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

被引:27
|
作者
Jin, Yang [1 ,2 ]
Fan, Jun-Ting [1 ]
Gu, Xiao-Ling [1 ]
Zhang, Li-Ying [1 ]
Han, Jing [3 ]
Du, Shu-Hu [1 ,2 ]
Zhane, Ai-Xia [1 ]
机构
[1] Nanjing Med Univ, Sch Pharm, Nanjing 211166, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Key Lab Cardiovasc & Cerebrovasc Drug Res Jiangsu, Nanjing 211166, Jiangsu, Peoples R China
[3] Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210023, Jiangsu, Peoples R China
来源
JOURNAL OF NATURAL PRODUCTS | 2017年 / 80卷 / 06期
基金
中国国家自然科学基金;
关键词
INDUCED-NEUROTOXICITY; OXIDATIVE-STRESS; NERVOUS-SYSTEM; APOPTOSIS; DEATH; GLUTAMATE; ACID; NEURONS; PROTEIN; STROKE;
D O I
10.1021/acs.jnatprod.6b00954
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
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.
引用
收藏
页码:1734 / 1741
页数:8
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