Department of Biological Science, Behavior Pharmacology and Ethnopharmacology Laboratory, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.
BMC Complement Altern Med. 2014 Aug 5;14:288. doi: 10.1186/1472-6882-14-288.
Flavonoids, 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.
The 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.
Six 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.
Our 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.
黄酮类化合物存在于多种植物中，已被证明对记忆具有有益的影响。一些研究报告称，源自夹竹桃科植物的黄酮类化合物可对记忆产生此类有益影响。本研究的目的是鉴定仪花(Erythrina falcata)茎皮粗提物（CE）中的黄酮类化合物，并对条件性恐惧记忆进行基于生物活性的研究。
采用高效液相色谱-二极管阵列检测-电喷雾串联质谱联用（HPLC-DAD-ESI/MSn）和核磁共振（NMR）鉴定 CE 的次生代谢产物。采用溶剂萃取法将 CE 分为正丁醇相（BuF）。通过快速色谱法得到 BuF 的各亚组分（BuF1-BuF6）和黄酮类组分（FfA 和 FfB）。采用高效液相色谱-光电二极管阵列检测（HPLC-PAD）对 BuF3 和 BuF4 进行分离，得到黄酮类化合物。通过高效液相色谱-二极管阵列检测（HPLC-DAD）对分离出的物质进行定量分析，并通过核磁共振（NMR）确定其结构。采用单次、下台阶抑制性回避（IA）任务监测 CE 和各亚组分的活性，以确定这些物质对大鼠条件性恐惧获得和消退的影响。
首次在 CE 中鉴定出 6 类黄酮类化合物。根据我们的行为学数据，CE、BuF、BuF3 和 BuF4（黄酮类组分）、牡荆素、异牡荆素和 6-C-糖苷-芹菜素改善了恐惧记忆的获得。接受 BuF、BuF3 和 BuF4 治疗的大鼠对消退特别具有抵抗力。然而，接受 FfA 和 FfB、牡荆素、异牡荆素和 6-C-糖苷-芹菜素治疗的大鼠在消退重测时，其条件性恐惧反应逐渐减少，在条件作用后 48 至 480 小时进行测量。
本研究结果表明，牡荆素、异牡荆素和芹菜素-6-C-葡萄糖苷以及黄酮类化合物可显著保留恐惧记忆，但不能防止恐惧记忆的消退。这些结果进一步证实，用纯黄酮类化合物或富含类黄酮的化合物治疗可能是治疗神经认知障碍、改善记忆获得和恐惧自发恢复的潜在治疗方法。
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