Xanthohumol Stimulates the Secretion of Catecholamines and Induces M2 Polarization in Raw 264.7 Macrophages

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Xanthohumol stimulates the secretion of catecholamines and induces M2 polarization in raw 264.7 macrophages

Samuels J., Alvarez S., Dinh H., Shashidharamurthy R., Rayalam S. Endocrine Reviews 2017 38:3 Supplement 1

AbstractAnti-inflammatory, anti-oxidant and anti-cancer effects of xanthohumol (XN), a prenylated chalcone extracted from common hop plants, are gaining attention and research has been expanding on thebeneficial effects of this compound. In this study, we have investigated the anti-inflammatory effects of XN using mouse monocytic cell line ( RAW 264.7). We hypothesized that the anti-inflammatory effects ofXN are due to M2 polarization of macrophages, which in turn is mediated partly through the activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. RAW264.7 cells were treated with either 0.1% DMSO or XN at varying concentrations for 24hr. Culture supernatant was collected for ELISA and whole cell lysates were collected for Western blotting experiments. Our results suggest that XN upregulated the secretion of interleukin 10 (IL10), a signature cytokine for M2 polarization, in RAW264.7 cells in a dose dependent manner after 24 hr. We further demonstrated that XN increased arginase expression, a marker for M2 polarization and failed to increase inducible nitric oxide synthase (iNOS) expression, a marker for M1 polarization. XN decreased lipopolysaccharide (LPS)-induced elevation of nitrite release, indicating the inhibitory effects of XN against M1 polarization. Additionally, XN at 25uM increased the secretion of catecholamines from macrophages comparable to interleukin 4 (IL4), an inducer of M2 phenotype. Finally, XN upregulated the expression of phospho-AMPK in RAW264.7 cells indicating the role of AMPK signaling pathway in XN-induced effects. These results provide evidence for the anti-inflammatory effects of XN-mediated induction of M2 polarization. The M2 macrophage mediated anti-inflammatory effects coupled with catecholamine secretion and previously reported anti-adipogenic effects makes XN an attractive molecule to study its beneficial effects on metabolic diseases like obesity and diabetes that are associated with underlying chronic low-grade inflammation.

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Endocrine Reviews






This abstract was published in Endocrine Reviews, Volume 38, Issue 3, Supplement 1.

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