3­‘,4‘­,7-Trihydroxyflavone Inhibits NO Production in LPS-activated MG6 Microglial Cells by Suppressing the JNK–STAT1 Pathway

We investigated the effects of the natural flavonoid 3',4',7-trihydroxyflavone on lipopolysaccharide (LPS)-induced neuroinflammatory responses in MG6 microglial cells. 3',4',7-Trihydroxyflavone inhibited LPS-induced nitric oxide (NO) production and the upregulation of inducible NO synthase (iNOS) in MG6 cells. 3',4',7-Trihydroxyflavone also suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1), which is crucial for iNOS expression. LPS stimulation induced rapid phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase (ERK) in MG6 cells. 3',4',7-Trihydroxyflavone significantly inhibited the LPS-induced phosphorylation of JNK, but not that of ERK and p38 MAPK. The inhibitory effect of 3',4',7-trihydroxyflavone on NO production was mimicked by pharmacological inhibition of the JNK signaling pathway with SP600125. Furthermore, SP600125 significantly inhibited LPS-induced phosphorylation of STAT1 in MG6 cells. These results suggest that 3',4',7-trihydroxyflavone exerts anti-neuroinflammatory effects via inhibition of the JNK-STAT1 pathway in microglia.