Berberine inhibits dyslipidemia in C57BL/6 mice with lipopolysaccharide induced inflammation

Pharmacol Rep. 2012;64(4):889-95. doi: 10.1016/s1734-1140(12)70883-6.

Abstract

Background: Inhibiting the action of proprotein convertase subtilisin/kexin type 9 (PCSK9) on the low-density lipoprotein receptor (LDLR) has emerged as a novel therapeutic target for hypercholesterolemia. Here we investigated the effect of berberine, natural plant extracts, on PCSK9-LDLR pathway in C57BL/6 mice with lipopolysaccharide (LPS) induced inflammation.

Methods: Forty female mice were divided into four groups (n =10): control, LPS (5 mg/kg), LPS + berberine 10 (5 mg/kg LPS plus 10 mg/kg berberine), and LPS + berberine 30 (5 mg/kg LPS plus 30 mg/kg berberine). Changes in the levels of blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)]; pro-inflammatory cytokines [interferon-γ (IFNγ), tumor necrosis factor α (TNFα), and interleukin-1α (IL-1α)], 8-isoprostane, hepatic expressions of PCSK9 and LDLR were determined.

Results: Berberine pretreatment reduced the expression of hepatic PCSK9, decreased the plasma TC, TG, LDL-C, IFNγ, TNFα, IL-1α, and 8-isoprostane concentrations; increased HDL-C level and LDLR expression in mice.

Conclusion: The present results suggest that berberine inhibits dyslipidemia in C57BL/6 mice with LPS induced inflammation through regulating PCSK9-LDLR pathway.

MeSH terms

  • Animals
  • Berberine / pharmacology*
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Dinoprost / metabolism
  • Dyslipidemias / chemically induced
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / metabolism
  • Female
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Interferon-gamma / metabolism
  • Interleukin-1alpha / metabolism
  • Lipids / blood
  • Lipopolysaccharides
  • Liver / drug effects
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Plant Extracts / pharmacology
  • Proprotein Convertase 9
  • Proprotein Convertases / metabolism
  • Receptors, LDL / metabolism
  • Serine Endopeptidases / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1alpha
  • Lipids
  • Lipopolysaccharides
  • Plant Extracts
  • Receptors, LDL
  • Tumor Necrosis Factor-alpha
  • Berberine
  • 8-epi-prostaglandin F2alpha
  • Interferon-gamma
  • Dinoprost
  • Pcsk9 protein, mouse
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases