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 Ca(2+) 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 Ca(2+) influx with similar potency and efficacy, but did not affect KCl-evoked Na(+) influx. However, honokiol was more specific for blocking NMDA-induced Ca(2+) influx, whereas magnolol influenced with both NMDA- and non-NMDA activated Ca(2+) 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.
Lin
Yi-Ruu
YR
Institute of Medical Sciences, Tzu Chi University, 701 Section 3 Chung Yang Road, Hualien 970, Taiwan.
Chen
Hwei-Hsien
HH
Ko
Chien-Hsin
CH
Chan
Ming-Huan
MH
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000737:chemistry / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D017705:Lignans / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D011189:Potassium Chloride / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D012964:Sodium / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
D014151:Anti-Anxiety Agents; D001713:Biphenyl Compounds; D002118:Calcium; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels; D017705:Lignans; D016202:N-Methylaspartate; D010975:Platelet Aggregation Inhibitors; D011189:Potassium Chloride; D011810:Quinoxalines; D012964:Sodium; C005498:magnolol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C056723:FG 9041