Lucidone inhibits iNOS and COX-2 expression in LPS-induced RAW 264.7 murine macrophage cells via NF-κB and MAPKs dual pathways

The anti-inflammatory mechanism of a natural product, lucidone, isolated from the fruits of Lindera erythrocarpa Makino was investigated. Our data indicates that lucidone significantly inhibits NO and PGE₂ autacoids production in LPS-induced RAW 264.7 murine macrophage cells. Moreover, it also notably decreased the secretion of tumor necrosis factor-alpha (TNF-α). Consistent with these observations, the mRNA and protein expression levels of iNOS and COX-2 were also inhibited by lucidone in a dose-dependent manner. Lucidone also inhibited the down-regulation of NF-κB induced by LPS, which was associated with the prevention of the degradation of I-κB, and subsequently decreased p65/p50 proteins level in the nucleus. Meanwhile, lucidone could inhibit NF-κB activation by impairing the binding of NF-κB to its cis-acting element. Our data further demonstrated that lucidone could inhibite c-Jun N-terminal kinase (JNK) and p38MAPKs signals, which are the most significantly involved signal in NO, PGE₂, TNF-α production and NF-κB/AP-1 activation. In summary, the anti-inflammatory activity of lucidone might cause by the inhibition of iNOS and COX-2 expressions through the down-regulation of NF-κB and AP-1 binding activity.

Lucidone