Dietary Apigenin Exerts Immune-Regulatory Activity in Vivo by Reducing NF-κB Activity, Halting Leukocyte Infiltration and Restoring Normal Metabolic Function

Int J Mol Sci. 2016 Mar 1;17(3):323. doi: 10.3390/ijms17030323.

Abstract

The increasing prevalence of inflammatory diseases and the adverse effects associated with the long-term use of current anti-inflammatory therapies prompt the identification of alternative approaches to reestablish immune balance. Apigenin, an abundant dietary flavonoid, is emerging as a potential regulator of inflammation. Here, we show that apigenin has immune-regulatory activity in vivo. Apigenin conferred survival to mice treated with a lethal dose of Lipopolysaccharide (LPS) restoring normal cardiac function and heart mitochondrial Complex I activity. Despite the adverse effects associated with high levels of splenocyte apoptosis in septic models, apigenin had no effect on reducing cell death. However, we found that apigenin decreased LPS-induced apoptosis in lungs, infiltration of inflammatory cells and chemotactic factors' accumulation, re-establishing normal lung architecture. Using NF-κB luciferase transgenic mice, we found that apigenin effectively modulated NF-κB activity in the lungs, suggesting the ability of dietary compounds to exert immune-regulatory activity in an organ-specific manner. Collectively, these findings provide novel insights into the underlying immune-regulatory mechanisms of dietary nutraceuticals in vivo.

Keywords: NF-κB; apigenin; apoptosis; cardiac dysfunction; flavonoids; inflammation; leukocytes; mitochondria; sepsis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Apigenin / administration & dosage
  • Apigenin / pharmacology*
  • Apigenin / therapeutic use
  • Apoptosis
  • Dietary Supplements
  • Leukemic Infiltration / drug therapy*
  • Leukemic Infiltration / immunology
  • Lipopolysaccharides / toxicity
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism*
  • Sepsis / drug therapy*
  • Sepsis / immunology
  • Spleen / drug effects
  • Spleen / metabolism
  • Spleen / pathology

Substances

  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • NF-kappa B
  • Apigenin