Meso-dihydroguaiaretic acid and licarin A of Machilus thunbergii protect against glutamate-induced toxicity in primary cultures of a rat cortical cells

1. We previously reported that four lignans isolated from the bark of Machilus thunbergii Sieb. et Zucc. (Lauraceae) protected primary cultures of rat cortical neurons from neurotoxicity induced by glutamate. 2. Among the lignans, meso-dihydroguaiarectic acid (MDGA) and licarin A significantly attenuated glutamate-induced neurotoxicity when added prior to or right after the excitotoxic glutamate challenge. 3. The neuroprotective activities of two lignans appeared to be more effective in protecting neurons against neurotoxicity induced by NMDA than that induced by kainic acid. 4. MDGA and licarin A diminished the calcium influx that routinely accompanies with the glutamate-induced neurotoxicity, and inhibited the subsequent overproduction of cellular nitric oxide and peroxide to the level of control cells. They also preserved cellular activities of antioxidative enzymes such as superoxide dismutase, glutathione peroxidase and glutathione reductase reduced in the glutamate-injured neuronal cells. 5. Thus, our results suggest that MDGA and licarin A significantly protect primary cultured neuronal cells against glutamate-induced oxidative stress, via antioxidative activities.