RESUMEN
We evaluated the antioxidant properties of mulberry leaves extract (MLE) and flavonoids isolated from MLE. MLE was prepared by extraction with methanol. Flavonoids were analyzed by high-performance liquid chromatography. Oxidative hemolysis of normal human red blood cells (RBCs) was induced by the aqueous peroxyl radical [2,2'-Azobis (2-amidinopropane) dihydrochloride, AAPH]. MLE contained three flavonoids in the order quercetin (QC) > kaempferol (KF) > astragalin (AG). Oxidative hemolysis of RBCs induced by AAPH was suppressed by MLE, AG, KF, and QC in a time- and dose-dependent manner. MLE and these three flavonoids prevented the depletion of cystosolic antioxidant glutathione (GSH) in RBCs. AG had the greatest protective effect against AAPH-induced oxidative hemolysis and GSH depletion in RBCs.
Asunto(s)
Antioxidantes/farmacología , Eritrocitos/efectos de los fármacos , Radicales Libres/antagonistas & inhibidores , Hemólisis/efectos de los fármacos , Quempferoles/farmacología , Morus , Antioxidantes/aislamiento & purificación , Eritrocitos/metabolismo , Radicales Libres/metabolismo , Hemólisis/fisiología , Humanos , Quempferoles/aislamiento & purificación , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Hojas de la PlantaRESUMEN
The Chung Hun Wha Dam Tang (CHWDT) herbal combination was reported to cease dizziness and phlegm. However, the effect of CHWDT in obesity has not yet been known mechanically. Therefore, we investigated whether this CHWDT could protect the cells from lipogenesis, gluconeogenesis, and inflammation in both in vivo and in vitro. CHWDT significantly decreased body weight, epididymal and perirenal fat content without affecting feed intake in high-fat diet-induced obese mice model. Additionally, CHWDT inhibited obesity-induced SREBP1, FAS, PGC1α, G6Pase, PEPCK and increased CPT1, ACO, and LCAD genes expression in vivo and in vitro. Proinflammatory cytokines like TNF-α and iNOS expression were reduced by CHWDT in both Raw264.7 macrophages and HepG2 cells. In addition, NO production was also significantly decreased by CHWDT in LPS-stimulated macrophages. Furthermore, AMPKα activation by CHWDT was involved in inhibition of obesity by reducing triglycerides production and increasing CPT1 expression. Based on all of the results, we suggest that CHWDT has inhibitory effects on obesity-induced lipogenesis, gluconeogenesis, and inflammation via AMPKα activation.
RESUMEN
Excess production of nitric oxide by activated macrophages via inducible nitric oxide synthase leads to the development of various inflammatory diseases. Heme oxygenase-1 expression via activation of nuclear factor-erythroid 2-related factor 2 inhibits nitric oxide production and inducible nitric oxide synthase expression in activated macrophages. Okanin is one of the most abundant chalcones found in the genus Bidens (Asteraceae) that is used as various folk medications in Korea and China for treating inflammation. Here, we found that okanin (possessing the α-ß unsaturated carbonyl group) induced heme oxygenase-1 expression via nuclear factor-erythroid 2-related factor 2 activation in RAW264.7 macrophages. 3-Penten-2-one, of which structure, as in okanin, possesses the α-ß unsaturated carbonyl group, also induced nuclear factor-erythroid 2-related factor 2-dependent heme oxygenase-1 expression, while both 2-pentanone (lacking a double bond) and 2-pentene (lacking a carbonyl group) were virtually inactive. In lipopolysaccharide-activated RAW264.7 macrophages, both okanin and 3-penten-2-one inhibited nitric oxide production and inducible nitric oxide synthase expression via heme oxygenase-1 expression. Collectively, our findings suggest that by virtue of its α-ß unsaturated carbonyl functional group, okanin can inhibit nitric oxide production and inducible nitric oxide synthase expression via nuclear factor-erythroid 2-related factor 2-dependent heme oxygenase-1 expression in lipopolysaccharide-activated macrophages.
RESUMEN
Morus alba L. has been used in traditional Chinese medicine and almost all parts of this plant are useful in cardiovascular, liver and spleen disorders. The present study was designed to investigate the inhibitory effect of a water extract from Morus alba L. (WMA) on vascular dysfunction in rat models fed a high fat and high cholesterol diet. Male rats were fed an atherogenic diet consisting of food with 7.5% cocoa butter and 1.25% cholesterol, with or without 100 or 200 mg/day/kg WMA, for 14 weeks. Chronic treatment with low (100 mg/kg/day) or high (200 mg/day/kg) doses of WMA markedly attenuated hypertension and the impairments of acetylcholine-induced relaxation of aortic rings in rats fed an atherogenic diet. WMA reduced intima/media thickness in rats fed an atherogenic diet. WMA improved plasma levels of triglyceride (TG) and augmented plasma levels of high-density lipoprotein (HDL) and plasma low-density lipoprotein (LDL), but did not affect blood glucose levels. Interestingly, WMA suppressed increased cell adhesion molecules such as E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) expression in the aorta. Taken together, these results suggested that Morus alba L. could improve an atherogenic diet-induced hypertension, hyperlipidemia, and vascular dysfunction through inhibition of cell adhesion molecules expression and induction of vascular relaxation.
Asunto(s)
Antihipertensivos/uso terapéutico , Colesterol en la Dieta/efectos adversos , Hiperlipidemias/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Morus/química , Fitoterapia , Acetilcolina , Animales , Antihipertensivos/farmacología , Moléculas de Adhesión Celular/sangre , Colesterol en la Dieta/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Dieta Aterogénica , Hiperlipidemias/sangre , Hiperlipidemias/patología , Hipertensión/sangre , Hipertensión/patología , Hipolipemiantes/farmacología , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Ratas , Ratas Sprague-Dawley , Triglicéridos/sangre , Túnica Íntima/efectos de los fármacos , Túnica Íntima/patología , Túnica Media/efectos de los fármacos , Túnica Media/patología , Vasodilatación/efectos de los fármacosRESUMEN
The bioassay-guided fractionation of a MeOH extract of the heartwood of Caesalpinia sappan L. provided two neuroprotective compounds, sappanchalcone (2) and 4-O-methylepisappanol (3), together with a methoxychalcone, isoliquiritigenin 2'-methyl ether (1), and three aromatic compounds, 4-O-methylsappanol (4), caesalpine J (5), pluchoic acid (6). At concentrations of 20-40 microM, compound 2 showed significant cytoprotective effects against glutamate-induced oxidative stress through the induction of heme oxygenase (HO)-1 in HT22-immortalized hippocampal cells. Compound 3 also showed moderate neuroprotective effect at 40 microM, but compounds 1, 4-6 did not show any protective effects against glutamate-induced cytotoxicity in HT22 cells.
Asunto(s)
Caesalpinia/química , Chalcona/análogos & derivados , Ácido Glutámico/efectos adversos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Western Blotting , Línea Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/enzimología , Núcleo Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Chalcona/aislamiento & purificación , Chalcona/farmacología , Citosol/efectos de los fármacos , Citosol/enzimología , Citosol/metabolismo , Relación Dosis-Respuesta a Droga , Hemo-Oxigenasa 1/biosíntesis , Hipocampo/citología , Ratones , Estructura Molecular , Fármacos Neuroprotectores/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad , MaderaRESUMEN
In this study, we investigated the effects of continentalic acid (CA, (-)-pimara-8(14), 15-diene-19-oic acid), a diterpenic acid, isolated from Aralia continentalis, on the proliferation and apoptosis induction of HepG2 cells. In 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the inhibitory effect became gradually stronger with the passage of time, 24, 48 and 72 h after treatment with CA, and the most significant effect was observed at 72 h. CA treatment for 72 h induced DNA fragmentation in a dose-dependent manner. Furthermore, flow cytometric analysis of HepG2 cells exposed to CA showed that apoptotic cells increased in a dose-dependent manner. The induction of apoptosis in HepG2 cells by CA was mediated through the activation of caspase-3, Bak, and Bax, and then through the cleavage of peroxisome proliferator-activated receptor (PARP) and the down-regulation of Bcl-2. These results demonstrate that CA efficiently induces apoptosis and is a good candidate for further evaluation as an effective chemotherapeutic agent.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Aralia/química , Diterpenos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Western Blotting , Caspasa 3/metabolismo , Línea Celular Tumoral , Fragmentación del ADN/efectos de los fármacos , Diterpenos/aislamiento & purificación , Citometría de Flujo , Colorantes Fluorescentes , Humanos , Indoles , L-Lactato Deshidrogenasa/metabolismo , Inhibidores de la Síntesis de la Proteína/farmacología , Sales de Tetrazolio , TiazolesRESUMEN
Cornuside is a bisiridoid glucoside compound isolated from the fruit of CORNUS OFFICINALIS Sieb. et Zucc. (Cornaceae). In the present study, we investigated the effect of cornuside on vascular tone in rat aortic tissue. Cornuside induced a concentration-dependent relaxation of the phenylephrine-precontracted rat aorta, which was abolished by removal of the endothelial layer. Pretreatment of the aortic tissues with either N(G)-nitro- L-arginine methyl ester (L-NAME) or 1 H- -oxadiazole-[4,3-alpha]-quinoxalin-1-one (ODQ) completely inhibited the relaxation induced by cornuside. However, the relaxant effect of cornuside was not blocked by pretreatment with verapamil, diltiazem, tetraethylammonium (TEA), glibenclamide, indomethacin, atropine, or propranolol. In addition, incubation of human umbilical vein endothelial cells (HUVECs) with cornuside increased the production of cGMP in a dose-dependent manner, but this effect was blocked by pretreatment with L-NAME and ODQ, respectively. Taken together, the present study suggests that cornuside dilates vascular smooth muscle via endothelium-dependent nitric oxide (NO)/cGMP signaling.
Asunto(s)
Cornus/química , GMP Cíclico/metabolismo , Endotelio Vascular/efectos de los fármacos , Frutas/química , Glucósidos/farmacología , Óxido Nítrico/metabolismo , Piranos/farmacología , Vasodilatación/efectos de los fármacos , Animales , Aorta/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Endotelio Vascular/fisiología , Glucósidos/química , Glucósidos/aislamiento & purificación , Masculino , Estructura Molecular , Piranos/química , Piranos/aislamiento & purificación , Ratas , Ratas Sprague-DawleyRESUMEN
Cornuside is a bisiridoid glucoside compound isolated from the fruit of Cornus officinalis SIEB. et ZUCC. The present study was designed to examine the effects of cornuside on expression levels of cytokine-induced proinflammatory and adhesion molecules in the human umbilical vein endothelial cells (HUVECs). Cornuside treatment attenuated tumor necrosis factor-alpha (TNF-alpha)-induced nuclear factor-kappa B (NF-kappaB) p65 translocation in HUVECs. In addition, cornuside suppressed the expression levels of endothelial cell adhesion molecules including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) induced by TNF-alpha. TNF-alpha-induced monocyte chemoattractant protein 1 (MCP-1) expression was also attenuated by treatment of cornuside. These inhibitory effects of cornuside on proinflammatory and adhesion molecules were not due to decreased HUVEC viability as assessed by MTT test. Taken together, the present study suggests that cornuside suppresses expression levels of cytokine-induced proinflammatory and adhesion molecules in the human endothelial cells.
Asunto(s)
Moléculas de Adhesión Celular/biosíntesis , Citocinas/antagonistas & inhibidores , Glucósidos/farmacología , Mediadores de Inflamación/metabolismo , Piranos/farmacología , Western Blotting , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Quimiocina CCL2/biosíntesis , Quimiocina CCL2/genética , Cornus/química , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Humanos , Indicadores y Reactivos , Molécula 1 de Adhesión Intercelular/biosíntesis , Molécula 1 de Adhesión Intercelular/genética , FN-kappa B/antagonistas & inhibidores , ARN/biosíntesis , ARN/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sales de Tetrazolio , Tiazoles , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/farmacología , Venas Umbilicales/citología , Venas Umbilicales/efectos de los fármacos , Venas Umbilicales/metabolismo , Molécula 1 de Adhesión Celular Vascular/biosíntesis , Molécula 1 de Adhesión Celular Vascular/genéticaRESUMEN
Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a major role in the pathogenesis of several diseases. The alpha-methylene-gamma-butyrolactone (CH2-BL) structural unit, which characterizes a group of naturally occurring sesquiterpene lactones, is known to possess numerous biological activities. In the present study, we evaluated dehydrocostus lactone possessing CH2-BL moiety, one of the bioactive constituents of the medicinal plant Saussurea lappa, as an inducer of cytoprotective HO-1. In HepG2 cells, treatment with dehydrocostus lactone induced HO-1 expression and increased HO activity in a concentration-dependent manner. Similar results were also observed when the cells were incubated with CH2-BL, a parent structure of dehydrocostus lactone. In contrast, mokko lactone, a reduced product of dehydrocostus lactone, and alpha-methyl-gamma-butyrolactone (CH3-BL), a parent structure of mokko lactone, did not induce HO-1 expression. Pretreatment with either dehydrocostus lactone or CH2-BL for 6 h protected the cells from hydrogen peroxide-mediated toxicity, whereas mokko lactone or CH3-BL failed to exert a cytoprotective action. Inhibition of HO-1 expression by HO-1 small interfering RNA (siRNA) abrogated cellular protection afforded by dehydrocostus lactone or CH2-BL. In addition, dehydrocostus lactone caused the nuclear accumulation of the nuclear factor E2-related factor 2 (Nrf2) and increased the promoter activity of antioxidant response element (ARE). Using Nrf2 siRNA, Nrf2 activation was confirmed to contribute to cytoprotective HO-1 expression by dehydrocostus lactone or CH2-BL. Collectively, our findings suggest that CH2-BL moiety in dehydrocostus lactone increases cellular resistance to oxidant injury in HepG2 cells, presumably through Nrf2/ARE-dependent HO-1 expression.
Asunto(s)
4-Butirolactona/análogos & derivados , Antioxidantes/farmacología , Citoprotección , Hemo-Oxigenasa 1/fisiología , Lactonas/farmacología , Factor 2 Relacionado con NF-E2/fisiología , Sesquiterpenos/farmacología , 4-Butirolactona/farmacología , Transporte Activo de Núcleo Celular , Línea Celular , Hemo-Oxigenasa 1/genética , Humanos , Lactonas/química , Elementos de Respuesta/fisiología , Sesquiterpenos/químicaRESUMEN
The mushroom Phellinus linteus (PL) has been shown to have antitumor and immunostimulatory effects. We hypothesized that the hot water extract of PL (WEPL) exerts its significant immunostimulatory effect by inducing production of the Th1-derived cytokine interferon-gamma (IFN-gamma) by T lymphocytes. T lymphocytes were isolated from the mice fed with 200 mg/kg of WEPL once a day for 4 weeks and then stimulated with the mitogen concanavaline A (Con A). IFN-gamma gene and intracellular protein expressions were analyzed by RT-PCR and flow cytometry, respectively. The production of IFN-gamma was measured by enzyme-linked immunosorbent assay. WEPL significantly enhanced the transcription of IFN-gamma mRNA. The effect of WEPL on IFN-gamma expression was further supported by a concomitant increase in the number of cells with intracellular IFN-gamma protein as well as the secretion of IFN-gamma. However, WEPL did not modulate either gene expression or protein secretion of interleukin-4, a Th2-associated cytokine, by Con A-stimulated T lymphocytes. Our results demonstrate that one of the potentially beneficial antitumor and immunostimulatory effects of WEPL may be mediated through the enhancement of IFN-gamma secretion by T lymphocytes.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Basidiomycota , Mezclas Complejas/administración & dosificación , Citocinas/biosíntesis , Regulación de la Expresión Génica/efectos de los fármacos , Células TH1/metabolismo , Células Th2/metabolismo , Adyuvantes Inmunológicos/química , Administración Oral , Animales , Basidiomycota/química , Células Cultivadas , Mezclas Complejas/química , Citocinas/inmunología , Evaluación Preclínica de Medicamentos , Femenino , Regulación de la Expresión Génica/inmunología , Técnicas In Vitro , Masculino , Ratones , Células TH1/citología , Células TH1/inmunología , Células Th2/citología , Células Th2/inmunologíaRESUMEN
Vasorelaxant and anti-inflammatory effects of a 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG) isolated from the root barks of Paeonia suffruticosa and possible mechanisms responsible were investigated. PGG induced a concentration-dependent relaxation of the phenylephrine-precontracted rat aorta. This effect disappeared with the removal of functional endothelium. Pretreatment of the aortic tissues with either N(G)-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]-oxadiazole-[4,3-alpha]-quinoxalin-1-one (ODQ) inhibited the relaxation induced by PGG. Incubation of human umbilical vein endothelial cells (HUVECs) or carotid arteries isolated from rats with PGG increased the production of cGMP in a dose-dependent manner, but this effect was blocked by pretreatment with L-NAME and ODQ, respectively. PGG treatment attenuated tumor necrosis factor-alpha (TNF-alpha)-induced nuclear factor-kappaB (NF-kappaB) p65 translocation in human umbilical vein endothelial cells. In addition, PGG suppressed the expression levels of adhesion molecules including intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) induced by TNF-alpha. TNF-alpha-induced monocyte chemoattractant protein-1 (MCP-1) expression was also attenuated by addition of PGG. PGG treatment inhibited cellular adhesion of U937 cells onto human umbilical vein endothelial cells induced by TNF-alpha. Taken together, the present study suggests that PGG dilates vascular smooth muscle and suppresses the vascular inflammatory process via endothelium-dependent nitric oxide (NO)/cGMP signaling.
Asunto(s)
Antiinflamatorios/farmacología , GMP Cíclico/fisiología , Taninos Hidrolizables/farmacología , Óxido Nítrico/fisiología , Transducción de Señal/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiología , Western Blotting , Arterias Carótidas/efectos de los fármacos , Arterias Carótidas/metabolismo , Adhesión Celular/efectos de los fármacos , Línea Celular , Quimiocina CCL2/genética , GMP Cíclico/biosíntesis , Relación Dosis-Respuesta a Droga , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Inhibidores Enzimáticos/farmacología , Expresión Génica/efectos de los fármacos , Guanilato Ciclasa/antagonistas & inhibidores , Humanos , Técnicas In Vitro , Molécula 1 de Adhesión Intercelular/genética , Masculino , FN-kappa B/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Oxadiazoles/farmacología , Paeonia/química , Corteza de la Planta/química , Raíces de Plantas/química , Quinoxalinas/farmacología , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/farmacología , Células U937 , Venas Umbilicales/citología , Molécula 1 de Adhesión Celular Vascular/genética , Vasodilatación/efectos de los fármacosRESUMEN
Hexane, ethylacetate (EtOAC), and n-butanol (n-BuOH) extracts of medicinal plants traditionally used in the East Asia, such as China, Korea, and Japan were screened for their vasorelaxant activity using isolated rat aorta. Among the 60 solvent-extracts from 20 medicinal plants, hexane and n-BuOH extracts of Diospyros kaki and Polygonum aviculare, hexane, EtOAC, and n-BuOH extracts of Magnolia liliflora, n-BuOH extract of Sorbus commixta, and EtOAC and n-BuOH extracts of Selaginella tamariscina were found to exhibit distinctive vasorelaxant activity. The activity disappeared by removal of functional endothelium or pre-treatment of the aortic tissues with N(G)-nitro-L-arginine methyl ester (L-NAME), which is an inhibitor of nitric oxide synthase. These findings suggest that the medicinal plants relax vascular smooth muscle via endothelium-dependent nitric oxide. These results will be useful to further analyze those medicinal plants that contain the vasorelaxant activity in order to identify the active principles.
Asunto(s)
Plantas Medicinales/química , Vasodilatadores/farmacología , Animales , Aorta Torácica/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/farmacología , Técnicas In Vitro , Contracción Isométrica/efectos de los fármacos , Corea (Geográfico) , Masculino , Medicina Tradicional de Asia Oriental , Tono Muscular/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo III , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries. In the present study we observed that, scorparone exhibited no cytotoxic effect in unstimulated macrophages, but reduced the release of nitric oxide (NO) and prostaglandin E2 (PGE2) upon stimulation by IFN-gamma/LPS or LPS. The inhibitory effects were found to be in conjuction with the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IFN-gamma/LPS stimulated RAW 264.7 cells. Moreover, scoparone also attenuated the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in LPS-stimulated RAW264.7 cells. These results suggest that scoparone decreases the production of the inflammatory mediators such as NO and PGE2 in macrophages by inhibiting iNOS and COX-2 expression.
Asunto(s)
Antiinflamatorios/farmacología , Artemisia/química , Cumarinas/farmacología , Mediadores de Inflamación/metabolismo , Interferón gamma/farmacología , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Animales , Antiinflamatorios/aislamiento & purificación , Western Blotting , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cumarinas/aislamiento & purificación , Ciclooxigenasa 2 , Citocinas/biosíntesis , Dinoprostona/biosíntesis , Macrófagos/efectos de los fármacos , Ratones , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa/biosíntesis , Óxido Nítrico Sintasa de Tipo II , Extractos Vegetales/química , Extractos Vegetales/farmacología , Prostaglandina-Endoperóxido Sintasas/metabolismo , Estimulación Química , Sales de Tetrazolio , TiazolesRESUMEN
Bioassay-guided fractionation of the EtOAc-soluble extract of Sedum sarmentosum afforded a new flavonoid, quercetin-3-O-alpha-(6'''-caffeoylglucosyl-beta-1,2-rhamnoside) (1), along with four known flavonoids, quercetin 3-O-alpha-(6'''-p-coumaroylglucosyl-beta-1,2-rhamnoside) (2), isorhamnetin-3-beta-glucopyranoside (3), quercetin-3-beta-glucopyranoside (4), and kaempferol-3-alpha-arabinopyranoside (5). Purification of these compounds was conducted with the application of various chromatographic methods. Compounds 1-5 inhibited angiotensin I converting enzyme (ACE) activity in a concentration-dependent manner. Compounds 1-5 had 50% inhibitory concentration values of 158.9+/-11.1 microgM, 351.6+/-3.9 microgM, 408.9+/-4.6 microgM, 708.8+/-23.1 microgM, and 392.8+/-13.4 microgM.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/aislamiento & purificación , Flavonoides/aislamiento & purificación , Peptidil-Dipeptidasa A/metabolismo , Sedum , Inhibidores de la Enzima Convertidora de Angiotensina/sangre , Inhibidores de la Enzima Convertidora de Angiotensina/química , Animales , Flavonoides/sangre , Flavonoides/química , Componentes Aéreos de las Plantas , Extractos Vegetales/sangre , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , RatasRESUMEN
We studied the effect of 4-acetyl-12,13-epoxyl-9-trichothecene-3, 15-diol (AETD) isolated from Isaria japonica, one of the most popular Chinese fungal medicines, on the induction of apoptosis in rat bladder carcinoma NBT-II cells. AETD was cytotoxic to NBT-II cells, and this cytotoxic effect appears to be attributed to its induction of apoptotic cell death, as AETD induced nuclear morphological changes and internucleosomal DNA fragmentation, and increased the proportion of hypodiploid cells and activity of caspase-3. AETD treatment also decreased the expression of the anti-apoptotic protein Bcl-2 and increased the expression of the pro-apoptotic protein Bax. These results provide important information in understanding the mechanism(s) of AETD-induced apoptosis.
Asunto(s)
Apoptosis/efectos de los fármacos , Carcinoma/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Tricotecenos/farmacología , Neoplasias de la Vejiga Urinaria/patología , Animales , Carcinoma/metabolismo , Caspasa 3 , Caspasas/metabolismo , Línea Celular Tumoral/efectos de los fármacos , Fragmentación del ADN , ADN de Neoplasias/análisis , Microscopía Fluorescente , Ratas , Neoplasias de la Vejiga Urinaria/metabolismo , Proteína X Asociada a bcl-2RESUMEN
The bioassay-guided fractionation of the n-BuOH extract of Abeliophyllum distichum afforded acteoside (1), isoacteoside (2), rutin (3), and hirsutrin (4). Compounds 1-3 moderately inhibited the angiotensin I converting enzyme activity in a dose-dependent manner. Compounds 1-3 showed the 50% inhibitory concentration values of 228 micro g/mL, 290 micro g/mL, and 278 micro g/mL, respectively.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Glicósidos/farmacología , Oleaceae , Peptidil-Dipeptidasa A/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Relación Dosis-Respuesta a Droga , Glucósidos/farmacología , Glicósidos/administración & dosificación , Glicósidos/uso terapéutico , Fenoles/farmacología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Ratas , Rutina/farmacologíaRESUMEN
A pharmacological inhibition of nitric oxide synthase (NOS) in rats for 4-6 weeks produces renal vasoconstriction, renal dysfunction, and severe hypertension. The present study was aimed at investigating whether Cudrania tricuspidata (C. tricuspidata) water extract ameliorates N(G)-Nitro-L-arginine methylester (L-NAME)-induced hypertension. Treatment of L-NAME (60 mg/L drinking water, 4 weeks) causes a sustained increase in systolic blood pressure (SBP). The concentration of plasma NO metabolites and NO/cGMP productions in the vascular tissues of the L-NAME-treated group were significantly reduced as compared with those in the control. C. tricuspidata water extract blocked increase of SBP in the L-NAME-treated group and restored SBP to normal level. Futhermore, C. tricuspidata water extract was able to preserve the vascular NO/cGMP production and plasma NO metabolites concentration. However, there are no changes in the expression of ecNOS and iNOS of thoracic aorta among the rats of control, L-NAME-treated group, and L-NAME and C. tricuspidata water extract co-treated group. The urinary sodium level, urine volume, and creatinine clearance were significantly higher in rats co-treated with C. tricuspidata water extract and L-NAME than in L-NAME-treated group. Taken together, these results suggest that C tricuspidata water extract prevents the increase of SBP in the L-NAME-induced hypertension that may have been caused by enhanced generation of vascular NO/cGMP.
Asunto(s)
Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Riñón/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Aorta Torácica/fisiopatología , Western Blotting , Peso Corporal/efectos de los fármacos , Creatinina/orina , GMP Cíclico/metabolismo , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Riñón/metabolismo , Masculino , NG-Nitroarginina Metil Éster/toxicidad , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo II , Óxido Nítrico Sintasa de Tipo III , Nitritos/metabolismo , Corteza de la Planta/química , Ratas , Ratas Sprague-Dawley , Sodio/orinaRESUMEN
Catalposide (1) and two related iridoids were isolated from the stem of Catalpa ovata (Bignoniaceae) by bioassay guided fractionation. Catalposide (1) significantly inhibited the production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in a dose-dependent manner. RT-PCR and Western blot analyses demonstrated that catalposide (1) suppressed the expression of inducible nitric oxide synthase (iNOS) gene and iNOS protein. Catalposide (1) also inhibited the activation of LPS-induced NF-kappaB as analyzed by electrophoretic mobility shift assay (EMSA). In addition to the inhibitory effect on NO production in LPS-stimulated RAW 264.7 cells, catalposide (1) significantly inhibited the NO production in cytokine-stimulated human DLD-1 and rat vascular smooth muscle (VSM) cells in a dose-dependent manner.
Asunto(s)
Bignoniaceae/química , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glucósidos/farmacología , Óxido Nítrico Sintasa/biosíntesis , Animales , Línea Celular , Macrófagos/efectos de los fármacos , Macrófagos/enzimología , Ratones , Estructura Molecular , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa de Tipo II , Plantas Medicinales/química , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
(5-Butyl-3-oxo-2,3-dihydrofuran-2-yl)-acetic acid was isolated from the flowers of Erigeron annuus as one of four germination inhibitory constituents. Its structure was determined by analysis of MS and NMR spectroscopic data. Three known compounds, 3-hydroxy-pyran-4-one, 4-hydroxycinnamic acid, and 3,4-dihydroxycinnamic acid methyl ester were also identified as active constituents. These compounds showed 50% inhibitory effects (IC(50)) on the germination of lettuce seed at concentrations of 2.13+/-0.03, 12.85+/-0.56, 4.97+/-0.24, and 4.87+/-0.25 mM, respectively. 4-Hydroxybenzoic acid was used as a positive control, displaying an IC(50) value of 4.02+/-0.39 mM.
Asunto(s)
Asteraceae/química , Germinación/efectos de los fármacos , Extractos Vegetales/farmacología , Flores/química , Concentración 50 Inhibidora , Lactuca/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Estructura Molecular , Semillas/efectos de los fármacosRESUMEN
Imperatorin, a biologically active furanocoumarin from the roots of Angelica dahurica (Umbelliferae), was found to induce apoptosis in human promyelocytic leukaemia, HL-60 cells. DNA fragmentation assay, morphology-based evaluation, and flow cytometric analysis demonstrated that imperatorin at micromolar concentrations was able to trigger apoptosis of HL-60 cells. Neither necrosis nor differentiation was observed at cytotoxic micromolar concentrations of imperatorin. Further studies showed that the cytochrome c/caspase-9 pathway was responsible for imperatorin-induced apoptosis; i.e., mitochondrial membrane was depolarized, Bcl-2 was down-regulated, cytochrome c was released from mitochondria, caspase-9 and caspase-3 were activated, and poly(ADP-ribose) polymerase was cleaved. Furthermore, imperatorin-induced apoptosis was significantly blocked by Z-VAD-FMK (a broad spectrum caspase inhibitor), Z-LEHD-FMK (a caspase-9 inhibitor) and Ac-DMQD-CHO (a caspase-3 inhibitor), but not by Z-IEDT-FMK (a caspase-8 inhibitor).