RESUMO
In the present study, we examined whether aqueous extract of Eucommia ulmoides Oliv. Bark (EUE) with graded doses exerted its neuroprotective effects on amyloid beta(25-35) (Aß(25-35))-induced learning and memory impairments in mice. Mice received a single intracerebroventricular (i.c.v.) injection of Aß(25-35) 6 nmol as the critical factor in Alzheimer's disease (AD), cognition was evaluated using Y-maze, passive avoidance, and Morris water maze tests. EUE significantly improved the Aß(25-35)-induced memory deficit in the Y-maze test. Also, EUE increased step-through latency time with Aß(25-35)-induced learning and memory deficits in the passive avoidance test. In addition, EUE decreased the escape latencies with Aß(25-35)-induced cognitive impairments in the Morris water maze test. In the probe trial session, EUE increased time spent in the target quadrant. In the in vitro study, EUE was found to inhibit acetylcholinesterase (AChE) activity in a dose-dependent manner (IC50 value; 172 µg/ml). Ex vivo study, EUE significantly inhibited AChE activity in the hippocampus and frontal cortex. These results demonstrate that EUE possesses potent neuroprotective effects and that its beneficial effects are mediated, in part, by AChE inhibition, and therefore, might be a potential candidate in neurodegenerative diseases such as AD.
Assuntos
Eucommiaceae , Transtornos da Memória/tratamento farmacológico , Fitoterapia/métodos , Casca de Planta/química , Preparações de Plantas/uso terapêutico , Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/enzimologia , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/patologia , Camundongos , Camundongos Endogâmicos ICR , Fragmentos de Peptídeos/toxicidade , Tempo de Reação/efeitos dos fármacos , Natação/psicologiaRESUMO
Chlorogenic acid is a major polyphenolic component of many plants and beverages, and is particularly abundant in coffee. We evaluated the neuroprotective effects of chlorogenic acid on learning and memory impairment induced by scopolamine (0.5 mg/kg, i.p.), a muscarinic antagonist, using the Y-maze, passive avoidance, and Morris water maze tests. The chlorogenic acid significantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze test, and significantly reversed cognitive impairments in mice as measured by the passive avoidance test. In addition, chlorogenic acid decreased escape latencies in the Morris water maze test. In a probe trial session, chlorogenic acid increased the latency time in the target quadrant in a dose-dependent manner. Ex vivo, chlorogenic acid inhibited acetylcholinesterase activity in the hippocampus and frontal cortex. Chlorogenic acid also decreased malondialdehyde levels in the hippocampus and frontal cortex. In vitro, chlorogenic acid was found to inhibit acetylcholinesterase activity (IC50=98.17 µg/ml) and free radical scavenging activity (IC50=3.09 µg/ml) in a dose-dependent manner. These results indicate that chlorogenic acid may exert anti-amnesic activity via inhibition of acetylcholinesterase and malondialdehyde in the hippocampus and frontal cortex.
Assuntos
Amnésia/tratamento farmacológico , Antioxidantes/uso terapêutico , Ácido Clorogênico/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Deficiências da Aprendizagem/tratamento farmacológico , Antagonistas Muscarínicos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Acetilcolinesterase , Doença de Alzheimer/tratamento farmacológico , Amnésia/induzido quimicamente , Amnésia/metabolismo , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Ácido Clorogênico/administração & dosagem , Ácido Clorogênico/farmacologia , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/farmacologia , Relação Dose-Resposta a Droga , Reação de Fuga/efeitos dos fármacos , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/enzimologia , Lobo Frontal/metabolismo , Proteínas Ligadas por GPI/antagonistas & inibidores , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Hipocampo/metabolismo , Deficiências da Aprendizagem/induzido quimicamente , Deficiências da Aprendizagem/metabolismo , Masculino , Malondialdeído/metabolismo , Memória de Curto Prazo/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/farmacologia , Proteínas do Tecido Nervoso/antagonistas & inibidores , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologiaRESUMO
We identified a bioactive herbal medicine with anti-inflammatory activity from an ethanol extract derived from the bark of Dioscorea batatas DECNE (BDB) in RAW264.7 cells. We examined the effects of BDB on nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in LPS-induced RAW264.7 cells. BDB consistently inhibited both NO and PGE(2) production in a dose-dependent manner, with an IC(50) of 87-71 µg/ml, respectively. The reduction of NO and PGE(2) production were accompanied by a reduction in iNOS and COX-2 protein expression, as evaluated by Western blotting. To evaluate the action mode of BDB and its ability to inhibit iNOS and COX-2 protein expression, we assessed the effects of BDB on nuclear factor-κB (NF-κB) DNA-binding activity, NF-κB-dependent reporter gene activity, inhibitory factor-κB (IκB) phosphorylation and degradation, and p65 nuclear translocation. BDB suppressed DNA-binding activity and reporter gene activity as well as translocation of the NF-κB p65 subunit. BDB also down-regulated IκB kinase (IKK), thus inhibiting LPS-induced both phosphorylation and the degradation of IκBα. In addition, BDB also inhibited the LPS-induced activation of ERK1/2.
Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Dioscorea/química , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Macrófagos/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/enzimologia , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação , Casca de Planta/químicaRESUMO
The effects of processed Aloe vera gel (PAG) on the course of established diet-induced non-insulin-dependent diabetes mellitus (NIDDM) were studied in C57BL/6J mice. NIDDM was induced in C57BL/6J mice by feeding them a high-fat diet. Mice exhibiting diet-induced obesity (DIO) with blood glucose levels above 180mg/dl were selected to examine the antidiabetic effects of PAG. Oral administration of PAG for 8 weeks reduced circulating blood glucose concentrations to a normal level in these DIO mice. In addition, the administration of PAG significantly decreased plasma insulin. The antidiabetic effects of PAG were also confirmed by intraperitoneal glucose tolerance testing. PAG appeared to lower blood glucose levels by decreasing insulin resistance. The administration of PAG also lowered triacylglyceride levels in liver and plasma. Histological examinations of periepididymal fat pad showed that PAG reduced the average size of adipocytes. These results demonstrate that the oral administration of PAG prevents the progression of NIDDM-related symptoms in high-fat diet-fed mice, and suggest that PAG could be useful for treating NIDDM.