Differential inhibitory effects of honokiol and magnolol on excitatory amino acid-evoked cation signals and NMDA-induced seizures

The effects of honokiol and magnolol, two major bioactive constituents of the bark of Magnolia officinalis, on Ca2+ and Na+ influx induced by various stimulants were investigated in cultured rat cerebellar granule cells by single-cell fura-2 or SBFI microfluorimetry. Honokiol and magnolol blocked the glutamate- and KCl-evoked Ca2+ influx with similar potency and efficacy, but did not affect KCl-evoked Na+ influx. However, honokiol was more specific for blocking NMDA-induced Ca2+ influx, whereas magnolol influenced with both NMDA- and non-NMDA activated Ca2+ and Na+ influx. Moreover, the anti-convulsant effects of these two compounds on NMDA-induced seizures were also evaluated. After honokiol or magnolol (1 and 5 mg/kg, i.p.) pretreatment, the seizure thresholds of NMRI mice were determined by tail-vein infusion of NMDA (10 mg/ml). Data showed that both honokiol and magnolol significantly increased the NMDA-induced seizure thresholds, and honokiol was more potent than magnolol. These results demonstrated that magnolol and honokiol have differential effects on NMDA and non-NMDA receptors, suggesting that the distinct therapeutic applications of these two compounds for neuroprotection should be considered.