The present study demonstrates the epigenetic mechanisms underlying the effect of Bacoside rich extract of Bacopa monniera-a nootropic herb, on scopolamine treated amnesic mice conferred via chromatin modifying enzymes. The focus of the work was to elucidate the modulation of the chromatin modifying enzymes: DNMT1, DNMT3a, DNMT3b, HDAC2, HDAC5 and CPB in scopolamine induced amnesic mice after treatment with bacoside rich extract of Bacopa monniera (BA) and BA encapsulated in lactoferrin conjugated PEG-PLA-PCL-OH based polymersomes (BAN). We observed remarkable difference between the results obtained after the treatment with BA and BAN. Interestingly BAN was found to be more efficient in downregulating DNA methylation and histone chain deacetylation. Scopolamine treatment showed up-regulation of DNMT1 expression in qRT-PCR by 3.14-fold as compared to the control, which was considerably decreased by 1.5-fold after treatment with BA and remarkably decreased 0.11-fold by BAN treatment. Scopolamine treatment up-regulated the expression of DNMT3a by 1.6-fold while for DNMT3b by 3.13-fold. In DNMT3a and DNMT3b the fold change decreased to 0.64 and 0.76 after BA treatment, whereas the BAN treatment further down-regulated to 0.32- and 0.63-fold, respectively. Similarly scopolamine up-regulated HDAC2 and HDAC5 by 3.12 fold and 3.64-fold, respectively. BA treatment reversed the changes by reducing HDAC2 mRNA to 0.89-fold and HDAC5 mRNA 0.83-fold. BAN further reduced expression of HDAC2 further to 0.39-fold and HDAC5 to 0.31-fold. On the other hand scopolamine down-regulated CBP mRNA expression by 0.28-fold and increased by 1.09 after BA treatment. BAN significantly increased the CPB expression by 1.65-fold as compared to BA treatment. These findings were consolidated by DNMT and HDAC enzyme activity assay, methylation in the promoter region of the memory related genes: ARC and BDNF and Dot blot assay for DNA methylation. The percent activity increase of DNMT and HDAC after scopolamine administration was 375.74 and 240.90 respectively. After treatment with BA the downfall in percent activity was observed as 167.99 in DMNT and 130.57 in HDAC. BAN treatment further decreased the percent enzyme activity of DNMT and HDAC significantly by 30.0 and 61.81 respectively. The potency of BAN in reversing the epigenetic changes of scopolamine induced amnesic mouse brain, can be attributed to the brain specific delivery of BA through polymersomes which are able to cross the blood brain barrier (BBB) via receptor mediated endocytosis.

中文翻译：

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乳铁蛋白缀合的PEG-PLA-PCL-OH基聚合物囊泡中的Bacosides在化学诱导的健忘症中充当表观遗传调节剂。

本研究表明表观遗传学机制的基础丰富的Bacopa monniera-一种促智药草的丰富的Bacoside提取物，通过染色质修饰酶赋予东sco碱治疗的健忘小鼠。研究的重点是阐明东pol碱诱导的健忘小鼠对染色质修饰酶DNMT1，DNMT3a，DNMT3b，HDAC2，HDAC5和CPB的调节，方法是用富含Bacopa monniera（BA）的bacoside提取物和包裹乳铁蛋白的BA包被PEG-PLA-PCL-OH基聚合物囊泡（BAN）。我们观察到用BA和BAN处理后获得的结果之间存在显着差异。有趣的是，发现BAN在下调DNA甲基化和组蛋白链脱乙酰基化方面更有效。co碱处理显示qRT-PCR中DNMT1表达的上调为3。与对照相比是14倍，用BA处理后显着降低了1.5倍，而通过BAN处理显着降低了0.11倍。co碱处理使DNMT3a的表达上调1.6倍，而DNMT3b的表达上调3.13倍。在DNMT3a和DNMT3b中，BA处理后，倍数变化降低至0.64和0.76，而BAN处理分别进一步下调至0.32和0.63倍。类似地，东pol碱分别上调HDAC2和HDAC5 3.12倍和3.64倍。BA处理通过将HDAC2 mRNA降低至0.89倍和HDAC5 mRNA 0.83倍来逆转这种变化。BAN将HDAC2的表达进一步降低至0.39倍，将HDAC5的表达降低至0.31倍。另一方面，东BA碱在BA处理后下调CBP mRNA表达0.28倍并增加1.09。与BA处理相比，BAN显着提高了CPB表达1.65倍。这些发现通过DNMT和HDAC酶活性测定，记忆相关基因（ARC和BDNF）的启动子区域的甲基化以及DNA甲基化的Dot印迹测定得到了巩固。东碱给药后，DNMT和HDAC的活性增加百分比分别为375.74和240.90。用BA处理后，在DMNT中观察到活性百分比下降，为167.99，在HDAC中观察到130.57。BAN处理进一步分别使DNMT和HDAC的酶活性百分比分别降低了30.0和61.81。BAN可以逆转东pol碱诱导的健忘小鼠脑表观遗传变化，