Jebelli Asiyeh, Khalaj-Kondori Mohammad, Bonyadi Mortaza, Hosseinpour Feizi Mohammad Ali, Rahmati-Yamchi Mohammad
Department of Animal Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Iran J Pharm Res. 2019 Spring;18(2):877-886. doi: 10.22037/ijpr.2019.1100665.
Physiological studies confirm improvement of memory by Olibanum, a resin from species, while little is known about the molecular mechanism by which it affects memory performance. Two master transcription factors, CREB-1 and CREB-2, regulate downstream memory-related genes expression, leading to the long-term memory potentiation. This study addresses the effects of Beta-boswellic acid (β-BA), the main ingredient of Olibanum, and ethanolic extract of the resin from on the expression of and genes in B65 cell line. B65 cells were treated with β-BA or ethanolic extract of Olibanum in different doses and time intervals and the cell viability/toxicity was measured by MTT assay. Total RNA was extracted from the treated and untreated control cells and cDNA was synthesized. The expression levels of and genes were quantified by Real-time PCR. MTT assays revealed 50% inhibitory concentrations of 42.05, 29.63, and 21.78 μg/mL for ethanolic extract of Olibanum and 89.54, 44.05, and 21.12 µM for β-BA at 24, 48, and 72 h time intervals respectively. Both β-BA and ethanolic extract of Olibanum altered and gene expression levels in time-dependent but not in dose-dependent way. However, β-BA showed stronger and more stable effects. The expression levels of the both genes followed an alternate upregulation and downregulation pattern, but in opposite directions, in response to the both solutions with the progress of time. These results suggest that Olibanum possibly improves memory performance, at least partially, by regulating the levels of CREB-1 and CREB-2 transcription factors via positive/negative-feedback loops.
生理学研究证实，乳香（一种来自[具体物种]的树脂）可改善记忆力，但其影响记忆表现的分子机制却鲜为人知。两种主要转录因子CREB-1和CREB-2调节下游与记忆相关的基因表达，从而导致长期记忆增强。本研究探讨了乳香的主要成分β-乳香酸（β-BA）以及[具体物种]树脂的乙醇提取物对B65细胞系中CREB-1和CREB-2基因表达的影响。用不同剂量和时间间隔的β-BA或乳香乙醇提取物处理B65细胞，并通过MTT法测定细胞活力/毒性。从处理过和未处理的对照细胞中提取总RNA并合成cDNA。通过实时PCR定量CREB-1和CREB-2基因的表达水平。MTT分析显示，在24、48和72小时时间间隔时，乳香乙醇提取物的50%抑制浓度分别为42.05、29.63和21.78μg/mL，β-乳香酸的50%抑制浓度分别为89.54、44.05和21.12μM。β-乳香酸和乳香乙醇提取物均以时间依赖性而非剂量依赖性方式改变CREB-1和CREB-2基因表达水平。然而，β-乳香酸显示出更强且更稳定的作用。随着时间的推移，响应于两种溶液，这两个基因的表达水平均呈现交替上调和下调模式，但方向相反。这些结果表明，乳香可能至少部分地通过正/负反馈回路调节CREB-1和CREB-2转录因子的水平来改善记忆表现。
