Abstract

The purpose of this study was to unravel pharmacological effects of quercetin (Q) on systemic inflammation in septic mice, and compare it to quercetin-3-glucuronide (Q3G), a major metabolite of Q. A suitable sepsis mouse model was first established using lipopolysaccharide (LPS) injected intraperitoneally (i.p.). Q or Q3G was administered i.p. to septic mice in a prophylactic or therapeutic manner. Pro-inflammatory (TNF-α, IL-1β and IL-6) and anti-inflammatory (IL-10) cytokine secretion profiles by peritoneal macrophages of the mice were measured using ELISA. Mice which received 8mg/kg BW LPS i.p. for 12h resulted in intermediate systemic inflammation, suggesting a useful mild septic mouse model. At non-toxic doses, Q or Q3G (0.06 or 0.15μmol/mouse) i.p. injected in a prophylactic manner significantly (P<0.05) increased anti-inflammatory IL-10 secretions by peritoneal macrophages of the LPS-induced septic mice. Q, but not Q3G, i.p. injected in a therapeutic manner significantly (P<0.05) increased IL-10 secretions by peritoneal macrophages of the septic mice. Our data suggest that Q, but not Q3G, has pharmacological effects to ameliorate systemic inflammation. These results are the first to show that Q has potent potential against sepsis in both prophylactic and therapeutic manners in vivo.

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