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In-vitro and in-vivo evidence for the anti-inflammatory activity of hop bitter acids in mouse
In recent years, evidence is rising for the anti-cancer [1,2,3] and anti-inflammatory [4,5] properties of hop (Humulus lupulus L.) bitter acids. In this report, we investigate three main groups of hop bitter acids, more specifically α-acids (AA), β-acids (BA) and iso-α-acids (IAA), on the molecular level regarding their potential influence on NF-κB-dependent gene signalling, a key pro-inflammatory transcription factor. Furthermore, we study the ability of AA and IAA to reduce acute local inflammation in mouse. Luciferase-coupled reporter gene assays in mouse fibroblasts (L929sA) show that AA, BA and IAA dose-dependently repress TNF-induced activation of several NF-κB-controlled promoters. At the used concentrations, no cytotoxic effects were detected (MTT assay and PI staining). Hop acids are 1000-fold less potent (BA > AA > IAA) than dexamethasone, a commonly used anti-inflammatory glucocorticoid. Interestingly, the six-membered ring compounds AA and BA showed equal potency, whereas the five-membered ring compounds, IAA, were effective only when used at higher concentrations. Furthermore, the mRNA and protein levels of IL6, a known NF-κB target, were lowered after treatment with hop acids, as determined by qPCR and ELISA, respectively. Administration of either 250µg AA or IAA i.p. to mice markedly reduced zymosan-induced footpad swelling. Our results demonstrate that total AA as well as BA and IAA effectively inhibit inflammation, albeit with different efficiencies, which may hold promise for the development of novel anti-inflammatory agents.
Acknowledgements: M. Van Cleemput is supported by a grant from Ghent University (BOF). K. De Bosscher is a postdoctoral fellow with the FWO Vlaanderen.
References: 1. Chen, L. (2006)J. Agric. Food. Chem. 52:55–64. 2. Shimamura et al. (2001) Biochem. Biophys. Res. Commun. 289:220–224. 3. Lee et al. (2007) Carcinogenesis 28:1491–1498. 4. Hougee et al. (2006) Planta Med 72:228–233. 5. Yamamoto et al. (2002) Adv. Exp. Med. Biol. 507:73–77.