BackgroundFlavonoids, which have been identified in a variety of plants, have been demonstrated to elicit beneficial effects on memory. Some studies have reported that flavonoids derived from Erythrina plants can provide such beneficial effects on memory. The aim of this study was to identify the flavonoids present in the stem bark crude extract of Erythrina falcata (CE) and to perform a bioactivity-guided study on conditioned fear memory.MethodsThe secondary metabolites of CE were identified by high performance liquid chromatography combined with a diode array detector, electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI/MSn) and nuclear magnetic resonance (NMR). The buthanolic fraction (BuF) was obtained by partitioning. Subfractions from BuF (BuF1 – BuF6) and fraction flavonoidic (FfA and FfB) were obtained by flash chromatography. The BuF3 and BuF4 fractions were used for the isolation of flavonoids, which was performed using HPLC-PAD. The isolated substances were quantified by HPLC-DAD and their structures were confirmed by nuclear magnetic resonance (NMR). The activities of CE and the subfractions were monitored using a one-trial, step-down inhibitory avoidance (IA) task to identify the effects of these substances on the acquisition and extinction of conditioned fear in rats.ResultsSix subclasses of flavonoids were identified for the first time in CE. According to our behavioral data, CE, BuF, BuF3 and BuF4, the flavonoidic fractions, vitexin, isovitexin and 6-C-glycoside-diosmetin improved the acquisition of fear memory. Rats treated with BuF, BuF3 and BuF4 were particularly resistant to extinction. Nevertheless, rats treated with FfA and FfB, vitexin, isovitexin and 6-C-glycoside-diosmetin exhibited gradual reduction in conditioned fear response during the extinction retest session, which was measured at 48 to 480 h after conditioning.ConclusionsOur results demonstrate that vitexin, isovitexin and diosmetin-6-C-glucoside and flavonoidic fractions resulted in a significant retention of fear memory but did not prevent the extinction of fear memory. These results further substantiate that the treatment with pure flavonoids or flavanoid-rich fractions might represent potential therapeutic approaches for the treatment of neurocognitive disorders, improvement of memory acquisition and spontaneous recovery of fear.
RESUMOOnze linhagens avançadas de amendoim, eretas e rasteiras, foram conduzidas em condições de sequeiro, em quatro estados nordestinos, visando-se avaliar a produtividade em vagens e sementes. Os ensaios foram conduzidos no período de 2005 a 2007, nos municípios de Araripina e Parnamirim, PE, Lagarto, SE, Cruz das Almas e Caetité, BA, Campina Grande e Itabaiana, PB. O delineamento experimental adotado foi em blocos ao acaso, com 13 tratamentos, constituídos de oito linhagens eretas e cinco rasteiros, com cinco repetições. As variáveis analisadas foram produtividades de vagens e de sementes. Em referência à análise estatística, realizaram-se análises de variância individual e conjunta e se adotou o teste de Tukey (p < 0,05) para comparação das médias dos tratamentos. A cultivar BR 1 foi utilizada como testemunha entre os genótipos eretos. A linhagem ereta LN-1B apresentou maior produção de vagens entre as demais do grupo, com 2.450 kg ha -1 , superando a média em 22% e a BR 1, em 11%; a produtividade média em sementes situou-se em 1.665 kg ha -1 , correspondendo a 21% acima da média do grupo e 10% acima da BR 1. Entre as linhagens rasteiras as médias de produtividade em vagens e em sementes foram consideradas baixas nas condições estudadas destacando-se, contudo, LI-3, LI-5 e LI-1, que produziram em média entre 1.722 kg ha -1 e 1.154 kg ha -1 , e superaram a média do grupo em 9.8 e 10%, respectivamente. A completely randomized block experimental design with five replications was used with 13 treatments (8 upright and 5 runner genotypes). The analyzed variables were pod and seed yields. Individual and joint variance analysis were carried out and Tukey (p < 0.05) test was used to compare treatments. The BR 1 cultivar was adopted as a control. The highest pod and seed yields were obtained by LN-1B, with 2,450 and 1,665 kg ha -1 , respectively, overcoming the mean of upright lines in 22 and 21%, and of the BR 1 cv. in 11 and 10%. As to runner lines, the pod and seed yields were not satisfactory under the conditions, however, LI-3, LI-5 and LI-1 overcame the group, with 1,722 and 1,154 kg ha -1 , corresponding to 9.8 and 10% over general mean, respectively. Palavras-chave:
The effects of flavonoids have been correlated with their ability to modulate the glutamatergic, serotoninergic, and GABAergic neurotransmission; the major targets of these substances are N-methyl-D-aspartic acid receptor (NMDARs), serotonin type1A receptor (5-HT1ARs), and the gamma-aminobutyric acid type A receptors (GABAARs). Several studies showed that these receptors are involved in the acquisition and extinction of fear memory. This study assessed the effects of treatment prior to conditioning with a flavonoid-rich fraction from the stem bark of Erythrina falcata (FfB) on the acquisition and extinction of the conditioned suppression following pharmacological manipulations and on gene expression in the dorsal hippocampus (DH). Adult male Wistar rats were treated before conditioned fear with FfB, vehicle, an agonist or antagonist of the 5-HT1AR, GABAARs or the GluN2B-NMDAR or one of these antagonists before FfB treatment. The effects of these treatments on fear memory retrieval, extinction training and extinction retrieval were evaluated at 48, 72, and 98 h after conditioning, respectively. We found that activation of GABAARs and inactivation of GluN2B-NMDARs play important roles in the acquisition of lick response suppression. FfB reversed the effect of blocking GluN2B-NMDARs on the conditioned fear and induced the spontaneous recovery. Blocking the 5-HT1AR and the GluN2B-NMDAR before FfB treatment seemed to be associated with weakening of the spontaneous recovery. Expression of analysis of DH samples via qPCR showed that FfB treatment resulted in the overexpression of Htr1a, Grin2a, Gabra5, and Erk2 after the retention test and of Htr1a and Erk2 after the extinction retention test. Moreover, blocking the 5-HT1ARs and the GluN2B-NMDARs before FfB treatment resulted in reduced Htr1a and Grin2b expression after the retention test, but played a distinct role in Grin2a and Erk2 expression, according session evaluated. We show for the first time that the serotoninergic and glutamatergic receptors are important targets for the effect of FfB on the conditioned fear and spontaneous recovery, in which the ERK signaling pathway appears to be modulated. Further, these results provide important information regarding the role of the DH in conditioned suppression. Taken together, our data suggest that FfB represents a potential therapy for preventing or treating memory impairments.
Increasing evidence suggests that flavones can modulate memory and anxiety-like behaviour. However, these therapeutic effects are inconsistent and induce of adverse effects, which have been associated with interactions at the Benzodiazepine (BZ)-binding site. To improve our understanding of flavone effects on memory and anxiety, we employed a plus-maze discriminative avoidance task. Furthermore, we evaluated the potential of the compounds in modulating GABA receptors via BZ-binding site using molecular modelling studies. Adult male Wistar rats were treated 30 min before training session with Vicenin-2 (0.1 and 0.25 mg/kg), Vitexin (0.1 and 0.25 mg/kg), Isovitexin (0.1 and 0.25 mg/kg) and 0.1 mg/kg 6-C-glycoside-Diosmetin, vehicle and a GABA receptor agonist. The analysis of the time spent in the non-aversive vs aversive enclosed arms during the test session and percentage of time in the open arms within the training session revealed that treatment with Isovitexin and 6-C-glycoside-Diosmetin had memory-enhancing and anxiolytic-like effects (P < 0.001). In contrast, treatment with a higher dose of Diazepam impaired short-and long-term memory when it alleviated anxiety level. Docking studies revealed that flavones docked in a very similar way to that observed to the Diazepam, except by a lack of interaction in residue α1His101 in the BZ-binding site on GABA receptors, which may be related to memory-enhancing effect. The occurrence of the αHis101 interaction could justify the memory-impairing observed following Diazepam treatment. These findings provide the first evidence that Isovitexin and 6-C-glycoside-Diosmetin could exert their memory-enhancing and anxiolytic-like effects via GABA receptor modulation, which likely occurs via their benzodiazepine-binding site.
Resumo -A BRS Havana é uma nova cultivar ereta de amendoim de película clara, desenvolvida pela Embrapa Algodão e destinada à indústria de alimentos. É resultante de vários ciclos de seleção exercidos no acesso paulista Película Havana e, em ensaios de rede conduzidos em 30 municípios da Região Nordeste, apresentou produtividade média de 1.900 kg ha -1 em vagens, ciclo vegetativo de 90 dias e tolerância ao estresse hídrico. Em condições irrigadas, a produtividade média situou-se em 4.900 kg ha -1 . No aspecto nutricional, a BRS Havana tem 43% de óleo (baixo teor) e apresenta 47% de proteína na farinha desengordurada. BRS Havana: a new tan color peanut cultivarAbstract -BRS Havana is a new upright tan color peanut cultivar, developed by Embrapa Algodão and destined to food industry. It was obtained by several selection cycles in access Película Havana, from São Paulo, Brazil, and in yield trials carried out in 30 municipal districts of Brazilian Northeast, BRS Havana showed high pod yield (1,900 kg ha -1 ), short cycle (90 days) and tolerance to drought. Under irrigation conditions, the average pod yield increased to 4,900 kg ha -1 . In the nutritional aspect, BRS Havana presents 43% oil and 47% protein content in its defatted flour. IntroduçãoA produção de amendoim no Brasil cresceu significativamente nos últimos oito anos, passando de 130 mil toneladas em 1998 para a atual estimativa de 280 mil toneladas (Conab, 2005). A região Sudeste apresentou maior crescimento, seguida da região Nordeste, com crescimento de área em torno de 14%.O interesse dos produtores pela cultura do amendoim reflete as boas cotações do produto no mercado, que favorecem a rentabilidade e capitalização do produtor rural. Na agroeconomia do Nordeste brasileiro, o amendoim tem se destacado por ser de fácil manejo, ciclo curto e preço atraente no mercado, além de se constituir em fonte adicional e agregadora de renda em razão das várias formas de produtos que podem ser processados, e que incentivam a agroindústria regional.A Embrapa Algodão tem desenvolvido pesquisas com amendoim desde a década de 80 e tem disponibilizado ao setor produtivo cultivares comerciais destinadas ao mercado brasileiro, cuja maior demanda é por cultivares de porte ereto e grãos vermelhos (tipo Valência), para atender ao mercado de consumo in natura. Recentemente, contudo, tem se percebido uma demanda crescente por produtos para atender ao mercado de alimentos, especialmente confeitaria e salgados (Godoy et al., 1999;Santos et al., 2005).Para atender esta exigência, a Embrapa Algodão desenvolveu a BRS Havana, uma cultivar de porte ereto, película clara e baixo teor de óleo, recomendada para produtores que vivem do agronegócio familiar, nas regiões de Zona da Mata, Agreste e Sertão nordestinos. Características da cultivarA BRS Havana foi obtida através de vários ciclos de seleção, exercidos no acesso CNPA 75 AM (Película Havana), originário de São Paulo e cedido pelo Instituto Agronômico (IAC) no início da década de 80. O acesso original apresentava ciclo entre 110 e ...
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