Corylifol A from Psoralea corylifolia L. Enhances Myogenesis and Alleviates Muscle Atrophy

Int J Mol Sci. 2020 Feb 25;21(5):1571. doi: 10.3390/ijms21051571.

Abstract

Inflammatory conditions caused by cancer, chronic diseases or aging can lead to skeletal muscle atrophy. We identified myogenic compounds from Psoralea corylifolia (PC), a medicinal plant that has been used for the treatment of inflammatory and skin diseases. C2C12 mouse skeletal myoblasts were differentiated in the presence of eight compounds isolated from PC to evaluate their myogenic potential. Among them, corylifol A showed the strongest transactivation of MyoD and increased expression of myogenic markers, such as MyoD, myogenin and myosin heavy chain (MHC). Corylifol A increased the number of multinucleated and MHC-expressing myotubes. We also found that the p38 MAPK signaling pathway is essential for the myogenic action of corylifol A. Atrophic condition was induced by treatment with dexamethasone. Corylifol A protected against dexamethasone-induced myotube loss by increasing the proportion of multinucleated MHC-expressing myotubes compared with dexamethasone-damaged myotubes. Corylifol A reduced the expression of muscle-specific ubiquitin-E3 ligases (MAFbx and MuRF1) and myostatin, while activating Akt. These dual effects of corylifol A, inhibition of catabolic and activation of anabolic pathways, protect myotubes against dexamethasone damage. In summary, corylifol A isolated from P. corylifolia alleviates muscle atrophic condition through activating myoblast differentiation and suppressing muscle degradation in atrophic conditions.

Keywords: C2C12 myoblast; Psoralea corylifolia; corylifol A; muscle atrophy; myogenesis.

MeSH terms

  • Animals
  • Cell Line
  • Flavones / pharmacology*
  • Mice
  • Muscle Development*
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / drug effects*
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscular Atrophy / metabolism*
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism
  • Tripartite Motif Proteins / genetics
  • Tripartite Motif Proteins / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Flavones
  • Muscle Proteins
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Tripartite Motif Proteins
  • corylifol A
  • Trim63 protein, mouse
  • Ubiquitin-Protein Ligases
  • p38 Mitogen-Activated Protein Kinases
  • Myosin Heavy Chains