 2D NMR spectroscopic data, the structure of the new compound was identified as erythro-8(S)-9(Z),16-heptadecadiene-4,6-diyne-2,3,8-triol. Isolated compounds were evaluated for their ability to inhibit NFAT transcription factor. While other components did not show activity, most of polyacetylene components markedly inhibit NFAT transcription factor. Of these compounds, gymnasterkoreayne B (3) was the most potent (IC(50) 1.44+/-0.59 microM). In term of the isomers, compound 1 (IC(50) 43.9+/-2.24 microM) with an erythro-configuration showed less inhibition than 2 (IC(50) 7.24+/-0.42 microM) with a threo-configuration.
Assuntos
Acetileno/análogos & derivados , Alcinos/síntese química , Alcinos/farmacologia , Asteraceae/química , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas Nucleares/antagonistas & inibidores , Fatores de Transcrição/antagonistas & inibidores , Acetileno/síntese química , Acetileno/farmacologia , Soluções Tampão , Humanos , Indicadores e Reagentes , Células Jurkat , Espectroscopia de Ressonância Magnética , Fatores de Transcrição NFATC , Extratos Vegetais/química , Vírus da Imunodeficiência Símia , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria Infravermelho , Sais de Tetrazólio , TiazóisRESUMO
The EtOAc extract of Youngia koidzumiana significantly inhibited the diacylglycerol acyltransferase (DGAT) from rat liver microsomes. Bioactivity-guided fractionation led to the isolation of nine compounds, the structures of which were established using physicochemical and spectral data. Of the isolated compounds, oleanolic acid (2), methyl ursolate (7) and corosolic aicd (8) inhibited DGAT, with IC50 values of 31.7, 26.4, and 44.3 microM, respectively. However, sesquiterpenoids showed only weak inhibitory effects toward DGAT.
Assuntos
Aciltransferases/antagonistas & inibidores , Asteraceae/química , Inibidores Enzimáticos/farmacologia , Terpenos/farmacologia , Animais , Cromatografia em Camada Fina , Diacilglicerol O-Aciltransferase , Inibidores Enzimáticos/isolamento & purificação , Técnicas In Vitro , Fígado/efeitos dos fármacos , Fígado/enzimologia , Espectroscopia de Ressonância Magnética , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Espectrofotometria Infravermelho , Terpenos/isolamento & purificaçãoRESUMO
Two new compounds were isolated from the stem and twigs of Ribes fasciculatum var. chinense and their structures were identified to be threo-(7S,8R)-1-(4-hydroxyphenyl)-2-[4-(E)-propenylphenoxy]-propan-1-ol (1), and 5,4'-dihydroxy-7-methoxyflavone-3-O-[alpha-L-rhamnopyranosyl(1-->3)-O-alpha-L-rhamnopyranosyl(1-->6)-O-beta-D-glucopyranoside] (2). With nine other known components, they were tested on inhibitory activity against nuclear factor of activated T cells (NFAT) transcription factor. Compound 1 showed a potent inhibitory activity (IC50=15.6 microM), while compounds 4, 5 and 9 showed moderate inhibitory activity (IC50 22.4, 24.5 and 25.7 microM, respectively).
Assuntos
Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas Nucleares/antagonistas & inibidores , Ribes , Fatores de Transcrição/antagonistas & inibidores , Transcrição Gênica/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Humanos , Células Jurkat , Fatores de Transcrição NFATC , Proteínas Nucleares/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Caules de Planta , Fatores de Transcrição/metabolismo , Transcrição Gênica/fisiologiaRESUMO
A new benzofuran derivative, named gymnastone [5-hydroxy-6-acetyl-2-(2-propane-1,2,3-triol)-benzofuran (1)], was isolated from the aerial part of Gymnaster koraiensis, together with viscidone (2) by repeated column chromatography. The structures of both compounds were identified by physico-chemical and spectral analysis including COSY, HMQC, and HMBC experiments.
Assuntos
Asteraceae/química , Benzofuranos/isolamento & purificação , Acetileno/química , Benzofuranos/química , Cromatografia/métodos , Glicosídeos/química , Glicosídeos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Caules de Planta/químicaRESUMO
Six diterpenoids and two diterpene glycosides were isolated from the dichloromethane and the water fractions of Acanthopanax koreanum roots, respectively. Of these compounds, 16alphaH, 17-isovaleryloxy-ent-kauran-19-oic acid containing an isovaleryloxy group at C-17 was found to exhibit the strongest inhibitory activity (IC(50), 6.7 microm) against NFAT transcription factor. However, sumogaside, 16alpha-hydroxy-ent-kauran-19-oic acid and paniculosides IV containing a hydroxy group at C-16 or a glycoside at C-4 carboxyl acid showed no activity.
Assuntos
Eleutherococcus , Fitoterapia , Extratos Vegetais/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Fatores de Transcrição/antagonistas & inibidores , Diterpenos/administração & dosagem , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Humanos , Concentração Inibidora 50 , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/uso terapêuticoRESUMO
Two triterpenoids (1,4) and two triterpenoid glycosides (2,3) were isolated from the root of Acanthopanax koreanum (Araliaceae). Their structures were identified as impressic acid (1), acankoreoside A (2), 3-epi-betulinic acid 28-O-[alpha-L-rhamnopyranosyl(1 --> 4)-beta-D-glucopyranosyl(1 --> 6)]-beta-D-glucopyranosyl] ester (3), and ursolic acid (4) by physicochemical and spectroscopic methods. Of these compounds, impressic acid (1) exhibited a potent inhibitory activity against NFAT transcription factor (IC50: 12.65 microM).
Assuntos
Proteínas de Ligação a DNA/antagonistas & inibidores , Eleutherococcus , Proteínas Nucleares/antagonistas & inibidores , Fatores de Transcrição/antagonistas & inibidores , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição NFATC , Proteínas Nucleares/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Raízes de Plantas , Fatores de Transcrição/metabolismo , Triterpenos/químicaRESUMO
The hepatoprotective effects of Acanthopanax koreanum Nakai (Araliaceae) were evaluated in D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mouse. Preparations of Acanthopanax koreanum used were an ethanol extract, a water extract, and the ethanol-soluble and ethanol-insoluble components of the water extract of roots or stems of the plant. Mice were pretreated with various extracts by intraperitoneal injection or orally, 12 and 1 h before intraperitoneal injection of D-galactosamine and lipopolysaccharide (LPS). Intraperitoneal pretreatment with the water extract or the ethanol-insoluble component of the water extract markedly reduced the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-alpha (TNF-alpha), reduced the histological changes in the liver, and attenuated hepatocyte apoptosis confirmed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and DNA fragmentation assay. Oral pretreatment with the ethanol-insoluble component of the water extract also reduced serum AST, ALT, and TNF-alpha levels. The present study shows that the ethanol-insoluble component of a water extract from Acanthopanax koreanum has a protective effect against the induction of fulminant hepatitis in mice by D-galactosamine and lipopolysaccharide.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Eleutherococcus , Fígado/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fragmentação do DNA/efeitos dos fármacos , Galactosamina , Hepatócitos/efeitos dos fármacos , Injeções Intraperitoneais , Lipopolissacarídeos , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Caules de Planta , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/uso terapêutico , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
A new diterpene glycoside, acantrifoside D ( 1), as well as three known diterpenes (2 - 4) were isolated from the stem bark of Acanthopanax trifoliatus from Vietnam. Based on 1D and 2D NMR spectroscopic data, their chemical structures were determined to be 16alpha,17-dihydroxy- ent-kauran-19-oic acid 16- O-beta- D-glucopyranoside 19- O-beta- D-glucopyranosyl ester (1), 16alpha H,17-isovalerate- ent-kauran-19-oic acid (2), ent-kaur-16-en-19-oic acid ( 3), and ent-pimara-8(14),15-dien-19-oic acid (4). Compounds 2 - 4 had strong inhibitory effects against COX-1 in an in vitro assay, with IC50 values of 0.21, 0.15 and 0.19 mM, respectively.