RESUMO
We isolated flavonoids from herbal specimens from the Tibetan region (Sophora yunnanensis and Rhodiola sacra) that suppress nitric oxide (NO) production in macrophages stimulated by lipopolysaccharide and interferon-γ. The isolated flavonoids carry symmetric substitutions in the B ring (R3'=R5'). We analyzed the quantitative structure-activity relationship of the inhibitory activity by comparative molecular field analysis (CoMFA) using this series of flavonoids. Use of flavonoids with symmetrical substitutions in the B ring made it simpler to align molecules because it was not necessary to consider a huge number of combinations due to the B-ring conformation. The CoMFA model, whose cross-validated q2 value was 0.705, suggested the existence of a hydroxy group at the 5-position, the choice of the A/C-ring scaffold (chromane or chromene) and electrostatic field around the B ring are important for NO inhibitory activity. Flavonoids synthesized based on the CoMFA model exhibited significant inhibitory potential against NO production, validating the predictive capability of the CoMFA model.
Assuntos
Produtos Biológicos/farmacologia , Flavonoides/farmacologia , Óxido Nítrico/antagonistas & inibidores , Animais , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Camundongos , Modelos Moleculares , Estrutura Molecular , Óxido Nítrico/biossíntese , Células RAW 264.7 , Rhodiola/química , Sophora/química , Relação Estrutura-AtividadeRESUMO
Six new sesquiterpene coumarin derivatives, fukanefuromarin H-M (1-6), were isolated from an 80% aqueous methanol extract of the roots of Ferula fukanensis. The structures were elucidated on the basis of spectroscopic evidence, particularly heteronuclear multiple-bond connectivity (HMBC) and high-resolution MS. The sesquiterpene coumarin derivatives inhibited nitric oxide (NO) and inducible NO synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) gene expression in a murine macrophage-like cell line (RAW264.7), which was activated by lipopolysaccharide (LPS) and recombinant mouse interferon-γ (IFN-γ).
Assuntos
Cumarínicos/química , Ferula/química , Sesquiterpenos/química , Animais , Linhagem Celular , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Interferon gama/genética , Interferon gama/metabolismo , Interferon gama/farmacologia , Interleucina-6/genética , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Raízes de Plantas/química , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Degradation of the components of Leonurus Herb was examined during drying. Compounds 1 and 2 were detected on TLC at lower temperature, but not at higher temperature. Their chemical structures were determined by spectral methods. They immediately decomposed even at 40°C in chloroform solution. They are believed to be transformed through a retro-aldol reaction. Compounds 1 and 2 have not been previously reported.
Assuntos
Diterpenos/isolamento & purificação , Leonurus/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Temperatura , Cromatografia em Camada Fina , Diterpenos/química , Espectrometria de Massas , Conformação Molecular , Extratos Vegetais/químicaRESUMO
Obesity is a serious health problem worldwide. We investigated the anti-obesity effect of the flower of Albizia julibrissin DURAZZ. (Leguminosae). A 90% EtOH extract of the flower inhibited adipogenesis in 3T3-L1 preadipocytes, as well as the activity of glycerol-3-phosphate dehydrogenase (GPDH) activity. New flavonol acylglycosides (1-4) and eighteen known compounds (5-22) were isolated by bioassay-directed fractionation. These new glycosides were elucidated to be 3â³-(E)-p-coumaroylquercitrin (1), 3â³-(E)-feruloylquercitrin (2), 3â³-(E)-cinnamoylquercitrin (3), and 2â³-(E)-cinnamoylquercitrin (4) on the basis of spectroscopic and chemical analysis. These compounds inhibited adipogenesis in 3T3-L1 preadipocytes. In particular, 2 exhibited potent inhibitory effects on triglyceride accumulation. Furthermore, GPDH activity was inhibited by 2. Additionally, 2 inhibited glucose uptake in 3T3-L1 adipocytes. These results indicate that the 90% EtOH extract and compounds isolated from the flower of A. julibrissin inhibit adipogenesis in 3T3-L1 preadipocytes and may have anti-obesity effect through the inhibition of preadipocyte differentiation.
Assuntos
Albizzia/química , Fármacos Antiobesidade/química , Flavonóis/química , Glicosídeos/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Células 3T3-L1 , Adipogenia/efeitos dos fármacos , Animais , Fármacos Antiobesidade/isolamento & purificação , Fármacos Antiobesidade/farmacologia , Diferenciação Celular/efeitos dos fármacos , Flores/química , Glicerolfosfato Desidrogenase/antagonistas & inibidores , Glicerolfosfato Desidrogenase/metabolismo , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Camundongos , Triglicerídeos/metabolismoRESUMO
A new flavonoid, (2R,3R)-3,7,4'-trihydroxy-3',5'-dimethoxyflavanone, named sophorayunnanol (1), together with eight known polyphenols (2-9), were isolated from the roots of Sophora yunnanensis C.Y.MA (Leguminosae). The structure including absolute stereochemistry of 1 was determined by spectroscopic (high resolution (HR)-MS, 1D- and 2D-NMR, and circular dichroism (CD)) methods. The inhibitory activity of these compounds was examined against nitric oxide (NO) production by lipopolysaccharide (LPS) and interferon (IFN)-γ activated macrophages, RAW264.7 cells. 3,7,3',5'-Tetrahydroxy-4'-methoxyflavone (6) and piceatannol (9) showed potent inhibitory activity against the production of NO with IC(50) values of 14.4±2.5 and 12.9±1.8 µM, respectively. This article is the first report on phytochemical study of S. yunnanensis.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Óxido Nítrico/antagonistas & inibidores , Polifenóis/química , Polifenóis/farmacologia , Sophora/química , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Interferon gama/imunologia , Lipopolissacarídeos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Óxido Nítrico/imunologia , Raízes de Plantas/química , Polifenóis/isolamento & purificaçãoRESUMO
New phenanthrenes, loddigesiinols A (1) and B (7), and stilbenes, loddigesiinols C (8) and D (9), were isolated from 80% ethanol extract of Dendrobium loddigesii ROLFE (Orcharedceae) along with known compounds, including five phenanthrenes, three stilbenes, two lignans, and three sterols. Their structures were determined by spectroscopic studies. These compounds were evaluated for their inhibitory activities against nitric oxide (NO) production and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging. Phenanthrenes (1-3, 7) and dihydrophenanthrenes (4-6) showed significant inhibitory activity against NO production. In particular, 2 showed stronger inhibitory activity against NO production than 5 and 6. This suggested that this phenanthrene is a stronger inhibitor of NO production than dihydrophenanthrene. The new phenanthrenes, loddigesiinols A (1) and B (7), significantly inhibited NO production with IC(50) values of 2.6 and 10.9 muM, respectively. One new dihydrostilbene, loddigesiinol D (9), showed weak inhibitory activity against NO production with an IC(50) value of 69.7 microM, but the other new dihydrostilbene, loddigesiinol C (8), did not show this activity at 100 microM.
Assuntos
Dendrobium/química , Dendrobium/classificação , Fenantrenos/química , Estilbenos/química , Animais , Linhagem Celular , Concentração Inibidora 50 , Macrófagos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Camundongos , Fenantrenos/farmacologia , Componentes Aéreos da Planta/químicaRESUMO
Endothelial progenitor cells (EPCs) are known to repair vascular injuries. Recent studies suggest that Saiko-ka-ryukotsu-borei-To (SKRBT), a traditional herbal medicine that has been used to treat stress-related neuropsychiatric disorders, has protective effects on cardiovascular diseases such as hypertension and arteriosclerosis. Spontaneously hypertensive rats (SHRs) were fed diets containing lyophilized SKRBT extract for 6 weeks. Peripheral blood mononuclear cells (MNCs) were isolated and cultured to assay EPC colony formation. Oxidative stress in MNCs was evaluated by thiobarbituric acid reactive substance (TBARS) assay and flowcytometric analyses. Treatment with SKRBT increased EPC colony numbers significantly (p<0.05) with decrease in oxidative stress and without affecting blood pressure in SHRs. Treatment with SKRBT did not reduce the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits in cardiovascular organs. Serum IL-6 level was significantly reduced. SKRBT is a feasible herbal medicine that protects against cardiovascular diseases through an increase in EPC function along with anti-oxidative effects, and may affect the link between chronic inflammation and cardiovascular disease.
Assuntos
Células da Medula Óssea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Hipertensão/prevenção & controle , Fitoterapia , Animais , Citocinas/sangue , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Leucócitos Mononucleares/metabolismo , Masculino , NADPH Oxidases/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR , Espécies Reativas de Oxigênio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
In our investigation on the chemical constituents of Hippophae rhamnoides L., the chloroform-soluble fraction of the 80% acetone extract of branch bark was observed to inhibit nitric oxide (NO) production in a lipopolysaccharide and recombinant mouse interferon-gamma-activated murine macrophage-like cell line, RAW 264.7 cells. Two new triterpenoids, 2-O-trans-p-coumaroyl maslinic acid (1) and 2-O-caffeoyl maslinic acid (2), and three known triterpenoids, oleanolic acid (3), 3-O-trans-p-coumaroyl oleanolic acid (4), and 3-O-caffeoyl oleanolic acid (5), and 6-methoxy-2H-1-benzopyran (6) and beta-sitosterol (7) were isolated from the branch bark extract. Their inhibitory activities on the production of NO in RAW 264.7 cells and radical-scavenging activities were examined.
Assuntos
Compostos de Bifenilo/química , Sequestradores de Radicais Livres/farmacologia , Hippophae/química , Hidrazinas/química , Óxido Nítrico/biossíntese , Triterpenos/farmacologia , Animais , Linhagem Celular , Camundongos , Picratos , Triterpenos/isolamento & purificaçãoRESUMO
In vitro anti-allergic screening of medicinal herbal extracts revealed that the chloroform extract of the rhizoma of Kadsura coccinea inhibited nitric oxide (NO) production in a lipopolysaccharide (LPS) and recombinant mouse interferon-gamma (IFN-gamma) activated murine macrophage like cell line RAW 264.7. Further fractionation of the chloroform extract led to the isolation of three new lignans, including two dibenzocyclooctadiene lignans and one arylnaphthalene lignan, together with other three known dibenzocyclooctadiene lignans. This is the first report of NO production inhibitory activity of Kadsura coccinea and first report about the isolation of arylnaphthalene lignan from K. coccinea.
Assuntos
Kadsura/química , Lignanas/química , Lignanas/farmacologia , Óxido Nítrico/análise , Animais , Antialérgicos/química , Antialérgicos/farmacologia , Linhagem Celular , Clorofórmio/química , Avaliação Pré-Clínica de Medicamentos , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Rizoma/químicaRESUMO
From a MeOH extract of the aerial part of Piper futokadsura, the tetrahydrofuran lignans, futokadsurin A [(7S,8S,7'S,8'R)-3,4,3'-trimethoxy-4'-hydroxy-7,7'-epoxylignan], futokadsurin B [(7R,8R,7'R,8'S)-3,4-dimethoxy-3',4'-methylenedioxy-7,7'-epoxylignan], and futokadsurin C [(7R,8R,7'S,8'S)-3,4-methylenedioxy-3',4'-dimethoxy-7,7'-epoxylignan] were isolated, together with nine known neolignans. In addition, L-tryptophan, pellitorine, phytol, elemicin, and 1,2,4-trimethoxyphenyl-5-aldehyde were isolated. The structures of the new compounds were elucidated using spectroscopic methods. These lignans inhibited nitric oxide production by a murine macrophage-like cell line (RAW 264.7), which was activated by lipopolysaccharide and interferon-gamma.
Assuntos
Lignanas/isolamento & purificação , Lignanas/farmacologia , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Piper , Animais , Linhagem Celular , Lignanas/química , Camundongos , Componentes Aéreos da Planta , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologiaRESUMO
Three novel chalcone derivatives, mallotophilippens C (1), D (2) and E (3) were isolated from the fruits of Mallotus philippinensis MUELL. ARG. These compounds were identified, using chemical and spectral data, as 1-[6-(3,7-dimethyl-octa-2,6-dienyl)-5,7-dihydroxy-2,2-dimethyl-2H-chromen-8-yl]-3-(4-hydroxy-phenyl)-propenone, 3-(3,4-dihydroxy-phenyl)-1-[6-(3,7-dimethyl-octa-2,6-dienyl)-5,7-dihydroxy-2,2-dimethyl-2H-chromen-8-yl]-propenone and 1-[5,7-dihydroxy-2-methyl-6-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-2H-chromen-8-yl]-3-(3,4-dihydroxy-phenyl)-propenone, respectively. They inhibited nitric oxide (NO) production and inducible NO synthase (iNOS) gene expression by a murine macrophage-like cell line (RAW 264.7), which was activated by lipopolysaccharide (LPS) and recombinant mouse interferon-gamma (IFN-gamma). Furthermore, they downregulated cyclooxygenase-2 (COX-2) gene, interleukin-6 (IL-6) gene and interleukin-1beta (IL-1beta) gene expression. These results suggest that they have anti-inflammatory and immunoregulatory effects.
Assuntos
Antialérgicos/farmacologia , Chalconas/farmacologia , Mallotus (Planta) , Óxido Nítrico/antagonistas & inibidores , Antialérgicos/química , Antialérgicos/isolamento & purificação , Chalconas/química , Chalconas/isolamento & purificação , Óxido Nítrico/biossíntese , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologiaRESUMO
Six new sesquiterpene coumarin derivatives, 2,3-dihydro-7-hydroxy-2R,3R-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]furo[3,2-c]coumarin (4), fukanefuromarin A (5), fukanefuromarin B (6), fukanefuromarin C (7), fukanefuromarin D (8), and fukanemarin A (9), were isolated from a 80% aqueous methanol extract of the roots of Ferula fukanensis. The structures were elucidated on the basis of spectral evidence, especially heteronuclear multiple-bond connectivity (HMBC), nuclear Overhauser exchange spectroscopy (NOESY), and high-resolution MS. An extract of F. fukanensis (FFE) and the sesquiterpene coumarin derivatives inhibited nitric oxide (NO) production and inducible NO synthase (iNOS) gene expression by a murine macrophage-like cell line (RAW 264.7), which was activated by lipopolysaccharide (LPS) and recombinant mouse interferon-gamma (IFN-gamma).
Assuntos
Cumarínicos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Ferula/química , Óxido Nítrico Sintase/antagonistas & inibidores , Plantas Medicinais/química , Sesquiterpenos/isolamento & purificação , Animais , China , Cumarínicos/química , Cumarínicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II , Nitritos/análise , Raízes de Plantas/química , RNA Mensageiro/análise , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Two new phloroglucinol derivatives, mallotophilippen A (1). and B (2). were isolated from the fruits of Mallotus philippensis. These compounds were identified, using chemical and spectral data, as 1-[5,7-dihydroxy-2,2-dimethyl-6-(2,4,6-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one and 1-[6-(3-Acetyl-2,4,6-trihydroxy-5-methyl-benzyl)-5,7-dihydroxy-2,2-dimethyl-2H-chromen-8-yl]-2-methyl-butan-1-one, respectively. They inhibited nitric oxide (NO) production and inducible NO synthase (iNOS) gene expression by a murine macrophage-like cell line (RAW 264.7), which was activated by lipopolysaccharide (LPS) and recombinant mouse interferon-gamma (IFN-gamma). Furthermore, they inhibited histamine release from rat peritoneal mast cells induced by Compound 48/80. These results suggest that the novel phloroglucinol derivatives have anti-inflammatory effects.