title: Kukoamine B, an amide alkaloid, protects against NMDA-induced neurotoxicity and potential mechanisms in vitro.
abstract: A major cause of cerebral ischemia is overactivation of the N-methyl-D-aspartate receptors (NMDARs). Therefore, NMDAR antagonists are needed for the treatment of cerebral ischemia. In our research, KuB protected the SH-SY5Y cells against NMDA-induced injury, apoptosis, LDH release and MMP loss. In addition, KuB could decrease MDA levels while increasing SOD activity. Meanwhile, KuB decreased NADPH oxidase-mediated ROS production, inhibited Ca(2+) influx, and increased the Bcl-2/Bax ratio. Furthermore, KuB not only down-regulated expression of the NR2B subunit of NMDAR but also actively modulated expression of the signaling molecules downstream of NR2B, including p-ERK, p-CREB, p-AKT and SAPKs. Finally, docking results showed that KuB had a high affinity for NR2B-containing NMDARs. Therefore, we conclude that KuB protected the SH-SY5Y cells from NMDA-induced injury likely by antagonizing NMDARs and reducing oxidative stress.
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China; Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Hu
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Guo
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Song
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Meng
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China. Electronic address: zhaoqingchun1967@163.com.
authors.forename: Qing-Chun
authors.initials: QC
authors.lastname: Zhao
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002109:Caffeic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D017136:Ion Transport; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000098:Acetophenones; D002109:Caffeic Acids; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C557784:kukoamine B; D013096:Spermine; D008315:Malondialdehyde; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C056165:acetovanillone; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D020782:Matrix Metalloproteinases; D002118:Calcium
keywords: Kukoamine B; Molecular docking; NADPH oxidase; NMDA receptors; Oxidative stress; SH-SY5Y cells