Involvement of P450s and nuclear receptors in the hepatoprotective effect of quercetin on liver injury by bacterial lipopolysaccharide

Immunopharmacol Immunotoxicol. 2020 Jun;42(3):211-220. doi: 10.1080/08923973.2020.1742154. Epub 2020 Apr 7.

Abstract

Objective: Quercetin (Que), a flavonoid, possesses anti-inflammatory and antioxidant properties. It has been shown to protect against liver injury induced by various factors. This study was designed to investigate the underlying mechanism of its protective effect against lipopolysaccharide (LPS)- induced liver damage.Methods: Mice were pretreated with Que for 7 consecutive days and then exposed to LPS. To study the hepatoprotective effect of Que, oxidative stress parameters, inflammatory cytokine levels in liver and serum liver function indexes were examined. Protein and mRNA expression of nuclear orphan receptors and cytochrome P450 enzymes were measured by Western Blotting and qPCR, respectively.Results: Que significantly reduced circulating ALT, AST, ALP, and ameliorated LPS-induced histological alterations. In addition, Que obviously decreased markers of oxidative stress and pro-inflammatory cytokines. Furthermore, Que carried out the hepatoprotective effect via regulation of the expression of nuclear orphan receptors (CAR, PXR) and cytochrome P450 enzymes (CYP1A2, CYP2E1, CYP2D22, CYP3A11).Conclusions: Our findings suggested that Que pretreatment could ameliorate LPS-induced liver injury.

Keywords: Quercetin; cytochrome P450s; lipopolysaccharide; liver injury; mice; nuclear receptors.

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury / immunology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cyclooxygenase 2 / metabolism
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Cytokines / genetics
  • Cytokines / immunology
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Lipopolysaccharides / toxicity
  • Liver / drug effects*
  • Liver / pathology
  • Liver Function Tests
  • Male
  • Mice, Inbred ICR
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology*
  • Quercetin / pharmacology*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • Cytokines
  • Lipopolysaccharides
  • Protective Agents
  • Receptors, Cytoplasmic and Nuclear
  • lipopolysaccharide, E coli O55-B5
  • Cytochrome P-450 Enzyme System
  • Quercetin
  • Cyclooxygenase 2