The anti-inflammatory effect of a pomegranate husk extract on inflamed adipocytes and macrophages cultivated independently, but not on the inflammatory vicious cycle between adipocytes and macrophages

Obese adipose tissues contain a higher proportion of inflamed macrophages than the normal adipose tissue. Adipocytes and macrophages are known to secrete pro-inflammatory markers that establish the systemic inflammation leading to metabolic complications. CCL-2 secreted by hypertrophied adipocytes attracts and activates macrophages in the adipose tissue. These cells, in turn, secrete TNFα and other pro-inflammatory molecules. The pomegranate husk extract and its phenolic constituents, punicalagin and ellagic acid, have exhibited an anti-inflammatory effect. In this study, we used an in vitro coculture system of 3T3-L1 murine adipocytes and RAW 264.7 macrophages to investigate the potential anti-inflammatory effects of these compounds on the vicious cycle between both cell types. The pomegranate husk extract presented an anti-inflammatory effect on the inflamed cells cultivated independently, as suggested by a decrease of (i) CCL-2 secretion by both cell types, (ii) adipocyte IL-6 expression and secretion, and (iii) macrophage TNFα secretion. Nevertheless and surprisingly, no anti-inflammatory effect was observed in coculture. Punicalagin, at the same concentration as that found in the pomegranate extract, had a more potent effect than the extract and in coculture; it reduced significantly the IL-6 secretion. Ellagic acid decreased TNFα and CCL-2 macrophage secretion, CCL-2 adipocyte secretion and, in coculture, it reduced IL-6 secretion and expression by adipocytes. These results indicate that the pomegranate husk extract has an anti-inflammatory action on adipocytes and macrophages but seems to be not able to reduce the inflammatory vicious cycle between both cells. Ellagitannin and punicalagin showed a better effect on inflammation suggesting that PHE will be a good candidate for more investigations.