Bakuchiol augments MyoD activation leading to enhanced myoblast differentiation

• Bakuchiol enhances muscle-specific gene expression and myotube formation.
• Bakuchiol stimulates promyogenic Cdo/p38MAPK/MyoD signaling pathway, thereby promoting myoblast differentiation.
• Bakuchiol elevates the formation of MyoD/E-protein complexes in myogenesis.
• Bakuchiol induces trans-differentiation of embryonic fibroblasts into myotubes.
• Bakuchiol improves the differentiation capacity of RD cells, thereby reducing tumorigenicity.

Myoblast differentiation is fundamental to skeletal muscle development and regeneration after injury and defects in this process are implicated in muscle atrophy associated with aging or pathological conditions. MyoD family transcription factors function as mater regulators in induction of muscle-specific genes during myoblast differentiation. We have identified bakuchiol, a prenylated phenolic monoterpene, as an inducer of MyoD-mediated transcription and myogenic differentiation. C2C12 myoblasts treated with bakuchiol exhibit enhanced muscle-specific gene expression and myotube formation. A key promyogenic kinase p38MAPK is activated dramatically by bakuchiol which in turn induced the formation of MyoD/E protein active transcription complexes. Consistently, the recruitment of MyoD and Baf60c to the Myogenin promoter is enhanced in bakuchiol-treated myoblasts. Furthermore, bakuchiol rescues defective p38MAPK activation and myogenic differentiation caused by Cdo-depletion or in RD rhabdomyosarcoma cells. Taken together, these results indicate that bakuchiol enhances myogenic differentiation through p38MAPK and MyoD activation. Thus bakuchiol can be developed into a potential agent to improve muscular regeneration and repair to treat muscular atrophy.