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通光薯蓣神经保护活性及其对 PC12 细胞 caspase-3 和 bax/bcl-2 信号通路的调控作用。

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

机构信息

School of Pharmacy, Nanjing University of Chinese Medicine , Nanjing 210023, People's Republic of China.

出版信息

J Nat Prod. 2017 Jun 23;80(6):1734-1741. doi: 10.1021/acs.jnatprod.6b00954. Epub 2017 Apr 10.

Abstract

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 acyl chain, showed the most potent protective effect in PC12 cells from glutamate injury, with an EC value of 2.5 μM. Moreover, at the molecular level, longan cerebroside II (11) downregulated the expression of caspase-9, caspase-3, and Bax, upregulated the expression of Bcl-2, and decreased the level of cytosolic cytochrome c in a concentration-dependent manner.

摘要

对独角莲根茎中具有潜在神经保护作用的天然产物成分进行研究,分离得到了两个新的脑苷脂,即 typhonoside E(1)和 F(2),以及 11 个已知类似物(3-13)。通过光谱数据分析阐明了化合物 1 和 2 的结构。研究了这些化合物对 PC12 细胞中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,这与脂肪酸链的长度有关。其中,龙眼脑苷脂 II(11)具有最长的脂肪酸链,在谷氨酸损伤的 PC12 细胞中表现出最强的保护作用,EC 值为 2.5 μM。此外,在分子水平上,龙眼脑苷脂 II(11)呈浓度依赖性地下调了 caspase-9、caspase-3 和 Bax 的表达,上调了 Bcl-2 的表达,并降低了细胞质细胞色素 c 的水平。

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