RESUMEN
The activity-guided fractionation of the MeOH extract of the rhizomes and roots of Nardostachys chinensis led to the isolation of two new sesquiterpenoids, narchinol B (8) and narchinol C (9), along with 10 known compounds, ursolic acid (1), nardosinone (2), pinoresinol (3), desoxo-narchinol A (4), kanshone B (5), epoxyconiferyl alcohol (6), debilon (7), 4α,5-dimethyl-1,3-dioxo-1,2,3,4,4α,5,6,7-octahydronaphthalene (10), p-coumaric acid (11), and isoferulic acid (12). Their structures were determined using spectroscopic techniques, which included 1D- and 2D-NMR. Among the isolates, compounds 2, 4, 5, 8 and 9 showed inhibitory activity against LPS-induced NO production with IC(50) values of 4.6-21.6 µM.
Asunto(s)
Macrófagos/citología , Nardostachys/metabolismo , Óxido Nítrico/metabolismo , Extractos Vegetales/farmacología , Animales , Diseño de Fármacos , Concentración 50 Inhibidora , Lipopolisacáridos/química , Espectroscopía de Resonancia Magnética/métodos , Metanol/química , Ratones , Modelos Químicos , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/química , Raíces de Plantas/metabolismo , Rizoma/química , Espectrofotometría/métodosRESUMEN
A new pyrrolidinone diterpenoid, excisusin F (1), was isolated from the aerial parts of Isodon excisus (Lamiaceae), together with four known compounds, and their structures were determined mainly by NMR (1D and 2D) and mass spectrometry. Excisusin F (1) and inflexarabdonin E (3) showed potent inhibitory effects of LPS-induced nitric oxide production in RAW264.7 cells with the IC(50) value of 10.4 and 3.8 µM, respectively.
Asunto(s)
Diterpenos/química , Isodon/química , Macrófagos/efectos de los fármacos , Óxido Nítrico/metabolismo , Pirrolidinonas/química , Animales , Línea Celular Tumoral , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Lipopolisacáridos/toxicidad , Macrófagos/metabolismo , Espectroscopía de Resonancia Magnética , Ratones , Conformación Molecular , Componentes Aéreos de las Plantas/química , Pirrolidinonas/aislamiento & purificación , Pirrolidinonas/farmacologíaRESUMEN
Bioactivity-guided isolation of the methanol extract of the stems of Dendrobium nobile yielded a new phenanthrene together with nine known phenanthrenes and three known bibenzyls. Their structures were elucidated by analysis of the spectroscopic data including 2D-NMR. All of the isolates were evaluated for their potential to inhibit the LPS-induced production of nitric oxide in murine macrophage RAW 264.7 cells. Compounds 1-4, 7-13 inhibited nitric oxide production with the IC(50) values ranging from 9.6 microM to 35.7 microM.
Asunto(s)
Dendrobium/química , Macrófagos/efectos de los fármacos , Óxido Nítrico/antagonistas & inhibidores , Fenantrenos/farmacología , Animales , Línea Celular , Concentración 50 Inhibidora , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Óxido Nítrico/biosíntesis , Fenantrenos/química , Fenantrenos/aislamiento & purificación , Extractos Vegetales , Relación Estructura-ActividadRESUMEN
Five ent-kaurane diterpenoids, 6beta,7beta,14beta-trihydroxy-1alpha,19-diacetoxy-7alpha,20-epoxy- ent-kaur-16-en-15-one (1), 1alpha,6beta,7beta-trihydroxy-11alpha,19-diacetoxy-7alpha,20-epoxy-ent-kaur-16-en-15-one (2), 6-hydroxy-1alpha,19-diacetoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide (3), 19-hydroxy-1alpha,6-diacetoxy-6,7-seco- ent-kaur-16-en-15-one-7,20-olide (4), and 6-aldehyde-1alpha,19-diacetoxy-6,7-seco- ent-kaur-16-en-15-one-7,20-olide (5), along with 10 known ent-kaurane diterpenoids, pseurata C (6), longikaurin C (7), effusanin C (8), longikaurin B (9), longikaurin D (10), effusanin D (11), excisanin B (12), lasiokaurin (13), megathyrin A (14), and loxothyrin A (15), were isolated from the aerial parts of Isodon japonicus. Their structures were determined on the basis of spectroscopic (1D-, 2D-NMR and MS) and chemical evidence. The isolates were evaluated for their inhibitory effects on LPS-induced production of nitric oxide in murine macrophage RAW264.7 cells.
Asunto(s)
Diterpenos de Tipo Kaurano/aislamiento & purificación , Isodon/química , Plantas Medicinales/química , Animales , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/farmacología , Corea (Geográfico) , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Ratones , Estructura Molecular , Óxido Nítrico/metabolismo , Resonancia Magnética Nuclear BiomolecularRESUMEN
We have previously reported that piperine, a known piperidine alkaloid from Piper longum, competitively inhibited mouse brain MAO-A and MAO-B activities. Piperine also showed in vivo antidepressant-like activity against the tail suspension test. In the present study, we further expanded on the identification of MAO inhibitors from the fruit of P. longum. Activity-guided fractionation of a methylene chloride soluble extract led to the isolation of three known piperine-related compounds, methylpiperate (1), guineensine (2), and piperlonguminine (3). Of these, methylpiperate (1) and guineensine (2) showed significant MAO inhibitory activities with IC50 values of 3.6 and 139.2 microM, respectively. Furthermore, methylpiperate (1) exhibited a selective inhibitory effect against MAO-B (IC50 value: 1.6 microM) than MAO-A (IC50 value: 27.1 microM). The kinetic study using the Lineweaver-Burk plots analysis suggested that methylpiperate (1) competitively inhibits MAO-A and MAO-B activities with the Ki values of 23.5 and 1.3 microM, respectively.
Asunto(s)
Alquenos/farmacología , Encéfalo/efectos de los fármacos , Dioxolanos/farmacología , Compuestos Heterocíclicos con 2 Anillos/farmacología , Inhibidores de la Monoaminooxidasa/farmacología , Monoaminooxidasa/metabolismo , Piper , Alquenos/aislamiento & purificación , Animales , Encéfalo/enzimología , Dioxolanos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Frutas , Compuestos Heterocíclicos con 2 Anillos/aislamiento & purificación , Cinética , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/enzimología , Inhibidores de la Monoaminooxidasa/aislamiento & purificación , Piper/químicaRESUMEN
Seven flavonoids were isolated from the whole plants and fruits of Cayratia japonica through the activity-guided isolation of a methanol extract using a monoamine oxidase (MAO) inhibition assay as a monitor. The chemical structures of the isolates were assigned as apigenin-7-O-beta-D-glucuronopyranoside (1), apigenin (2), luteolin (3), luteolin-7-O-beta-D-glucopyranoside (4), (+)-dihydroquercetin (taxifolin) (5), (+)-dihydrokaempferol (aromadendrin) (6) and quercetin (7). Among the isolated compounds, flavones such as apigenin (2) and luteolin (3), as well as the flavonol, quercetin (7) showed potent inhibitory effects against the MAO activity with IC50 values of 6.5, 22.6, and 31.6 microM, respectively. However, the flavone glycosides, apigenin-7-O-beta-D-glucuronopyranoside (1) and luteolin-7-O-beta-D-glucopyranoside (4), showed mild MAO inhibition (IC50 values: 81.7 and 118.6 microM, respectively). The flavanonol derivatives, taxifolin (5) and aromadendrin (6), also showed weak inhibition (IC50 values: 154.7 and 153.1 microM, respectively). Furthermore, quercetin (7) had a more potent inhibitory effect on MAO-A (IC50 value: 2.8 microM) than MAO-B (IC50 value: 90.0 microM). Apigenin (2) and luteolin (3) also preferentially inhibited MAO-A (IC50 values: 1.7 and 4.9 microM, respectively) compared with MAO-B (IC50 values: 12.8 and 59.7 microM, respectively).
Asunto(s)
Ansiolíticos/farmacología , Antidepresivos/farmacología , Encéfalo/efectos de los fármacos , Flavonoides/farmacología , Inhibidores de la Monoaminooxidasa/farmacología , Vitaceae , Animales , Ansiolíticos/química , Ansiolíticos/aislamiento & purificación , Antidepresivos/química , Antidepresivos/aislamiento & purificación , Bioensayo/métodos , Encéfalo/enzimología , Fraccionamiento Químico/métodos , Flavonoides/química , Flavonoides/aislamiento & purificación , Técnicas In Vitro , Isoenzimas , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Ratones , Estructura Molecular , Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/aislamiento & purificación , Extractos Vegetales/química , Solventes/química , Relación Estructura-ActividadRESUMEN
The methanol extract from the aerial parts of Dictamnus albus was active in inhibiting monoamine oxidase (MAO) from the mouse brain. Activity-guided fractionation led to the isolation of four known coumarins, 7-(6'R-hydroxy-3', 7'-dimethyl-2'E, 7'-octadienyloxy) coumarin (1), auraptene (2), umbelliferone (3), and xanthotoxin (4), as active compounds along with an inactive alkaloid, skimmianine (5). Compounds 1 and 2 inhibited MAO activity in a concentration-dependent manner with IC50 values of 0.7 and 1.7 microM, respectively. Compounds 1 and 2 showed a slight and potently selective inhibitory effect against MAO-B (IC50 0.5 and 0.6 microM, respectively) compared to MAO-A (IC50 1.3 and 34.6 microM, respectively). According to kinetic analyses derived by Lineweaver-Burk reciprocal plots, compounds 1 and 2 exhibited a competitive inhibition to MAO-B.
Asunto(s)
Cumarinas/farmacología , Dictamnus/química , Inhibidores de la Monoaminooxidasa , Animales , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Clorgilina/farmacología , Relación Dosis-Respuesta a Droga , Técnicas In Vitro , Cinética , Espectroscopía de Resonancia Magnética , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/enzimología , Monoaminooxidasa/metabolismo , Selegilina/farmacología , Espectrofotometría Infrarroja , Espectrofotometría UltravioletaRESUMEN
In our search for monoamine oxidase (MAO) inhibitors from natural resources, we found that the methanol extract of the roots of Sophora flavescens showed an inhibitory effect on mouse brain monoamine oxidase (MAO). Bioactivity-guided isolation of the extract yielded two known flavonoids, formononetin (1) and kushenol F (2), as active compounds along with three inactive compounds, oxymatrine (3), trifolirhizin (4), and beta-sitosterol (5). Formononetin (1) and kushenol F (2) showed significant inhibitory effects on MAO in a dose-dependent manner with IC50 values of 13.2 and 69.9 microM, respectively. Formononetin (1) showed a slightly more potent inhibitory effect against MAO-B (IC50: 11.0 microM) than MAO-A (IC50: 21.2 microM). Kushenol F (2) also preferentially inhibited the MAO-B activity than MAO-A activity with the IC50 values of 63.1 and 103.7 microM, respectively.
Asunto(s)
Inhibidores de la Monoaminooxidasa/farmacología , Sophora/química , Animales , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Secuencia de Carbohidratos , Cromatografía en Capa Delgada , Isoenzimas/antagonistas & inhibidores , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas , Ratones , Ratones Endogámicos ICR , Mitocondrias/efectos de los fármacos , Mitocondrias/enzimología , Datos de Secuencia Molecular , Inhibidores de la Monoaminooxidasa/aislamiento & purificación , Raíces de Plantas/química , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Relación Estructura-ActividadRESUMEN
A methylene chloride soluble fraction of the fruits of Cudrania tricuspidata significantly inhibited the mouse brain monoamine oxidase (MAO). Three known prenylated isoflavones were isolated and identified by activity-guided fractionation. Gancaonin A (1), 4'-O-methylalpinumisoflavone (2), and alpinumisoflavone (3) inhibited MAO activity in a concentration-dependent manner with IC50 values of 19.4, 23.9, and 25.8 microM, respectively. Of these, gancaonin A (1) showed a selective and potent inhibitory effect against MAO-B (IC50 0.8 microM) than MAO-A (IC50 >800 microM). The kinetic analysis using Lineweaver-Burk plots indicated that gancaonin A (1) competitively inhibited MAO-B.
Asunto(s)
Frutas/química , Maclura , Inhibidores de la Monoaminooxidasa/aislamiento & purificación , Animales , Encéfalo/enzimología , Relación Dosis-Respuesta a Droga , Isoflavonas/química , Isoflavonas/aislamiento & purificación , Isoflavonas/farmacología , Cinética , Cloruro de Metileno/química , Ratones , Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/farmacología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Plantas Medicinales/químicaRESUMEN
Two new melampolide-type sesquiterpene lactones, 8beta-epoxyangeloyloxy-9alpha-ethoxy-14-oxo-acanthospermolide (1) and 8beta-angeloyloxy-9alpha-ethoxy-14-oxo-acanthospermolide (2), were isolated from the leaves of yacon [Smallanthus sonchifolia (POEPP. et ENDL.) H. Robinson] along with eleven known melampolides, allo-schkuhriolide (3), enhydrin (4), polymatin A (5), fluctuanin (6), 8beta-angeloyloxy-9alpha-acetoxy-14-oxo-acanthospermolide (7), 8beta-angeloyloxy-14-oxo-acanthospermolide (8), 8beta-methacryloyloxymelampolid-14-oic acid methyl ester (9), uvedalin (10), polymatin B (11), 8beta-tigloyloxymelampolid-14-oic acid methyl ester (12), and sonchifolin (13). Their structures were established on the basis of spectroscopic evidence including 1D- and 2D-NMR experiments. All isolates were evaluated for inhibition of LPS-induced nitric oxide production in murine macrophage RAW 264.7 cells.
Asunto(s)
Asteraceae/química , Lactonas/química , Lactonas/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Óxido Nítrico/biosíntesis , Sesquiterpenos/química , Sesquiterpenos/farmacología , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Cristalografía por Rayos X , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Modelos Moleculares , Extractos Vegetales/análisis , Hojas de la Planta/química , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría Infrarroja , Espectrofotometría UltravioletaRESUMEN
A new butyrolactone sesquilignan, isolappaol C (1), together with four known lignans, lappaol C (2), lappaol D (3), lappaol F (4), and diarctigenin (5), were isolated from the methanolic extract of the seeds from the Arctium lappa plant. The structure of isolappaol C (1) was determined by spectral analysis including 1D- and 2D-NMR. All the isolates were evaluated for their inhibitory effects on the LPS-induced nitric oxide production using murine macrophage RAW264.7 cells. Lappaol F (4) and diarctigenin (5) strongly inhibited NO production in the LPS-stimulated RAW264.7 cells with IC(50) values of 9.5 and 9.6 microM, respectively.
Asunto(s)
Arctium/química , Lignanos/farmacología , Lipopolisacáridos/farmacología , Óxido Nítrico/biosíntesis , Animales , Línea Celular , Ratones , Análisis Espectral/métodosRESUMEN
Four new prenylated xanthones, cudratricusxanthones J-M (1-4), were isolated from the CH2Cl2-soluble extract of the root bark of Cudrania tricuspidata, along with four known prenylated xanthones, isocudraxanthone K (5), cudraxanthone C (6), cudratricusxanthone A (7), and cudraxanthone L (8), and three known prenylated flavonoids, cudraflavone A (9), cudraflavanone A (10), and cudraflavone B (11). The structures of compounds 1-4 were elucidated using spectroscopic methods. Cudratricusxanthone A (7), cudraflavanone A (10), and cudraflavone B (11) showed moderate inhibitory effects on mouse brain monoamine oxidase (MAO) with IC50 values of 88.3, 89.7, and 80.0 microM, respectively.
Asunto(s)
Inhibidores de la Monoaminooxidasa/aislamiento & purificación , Moraceae/química , Plantas Medicinales/química , Xantonas/aislamiento & purificación , Animales , Encéfalo/enzimología , Ratones , Estructura Molecular , Inhibidores de la Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/farmacología , Corteza de la Planta/química , Raíces de Plantas/química , Xantonas/química , Xantonas/farmacologíaRESUMEN
A bioassay-guided isolation of the ethanol extract from the fruits of Piper longum yielded a known piperidine alkaloid, piperine, as a monoamine oxidase (MAO) inhibitor. Piperine showed an inhibitory effect against MAO-A (IC50 value: 20.9 microM) and MAO-B (IC50 value: 7.0 microM). Kinetic analyses by a Lineweaver-Burk plot clearly indicated that piperine competitively inhibited MAO-A and MAO-B with Ki values of 19.0+/-0.9 microM and 3.19+/-0.5 microM, respectively. The inhibition by piperine was found to be reversible by dialysis of the incubation mixture. In addition, the immobility times in the tail suspension test were significantly reduced by piperine, similar to that of the reference antidepressant fluoxetine, without accompanying changes in ambulation when assessed in an open-field. These results suggest that piperine possesses potent antidepressant-like properties that are mediated in part through the inhibition of MAO activity, and therefore represent a promising pharmacotherapeutic candidate as an antidepressant agent.