Kazinol-P from Broussonetia kazinoki enhances skeletal muscle differentiation via p38MAPK and MyoD

Biochem Biophys Res Commun. 2015 Jan 2;456(1):471-5. doi: 10.1016/j.bbrc.2014.11.109. Epub 2014 Dec 5.

Abstract

The activation of MyoD family transcription factors is critical for myogenic differentiation, which is fundamental to the regeneration of skeletal muscle after injury. Kazinol-P (KP) from Broussonetia kazinoki (B. kazinoki), a natural compound, has been reported to possess an anti-oxidant function. In a screen of natural compounds for agonists of the MyoD activity, we identified KP and examined its effect on myoblast differentiation. Consistently, KP enhanced the myotube formation, accompanied with upregulation of myogenic markers such as MHC, Myogenin and Troponin-T. KP treatment in C2C12 myoblasts led to strong activation of a key promyogenic kinase p38MAPK in a dose, and time-dependent manner. Furthermore, KP treatment enhanced the MyoD-mediated trans-differentiation of 10T1/2 fibroblasts into myoblasts. Taken together, KP promotes myogenic differentiation through activation of p38MAPK and MyoD transcription activities. Thus KP may be a potential therapeutic candidate to prevent fibrosis and improve muscle regeneration and repair.

Keywords: Broussonetia kazinoki; Kazinol-P; MyoD; Myoblast differentiation; Trans-differentiation; p38MAPK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Broussonetia / chemistry*
  • Cell Differentiation
  • Cell Line
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibrosis / drug therapy
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Mice
  • Muscle Development
  • Muscle, Skeletal / drug effects*
  • MyoD Protein / metabolism*
  • Myoblasts / drug effects
  • Myogenin
  • Plant Extracts / pharmacology*
  • Regeneration
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Antioxidants
  • Heterocyclic Compounds, 4 or More Rings
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Myogenin
  • Plant Extracts
  • kazinol-P
  • p38 Mitogen-Activated Protein Kinases