Institute of Mental Health, Peking University, 100083 Beijing, China.
Acta Physiol (Oxf). 2009 Aug;196(4):419-25. doi: 10.1111/j.1748-1716.2009.01961.x. Epub 2009 Feb 5.
Previous studies have shown that tenuigenin, a crude extract of Polygala tenuifolia Willd. that is commonly used in traditional Chinese herbal medicine for memory loss, can reduce the secretion of Abeta from cultured cells. However, the mechanism underlying this effect and the active compound derived from tenuigenin is unknown. In this study, a purified component of tenuigenin, tenuifolin, was examined and revealed to be an effective compound in vitro.
Abeta secretion from three sets of COS-7 cells, each carrying a plasmid expressing a different form of APP was examined following the treatment with tenuifolin. Initially, tenuifolin was determined to have no inherent toxicity to either the transfected or wild type cells at the effective concentrations. Cells were then treated with 0.5-2.0 microg mL(-1) tenuifolin for 12 h and their media were examined via an ELISA for Abeta1-40 and Abeta-42.
We found that treatment with 2.0 microg mL(-1) tenuifolin significantly decreased Abeta secretion from COS-7 cells without altering the ratio of Abeta1-40 and Abeta-42. This effect is most probably due to inhibition of the beta-site APP cleaving enzyme as Abeta secretion was not inhibited from cells expressing the C99 fragment.
Tenuifolin is an effective compound from tenuigenin. We believe that this finding should lead the way for future experiments to determine the exact mechanism for tenuifolin's effect on Abeta secretion.
先前的研究表明,远志中的一种粗提物-tenuigenin,常用于传统中药治疗健忘,可减少培养细胞中 Abeta 的分泌。然而,其作用机制及来源于 tenuigenin 的活性化合物仍不清楚。在本研究中,tenuifolin(远志中的一种纯化成分)被检测到是一种有效的体外化合物。
用 3 组表达不同 APP 形式的 COS-7 细胞检测 tenuifolin 处理后的 Abeta 分泌情况。首先,在有效浓度下,tenuifolin 对转染细胞和野生型细胞均无固有毒性。然后,用 0.5-2.0μg/ml tenuifolin 处理细胞 12 小时,通过 ELISA 检测 Abeta1-40 和 Abeta-42 。
我们发现,用 2.0μg/ml tenuifolin 处理可显著减少 COS-7 细胞中 Abeta 的分泌,而不改变 Abeta1-40 和 Abeta-42 的比值。这种作用可能是由于抑制了β位 APP 切割酶,因为表达 C99 片段的细胞中 Abeta 的分泌没有被抑制。
tenuifolin 是 tenuigenin 的一种有效化合物。我们相信,这一发现将为未来确定 tenuifolin 对 Abeta 分泌作用的确切机制的实验铺平道路。