Alpinetin inhibits LPS-induced inflammatory mediator response by activating PPAR-γ in THP-1-derived macrophages

Alpinetin, a novel plant flavonoid derived from Alpinia katsumadai Huyata, has been reported to have anti-inflammatory properties. However, the anti-inflammatory mechanism of alpinetin has not been Fully elucidated. The purpose of this study was to investigate the anti-inflammatory mechanism of alpinetin in modifying lipopolysaccharide (LPS)-induced signaling pathways in human THP-1 macrophages. The cells were stimulated with [PS in the presence or absence of alpinetin. The pro-inflammatory cytokines were evaluated by ELISA and qRT-PCR. Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-kappa B), inhibitory kappa B (I kappa B alpha) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and PPAR-gamma were determined by Western blotting. The results showed that alpinetin inhibited TNF-alpha, IL-6 and IL-1 beta expression in LPS-stimulated human THP-1 macrophages in a dose-dependent manner. Western blot analysis showed that alpinetin suppressed LPS-induced NF-kappa B activation, I kappa B alpha degradation, phosphorylation of ERK, JNK and P38. Furthermore, alpinetin could significantly down-regulated the expression of TLR4 stimulating by [PS. We also found that alpinetin could activate PPAR-gamma and the anti-inflammatory effects of alpinetin can be reversed by GW9662, a specific antagonist for PPAR-gamma. These results suggest that alpinetin activates PPAR-gamma, thereby attenuating TLR4 expression and TLR4 mediated NF-kappa B and MAPK activation and the release of proinflammatory cytokines. These findings suggest that alpinetin may be a therapeutic agent against inflammatory diseases. (C) 2013 Published by Elsevier B.V,