Identification of Paracentrone in Fucoxanthin-Fed Mice and Anti-Inflammatory Effect against Lipopolysaccharide-Stimulated Macrophages and Adipocytes.

SCOPE: Fucoxanthin is converted to fucoxanthinol and amarouciaxanthin A in the mouse body. However, further metabolism such as cleavage products (i.e., apocarotenoids) remains unclear. The fucoxanthin-derived apocarotenoid in vivo is investigated and the anti-inflammatory effect of apocarotenoids with fucoxanthin partial structure such as allenic bond and epoxide residue against activated macrophages and adipocytes in vitro is evaluated. METHODS AND RESULTS: LC-MS analysis indicates the presence of paracentrone, a C31 -allenic-apocarotenoid, in white adipose tissue of diabetic/obese KK-Ay and normal C57BL/6J mice fed 0.2% fucoxanthin diet for 1 week. In lipopolysaccharide-activated RAW264.7 macrophages, paracentrone as well as C26 - and C28 -allenic-apocarotenoids suppresses the overexpression of inflammatory factors. Further, apo-10'-fucoxanthinal, a fucoxanthin-derived apocarotenoid which retained epoxide residue, exhibits a most potent anti-inflammatory activity through regulating mitogen-activated protein kinases and nuclear factor-κB inflammatory signal pathways. In contrast, ß-apo-8'-carotenal without allenic bond and epoxide residue lacks suppressed inflammation. In 3T3-L1 adipocytes, paracentrone, and apo-10'-fucoxanthinal downregulate the mRNA expression of proinflammatory mediators and chemokines induced by co-culture with RAW264.7 cells. CONCLUSION: Dietary fucoxanthin accumulates as paracentrone as well as fucoxanthinol and amarouciaxanthin A in the mouse body. Allenic bond and epoxide residue of fucoxanthin-derived apocarotenoids have pivotal roles for anti-inflammatory action against activated macrophages and adipocytes.

Docosapentaenoic Acid (22:5n-3) Downregulates mRNA Expression of Pro-inflammatory Factors in LPS-activated Murine Macrophage Like RAW264.7 Cells.

Docosapentaenoic acid (22:5n-3, n-3 DPA) is a n-3 polyunsaturated fatty acid (PUFA) found in fish oil, and has been reported to have health benefits. This study investigated conversion of n-3 DPA, and examined the anti-inflammatory effects of n-3 DPA on activated macrophages. Murine macrophage-like RAW264.7 cells were incubated in culture media containing n-3 DPA for 72 h. The level of n-3 DPA in the fatty acid composition of the total lipid fraction increased in a dose-dependent manner. Furthermore, the levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were higher in treated cells than in control cells. In RAW264.7 cells stimulated by lipopolysaccharide (LPS), n-3 DPA significantly down-regulated mRNA expression of pro-inflammatory factors such as IL-6, IL-1ß, iNOS and COX-2. Production of IL-6 was also reduced by n-3 DPA in a dose-dependent manner. We found that n-3 DPA treatment resulted in greater IL-6 mRNA down-regulation than that achieved with EPA treatment, and was similar to that of DHA treatment. Furthermore, expression levels of IL-6 and IL-1ß mRNAs were measured in the presence of the delta-6 desaturase inhibitor SC26196 in the culture medium to inhibit the conversion of n-3 DPA to DHA. There was no significant difference in the down-regulation in the mRNA expression of pro-inflammatory cytokines in RAW264.7 cells by n-3 DPA with or without presence of SC26196. These results demonstrate that n-3 DPA exhibits anti-inflammatory effects in activated RAW264.7 cells, which are independent of DHA conversion.