RESUMEN
Paeonia suffruticosa has been traditionally employed for vitalizing blood circulation and alleviating liver and inflammatory diseases. The pathways by which palbinone (PB) isolated from P. suffruticosa mediates heme oxygenase-1 (HO-1) induction were investigated using the specific inhibitors for PI3K and mitogen activated protein kinases pathways. The effect of PB-treatment on Nrf2 translocalization and HO-1-antioxidant response element (ARE) regulation was examined employing Western blot and luciferase assays. PB induced HO-1 expression via the activation of Nrf2 in the hepatic cells, and ARE-dependent genes were stimulated via the PB-mediated Nrf2 activation. PB-mediated HO-1 expression could be involved with PI3K/Akt and ERK1/2 pathways. Our study suggests the mechanism by which PB induces HO-1 expression in the hepatic cells. This might substantiate the traditional applications of P. suffruticosa for the treatment of oxidative stress-related diseases including oxidant and inflammatory-mediated vascular and liver diseases.
Asunto(s)
Hemo-Oxigenasa 1/metabolismo , Hepatocitos/efectos de los fármacos , Paeonia/química , Transducción de Señal/efectos de los fármacos , Terpenos/farmacología , Elementos de Respuesta Antioxidante , Línea Celular , Hemo-Oxigenasa 1/genética , Hepatocitos/metabolismo , Humanos , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Raíces de Plantas/química , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Activación Transcripcional , Regulación hacia ArribaRESUMEN
Magnolol, a neolignan from the traditional medicinal plant Magnolia obovata, has been shown to possess neuroprotective, anti-inflammatory, anticancer and anti-angiogenic activities. However, the precise mechanism of the anti-angiogenic activity of magnolol remains to be elucidated. In the present study, the anti-angiogenic effect of magnolol was evaluated in mouse embryonic stem (mES)/embryoid body (EB)-derived endothelial-like cells. The endothelial-like cells were obtained by differentiation from mES/EB cells. Magnolol (20 µM) significantly suppressed the transcriptional and translational expression of platelet endothelial cell adhesion molecule (PECAM), an endothelial biomarker, in mES/EB-derived endothelial-like cells. To further understand the molecular mechanism of the suppression of PECAM expression, signaling pathways were analyzed in the mES/EB-derived endothelial-like cells. Magnolol induced the generation of reactive oxygen species (ROS) by mitochondria, a process that was associated with the induction of apoptosis as determined by positive Annexin V staining and the activation of cleaved caspase-3. The involvement of ROS generation by magnolol was confirmed by treatment with an antioxidant, N-acetyl-cysteine (NAC). NAC inhibited the magnolol-mediated induction of ROS generation and suppression of PECAM expression. In addition, magnolol suppressed the activation of MAPKs (ERK, JNK and p38) and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells. Taken together, these findings demonstrate for the first time that the anti-angiogenic activity of magnolol may be associated with ROS-mediated apoptosis and the suppression of the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Apoptosis/efectos de los fármacos , Compuestos de Bifenilo/farmacología , Lignanos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Acetilcisteína/metabolismo , Animales , Caspasa 3/biosíntesis , Caspasa 3/efectos de los fármacos , Caspasa 3/metabolismo , Diferenciación Celular , Línea Celular , Células Madre Embrionarias/citología , Células Madre Embrionarias/efectos de los fármacos , Células Madre Embrionarias/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Activación Enzimática/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasas/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/biosíntesis , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
There is a growing interest in natural products that potentially have anti-inflammatory properties and inhibit P-glycoprotein (P-gp) function. In this report, we assessed the effects of anthraquinone derivatives from rhubarb on LPS-induced RAW 264.7 macrophages to determine their anti-inflammatory potential. The derivatives were also tested in Caco-2 cell lines to evaluate the inhibition of the drug efflux function of P-gp. The transport abilities were examined and the cellular accumulation of rhodamine-123 (R-123) was also measured. Electorphoretic mobility shift assay (EMSA) was performed to check the activator protein-1 (AP-1) DNA binding affinity. Five anthraquinones were tested to determine their inhibitory activities on NO production and the protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, the level of prostaglandin E(2) (PGE(2)) was determined in LPS-induced RAW264.7 macrophages. Emodin was found to be the most potent inhibitor, and it also reduced paw swelling in the mouse model of carrageenan-induced paw edema. In Caco-2 cells, emodin elevated the accumulation of R-123 and decreased the efflux ratio of R-123, which indicates the inhibition of P-gp function. The inhibition of COX-2 protein by emodin paralleled the decrease in P-gp expression. In addition, mitogen-activated protein kinase (MAPK) expression was decreased through the prevention of AP-1 DNA binding, which leads to downregulation in the expression of P-gp. Our data indicate that the decrease of P-gp expression is caused by the decreased expression of COX-2 through the MAPK/AP-1 pathway. Based on our results, we suggest that anti-inflammatory drugs with COX-2 inhibitory activity might be used to modulate P-gp function and expression.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antraquinonas/uso terapéutico , Antiinflamatorios/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Extractos Vegetales/uso terapéutico , Rheum , Animales , Antraquinonas/farmacología , Antiinflamatorios/farmacología , Células CACO-2 , Carragenina , Línea Celular , Supervivencia Celular/efectos de los fármacos , Ciclooxigenasa 2/genética , Inhibidores de la Ciclooxigenasa 2/farmacología , Dinoprostona/metabolismo , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/patología , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Fitoterapia , Extractos Vegetales/farmacología , ARN Mensajero/metabolismo , RizomaRESUMEN
Vitis amurensis (Vitaceae) has been reported to have anti-oxidant and anti-inflammatory activities. The present study investigated a methanol extract from the leaf and stem of V. amurensis for neuroprotective effects on cerebral ischemic damage in rats and on excitotoxicity induced by glutamate in cultured rat cortical neurons. Transient focal cerebral ischemia was induced by 2h middle cerebral artery occlusion followed by 24h reperfusion (MCAO/reperfusion) in rats. Orally administered V. amurensis (25-100 mg/kg) reduced MCAO/reperfusion-induced infarct and edema formation, neurological deficits, and neuronal death. Depletion of glutathione (GSH) level and lipid peroxidation induced by MCAO/reperfusion was inhibited by administration of V. amurensis. The increase of phosphorylated mitogen-activated protein kinases (MAPKs), cyclooxygenase-2 (COX-2), and pro-apoptotic proteins and the decrease of anti-apoptotic protein in MCAO/reperfusion rats were significantly inhibited by treatment with V. amurensis. Exposure of cultured cortical neurons to 500 µM glutamate for 12h induced neuronal cell death. V. amurensis (1-50 µg/ml) and (+)-ampelopsin A, γ-2-viniferin, and trans-ε-viniferin isolated from the leaf and stem of V. amurensis inhibited glutamate-induced neuronal death, the elevation of intracellular calcium ([Ca(2+)](i)), the generation of reactive oxygen species (ROS), and changes of apoptosis-related proteins in cultured cortical neurons, suggesting that the neuroprotective effect of V. amurensis may be partially attributed to these compounds. These results suggest that the neuroprotective effect of V. amurensis against focal cerebral ischemic injury might be due to its anti-apoptotic effect, resulting from anti-excitotoxic, anti-oxidative, and anti-inflammatory effects and that the leaf and stem of V. amurensis have possible therapeutic roles for preventing neurodegeneration in stroke.
Asunto(s)
Lesiones Encefálicas/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Vitis/química , Animales , Antiinflamatorios/química , Antioxidantes/química , Apoptosis , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/patología , Isquemia Encefálica/patología , Ciclooxigenasa 2/química , Femenino , Ácido Glutámico/toxicidad , Glutatión/química , Peroxidación de Lípido , Masculino , Metanol/química , Estructura Molecular , Fármacos Neuroprotectores/química , Síndromes de Neurotoxicidad/patología , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Tallos de la Planta/química , Embarazo , Cultivo Primario de Células , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/química , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patologíaRESUMEN
Four new biphenyl and biphenyl ether quinolizidine N-oxide alkaloids, 5- EPI-dihydrolyfoline N-oxide (1), decamine N-oxide (2), lagerstroemine N-oxide (3), and lagerine N-oxide (4), were isolated from the aerial parts of Lagerstroemia indica, and their structures were established by extensive spectroscopic studies. In addition, the inhibitory effects of isolated compounds on rat lens aldose reductase (RLAR) were examined.
Asunto(s)
Alcaloides/química , Compuestos de Bifenilo/química , Óxidos N-Cíclicos/química , Lagerstroemia/química , Quinolizidinas/química , Aldehído Reductasa/efectos de los fármacos , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Animales , Compuestos de Bifenilo/aislamiento & purificación , Compuestos de Bifenilo/farmacología , Fraccionamiento Químico , Óxidos N-Cíclicos/aislamiento & purificación , Óxidos N-Cíclicos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Éteres/química , Espectroscopía de Resonancia Magnética , Componentes Aéreos de las Plantas/química , Quinolizidinas/aislamiento & purificación , Quinolizidinas/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
Rosmarinic acid, its analogues, and a phenolic compound were obtained from G. hederacea var. longituba. There were two new compounds, methyl isoferuloyl-7-(3,4-dihydroxyphenyl) lactate (1) and benzyl-4'-hydroxy-benzoyl-3'-O-ß-D-glucopyranoside (4), and four known compounds (2, 3, 5 and 6). The structures of these compounds were determined on the basis of spectroscopic methods. Each compound was tested by NF-κB luciferase assay and three rosmarinic acid analogues inhibited NF-κB production and the induction of COX-2 and iNOS mRNA in HepG2 cells.
Asunto(s)
Antiinflamatorios/química , Antiinflamatorios/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Lamiaceae/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antiinflamatorios/aislamiento & purificación , Células Hep G2 , Humanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The antiallergic activity of rhubarb and its constituents, anthraquinones, has been reported previously. For further evaluation of the antiallergic activity, a 70% ethanol extract of the rhizomes of Rheum tanguticum (RTE) was prepared and its inhibitory activity on an animal model of atopic dermatitis (AD) was examined for the first time. Oral administration of RTE (30-300 mg/kg/day) for 5 weeks significantly inhibited hapten-induced dermatitis in NC/Nga mice based on the skin severity score. In addition, treatment with RTE at 100 mg/kg/day also reduced the numbers of white blood cells, neutrophils and eosinophils in the blood, and led to a significant reduction in the IgE concentration in the serum. In rat basophilic leukemia (RBL)-1 cells, RTE inhibited 5-lipoxygenase (5-LOX)-catalysed leukotriene production (IC(50) = 43.6 µg/mL). Among the anthraquinone derivatives isolated, emodin strongly inhibited this parameter (IC(50) = 4.3 µM). Taken together, these findings suggest that rhubarb exerts inhibitory activity against AD, and that the 5-LOX inhibitory activity of its major constituent, emodin, may contribute to this inhibitory action.
Asunto(s)
Antialérgicos/farmacología , Dermatitis Atópica/tratamiento farmacológico , Emodina/farmacología , Inhibidores de la Lipooxigenasa/farmacología , Extractos Vegetales/farmacología , Rheum/química , Administración Oral , Animales , Antraquinonas/química , Antraquinonas/farmacología , Antraquinonas/uso terapéutico , Antialérgicos/uso terapéutico , Recuento de Células Sanguíneas , Células Sanguíneas/efectos de los fármacos , Dermatitis Atópica/inducido químicamente , Emodina/aislamiento & purificación , Emodina/uso terapéutico , Haptenos/efectos adversos , Inmunoglobulina E/sangre , Inmunoglobulina E/efectos de los fármacos , Inhibidores de la Lipooxigenasa/aislamiento & purificación , Inhibidores de la Lipooxigenasa/uso terapéutico , Masculino , Ratones , Modelos Animales , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Ratas , Rizoma/química , Piel/efectos de los fármacos , Piel/patologíaRESUMEN
Ganoderma lucidum is known as a medicinal mushroom used in traditional medicine. In our study, the cytotoxic activities of 17 compounds (1-17) isolated from the fruiting bodies of G. lucidum were investigated. Among them, ergosta-7,22-diene-2ß,3α,9α-triol (EGDT) induced apoptosis in HL-60 human premyelocytic leukemia cells. EGDT activated the apoptotic process, including DNA fragmentation and caspase-3 activity. In immunoblotting analysis, treatment with EGDT resulted in the cleavage of procaspase-3 and poly(ADP-ribose) polymerase (PARP) into active forms. In the in vivo study, the administration (i.p.) of EGDT to Lewis lung carcinoma (LLC)-inoculated mice evidenced a significant inhibition of tumor growth. These results indicate that EGDT was one of the apoptotic constituents of G. lucidum, and might be an antitumor agent.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Fitosteroles/farmacología , Reishi/química , Animales , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Caspasa 3/metabolismo , Fragmentación del ADN , Femenino , Células HL-60/efectos de los fármacos , Humanos , RatonesRESUMEN
Three new sesquiterpene lactones, 1 α,10 ß-epoxy-4-hydroxy-glechoma-5-en-olide (1), 1 ß,10 α-epoxy-4,8-dihydroxy-glechoma-5-en-olide (2), and 1 ß,10 α;4 α,5 ß-diepoxy-8-methoxy-glechoman-8 α,12-olide (3), were isolated from the whole plant of Glechoma hederacea, together with four known sesquiterpene lactones. The structures of the three new sesquiterpene lactones were determined by spectroscopic evidence. Cytotoxic effects of the isolated compounds were examined against MDA-MB-231 (breast), HCT116 (colon), SW620 (colon), and DU145 (prostate) human cancer cell lines.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Lactonas/farmacología , Lamiaceae/química , Extractos Vegetales/farmacología , Sesquiterpenos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Humanos , Lactonas/química , Lactonas/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificaciónRESUMEN
Two new lignans, (2 R,3 R)-2 ß-(4''-hydroxy-3''-methoxybenzyl)-3 α-(4'-hydroxy-3'-methoxybenzyl)-γ-butyrolactone 2-O-( ß-D-glucopyranoside) (1) and (1 S,2 R,3 S)-dimethyl-1,2,3,4-tetrahydro-3,6,7-trihydroxy-1-(3',4'-dihydroxyphenyl)naphthalene-2,3-dicarboxylate (2) together with nine known compounds (3-11) were isolated from the ethyl acetate fraction of the roots of Pulsatilla koreana. Their chemical structures were established based on physicochemical and spectroscopic data analyses. All isolates were investigated for their inhibition effects against the classical pathway of the complement system. Among them, compound 6 showed significant inhibitory activity with an IC (50) value of 75.9 µM, compounds 8 and 9 had moderate effects with IC (50) values of 182.2 and 166.5 µM, respectively.
Asunto(s)
Lignanos/farmacología , Pulsatilla/química , Fraccionamiento Químico , Proteínas del Sistema Complemento/química , Lignanos/química , Lignanos/aislamiento & purificación , Extractos Vegetales/química , Raíces de Plantas/químicaRESUMEN
AIMS OF THE STUDY: Ilex latifolia (Aquifoliaceae), a primary component of "kudingcha", has been used in Chinese folk medicine to treat various kinds of diseases including headaches, inflammatory diseases, and cardiac ischemic injury. The present study investigated the protective effect of the ethanol extract of Ilex latifolia against transient, focal, ischemia-induced neuronal damage. MATERIALS AND METHODS: Transient focal ischemia was induced by 2 h middle cerebral artery occlusion followed by 24 h reperfusion (MCAO/reperfusion) in rats. After MCAO/reperfusion, brain infarction and neuronal death were measured by triphenyltetrazolium chloride and hematoxylin and eosin staining, respectively. Glutathione concentration and lipid peroxidation rate were measured. The expression levels of phosphorylated mitogen activated proteins kinases (MAPKs), cyclooxygenase 2 (COX-2), and anti-apoptotic and pro-apoptotic proteins were detected by Western blot. RESULTS: Ilex latifolia (50-200 mg/kg) significantly reduced MCAO/reperfusion-induced infarction and edema formation, neurological deficits, and brain cell death. Depletion of glutathione level and lipid peroxidation induced by MCAO/reperfusion were inhibited by administration of Ilex latifolia. The increase of phosphorylated MAPKs, COX-2, and proapoptotic proteins and the decrease of antiapoptotic protein in MCAO/reperfusion rats were significantly inhibited by treatment with Ilex latifolia. CONCLUSION: Ilex latifolia ameliorated ischemic injury induced by MCAO/reperfusion in rats, and this neuroprotective effect might be associated with its anti-apoptotic effect, resulting from anti-oxidative and anti-inflammatory actions.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Ilex , Fármacos Neuroprotectores/farmacología , Fitoterapia , Animales , Conducta Animal/efectos de los fármacos , Isquemia Encefálica/patología , Isquemia Encefálica/fisiopatología , Ciclooxigenasa 2/metabolismo , Medicamentos Herbarios Chinos/farmacología , Etnofarmacología , Glutatión/metabolismo , Humanos , Ilex/química , Peroxidación de Lípido/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Medicina Tradicional China , Neuronas/efectos de los fármacos , Neuronas/patología , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patologíaRESUMEN
A simple and efficient HPLC method was developed to evaluate the quality of traditional herbal medicines made from cinnamon bark (CB) and cinnamon twig (CT). Seven major bioactive ingredients in 56 samples (24 CB and 32 CT) collected from China, Vietnam, and Indonesia were separated and quantified. The method was validated following the International Conference on Harmonisation (ICH) guidelines. A fingerprint analysis method to discriminate between CB and CT using major component content levels was developed. The discrimination process included the use of similarity indices and partial least-squares discriminant analysis (PLS-DA). Classification accuracy by the PLS-DA method was about 98%. The pattern analysis method was specific and could be readily used for the comprehensive evaluation of cinnamon samples. Therefore, an HPLC fingerprint in combination with pattern analysis provides a very flexible and reliable method for quality assessment of herbal drugs.
RESUMEN
The aim of the present study was to investigate effects of the ethyl acetate fraction of an ethanol extract of Coix lachryma-jobi (ECLJ) on glucose uptake and adipocyte differentiation in 3T3-L1 cells. ECLJ phosphorylated AMP-activated protein kinase (AMPK) and its downstream substrate acetyl-coenzymeA carboxylase in 3T3-L1 cells in a time- and dose-dependent manner. Moreover, we discovered that compound C inhibits ECLJ-stimulated ACC phosphorylation. In addition, ECLJ exhibited a dose-dependent stimulation of glucose uptake in 3T3-L1 cells, and this increase was obviously attenuated by compound C. ECLJ also caused a decrease in the expression levels of adipogenesis factors such as fatty acid synthase, sterol-regulatory-element-binding protein-1c, peroxisome proliferator-activated receptor γ, and CAATT/enhancer binding protein α in a dose-dependent manner. Differentiation was examined by Oil red O staining activity after ECLJ treatment for 6 days. ECLJ decreased mean droplet size. These results suggest a possible role for AMPK in the process of adipose differentiation and that ECLJ targeted for adipocyte functions could be effective in improving the symptoms of metabolic syndrome.
Asunto(s)
Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipogénesis/efectos de los fármacos , Coix/química , Glucosa/metabolismo , Extractos Vegetales/farmacología , Semillas/química , Células 3T3-L1 , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Acetil-CoA Carboxilasa/metabolismo , Adipocitos/citología , Animales , Cinamatos/análisis , Desoxiglucosa/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Obesidad/tratamiento farmacológico , Fenoles/análisis , Fosforilación/efectos de los fármacos , Fitoterapia , Extractos Vegetales/química , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
This study investigated a methanol extract from the leaf and stem of Vitis amurensis (Vitaceae) for possible neuroprotective effects on neurotoxicity induced by amyloid ß protein (Aß) (25-35) in cultured rat cortical neurons and also for antidementia activity in mice. Exposure of cultured cortical neurons to 10 µM Aß (25-35) for 36 h induced neuronal apoptotic death. At concentrations of 1-10 µg/mL, V. amurensis inhibited neuronal death, the elevation of intracellular calcium ([Ca(2+)](i)) and the generation of reactive oxygen species (ROS), all of which were induced by Aß (25-35) in primary cultures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of ICR mice with 16 nmol Aß (25-35) was inhibited by chronic treatment with V. amurensis extract (50 and 100 mg/kg, p.o. for 7 days), as measured by a passive avoidance test. Amurensin G, r-2-viniferin and trans-É-viniferin isolated from V. amurensis also inhibited neuronal death, the elevation of [Ca(2+)](i) and the generation of ROS induced by Aß (25-35) in cultured rat cortical neurons. These results suggest that the neuroprotective effect of V. amurensis may be partially attributable to these compounds. These results suggest that the antidementia effect of V. amurensis is due to its neuroprotective effect against Aß (25-35)-induced neurotoxicity and that the leaf and stem of V. amurensis have possible therapeutic roles for preventing the progression of Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer/prevención & control , Péptidos beta-Amiloides/toxicidad , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Fragmentos de Péptidos/toxicidad , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Vitis/química , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Apoptosis/efectos de los fármacos , Benzofuranos/química , Benzofuranos/aislamiento & purificación , Benzofuranos/farmacología , Células Cultivadas , Corteza Cerebral/citología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Dibenzocicloheptenos/química , Dibenzocicloheptenos/aislamiento & purificación , Dibenzocicloheptenos/farmacología , Relación Dosis-Respuesta a Droga , Embrión de Mamíferos , Proteínas Ligadas a GPI/metabolismo , Masculino , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/prevención & control , Ratones , Ratones Endogámicos ICR , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Fitoterapia , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Hojas de la Planta/química , Tallos de la Planta/química , Ratas , Ratas Sprague-Dawley , Resorcinoles/química , Resorcinoles/aislamiento & purificación , Resorcinoles/farmacología , Estilbenos/química , Estilbenos/aislamiento & purificación , Estilbenos/farmacologíaRESUMEN
The roots of two Paeoniaceae family members have long been used as traditional medicines in Korea, China, and Japan. Dry roots of Paeonia lactiflora and dry root bark of P. suffruticosa are used under the traditional names of Paeoniae Radix and Moutan Cortex, respectively. Both Paeoniae Radix and Moutan Cortex have been used as remedies for cardiovascular diseases, for improving blood circulation, or for other uses. It was postulated that both plants may contain common active constituents that contribute to inhibiting blood coagulation and/or platelet aggregation. Eighteen compounds, which have been reported to be present in both plant medicines, were evaluated for their effects on platelet aggregation and blood coagulation. Paeonol (5), paeoniflorin (9), benzoylpaeoniflorin (11), and benzoyloxypaeoniflorin (12) were found to be the major common active constituents and they would collectively contribute to improving blood circulation through their inhibitory effects on both platelet aggregation and blood coagulation. In addition, methylgallate (4), (+)-catechin (7), paeoniflorigenone (8), galloylpaeoniflorin (13), and daucosterol (16) may also take part in improving blood circulation by inhibiting ether platelet aggregation and/or blood coagulation.
Asunto(s)
Anticoagulantes/química , Anticoagulantes/farmacología , Paeonia/química , Inhibidores de Agregación Plaquetaria/química , Inhibidores de Agregación Plaquetaria/farmacología , Animales , Humanos , Técnicas In Vitro , Corea (Geográfico) , Masculino , Extractos Vegetales/química , Extractos Vegetales/farmacología , Agregación Plaquetaria/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
Cinnamomum cassia is a well-known traditional medicine for improvement of blood circulation. An extract of this plant showed both platelet anti-aggregation and blood anti-coagulation effects in preliminary testing. Among the 13 compounds obtained from this plant, eugenol (2), amygdalactone (4), cinnamic alcohol (5), 2-hydroxycinnamaldehyde (7), 2-methoxycinnamaldehyde (8), and coniferaldehyde (9) showed 1.5-73-fold greater inhibitory effects than acetylsalicylic acid (ASA) on arachidonic acid (AA)-induced aggregation (50% inhibitory concentration [IC50] = 3.8, 5.16, 31.2, 40.0, 16.9, and 0.82 µM, respectively, vs. 60.3 µM) and 6.3-730-fold stronger effect than ASA on U46619 (a thromboxane A2 mimic)-induced aggregation (IC50 = 3.51, 33.9, 31.0, 51.3, 14.6, and 0.44 µM, respectively, vs. 321 µM). The other compounds, coumarin (3), cinnamaldehyde (6), cinnamic acid (10), icariside DC (11), and dihydrocinnacasside (12), also inhibited (2.5 to four times greater than ASA) U46619-induced aggregation. In addition, compounds 2, 4, 5, 6, 7, 8, and 9 were 1.3-87 times more effective than ASA against epinephrine-induced aggregation (IC50 = 1.86, 1.10, 37.7, 25.0, 16.8, 15.3, and 0.57 µM, respectively, vs. 50.0 µM). However, the 13 compounds were only very mildly effective against blood coagulation, if at all. In conclusion, compounds 2, 4, 8, and 9 showed stronger inhibitory potencies than others on AA-, U46619-, and epinephrine-induced platelet aggregation. Eugenol (2) and coniferaldehyde (9) were the two of the most active anti-platelet constituents of C. cassia.
Asunto(s)
Cinnamomum aromaticum/química , Extractos Vegetales/química , Inhibidores de Agregación Plaquetaria/farmacología , Animales , Anticoagulantes/aislamiento & purificación , Anticoagulantes/farmacología , Plaquetas/química , Fibrinolíticos/aislamiento & purificación , Fibrinolíticos/farmacología , Tiempo de Tromboplastina Parcial , Corteza de la Planta/química , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/aislamiento & purificación , Tiempo de Protrombina , Ratas , Ratas Sprague-Dawley , Tiempo de Trombina , Tromboxano A2/sangre , Tromboxano B2/sangreRESUMEN
To investigate the adipogenesis inhibitory effect on lipid accumulation, 3T3-L1 cells were treated with fractions and isolated flavonoids of Spirodela polyrhiza. An ethanol extract of S. polyrhiza was fractionated into three fractions. The butanol soluble fraction (SPB) exhibited potent antiadipogenesis activity and decreased C/EBPα and PPARγ protein expression level in 3T3-L1 cells without significant cytotoxicity. The flavonoids were isolated from SPB and their chemical structures were identified as chrysoeriol (1), apigenin (2), luteolin (3), vitexin (4), cosmosin (5), orientin (6) and luteolin-7-O-ß-d-glucoside (7) by spectroscopic analysis. Studies on the adipogenesis and intracellular triglyceride accumulation inhibitory effect showed that compounds 4 and 6 had the highest activity and decreased C/EBPα and PPARγ protein expression level in 3T3-L1 cells. These results suggest that the flavonoids isolated from SPB, especially compounds 4 and 6, contribute to the inhibitory activity of S. polyrhiza in 3T3-L1 cells.
Asunto(s)
Adipogénesis/efectos de los fármacos , Apigenina/farmacología , Araceae/química , Flavonoides/farmacología , Glucósidos/farmacología , Células 3T3-L1 , Animales , Apigenina/aislamiento & purificación , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Flavonoides/aislamiento & purificación , Glucósidos/aislamiento & purificación , Ratones , Estructura Molecular , PPAR gamma/metabolismo , Triglicéridos/análisisRESUMEN
In an ongoing investigation of compounds from natural products that exhibit anti-aging properties, hydroxyhibiscone A (1), a new furanosesquiterpenoid, together with hibiscone D (2), was isolated from the root bark of Hibiscus syriacus. Utilizing UV, IR, NMR, and MS spectroscopic analyses, these chemical structures were revealed. Compounds 1 and 2 were found to possess significant anti-aging properties on the human neutrophil elastase (HNE) assay, exhibiting HNE inhibitory activities with IC50 values of 5.2 and 4.6 micronM, respectively.
Asunto(s)
Hibiscus/química , Elastasa de Leucocito/antagonistas & inhibidores , Extractos Vegetales/farmacología , Proteínas Inhibidoras de Proteinasas Secretoras/farmacología , Hibiscus/metabolismo , Humanos , Elastasa de Leucocito/análisis , Elastasa de Leucocito/metabolismo , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Proteínas Inhibidoras de Proteinasas Secretoras/química , Proteínas Inhibidoras de Proteinasas Secretoras/metabolismoRESUMEN
AIM OF THE STUDY: To evaluate the effect of selected compounds derived from Moutan Cortex on glucose uptake and glycogen synthesis associated with AMPK activation in insulin-resistant human HepG2 cell. MATERIALS AND METHODS: The effect of isolated compounds (1-16) on glucose uptake and glycogen synthesis was performed using HepG2 cells. The western blot was used to determine the expression of AMPK and its downstream substrates, ACC, p-ACC, and p-GSK-3beta. RESULTS: The effects of the 16 compounds from Moutan Cortex on glucose metabolism in HepG2 cells under high glucose conditions were evaluated. Compounds 2, 3, and 6 displayed highly potent effects on the stimulation of glucose uptake and glycogen synthesis in human HepG2 cells under high glucose conditions. Compounds 2, 3, and 6 phosphorylate AMPK (AMP-activated protein kinase), and resulted in increased phosphorylation of GSK-3beta and suppression of lipogenic expression (ACC and FAS) in a dose-dependent manner. Compounds 2, 3, and 6 also demonstrated interesting, strong eNOS phosphorylation in human umbilical vein endothelial cells (HUVECs). Compounds 1, 4, 5-12, and 14 displayed considerable effects on hepatic glucose production, AMPK activation, and phosphorylation of GSK-3beta in HepG2 cells under high glucose conditions. CONCLUSIONS: These effects may indicate that the activation of AMPK by the active compounds from Moutan Cortex has considerable potential for reversing the metabolic abnormalities associated with type-2 diabetes.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Medicamentos Herbarios Chinos/farmacología , Endotelio Vascular/efectos de los fármacos , Glucosa/metabolismo , Glucógeno/biosíntesis , Hipoglucemiantes/farmacología , Hígado/efectos de los fármacos , Acetil-CoA Carboxilasa/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/química , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Endotelio Vascular/metabolismo , Ácido Graso Sintasas/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Células Hep G2 , Humanos , Hígado/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Paeonia/química , Fosforilación , Corteza de la Planta , Raíces de Plantas , Venas UmbilicalesRESUMEN
Corosolic acid is one of the triterpenoids present in the leaves of Weigela subsessilis. The antidiabetic activity of corosolic acid has been reported previously, but to date, the anticancer effects on gastric cancer have been poorly studied. In this study, corosolic acid showed growth inhibition on SNU-601 human gastric cancer cells, with an IC50 value of 16.9 ± 2.9 µM. Corosolic acid also triggered the activation of caspase-3 and poly (ADP-ribose) polymerase, while it was recovered by Z-VAD-FMK. Moreover, the cell growth/apoptosis activities of corosolic acid were regulated by the AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signals. These results showed that corosolic acid-mediated AMPK activation leads to inhibition of mTOR, thus providing a possible mechanism of action of corosolic acid in the inhibition of cancer cell growth and the induction of apoptosis.