Lian-Wu Xie1, Atanas G Atanasov2, De-An Guo3, Clemens Malainer2, Jing-Xian Zhang3, Martin Zehl2, Shu-Hong Guan3, Elke H Heiss2, Ernst Urban4, Verena M Dirsch2, Brigitte Kopp5. 1. School of Sciences, Central South University of Forestry and Technology, 498 South Shaoshan Road, 410004 Changsha, Hunan, PR China; Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria; Hunan University of Chinese Medicine, Hanpu S&E District, 410208 Changsha, Hunan, PR China. 2. Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria. 3. Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, 201203 Shanghai, PR China. 4. Department of Medicinal Chemistry, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria. 5. Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria. Electronic address: brigitte.kopp@univie.ac.at.
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-κB) is a key regulator of inflammation, while the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) is a key modulator of genes involved in diabetes development. To identify putative active compound(s) from Lycii radicis cortex inhibiting NF-κB or activating PPARγ. 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-κB inhibition and PPARγ 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-α)-induced activation of NF-κB, while the dichloromethane extract activated PPARγ. Nine phenolic amide analogues, including trans-N-(p-coumaroyl)tyramine (1), trans-N-feruloyltyramine (2), trans-N-caffeoyltyramine (3), dihydro-N-caffeoyltyramine (4), three neolignanamides (5-7), and two lignanamide (8, 9), were isolated and their inhibitory potential on NF-κB was determined (1-4 were also contained in water decoction). Two of the nine isolated phenolic amides inhibited TNF-α-induced NF-κB activation. Trans-N-caffeoyltyramine was verified as the key component responsible for the NF-κB inhibition with an IC50 of 18.4μM in our cell-based test system. Activation of PPARγ was attributed to a palmitic-acid enriched fraction which displayed concentration-dependent effect ablated upon co-treatment with the PPARγ antagonist T0070907. CONCLUSIONS: Phenolic amides were confirmed as main components from Lycii radicis cortex responsible for NF-κB inhibition. Fatty acids were identified as the major plant constituent responsible for the PPARγ activation. Structure-activity relationship analysis suggests that the NF-κB inhibitory activity of trans-N-caffeoyltyramine may be attributed to its Michael acceptor-type structure (α,β-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.
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-κB) is a key regulator of inflammation, while the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) is a key modulator of genes involved in diabetes development. To identify putative active compound(s) from Lycii radicis cortex inhibiting NF-κB or activating PPARγ. 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-κB inhibition and PPARγ 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 tumornecrosis factor alpha (TNF-α)-induced activation of NF-κB, while the dichloromethane extract activated PPARγ. Nine phenolic amide analogues, including trans-N-(p-coumaroyl)tyramine (1), trans-N-feruloyltyramine (2), trans-N-caffeoyltyramine (3), dihydro-N-caffeoyltyramine (4), three neolignanamides (5-7), and two lignanamide (8, 9), were isolated and their inhibitory potential on NF-κB was determined (1-4 were also contained in water decoction). Two of the nine isolated phenolic amides inhibited TNF-α-induced NF-κB activation. Trans-N-caffeoyltyramine was verified as the key component responsible for the NF-κB inhibition with an IC50 of 18.4μM in our cell-based test system. Activation of PPARγ was attributed to a palmitic-acid enriched fraction which displayed concentration-dependent effect ablated upon co-treatment with the PPARγ antagonist T0070907. CONCLUSIONS: Phenolic amides were confirmed as main components from Lycii radicis cortex responsible for NF-κB inhibition. Fatty acids were identified as the major plant constituent responsible for the PPARγ activation. Structure-activity relationship analysis suggests that the NF-κB inhibitory activity of trans-N-caffeoyltyramine may be attributed to its Michael acceptor-type structure (α,β-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.
Authors: Atanas G Atanasov; Birgit Waltenberger; Eva-Maria Pferschy-Wenzig; Thomas Linder; Christoph Wawrosch; Pavel Uhrin; Veronika Temml; Limei Wang; Stefan Schwaiger; Elke H Heiss; Judith M Rollinger; Daniela Schuster; Johannes M Breuss; Valery Bochkov; Marko D Mihovilovic; Brigitte Kopp; Rudolf Bauer; Verena M Dirsch; Hermann Stuppner Journal: Biotechnol Adv Date: 2015-08-15 Impact factor: 14.227
Authors: Limei Wang; Birgit Waltenberger; Eva-Maria Pferschy-Wenzig; Martina Blunder; Xin Liu; Clemens Malainer; Tina Blazevic; Stefan Schwaiger; Judith M Rollinger; Elke H Heiss; Daniela Schuster; Brigitte Kopp; Rudolf Bauer; Hermann Stuppner; Verena M Dirsch; Atanas G Atanasov Journal: Biochem Pharmacol Date: 2014-07-30 Impact factor: 5.858
Authors: Xin Liu; Simone Latkolik; Atanas G Atanasov; Olaf Kunert; Eva-Maria Pferschy-Wenzig; Elke H Heiss; Clemens Malainer; Andreas Schinkovitz; Manfred Kollroser; Verena M Dirsch; Rudolf Bauer Journal: Planta Med Date: 2017-09-08 Impact factor: 3.352