Polysaccharides from lycium barbarum antagonize glutamate excitotoxicity in cultured cortical neurons

Abstract

Glutamate excitotoxicity is involved in the pathogenesis of a number of neurodegenerative diseases including Alzheimer’s disease (AD). Lycium barbarum is an oriental herb that has been used for anti-aging. Recent studies have shown that polysaccharides from L. barbarum can ameliorate aging-related pathological conditions as well as protect cortical neurons against beta-amyloid neurotoxicity. We hypothesize that polysaccharides from L. barbarum (LBA) can function as disease-modifying agent to protect neurons from glutamate excitotoxicity. Primary cultures of cortical neurons form embryonic Sprague-Dawley rats were treated with LBA 1 h prior to application of glutamate. Neuronal cell death and apoptosis were determined by the release of LDH and the activity of caspase-3. Treatment of LBA reduced glutamate-induced LDH release and activity of caspase-3 in a dose-dependent manner. The neuroprotective effect LBA was comparable to memantine, a N-methyl D-aspartate (NMDA) receptor antagonist. In addition, LBA also protect neurons against NMDA-induced neuronal apoptosis. Our findings suggest that the protective effect of LBA was unlikely mediated by any anti-oxidant properties. LBA could not attenuate the toxicity of hydrogen peroxide. By using NBT assay, we found that LBA did not attenuate oxidation induced by glutamate. Western blot analysis indicated that treatment with LBA significantly attenuated glutamate-induced phosphorylation of c-jun N-terminal kinase (JNK). Our results suggest that LBA exerts neuroprotective effects on cultured cortical neurons exposed to glutamate.