Aristolactam BII of Saururus chinensis Attenuates Glutamate-Induced Neurotoxicity in Rat Cortical Cultures Probably by Inhibiting Nitric Oxide Production

Abstract

Saurolactam and aristolactam BII, aristolactam-type alkaloids isolated from the aerial part of Saururus chinensis (Lour.) Ball (Saururaceae), showed significant neuroprotective activity against glutamate-induced toxicity in primary cultured rat cortical cells. The action mechanism of aristolactam BII, the more potent neuroprotective compound, was investigated using primary cultures of rat cortical cells as an in vitro system. Aristolactam BII attenuated glutamate-induced neurotoxicity significantly when it was added immediately or up to 9 h after the excitotoxic glutamate challenge. The alkaloid could not protect cultured neuronal cells from neurotoxicity induced by kainic acid or N-methyl-D-aspartate in a pre-treatment paradigm. However, aristolactam BII successfully reduced the overproduction of nitric oxide and the level of cellular peroxide in cultured neurons when it was treated as a post-treatment paradigm. These results may suggest that aristolactam BII exerts its significant neuroprotective effects on glutamate-injured primary cultures of rat cortical cells by directly inhibiting the production of nitric oxide.

Abbreviations

CNQX:6-cyano-7-nitroquinoxaline-2,3-dione

DMEM:Dulbecco's modified Eagle's medium

FBS:fetal bovine serum

GSH-px:glutathione peroxidase

GSSG-R:glutathione reductase

HBSS:Hank's balanced salt solution

KA:kainic acid

MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium

NMDA:N-methyl-D-aspartate

NO:nitric oxide

NOS:nitric oxide synthase

SOD:superoxide dismutase

Aristolactam alkaloid - Saururus chinensis - Saururaceae - neuroprotection - glutamate-induced toxicity - nitric oxide production

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