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

Authors Xie, Lian-Wu; Atanasov, Atanas G.; Guo, De-An; Malainer, Clemens; Zhang, Jing-Xian; Zehl, Martin; Guan, Shu-Hong; Heiss, Elke H.; Urban, Ernst; Dirsch, Verena M.; Kopp, Brigitte

Journal JOURNAL OF ETHNOPHARMACOLOGY , MAY 26 2015,:166

DOI 10.1016/j.jep.2015.02.046 PubMed 25732836

Abstract 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.

Species covered 枸杞 Lycium chinense