气候变化领域集成服务门户(CCPortal): Flavonoid compounds isolated from Tibetan herbs, binding to GABA(A) receptor with anxiolytic property

CCPortal

DOI	10.1016/j.jep.2020.113630
	Flavonoid compounds isolated from Tibetan herbs, binding to GABA(A) receptor with anxiolytic property
	Liu, Zenggen; Silva, Joshua; Shao, Amy S.; Liang, Jing; Wallner, Martin; Shao, Xuesi M.; Li, Mingzhu; Olsen, Richard W.
通讯作者	Liu, ZG (通讯作者)，Chinese Acad Sci, Northwest Inst Plateau Biol, Key Lab Tibetan Med Res, 23 Xinning Rd, Xining 810001, Peoples R China. ; Olsen, RW (通讯作者)，UCLA, David Geffen Sch Med, Dept Mol & Med Pharmacol, 650 Young Dr South, Los Angeles, CA 90095 USA.
发表日期	2021
ISSN	0378-8741
EISSN	1872-7573
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 alpha 2/3-containing GABA(A) receptors (GABA(A)Rs) have been demonstrated through the genetic and pharmacological studies. Flavonoids, such as flavones and flavanols, are a class of ligands that act at GABA(A)Rs 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 GABA(A)R 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 GABA(A)Rs were detected by the radioreceptor binding assay with bovine cerebellum membranes, in which the different recombinant subunits-containing GABA(A)Rs 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 GABA(A)Rs, which were based on the result of structure-activity relationships analysis. Demethoxysudachitin (DMS, K-i = 0.59 mu M), a flavone that binds to recombinant alpha 1-3/5 subunit-containing GABA(A)Rs, 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 GABA(A)Rs. Conclusions: This present study indicated that the flavones, especially DMS, are novel GABA(A)R ligands and therapeutic potential candidates for anxiety.
关键词	BLOOD-BRAIN-BARRIER SCUTELLARIA-BAICALENSIS PLUS-MAZE BENZODIAZEPINES CONSTITUENTS ANTIDEPRESSANT MODULATION BEHAVIOR SUBTYPES ANXIETY
英文关键词	Flavonoids; Tibetan herbs; GABA(A) receptor; Structure-activity relationships; Anxiety
语种	英语
WOS研究方向	Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
WOS类目	Plant Sciences ; Chemistry, Medicinal ; Integrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS记录号	WOS:000606381100008
来源期刊	JOURNAL OF ETHNOPHARMACOLOGY
来源机构	中国科学院西北生态环境资源研究院
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/254263
作者单位	[Liu, Zenggen; Li, Mingzhu] Chinese Acad Sci, Northwest Inst Plateau Biol, Key Lab Tibetan Med Res, 23 Xinning Rd, Xining 810001, Peoples R China; [Liu, Zenggen; Li, Mingzhu] Qinghai Prov Key Lab Tibetan Med Res, Xining 810001, Peoples R China; [Silva, Joshua; Liang, Jing] USC, Sch Pharm, Titus Family Dept Clin Pharm, Los Angeles, CA 90089 USA; [Shao, Amy S.] Western Michigan Univ, Homer Stryker MD Sch Med, Kalamazoo, MI 49007 USA; [Wallner, Martin; Olsen, Richard W.] UCLA, David Geffen Sch Med, Dept Mol & Med Pharmacol, 650 Young Dr South, Los Angeles, CA 90095 USA; [Shao, Xuesi M.] UCLA, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA
推荐引用方式 GB/T 7714	Liu, Zenggen,Silva, Joshua,Shao, Amy S.,et al. Flavonoid compounds isolated from Tibetan herbs, binding to GABA(A) receptor with anxiolytic property[J]. 中国科学院西北生态环境资源研究院,2021,267.
APA	Liu, Zenggen.,Silva, Joshua.,Shao, Amy S..,Liang, Jing.,Wallner, Martin.,...&Olsen, Richard W..(2021).Flavonoid compounds isolated from Tibetan herbs, binding to GABA(A) receptor with anxiolytic property.JOURNAL OF ETHNOPHARMACOLOGY,267.
MLA	Liu, Zenggen,et al."Flavonoid compounds isolated from Tibetan herbs, binding to GABA(A) receptor with anxiolytic property".JOURNAL OF ETHNOPHARMACOLOGY 267(2021).