Effect of scutellarin on nitric oxide production in early stages of neuron damage induced by hydrogen peroxide.
The aims of the present study were to investigate the regulatory function of scutellarin on production of nitric oxide (NO) as well as activities of constitutive NO synthase (cNOS) and inducible NO synthase (iNOS) in early stages of neuron damage induced by hydrogen peroxide. Direct detection of NO production was performed on primary cultures of living rat neuronal cells with an electrochemical sensor. Hydrogen peroxide significantly increased culture supernatant levels of NO, the total integral value of the defined areas (500-6500 sxpA) reached 3.68 x 10(6). Pre-treatment with scutellarin, caused the total integral value to decrease in a dose-dependent fashion (3.24 x 10(6), 2.15 x 10(6), 1.84 x 10(6) for groups 10, 50, and 100 uM scutellarin, respectively). After exposure to 2.0mM hydrogen peroxide for 2h, malondialdehyde (MDA) level, a marker of lipid peroxidation, was remarkably increased. The elevation can be suppressed by scutellarin. Hydrogen peroxide also caused significant loss of neuron viability. In comparison with the control group, scutellarin significant attenuated the loss. Results also showed that hydrogen peroxide increased activity of cNOS, which was markedly inhibited by scutellarin. However, exposure of neuronal cells to hydrogen peroxide did not lead to an increase in iNOS activity. In conclusion, our results suggest that NO production, which increased in early stages of neuron damage induced by hydrogen peroxide can be effectively inhibited by scutellarin. Moreover, our results indicate that increase in NO production is mediated by cNOS.
Liu
Hong
H
Department of Pharmacy, Wuhan General Hospital of Guangzhou Command, Wuhan 430070, PR China. hustpharm804@163.com
Yang
Xianliang
X
Tang
Ren
R
Liu
Jie
J
Xu
Huibi
H
D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005965:Glucuronates / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D005965:Glucuronates; C484876:scutellarin; D009569:Nitric Oxide; D047310:Apigenin; D006861:Hydrogen Peroxide