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

• Published in: International journal of molecular sciences Vol. 16; no. 9; pp. 22795 - 22810
• Main Authors: Zhao, Jiaqiang, Peng, Lizhi, Zheng, Wenhua, Wang, Rikang, Zhang, Lei, Yang, Jian, Chen, Heru
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.09.2015; MDPI
• Subjects: amantadine; Amantadine - analogs & derivatives; Amantadine - pharmacology; Animals; Apoptosis; Apoptosis - drug effects; Biochemistry; Cellular biology; Corticosterone - adverse effects; eNOS; gardenamide A; Iridoids - chemistry; Iridoids - pharmacology; Ligands; neuroprotection; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; NMDA; nNOS; PC12 Cells; Rats; Reactive Oxygen Species - metabolism; NMDA; gardenamide A; eNOS; amantadine; neuroprotection; nNOS
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms160922795

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.