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

• Published in: Food chemistry Vol. 135; no. 3; pp. 967 - 975
• Main Authors: Yoo, Min-Sang, Shin, Ji-Sun, Choi, Hye-Eun, Cho, Young-Wuk, Bang, Myun-Ho, Baek, Nam-In, Lee, Kyung-Tae
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2012
• Subjects: Animals; anti-inflammatory activity; Cell Line; cytokines; Cytokines - genetics; Cytokines - immunology; DNA; Down-Regulation - drug effects; Fucosterol; Gene Expression Regulation - drug effects; Inflammation; Inflammation Mediators - immunology; interleukin-6; lipopolysaccharides; Lipopolysaccharides - immunology; macrophages; Macrophages - drug effects; Macrophages - immunology; Mice; mitogen-activated protein kinase; mitogen-activated protein kinase kinase kinase; MK2; MKK3/6; necrosis; neoplasms; NF-kappa B - genetics; NF-kappa B - immunology; NF-κB; nitric oxide; Nitric Oxide - immunology; nitric oxide synthase; p38 MAPK; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - immunology; protein phosphorylation; Stigmasterol - analogs & derivatives; Stigmasterol - isolation & purification; Stigmasterol - pharmacology; Undaria - chemistry; Undaria pinnatifida; NF-κB; Inflammation; Fucosterol; MKK3/6; MK2; p38 MAPK
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2012.05.039

► No report has previously been published on the anti-inflammatory activity in macrophages. ► Fucosterol inhibited NO production, iNOS expression, and iNOS promoter activity. ► Fucosterol suppressed LPS-induced NF-κB activation. ► Fucosterol coordinately suppressed the activities of IKK-β and MKK3/6/p38 MAPK/MK2 pathway. ► Fucosterol appears to have the potential to prevent inflammatory diseases. 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.