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 Hayata, 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 LPS 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-κB (NF-κB), inhibitory kappa B (IκBα) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and PPAR-γ were determined by Western blotting. The results showed that alpinetin inhibited TNF-α, IL-6 and IL-1β expression in LPS-stimulated human THP-1 macrophages in a dose-dependent manner. Western blot analysis showed that alpinetin suppressed LPS-induced NF-κB activation, IκBα degradation, phosphorylation of ERK, JNK and P38. Furthermore, alpinetin could significantly down-regulated the expression of TLR4 stimulating by LPS. We also found that alpinetin could activate PPAR-γ and the anti-inflammatory effects of alpinetin can be reversed by GW9662, a specific antagonist for PPAR-γ. These results suggest that alpinetin activates PPAR-γ, thereby attenuating TLR4 expression and TLR4 mediated NF-κB and MAPK activation and the release of pro-inflammatory cytokines. These findings suggest that alpinetin may be a therapeutic agent against inflammatory diseases.