Chemically Bonding of Amantadine with Gardenamide A Enhances the Neuroprotective Effects against Corticosterone-Induced Insults in PC12 Cells

被引：11

作者：

Zhao, Jiaqiang ^{[1
]}

Peng, Lizhi ^{[1
]}

Zheng, Wenhua ^{[2
]}

Wang, Rikang ^{[3
]}

Zhang, Lei ^{[1
]}

Yang, Jian ^{[1
]}

Chen, Heru ^{[1
,4
]}

机构：

[1] Jinan Univ, Inst Tradit Chinese Med & Nat Prod, Coll Pharm, Guangzhou 510632, Guangdong, Peoples R China

[2] Univ Macao, Fac Hlth Sci, Taipa, Macao, Peoples R China

[3] Jiangxi Univ Tradit Chinese Med, Natl Pharmaceut Engn Ctr Solid Preparat Chinese H, Nanchang 330006, Peoples R China

[4] Guangdong Prov Key Lab Pharmacodynam Constituents, Guangzhou 510632, Guangdong, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2015年 / 16卷 / 09期

基金：

中国国家自然科学基金;

关键词：

gardenamide A; amantadine; neuroprotection; nNOS; eNOS; NMDA; NITRIC-OXIDE SYNTHASE; RAT HIPPOCAMPUS; DEPRESSION; STRESS; EXPRESSION; GLUCOCORTICOIDS; 7-NITROINDAZOLE; TRANSLOCATION; RECEPTOR; CHANNEL;

D O I：

10.3390/ijms160922795

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Two amantadine (ATD)-gardenamide A (GA) ligands have been designed and synthesized. The bonding of ATD with GA through a methylene carbonyl brigde (L1) enhances the neuroprotective effect against corticosterone (CORT)-induced impairments in PC12 cells; while the bonding through a succinyl brigde (L2) does not. L1 reduces the level of reactive oxygen species (ROS) and cell apoptosis generated by CORT. It restores CORT-changed cell morphology to a state that is closed to normal PC12 cells. One mechanism of L1 to attenuate CORT-induced cell apoptosis is through the adjustment of both caspase-3 and Bcl-2 proteins. Like GA, both nNOS and eNOS might be involved in the neuroprotective mechanism of L1. All the evidences suggest that L1 may be a potential agent to treat depression.

引用

页码：22795 / 22810

页数：16

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