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DOI	10.1016/j.jep.2020.113630
	Flavonoid compounds isolated from Tibetan herbs; binding to GABAA receptor with anxiolytic property
	Liu Z.; Silva J.; Shao A.S.; Liang J.; Wallner M.; Shao X.M.; Li M.; Olsen R.W.
发表日期	2021
ISSN	3788741
卷号	267
英文摘要	Ethnopharmacological relevance: Previously, the phytochemical constituents of Biebersteinia heterostemon Maxim (BHM) and Arenaria kansuensis Maxim (AKM) were studied and the evaluation of anxiolytic effect based on their extracts was also investigated. The two traditional Tibetan herbs, BHM and AKM, have been widely used in Qinghai-Tibet Plateau for cardiopulmonary disorders and neuropsychiatric diseases. The anxiolytic activities of a number of agents mediated by α2/3-containing GABAA receptors (GABAARs) have been demonstrated through the genetic and pharmacological studies. Flavonoids, such as flavones and flavanols, are a class of ligands that act at GABAARs and exhibit anxiolytic effects in vivo. Here, the flavonoids are the predominant constituents isolated from BHM and AKM. And our purpose is to investigate structure-activity relationships of the flavonoid compounds with binding to BZ-S of GABAAR complexes, and to search for anxiolytic constituents that lack undesirable-effects such as sedation and myorelaxation. Materials and methods: The flavonoid constituents were separated and purified through the repeatedly silica gel or/and C18 column chromatography. The affinities of the compounds for BZ-S of GABAARs were detected by the radioreceptor binding assay with bovine cerebellum membranes, in which the different recombinant subunits-containing GABAARs were expressed in HEK 293T cells. The behavior tests, including elevated plus maze, locomotor activity, holeboard, rotarod and horizontal wire, were used to determine and evaluate the anxiolytic, sedative, and myorelaxant effects of these flavonoids. Results: Eleven total flavonoid compounds were obtained from the Tibetan herbs (BHM and AKM). The flavones with 6-and/or 8-OMe possessed the most potent binding affinity to GABAARs, which were based on the result of structure-activity relationships analysis. Demethoxysudachitin (DMS, Ki = 0.59 μM), a flavone that binds to recombinant α1-3/5 subunit-containing GABAARs, was isolated from BHM, and exhibited high anxiolytic activity, without inducing sedation and myorelaxation. Moreover, the anxiolytic effect of DMS was antagonized by flumazenil, suggesting that a mode of action was mediated via the BZ-S of GABAARs. Conclusions: This present study indicated that the flavones, especially DMS, are novel GABAAR ligands and therapeutic potential candidates for anxiety. © 2020 Elsevier B.V.
英文关键词	Anxiety; Flavonoids; GABAA receptor; Structure-activity relationships; Tibetan herbs
语种	英语
scopus关键词	Journal of Ethnopharmacology
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/158265
作者单位	Key Laboratory of Tibetan Medicine Research; Northwest Institute of Plateau Biology; CAS; Xining; 810001; China; Qinghai Provincial Key Laboratory of Tibetan Medicine Research; Xining; 810001; China; Titus Family Department of Clinical Pharmacy; School of Pharmacy; USC; Los Angeles; CA 90089; United States; Homer Stryker M.D. School of Medicine; Western Michigan University; Kalamazoo; MI 49007; United States; Department of Molecular & Medical Pharmacology; David Geffen School of Medicine at UCLA; Los Angeles; CA 90095; United States; Department of Neurobiology; David Geffen School of Medicine at UCLA; Los Angeles; CA 90095; United States
推荐引用方式 GB/T 7714	Liu Z.,Silva J.,Shao A.S.,et al. Flavonoid compounds isolated from Tibetan herbs; binding to GABAA receptor with anxiolytic property[J],2021,267.
APA	Liu Z..,Silva J..,Shao A.S..,Liang J..,Wallner M..,...&Olsen R.W..(2021).Flavonoid compounds isolated from Tibetan herbs; binding to GABAA receptor with anxiolytic property.,267.
MLA	Liu Z.,et al."Flavonoid compounds isolated from Tibetan herbs; binding to GABAA receptor with anxiolytic property".267(2021).