Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/benzodiazepine receptor complex in mice
Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/benzodiazepine receptor complex in mice
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厚朴酚是厚朴树皮的主要生物活性成分，通过 GABA/苯二氮卓受体复合物在小鼠体内发挥抗癫痫作用
DOI：
10.1111/j.1476-5381.2011.01456.x
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发表时间：
2011-11-01
影响因子：
7.3
通讯作者：
Huang, Z. L.
中科院分区：
文献类型：
--
作者：
Chen, C. R.;Tan, R.;Huang, Z. L.
背景和结论本研究的目的是评价厚朴酚（6，6 ′，7，12-tetramethoxy-2，2 ′-dimethyl-1-beta-berbaman，C18 H18 O2）的抗惊厥作用及其机制。实验方法小鼠在注射戊四唑（PTZ，60 mg.kg（-1），i. p.）前30分钟用厚朴酚（20，40和80mg.kg（-1））处理。使用行为学、EEG和体外电生理学以及海马和皮层中c-Fos表达的癫痫发作模型分析了厚朴酚的抗癫痫发作作用。与溶剂处理的动物相比，40和80剂量的厚朴酚显著延迟了肌阵挛性抽搐和全身阵挛性癫痫发作的发作，并降低了癫痫发作阶段和死亡率。mg.kg EEG记录显示，厚朴酚（40和80 mg.kg（-1））延长了癫痫发作的潜伏期，减少了癫痫发作的棘波数。厚朴酚的抗癫痫作用可被GABA（A）/苯二氮卓类受体拮抗剂氟马西尼逆转。氟马西尼预处理可减弱厚朴酚延长癫痫发作潜伏期和缩短癫痫发作期的作用。在无镁癫痫样活动模型中，使用多电极阵列记录小鼠海马脑片，厚朴酚减少自发性癫痫样放电。厚朴酚还显着降低了梨状皮质，齿状回和海马CA 1区的Fos免疫反应性。结论和意义这些发现表明厚朴酚对癫痫样活动的抑制作用是由GABA（A）/苯二氮卓受体复合物介导的。
BACKGROUND AND PURPOSEThe aim of this study was to evaluate the anti-convulsant effects of magnolol (6, 6', 7, 12-tetramethoxy-2, 2'-dimethyl-1-beta-berbaman, C18H18O2) and the mechanisms involved.EXPERIMENTAL APPROACHMice were treated with magnolol (20, 40 and 80 mg.kg(-1)) 30 min before injection with pentylenetetrazol (PTZ, 60 mg.kg(-1), i.p.). The anti-seizure effects of magnolol were analysed using seizure models of behaviour, EEG and in vitro electrophysiology and c-Fos expression in the hippocampus and cortex.KEY RESULTSMagnolol at doses of 40 and 80 mg.kg(-1) significantly delayed the onset of myoclonic jerks and generalized clonic seizures, and decreased the seizure stage and mortality compared with those of the vehicle-treated animals. EEG recordings showed that magnolol (40 and 80 mg.kg(-1)) prolonged the latency of seizure onset and decreased the number of seizure spikes. The anti-epileptic effect of magnolol was reversed by the GABA(A)/benzodiazepine receptor antagonist flumazenil. Pretreatment with flumazenil decreased the effects of magnolol on prolongation of seizure latency and decline of seizure stage. In a Mg2+-free model of epileptiform activity, using multi-electrode array recordings in mouse hippocampal slices, magnolol decreased spontaneous epileptiform discharges. Magnolol also significantly decreased seizure-induced Fos immunoreactivity in the piriform cortex, dentate gyrus and hippocampal area CA1. These effects were attenuated by pretreatment with flumazenil.CONCLUSIONS AND IMPLICATIONSThese findings indicate that the inhibitory effects of magnolol on epileptiform activity were mediated by the GABA(A)/benzodiazepine receptor complex.