Prenylated chalcone from Sophora flavescens suppresses Th2 chemokine expression induced by cytokines via heme oxygenase-1 in human keratinocytes

Abstract

We recently reported the inhibitory effect of an oral administration of a Sophora flavescens Aiton methanol extract on the development of atopic dermatitis in the NC/Nga model mice. Heme oxygenase (HO)-1 has recently emerged as an important cytoprotective enzyme against oxidative stress and inflammatory responses in many cell types. The aim of this study was to investigate the possible mechanism by which prenylated chalcone (PC, 7,9,2',4'-tetrahydroxy-8-isopentenyl-5-methoxychalcone), a natural product isolated from S. flavescens, inhibited cytokine-induced Th2 chemokine expression in human keratinocytes, HaCaT cells. The level of chemokine expression was measured by reverse transcription-polymerase chain reaction and HO-1 study was performed by Western blot analysis. Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha)-induced thymus- and activation-regulated chemokine (TARC/CCL17), macrophage-derived chemokine (MDC/CCL22), cutaneous T-cell attracting chemokine (CTACK/CCL27) expression in a dose-dependent manner. Interestingly, PC significantly suppressed IFN-gamma and TNF-alpha-induced TARC/CCL17, MDC/CCL22 and CTACK/CCL27 expression via the induction of heme oxygenase (HO)-1. This suppression was completely restored by HO-1 siRNA, suggesting a direct role of HO-1 for the suppressive effect. Furthermore, exogenous CO, but not other end products of HO-1 activity, also suppressed IFN-gamma and TNF-alpha-induced TARC/CCL17, MDC/CCL22 and CTACK/CCL27 expression. These results demonstrate that prenylated chalcone induces HO-1 expression, which in turn HO-1 and/or CO suppresses Th2 chemokine expressions induced by cytokines in human HaCaT cells.

Dietary chalcones with chemopreventive and chemotherapeutic potential

“…A similar mechanism was observed for cardamonin (22), a natural product from Artemisia absinthium. NF-jB activation and related iNOS production in LPS-stimulated cells were inhibited by a direct effect on the capacity of the transcription factor to bind DNA [50].…”

“…Heme oxygenase-1 activity results in cytoprotection against oxidative injury and cellular stresses [5]. As reported, the prenylated chalcone 7,9,2 0 ,4 0 -tetrahydroxy-8-isopentenyl-5-methoxychalcone (19) from Sophora flavescens successfully inhibited expression of interferon (INF)-c and tumor necrosis factor alpha (TNF-a)-induced chemokines (TARC/CCL17, MDC/CCL22, CTACK/CCL27) via induction of HO-1 [22].…”

Bioinformatics: Inflammatory Cytokines and Attenuation of Diabetes Hypercholesterolemia-Induced Renal Injury Using Morning Glory and Necklace Pod Extracts

“…It has an antiinflammatory property, reduced proinflammatory cytokines production via obstruction of the NF-κB and MAPK transmission. Production levels of interferon-gamma and TNF-α were decreased by the extract of root of S. flavescens (Sophora radix, SR) in vivo [34]. Finally, the release of histamine and β-hexosaminidase and migration were inhibited by the treatment with this extract.…”

Effect of Sophora flavescens Aiton extract on degranulation of mast cells and contact dermatitis induced by dinitrofluorobenzene in mice

“…IFN-g, the hallmark of the Th 1 skewing reaction of T cells, is responsible for the increased production in the skin of various cytokines and chemokines such as interleukin-1, TNF-a, granulocyte-macrophage colony-stimulating factor and macrophage inflammatory protein-2, resulting in massive infiltration of leukocytes (Kobayashi, 2008). Prenylated chalcone isolated from SR suppresses the expression of chemokines induced by IFN-g and TNF-a in human keratinocytes (Choi et al, 2010). Skin contact with the hapten induces the release of TNF-a, which is another Th1 cytokine, and IL-lb during the sensitization phase (Saint-Mezard et al, 2004).…”