Fucosterol isolated from Undaria pinnatifida inhibits lipopolysaccharide-induced production of nitric oxide and pro-inflammatory cytokines via the inactivation of nuclear factor-κB and p38 mitogen-activated protein kinase in RAW264.7 macrophages.

It has been reported that fucosterol has anti-diabetic, anti-oxidant, and anti-osteoporotic effects. We investigated the anti-inflammatory effects and the underlying molecular mechanism of fucosterol in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Fucosterol suppressed the expressions of inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) by downregulating their transcriptions, and subsequently inhibited the productions of nitric oxide, TNF-α, and IL-6. In addition, fucosterol attenuated LPS-induced DNA binding and the transcriptional activity of nuclear factor-κB (NF-κB). These reductions were accompanied by parallel reductions in the phosphorylation and nuclear translocation of NF-κB. Furthermore, fucosterol attenuated the phosphorylations of mitogen-activated protein kinase kinases 3/6 (MKK3/6) and mitogen-activated protein kinase-activated protein kinase 2 (MK2), which are both involved in the p38 MAPK pathway. These results suggest that the anti-inflammatory effects of fucosterol are associated with the suppression of the NF-κB and p38 MAPK pathways.