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Published on: August 12, 2019
Sulfated and Glucuronated trans-Resveratrol Metabolites Regulate Chemokines and Sirtuin-1 Expression in U-937
Katharina Schueller1, Marc Pignitter1, Veronika Somoza1
1†Department of Nutritional and Physiological Chemistry, Faculty of Chemistry, and ‡Christian Doppler Laboratory for Bioactive Aroma Compounds, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
Abstract:
The natural anti-inflammatory compound resveratrol (RES) is metabolized upon ingestion. After dietary-scale doses, plasma concentrations of sulfated and glucuronated metabolites in humans exceed those of RES. The aim of this in vitro study was to assess the effect of physiological concentrations (1 μM) of the most abundant RES metabolites (RES-3-O-sulfate, R3S; RES-disulfates, RdS; RES-3-O-glucuronide, R3G; RES-4'-O-glucuronide, R4G) on genes and proteins involved in immune cell chemotaxis and inflammation (IL-8, MIP-1b, MCP-1, CCR1, CCR2, CXCR2, SIRT1) in a cell model of lipopolysaccharide (LPS)-activated U-937 macrophages. Levels of MCP-1 mRNA were comparably decreased after 3 h of treatment with R3S and RdS by -24.7 ± 5.51 and -28.7 ± 19.2%, respectively. LPS-induced MCP-1 protein release was reduced after 3 h of treatment by R3S (-20.8 ± 13.9%) and RdS (-25.7 ± 8.29%). After a 9 h treatment, RdS also inhibited IL-8 and MIP-1b protein release by -22.9 ± 3.57 and -20.1 ± 7.00%, respectively. Glucuronides showed differential effects after 6 h of treatment, with R4G up-regulating mRNA of MIP-1b (24.5 ± 14.8%) and R3G and R4G down-regulating CXCR2 surface protein compared to cells treated with LPS alone, by -5.33 ± 4.18 and -15.2 ± 5.99%, respectively. On the contrary, R3G and R4G up-regulated SIRT1 mRNA by 22.7 ± 17.9 and 22.8 ± 16.9%, respectively, in LPS-stimulated U-937 macrophages, showing anti-inflammatory properties. In conclusion, sulfated RES metabolites show an interesting beneficial potential for attenuating inflammatory immune processes.
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