Activity-guided isolation of NF-kappa B inhibitors and PPAR gamma agonists from the root bark of Lycium chinense Miller

doi:10.1016/j.jep.2014.01.029

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	Activity-guided isolation of NF-kappa B inhibitors and PPAR gamma agonists from the root bark of Lycium chinense Miller
	Xie, Lian-Wu 1,2,5; Atanasov, Atanas G.2; Guo, De-An3 ; Malainer, Clemens 2; Zhang, Jing-Xian 3; Zehl, Martin 2; Guan, Shu-Hong3 ; Heiss, Elke H.2; Urban, Ernst 4; Dirsch, Verena M.2
刊名	JOURNAL OF ETHNOPHARMACOLOGY
	2014-03-28
卷号	152 期号:3 页码:470-477
关键词	Lycium chinense Miller Lycii Radicis Cortex NF-kappa B PPAR gamma Phenolic amides Fatty acids
ISSN号	0378-8741
DOI	10.1016/j.jep.2014.01.029
文献子类	Article
英文摘要	Ethnopharmacological relevance: The root bark of Lycium chinense Miller, Lycii Radicis Cortex, has been used in traditional Chinese medicine (TCM) to treat different inflammation-related symptoms, such as diabetes mellitus. The pro-inflammatory transcription factor nuclear factor kappa B (NF-kappa B) is a key regulator of inflammation, while the transcription factor peroxisome proliferator-activated receptor gamma (PPAR gamma) is. a key modulator of genes involved in diabetes development. To identify putative active compound(s) from Lycii Radicis Cortex inhibiting NF-kappa B or activating PPAR gamma. Material and methods: Using activity-guided fractionation, six extracts with different polarity, isolated fractions, and purified compounds from Lycii Radicis Cortex were tested for NF-kappa B inhibition and PPAR gamma activation in vitro. The structure of the purified compounds was elucidated by NMR and MS techniques. Results: The ethyl acetate extract and the methanol extract of Lycii Radicis Cortex suppressed tumor necrosis factor alpha (TNF-alpha)-induced activation of NF kappa B, while the dichloromethane extract activated PPAR gamma. Nine phenolic amide analogues, including trans-N-(p-coumaroyl)tyramine (1), trans-N-feruloyltyramine (2), transN-caffeoyltyramine (3), dihydro-N-caffeoyltyramine (4), three neolignanamides (5-7), and two lignanamide (8, 9), were isolated and their inhibitory potential on NF-kappa B was determined (1-4 were also contained in water decoction). Two of the nine isolated phenolic amides inhibited TNF-alpha-induced NF-kappa B activation. Trans-N-caffeoyltyramine was verified as the key component responsible for the NF-kappa B inhibition with an IC50 of 18.4 mu M in our cell-based test system. Activation of PPAR gamma was attributed to a palmitic-acid enriched fraction which displayed concentration-dependent effect ablated upon co-treatment with the PPAR gamma antagonist T0070907. Conclusions: Phenolic amides were confirmed as main components from Lycii Radicis Cortex responsible for NF-kappa B inhibition. Fatty acids were identified as the major plant constituent responsible for the PPAR gamma activation. Structure-activity relationship analysis suggests that the NF-kappa B inhibitory activity of trans-N-caffeoyltyramine may be attributed to its Michael acceptor-type structure (alpha,beta-unsaturated carbonyl group). The data of this study contribute to a better understanding of the molecular mechanism of action of Lycii Radicis Cortex extracts in the context of inflammation. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
资助项目	Sino-Austria Project (China-TCM-Cluster Project)[PP06] ; China Postdoctoral Science Foundation[2013M531787] ; Planned Science and Technology Project of Hunan Province, China[2013RS4035] ; Austrian Science Fund (FWF): (NFN Drugs from Nature Targeting Inflammation (DNTI))[S10704]
WOS关键词	ACTIVATED-RECEPTOR-GAMMA ; PHENOLIC AMIDES ; CORTEX-LYCII ; INFLAMMATION ; METABOLISM ; DISEASES ; OBESITY ; ALPHA ; CELLS ; ASSAY
WOS研究方向	Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000334818100010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277148]
专题	上海中药现代化研究中心成果转移转化处
通讯作者	Kopp, Brigitte
作者单位	1.Cent South Univ Forestry & Technol, Sch Sci, Changsha 410004, Hunan, Peoples R China; 2.Univ Vienna, Dept Pharmacognosy, A-1090 Vienna, Austria; 3.Chinese Acad Sci, Shanghai Res Ctr Modernizat Tradit Chinese Med, Shanghai Inst Mat Med, Natl Engn Lab TCM Standardizat Technol, Shanghai 201203, Peoples R China; 4.Univ Vienna, Dept Med Chem, A-1090 Vienna, Austria; 5.Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China
推荐引用方式 GB/T 7714	Xie, Lian-Wu,Atanasov, Atanas G.,Guo, De-An,et al. Activity-guided isolation of NF-kappa B inhibitors and PPAR gamma agonists from the root bark of Lycium chinense Miller[J]. JOURNAL OF ETHNOPHARMACOLOGY,2014,152(3):470-477.
APA	Xie, Lian-Wu.,Atanasov, Atanas G..,Guo, De-An.,Malainer, Clemens.,Zhang, Jing-Xian.,...&Kopp, Brigitte.(2014).Activity-guided isolation of NF-kappa B inhibitors and PPAR gamma agonists from the root bark of Lycium chinense Miller.JOURNAL OF ETHNOPHARMACOLOGY,152(3),470-477.
MLA	Xie, Lian-Wu,et al."Activity-guided isolation of NF-kappa B inhibitors and PPAR gamma agonists from the root bark of Lycium chinense Miller".JOURNAL OF ETHNOPHARMACOLOGY 152.3(2014):470-477.