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

被引：29
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
相关论文
共 37 条
[1]   Human ICE/CED-3 protease nomenclature [J].
Alnemri, ES ;
Livingston, DJ ;
Nicholson, DW ;
Salvesen, G ;
Thornberry, NA ;
Wong, WW ;
Yuan, JY .
CELL, 1996, 87 (02) :171-171
[2]   The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions [J].
Borner, C .
MOLECULAR IMMUNOLOGY, 2003, 39 (11) :615-647
[3]   Apoptotic mechanisms involved in neurodegenerative diseases:: Experimental and therapeutic approaches [J].
Camins, A. ;
Pallas, M. ;
Silvestre, J. S. .
METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY, 2008, 30 (01) :43-65
[4]   Effect of Tacrine-3-caffeic Acid, A Novel Multifunctional Anti-Alzheimer's Dimer, Against Oxidative-Stress-Induced Cell Death in HT22 Hippocampal Neurons: Involvement of Nrf2/HO-1 Pathway [J].
Chao, Xiao-Juan ;
Chen, Zi-Wei ;
Liu, An-Min ;
He, Xi-Xin ;
Wang, Shao-Gui ;
Wang, Yu-Ting ;
Liu, Pei-Qing ;
Ramassamy, Charles ;
Mak, Shing-Hung ;
Cui, Wei ;
Kong, Ah-Ng ;
Yu, Zhi-Ling ;
Han, Yi-Fan ;
Pi, Rong-Biao .
CNS NEUROSCIENCE & THERAPEUTICS, 2014, 20 (09) :840-850
[5]   Isolation, identification and antioxidative capacity of water-soluble phenylpropanoid compounds from Rhodiola crenulata [J].
Chen, Danjun ;
Fan, Junting ;
Wang, Peng ;
Zhu, Lanying ;
Jin, Yang ;
Peng, Yan ;
Du, Shuhu .
FOOD CHEMISTRY, 2012, 134 (04) :2126-2133
[6]   Chemical constituents of Typhonium giganteum Engl. [J].
Chen, XS ;
Chen, DH ;
Si, JY ;
Tu, GZ .
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH, 2001, 3 (04) :277-283
[7]   Structure determination and synthesis of a new cerebroside isolated from the traditional Chinese medicine Typhonium giganteum Engl. [J].
Chen, XS ;
Wu, YL ;
Chen, DH .
TETRAHEDRON LETTERS, 2002, 43 (19) :3529-3532
[8]   Baifuzi reduces transient ischemic brain damage through an interaction with the STREX domain of BKCa channels [J].
Chi, S. ;
Cai, W. ;
Liu, P. ;
Zhang, Z. ;
Chen, X. ;
Gao, L. ;
Qi, J. ;
Bi, L. ;
Chen, L. ;
Qi, Z. .
CELL DEATH & DISEASE, 2010, 1 :e13-e13
[9]  
CHOI DW, 1990, ANNU REV NEUROSCI, V13, P171, DOI 10.1146/annurev.neuro.13.1.171
[10]   OXIDATIVE STRESS, GLUTAMATE, AND NEURODEGENERATIVE DISORDERS [J].
COYLE, JT ;
PUTTFARCKEN, P .
SCIENCE, 1993, 262 (5134) :689-695
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