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

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...

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Autores principales: Zhao, Jiaqiang, Peng, Lizhi, Zheng, Wenhua, Wang, Rikang, Zhang, Lei, Yang, Jian, Chen, Heru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613336/
https://www.ncbi.nlm.nih.gov/pubmed/26402670
http://dx.doi.org/10.3390/ijms160922795
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author Zhao, Jiaqiang
Peng, Lizhi
Zheng, Wenhua
Wang, Rikang
Zhang, Lei
Yang, Jian
Chen, Heru
author_facet Zhao, Jiaqiang
Peng, Lizhi
Zheng, Wenhua
Wang, Rikang
Zhang, Lei
Yang, Jian
Chen, Heru
author_sort Zhao, Jiaqiang
collection PubMed
description 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.
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spelling pubmed-46133362015-10-26 Chemically Bonding of Amantadine with Gardenamide A Enhances the Neuroprotective Effects against Corticosterone-Induced Insults in PC12 Cells Zhao, Jiaqiang Peng, Lizhi Zheng, Wenhua Wang, Rikang Zhang, Lei Yang, Jian Chen, Heru Int J Mol Sci Article 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. MDPI 2015-09-21 /pmc/articles/PMC4613336/ /pubmed/26402670 http://dx.doi.org/10.3390/ijms160922795 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhao, Jiaqiang
Peng, Lizhi
Zheng, Wenhua
Wang, Rikang
Zhang, Lei
Yang, Jian
Chen, Heru
Chemically Bonding of Amantadine with Gardenamide A Enhances the Neuroprotective Effects against Corticosterone-Induced Insults in PC12 Cells
title Chemically Bonding of Amantadine with Gardenamide A Enhances the Neuroprotective Effects against Corticosterone-Induced Insults in PC12 Cells
title_full Chemically Bonding of Amantadine with Gardenamide A Enhances the Neuroprotective Effects against Corticosterone-Induced Insults in PC12 Cells
title_fullStr Chemically Bonding of Amantadine with Gardenamide A Enhances the Neuroprotective Effects against Corticosterone-Induced Insults in PC12 Cells
title_full_unstemmed Chemically Bonding of Amantadine with Gardenamide A Enhances the Neuroprotective Effects against Corticosterone-Induced Insults in PC12 Cells
title_short Chemically Bonding of Amantadine with Gardenamide A Enhances the Neuroprotective Effects against Corticosterone-Induced Insults in PC12 Cells
title_sort chemically bonding of amantadine with gardenamide a enhances the neuroprotective effects against corticosterone-induced insults in pc12 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613336/
https://www.ncbi.nlm.nih.gov/pubmed/26402670
http://dx.doi.org/10.3390/ijms160922795
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