Justus-Liebig-University, Giessen, Germany.
HG&H Pharmaceuticals (Pty) Ltd., Bryanston, South Africa.
J Ethnopharmacol. 2018 Sep 15;223:135-141. doi: 10.1016/j.jep.2018.05.010. Epub 2018 May 22.
Sceletium tortuosum (Mesembryanthemaceae), a succulent plant indigenous to South Africa. is consumed in the form of teas, decoctions and tinctures and is sometimes smoked and used as snuff. In recent years, Sceletium has received a great deal of commercial interest for relieving stress in healthy people, and for treating a broad range of psychological, psychiatric and inflammatory conditions.
The whole extract (Zembrin®) was tested ex vivo in the hippocampus slice preparation after one week of daily oral administration of 5 and 10 mg/kg. Four alkaloids - mesembrine, mesembranol, mesembrenol and mesembrenone - were tested directly in vitro. All four were also tested in the presence of different glutamate receptor agonists.
Zembrin® ex vivo as well as all alkaloids in vitro attenuated the amplitude of the population spike during electric stimulation as single shock as well as theta burst stimulation. Only Mesembranol and Mesembrenol having a hydroxyl group at position C6 instead of carbonyl group as in mesembrine and mesembrenone acted by attenuation of AMPA receptor mediated transmission as documented for the whole extract.
The current experimental series revealed a new physiological effect of Zembrin on the electric activity of the hippocampus. Attenuation of AMPA mediated transmission has been related to successful adjunctive treatment of epileptic patients. Administered doses of 5 and 10 mg/kg are in line with a dosage of 50 mg/subject as tested clinically.
We have discovered a new structure activity relationship for Sceletium alkaloids. Since attenuation of AMPA mediated transmission has been related to successful adjunctive treatment of epileptic patients), Mesembrenol and Mesembranol may serve as new chemical leads for the development of new drugs for the treatment of epilepsy.
南非特有的肉质植物醉茄（Mesembryanthemaceae），以茶、煎剂和酊剂的形式被消耗，有时也被吸烟和用作鼻烟。近年来，醉茄因其能缓解健康人群的压力，以及治疗广泛的心理、精神和炎症疾病而受到极大的商业关注。
在为期一周的每天口服 5 毫克/千克和 10 毫克/千克后，整个提取物（Zembrin®）在海马切片制备中进行了离体测试。四种生物碱 - 美沙比林、美沙醇、美沙醇和美沙酮 - 在体外直接进行了测试。所有四种生物碱都在不同的谷氨酸受体激动剂存在的情况下进行了测试。
Zembrin®在体和所有生物碱在离体均减弱了电刺激单刺激和θ爆发刺激时群体峰的幅度。只有 Mesembranol 和 Mesembrenol 在 C6 位有羟基而不是羰基，与美沙比林和美沙酮不同，它们通过衰减 AMPA 受体介导的传递起作用，正如整个提取物所证明的那样。
当前的实验系列揭示了 Zembrin 对海马电活动的新生理作用。AMPAR 介导的传递衰减与成功辅助治疗癫痫患者有关。给予 5 毫克/千克和 10 毫克/千克的剂量与临床测试的 50 毫克/受试者剂量一致。
我们发现了醉茄生物碱的新构效关系。由于 AMPA 介导的传递衰减与成功辅助治疗癫痫患者有关），Mesembrenol 和 Mesembranol 可能成为开发治疗癫痫新药物的新化学先导。
