Neuroprotective Activity of Cerebrosides from Typhonium giganteum by Regulating Caspase-3 and Bax/Bcl-2 Signaling Pathways in PC12 Cells

Neuroprotective Activity of Cerebrosides from Typhonium giganteum by Regulating Caspase-3 and Bax/Bcl-2 Signaling Pathways in PC12 Cells
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大风草脑苷脂通过调节 PC12 细胞中的 Caspase-3 和 Bax/Bcl-2 信号通路发挥神经保护活性

DOI:
10.1021/acs.jnatprod.6b00954
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发表时间:
2017-06-01
影响因子:
5.1
通讯作者:
Zhane, Ai-Xia
Zhane, Ai-Xia
中科院分区:
生物学2区
文献类型:
--
作者:
Jin, Yang;Fan, Jun-Ting;Zhane, Ai-Xia

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对白附子根茎的潜在神经保护天然产物成分的研究导致分离出两种新的白附子苷,白附子苷E(1)和F(2),沿着有11种已知的类似物(3-13)。化合物1和2的结构通过光谱数据解析确定。在PC 12细胞中研究了这些化合物对谷氨酸诱导的细胞凋亡的活性。所有化合物均表现出这种活性,这与脂肪酰基链的长度有关。其中,具有最长脂肪芳基链的龙眼肉苷II(11)对谷氨酸损伤的PC 12细胞显示出最强的保护作用,其EC 50值为2.5 μ M。此外,在分子水平上,龙眼肉苷II(11)呈浓度依赖性下调caspase-9、caspase-3和Box的表达,上调Bcl-2的表达,降低胞浆细胞色素c的水平。
An investigation of the potential neuroprotective natural product constituents of the rhizomes of Typhonium giganteum led to the isolation of two new cerebrosides, typhonosides E (1) and F (2), along with 11 known analogues (3-13). The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. The activity of these compounds against glutamate-induced cell apoptosis was investigated in PC12 cells. All compounds exhibited such activity, which was related to the length of the fatty acyl chain. Among them, longan cerebroside II (11), with the longest fatty aryl chain, showed the most potent protective effect in PC12 cells from glutamate injury, with an EC50 value of 2.5 mu M. Moreover, at the molecular level, longan cerebroside II (11) downregulated the expression of caspase-9, caspase-3, and Box, upregulated the expression of Bcl-2, and decreased the level of cytosolic cytochrome c in a concentration-dependent manner.