The School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Phytother Res. 2011 Mar;25(3):435-43. doi: 10.1002/ptr.3269. Epub 2010 Aug 24.
Aggregated beta-amyloid (Aβ) and elevated plasma levels of homocysteine have been implicated as critical factors in the pathogenesis of Alzheimer's disease. The neuroprotective effects and possible mechanism of four structurally similar dibenzocyclooctadiene lignans (namely schisandrin, schisantherin A, schisandrin B and schisandrin C) isolated from the fruit of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) against Aβ₂₅₋₃₅ and homocysteine toxicity in PC12 cells was studied. Exposure of PC12 cells to 0.5 µm Aβ₂₅₋₃₅ caused significant cell death, increased the number of apoptotic cells, elevated reactive oxygen species, increased the levels of the pro-apoptotic protein Bax and caspase-3 activation. All these effects induced by Aβ₂₅₋₃₅ were markedly reversed by schisandrin B and schisandrin C pretreatment, while schisandrin and schisantherin A had no obvious effects. Meanwhile, schisandrin B and schisandrin C reversed homocysteine-induced cytotoxicity. The results indicated that schisandrin B and schisandrin C protected PC12 cells against Aβ toxicity by attenuating ROS production and modulating the apoptotic signal pathway through Bax and caspase-3. Further structure-activity analysis of Schisandra lignans and evaluations of their neuroprotective effects using AD animal models are warranted.
聚集的β-淀粉样蛋白（Aβ）和同型半胱氨酸的升高水平已被认为是阿尔茨海默病发病机制中的关键因素。从五味子（Turcz.）Baill 的果实中分离出的四种结构相似的二苯并环辛二烯木脂素（即五味子素、五味子甲素、五味子乙素和五味子丙素）具有神经保护作用，其对 Aβ₂₅₋₃₅和同型半胱氨酸毒性的可能机制及其在 PC12 细胞中的作用也进行了研究。PC12 细胞暴露于 0.5µm Aβ₂₅₋₃₅会导致明显的细胞死亡，增加凋亡细胞的数量，增加活性氧的产生，增加促凋亡蛋白 Bax 的水平，并激活半胱氨酸蛋白酶-3。Aβ₂₅₋₃₅诱导的所有这些效应均被五味子乙素和五味子丙素预处理明显逆转，而五味子素和五味子甲素则无明显作用。同时，五味子乙素和五味子丙素逆转了同型半胱氨酸诱导的细胞毒性。结果表明，五味子乙素和五味子丙素通过减轻 ROS 产生并通过 Bax 和半胱氨酸蛋白酶-3调节凋亡信号通路来保护 PC12 细胞免受 Aβ毒性。进一步对五味子木脂素进行结构活性分析，并使用 AD 动物模型评估其神经保护作用，是必要的。
