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Updated: Apr 10, 2026

A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
Kukoamine B, an amide alkaloid, protects against NMDA-induced neurotoxicity and potential mechanisms in vitro
Xiao-Long Hu1, Li-Ping Guo2, Qi Song2
1Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China; Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
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.
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