The natural products magnolol and honokiol are positive allosteric modulators of both synaptic and extra-synaptic GABA(A) receptors.
The natural products magnolol and honokiol are positive allosteric modulators of both synaptic and extra-synaptic GABA(A) receptors.
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DOI：
10.1016/j.neuropharm.2012.03.002
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发表时间：
2012-06
影响因子：
4.7
通讯作者：
Fisher JL
中科院分区：
文献类型：
--
作者：
Alexeev M;Grosenbaugh DK;Mott DD;Fisher JL
国家补充和替代医学中心（NCCAM）估计，美国近40%的成年人使用替代药物，通常以草药补充剂的形式。几个世纪以来，中国和日本的传统医学一直使用银杏树树皮提取物来治疗各种神经系统疾病，包括焦虑症、抑郁症和癫痫发作。提取物中的活性成分已被鉴定为双酚异构体厚朴酚和和厚朴酚。这些化合物显示出增强GABAA受体的活性，与其生物学效应一致。GABAA受体表现出实质性的亚基异质性，这影响了它们的功能和药理学性质。我们检查了木兰酚和和厚朴酚对神经元和重组GABAA受体不同群体的活性，以表征其作用机制，并确定对调节的敏感性是否取决于受体的亚基组成。我们发现厚朴酚和和厚朴酚增强海马齿状颗粒神经元的时相性和强直性GABA能神经传递。此外，尽管化合物对含δ受体显示出特别高的功效，但检查的所有重组受体均对调节敏感，无论α、β或γ亚基亚型的身份如何。GABAA受体的突触和突触外群体的这种直接正调节表明，含有厚朴酚和/或和厚朴酚的补充剂将是有效的抗焦虑剂、镇静剂和抗惊厥剂。然而，也预期会有显著的副作用和药物相互作用的风险。
The National Center for Complementary and Alternative Medicine (NCCAM) estimates that nearly 40% of adults in the United States use alternative medicines, often in the form of an herbal supplement. Extracts from the tree bark of magnolia species have been used for centuries in traditional Chinese and Japanese medicines to treat a variety of neurological diseases, including anxiety, depression, and seizures. The active ingredients in the extracts have been identified as the bi-phenolic isomers magnolol and honokiol. These compounds were shown to enhance the activity of GABAA receptors, consistent with their biological effects. The GABAA receptors exhibit substantial subunit heterogeneity, which influences both their functional and pharmacological properties. We examined the activity of magnolol and honokiol at different populations of both neuronal and recombinant GABAA receptors to characterize their mechanism of action and to determine whether sensitivity to modulation was dependent upon the receptor’s subunit composition. We found that magnolol and honokiol enhanced both phasic and tonic GABAergic neurotransmission in hippocampal dentate granule neurons. In addition, all recombinant receptors examined were sensitive to modulation, regardless of the identity of the α, β, or γ subunit subtype, although the compounds showed particularly high efficacy at δ-containing receptors. This direct positive modulation of both synaptic and extra-synaptic populations of GABAA receptors suggests that supplements containing magnolol and/or honokiol would be effective anxiolytics, sedatives, and anti-convulsants. However, significant side-effects and risk of drug interactions would also be expected.
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依赖激动剂的单个通道电流和alpha4beta2delta和alpha1beta2gamma2s Gabaa受体中的单个通道电流和门控。
影响因子：
3.8
作者：
Keramidas, Angelo;Harrison, Neil L.
通讯作者：
Harrison, Neil L.
影响因子：
3.1
作者：
Ai, JL;Wang, XM;Nielsen, M
通讯作者：
Nielsen, M
DOI：
10.1016/s1054-3589(06)54012-8
发表时间：
2006-01-01
期刊：
GABA
影响因子：
--
作者：
Johnston, Graham A. R.;Hanrahan, Jane R.;Mewett, Kenneth N.
通讯作者：
Mewett, Kenneth N.
影响因子：
3.3
作者：
Kuribara, H;Kishi, E;Maruyama, Y
通讯作者：
Maruyama, Y
影响因子：
5.3
作者：
Garcia PS;Kolesky SE;Jenkins A
通讯作者：
Jenkins A