Flavonoids isolated from Tibetan medicines, binding to GABA(A) receptor and the anticonvulsant activity

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	Flavonoids isolated from Tibetan medicines, binding to GABA(A) receptor and the anticonvulsant activity
	Liu, Zenggen; Lindemeyer, A. Kerstin; Liang, Jing; Wanner, Martin; Shao, Xuesi M.; Shao, Yun; Tao, Yanduo; Olsen, Richard W.
	2018
发表期刊	PHYTOMEDICINE
卷号	50
摘要	Background: : Our previous studies on Asterothamnus centrali-asiaticus Novopokr. (ACN) and Arenaria kansuensis Maxim. (AKM) had led to the isolation of some phytochemical constituents and evaluation of anticonvulsant effect based on their extracts. ACN and AKM have been widely used in traditional Tibetan herbs for neuropsychiatric diseases and cardiopulmonary disorders. Purpose: : The purpose is to investigate structure-activity relationships of flavonoids isolated from ACN and AKM, for binding to the benzodiazepine site (BZ-S) of gamma-aminobutyric acid type A (GABA(A)) receptor complex, and to search for anticonvulsant compounds without undesirable effects such as myorelaxation and sedation. Study design and methods: : The affinities of these flavonoids for the BZ-S of GABA(A) receptors were determined by [H-3]flunitrazepam binding to mouse cerebellum membranes in vitro. And the anticonvulsant, myorelaxant and sedative effects were determined by pentylenetetrazol (PTZ)-induced seizure and electrogenic seizure protection, rotarod test and locomotor activity test, respectively. Results: : Fifteen and thirteen flavonoids were isolated from ACN and AKM, respectively. Structure-activity relationships analysis indicated that 6-and/or 8-OMe flavones exhibited the most potent binding affinity to GABA(A) receptors. Furthermore, 2',4',5,7-tetrahydroxy-5',6-dimethoxyflavone (DMF, IC50 value of 0.10 mu M), a flavone isolated from ACN, presented high anticonvulsant activity against chemical-induced seizures and electrogenic seizures, without myorelaxation and sedation. Conclusion: : This study suggested that these flavones, especially DMF, are new BZ receptor ligands and prospective therapeutic candidates for seizures.
关键词	Flavonoids Tibetan herbs GABA(A) receptor Structure-activity relationships Seizures
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/59938
专题	中国科学院西北高原生物研究所
推荐引用方式 GB/T 7714	Liu, Zenggen,Lindemeyer, A. Kerstin,Liang, Jing,et al. Flavonoids isolated from Tibetan medicines, binding to GABA(A) receptor and the anticonvulsant activity[J]. PHYTOMEDICINE,2018,50.
APA	Liu, Zenggen.,Lindemeyer, A. Kerstin.,Liang, Jing.,Wanner, Martin.,Shao, Xuesi M..,...&Olsen, Richard W..(2018).Flavonoids isolated from Tibetan medicines, binding to GABA(A) receptor and the anticonvulsant activity.PHYTOMEDICINE,50.
MLA	Liu, Zenggen,et al."Flavonoids isolated from Tibetan medicines, binding to GABA(A) receptor and the anticonvulsant activity".PHYTOMEDICINE 50(2018).