Quercetin intraperitoneal administration ameliorates lipopolysaccharide-induced systemic inflammation in mice

Life Sci. 2015 Sep 15:137:89-97. doi: 10.1016/j.lfs.2015.07.015. Epub 2015 Jul 22.

Abstract

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-α, IL-1β 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 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.

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.

Keywords: Intraperitoneal administration; Lipopolysaccharide-induced systemic inflammation; Macrophages; Pro-/anti-inflammatory cytokines; Quercetin; Quercetin-3-glucuronide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Female
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism
  • Injections, Intraperitoneal
  • Lipopolysaccharides / immunology*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Quercetin / administration & dosage*
  • Quercetin / analogs & derivatives
  • Quercetin / pharmacology
  • Quercetin / therapeutic use*
  • Sepsis / complications
  • Sepsis / metabolism

Substances

  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Lipopolysaccharides
  • Quercetin