Baur Roland, Schuehly Wolfgang, Sigel Erwin
Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstr. 28, CH-3012 Bern, Switzerland.
Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University, Universitätsplatz 4, 8010 Graz, Austria.
Biochim Biophys Acta. 2014 Oct;1840(10):3017-21. doi: 10.1016/j.bbagen.2014.06.016. Epub 2014 Jun 25.
Magnolia bark preparations from Magnolia officinalis of Asian medicinal systems are known for their muscle relaxant effect and anticonvulsant activity. These CNS related effects are ascribed to the presence of the biphenyl-type neolignans honokiol and magnolol that exert a potentiating effect on GABAA receptors. 4-O-methylhonokiol isolated from seeds of the North-American M. grandiflora was compared to honokiol for its activity to potentiate GABAA receptors and its GABAA receptor subtype-specificity was established.
Different recombinant GABAA receptors were functionally expressed in Xenopus oocytes and electrophysiological techniques were used determine to their modulation by 4-O-methylhonokiol.
3μM 4-O-methylhonokiol is shown here to potentiate responses of the α₁β₂γ₂ GABAA receptor about 20-fold stronger than the same concentration of honokiol. In the present study potentiation by 4-O-methylhonokiol is also detailed for 12 GABAA receptor subtypes to assess GABAA receptor subunits that are responsible for the potentiating effect.
The much higher potentiation of GABAA receptors at identical concentrations of 4-O-methylhonokiol as compared to honokiol parallels previous observations made in other systems of potentiated pharmacological activity of 4-O-methylhonokiol over honokiol.
The results point to the use of 4-O-methylhonokiol as a lead for GABAA receptor potentiation and corroborate the use of M. grandiflora seeds against convulsions in Mexican folk medicine.
亚洲医药体系中厚朴的树皮制剂以其肌肉松弛作用和抗惊厥活性而闻名。这些与中枢神经系统相关的作用归因于联苯型新木脂素和厚朴酚的存在，它们对GABAA受体具有增强作用。将从北美大花木兰种子中分离出的4-O-甲基厚朴酚与厚朴酚在增强GABAA受体活性方面进行了比较，并确定了其GABAA受体亚型特异性。
不同的重组GABAA受体在非洲爪蟾卵母细胞中进行功能表达，并用电生理技术测定4-O-甲基厚朴酚对它们的调节作用。
在此显示，3μM的4-O-甲基厚朴酚增强α₁β₂γ₂ GABAA受体反应的能力比相同浓度的厚朴酚强约20倍。在本研究中，还详细研究了4-O-甲基厚朴酚对12种GABAA受体亚型的增强作用，以评估负责增强作用的GABAA受体亚基。
与厚朴酚相比，在相同浓度的4-O-甲基厚朴酚下，其对GABAA受体的增强作用要强得多，这与之前在其他系统中观察到的4-O-甲基厚朴酚相对于厚朴酚增强的药理活性相一致。
结果表明4-O-甲基厚朴酚可作为增强GABAA受体的先导化合物，并证实了大花木兰种子在墨西哥民间医学中用于抗惊厥的用途。
