Journal
LIFE SCIENCES
Volume 137, Issue -, Pages 89-97Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2015.07.015
Keywords
Intraperitoneal administration; Lipopolysaccharide-induced systemic inflammation; Macrophages; Pro-/anti-inflammatory cytokines; Quercetin; Quercetin-3-glucuronide
Funding
- National Science Council Taiwan [NSC99-2628-B-005-004-MY3]
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Aims: 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. Main methods: 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-alpha, IL-1 beta and IL-6) and anti-inflammatory (IL-10) cytokine secretion profiles by peritoneal macrophages of the mice were measured using ELISA. Key findings: Mice which received 8 mg/kg BWLPS i.p. for 12 h resulted in intermediate systemic inflammation, suggesting a useful mild septic mouse model. At non-toxic doses, Q or Q3G (0.06 or 0.15 mu mol/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. Significance: 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. (C) 2015 Elsevier Inc. All rights reserved.
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