title: Chemically Bonding of Amantadine with Gardenamide A Enhances the Neuroprotective Effects against Corticosterone-Induced Insults in PC12 Cells.
abstract: 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.
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China. jqzhaodzs@163.com.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China. 15900088863@163.com.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Peng
authors.affiliation: Faculty of Health Sciences, University of Macao, Taipa, Macao, China. Wenhuazheng@umac.com.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zheng
authors.affiliation: National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China. wrk168ok@163.com.
authors.forename: Rikang
authors.initials: R
authors.lastname: Wang
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China. 13247377339@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China. 13187048948@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China. thrchen@jnu.edu.cn.|Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Guangzhou 510632, China. thrchen@jnu.edu.cn.
authors.forename: Heru
authors.initials: H
authors.lastname: Chen
mesh_terms: D000547:Amantadine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003345:Corticosterone / Q000009:adverse effects; D039823:Iridoids / Q000737:chemistry* / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D039823:Iridoids; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C000601173:gardenamide A; D000547:Amantadine; D003345:Corticosterone
keywords: NMDA; amantadine; eNOS; gardenamide A; nNOS; neuroprotection