Luteolin inhibits inflammatory responses by downregulating the JNK, NF-κB, and AP-1 pathways in TNF-α activated HepG2 cells

The inhibitory mechanism of luteolin on tumor necrosis factor (TNF)-α-induced inflammation was investigated in HepG2 cells. Luteolin significantly suppressed TNF-α-stimulated inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner without cytotoxicity. Phosphorylation and nuclear translocation of both transcription factors, nuclear factor (NF)-κB and activator protein (AP)-1, were also inhibited by luteolin treatment. Additionally, luteolin suppressed TNF-α-induced c-Jun N-terminal kinase (JNK) phosphorylation, which is crucially related to regulating inflammation. SP600125, a JNK selective inhibitor, abolished the TNF-α triggered inflammatory signaling cascade. These results suggest that luteolin attenuates inflammatory responses by blocking NF-κB and AP-1 activation through suppressed JNK phosphorylation in TNF-α-stimulated HepG2 cells.