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Int. J. Mol. Sci. 2015, 16(9), 22795-22810; doi:10.3390/ijms160922795

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

2,* , 3,†
Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China
Faculty of Health Sciences, University of Macao, Taipa, Macao, China
National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China
Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Guangzhou 510632, China
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Maurizio Battino
Received: 25 July 2015 / Revised: 25 August 2015 / Accepted: 6 September 2015 / Published: 21 September 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [899 KB, uploaded 21 September 2015]   |  


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. View Full-Text
Keywords: gardenamide A; amantadine; neuroprotection; nNOS; eNOS; NMDA gardenamide A; amantadine; neuroprotection; nNOS; eNOS; NMDA

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Zhao, J.; Peng, L.; Zheng, W.; Wang, R.; Zhang, L.; Yang, J.; Chen, H. Chemically Bonding of Amantadine with Gardenamide A Enhances the Neuroprotective Effects against Corticosterone-Induced Insults in PC12 Cells. Int. J. Mol. Sci. 2015, 16, 22795-22810.

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