Memory-enhancing agents have long been required for various reasons such as for obtaining a good score in a test in the young and for retaining memory in the aged. Although many studies have found that several natural products may be good candidates for memory enhancement, there is still a need for better agents. The present study investigated whether rubrofusarin, an active ingredient in Cassiae semen, enhances learning and memory in normal mice. Passive avoidance and Morris water maze tests were performed to determine the memory-enhancing ability of rubrofusarin. To investigate synaptic function, hippocampal long-term potentiation (LTP) was measured. Western blotting was performed to determine protein levels. To investigate neurite outgrowth, DCX immunohistochemistry and cell culture were utilised. Rubrofusarin (1, 3, 10, 30 mg/kg) enhanced memory in passive avoidance and Morris water maze tests. Moreover, rubrofusarin ameliorated scopolamine-induced memory impairment. In the rubrofusarin-treated group, high-frequency stimulation induced higher LTP in the hippocampal Schaffer-collateral pathway compared to the control group. The rubrofusarin-treated group showed a higher number of DCX-positive immature neurons with an increase in the length of dendrites compared to the control group in the hippocampal dentate gyrus region. In vitro experiments showed that rubrofusarin facilitated neurite outgrowth in neuro2a cells through extracellular signal-regulated kinase (ERK). Finally, we found that extracellular signal-regulated kinase (ERK) is required for rubrofusarin-induced enhancement of neurite outgrowth, learning and memory. These results demonstrate that rubrofusarin enhances learning and memory and neurite outgrowth, and these might need activation of ERK pathway.

长期以来，出于各种原因，例如为了在年轻人的考试中获得好成绩以及为了在老年人中保持记忆，一直需要记忆增强剂。尽管许多研究发现几种天然产品可能是增强记忆力的良好候选者，但仍然需要更好的药物。本研究调查了决明子精液中的活性成分红霉素是否能增强正常小鼠的学习和记忆力。进行了被动回避和莫里斯水迷宫测试以确定红霉素的记忆增强能力。为了研究突触功能，测量了海马长时程增强 (LTP)。进行蛋白质印迹以确定蛋白质水平。为了研究神经突的生长，使用了 DCX 免疫组织化学和细胞培养。红霉素 (1, 3, 10, 30 mg/kg) 在被动回避和莫里斯水迷宫测试中增强记忆力。此外，红霉素可改善东莨菪碱引起的记忆障碍。与对照组相比，在红红霉素治疗组中，高频刺激在海马 Schaffer 侧支通路中诱导了更高的 LTP。与海马齿状回区域的对照组相比，红霉素治疗组的 DCX 阳性未成熟神经元数量增加，树突长度增加。体外实验表明，红霉素通过细胞外信号调节激酶 (ERK) 促进神经 2a 细胞中的神经突生长。最后，我们发现红霉素诱导的神经突生长、学习和记忆增强需要细胞外信号调节激酶 (ERK)。这些结果表明红红霉素可增强学习和记忆以及神经突的生长，这些可能需要激活 ERK 通路。