A novel neuroprotective agent with antioxidant and nitric oxide synthase inhibitory action

Abstract

N^α-vanillyl-N^ω-nitroarginine (N − 1) that combines the active functions of natural antioxidant and nitric oxide synthase inhibitor was developed for its neuroprotective properties. N − 1 exhibited protective effects against hydrogen peroxide-induced cell damage and the inhibitory effect on nitric oxide ‘NO’ production induced by calcium ionophore in NG 108-15 cells. N − 1 inhibited the constitutive NOS isolated from rat cerebellar in a greater extent than constitutive NOS from human endothelial cells. Low binding energy ( − 10.2 kcal/mol) obtained from docking N − 1 to nNOS supported the additional mode of action of N − 1 as an nNOS inhibitor. The in vivo neuroprotective effect on kainic acid-induced nitric oxide production and neuronal cell death in rat brain was investigated via microdialysis. Rats were injected intra-peritonially with N − 1 at 75 μmol/kg before kainic acid injection (10 mg/kg). The significant suppression effect on kainic acid-induced NO and significant increase in surviving cells were observed in the hippocampus at 40 min after the induction.

• Nitric oxide synthase
• neuroprotection
• cell culture
• NG108-15
• microdialysis
• nitro arginine