Flavones from Erythrina falcata are modulators of fear memory

Abstract

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.

Protective, Preventive and Enhancing-Memory Effects of the Flavonoidic-Rich Plants or Flavonoidic Molecules: Behavioural, Neurochemical and Pharmacological Correlates

“…Similar results were seen after a single dose treatment with crude extract of Erythrina falcata (CE), pure flavonoids or flavonoid-rich fractions from the stem bark of E. falcata using a one-trial, step-down inhibitory avoidance (IA) [9] or conditioned lick suppression (CLS) [8] tasks.…”

“…Our data has established that the treatment with flavonoidrich plants or flavonoidic molecules resulted in a significant retention of long-term fear memory and its spontaneous recovery evaluated during extinction test sessions, although FfB did not prevent the acquisition of the extinction of fear conditioning within-sessions [6,9]. Moreover, our data showed, through pharmacological manipulation and genetic analysis, that acquisition of lick suppression is mediated by hydroxytryptamine (serotonin) receptor, subunit 1A (5-HT 1A R), gamma-aminobutyric acid type A receptor (GABA A R) and GluN2B-NMDAR in the dorsal hippocampal formation (dHF).…”

Triterpenoid saponins and C-glycosyl flavones from stem bark of Erythrina abyssinica Lam and their cytotoxic effects.

“…For various reasons, these preceding researches have been focused toward the medium polar constituents of the E. abyssinica stem bark, while the knowledge concerning to the most polar secondary metabolites remains limited up to now. In contrast, the stem bark from other Erythrina species have been previously studied for their polar constituents, resulting in the isolation of other classes of secondary metabolites such as triterpenoid saponins (Kouam et al, 1991(Kouam et al, , 2007(Kouam et al, , 2008Mbafor et al, 1997), also found to exert a wide range of pharmacological properties including cytotoxicity (Podolak et al, 2010), and most recently C-glycosyl flavones (De Oliveira et al, 2014). Though flavonoids most often are distinguished by their antioxidant, antiallergic and anti-inflammatory activities, some representative cases such as quercetin, catechin, gallocatechin and apigenin have been investigated as potential chemopreventive or chemotherapeutic agents against cancer (Di Carlo et al, 1999;Marchand, 2002).…”

Flavones-bound in benzodiazepine site on GABA A receptor: Concomitant anxiolytic-like and cognitive-enhancing effects produced by Isovitexin and 6-C-glycoside-Diosmetin

“…T anticonvulsant, myorelaxant and cognitive-impairing effects (de Oliveira et al, 2014(de Oliveira et al, , 2015Griffin et al, 2013;Rich et al, 2006;Verwey et al, 2005).…”