The soy isoflavone genistein blunts nuclear factor kappa-B, MAPKs and TNF-α activation and ameliorates muscle function and morphology in mdx mice

Neuromuscul Disord. 2011 Aug;21(8):579-89. doi: 10.1016/j.nmd.2011.04.014. Epub 2011 Jun 11.

Abstract

Several lines of evidence suggest a detrimental role of the nuclear factor-κB (NF-κB) activation in the dystrophic process. We showed in previous studies that its inhibition through drugs with antioxidant properties, have beneficial effects in mdx mice. We tested whether genistein, a well-known isoflavone, inhibitor of NF-κB, MAPK and TNF-α and readily available for clinical use, could have a beneficial effect in mdx mice in comparison with methylprednisolone, the gold standard treatment for DMD patients. Five-week old mdx mice received for five weeks: genistein (daily or 3-times/week), methylprednisolone or vehicle. Genistein treatment: (1) increased forelimb strength and strength normalized to weight; (2) reduced serum creatine-kinase levels; (3) reduced markers of oxidative stress; (4) reduced muscle necrosis and enhanced regeneration. The positive results were more evident with the daily administration of genistein and were comparable to the effect of corticosteroids. Our data support the novel hypothesis that, as other more specific therapeutic approaches are still under development, this soy-derived compound is a promising option to be further investigated in dystrophic process.

MeSH terms

  • Animals
  • Creatine Kinase / blood
  • Disease Models, Animal
  • Genistein / pharmacology*
  • Genistein / therapeutic use
  • Glucocorticoids / pharmacology
  • Glucocorticoids / therapeutic use
  • Male
  • Methylprednisolone / pharmacology
  • Methylprednisolone / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Muscle Strength / drug effects
  • Muscle Strength / physiology
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Muscular Dystrophy, Duchenne / drug therapy
  • Muscular Dystrophy, Duchenne / pathology
  • Muscular Dystrophy, Duchenne / physiopathology*
  • NF-kappa B / antagonists & inhibitors*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Regeneration / drug effects
  • Regeneration / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Glucocorticoids
  • NF-kappa B
  • Protein Kinase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Genistein
  • Mitogen-Activated Protein Kinase Kinases
  • Creatine Kinase
  • Methylprednisolone