Systemic administration of the NF-kappa B inhibitor curcumin stimulates muscle regeneration after traumatic injury

Skeletal muscle is often the site of tissue injury due to trauma, disease, developmental defects or surgery. Yet, to date, no effective treatment is a vailable to stimulate the repair of skeletal muscle. We show that the kinet ics and extent of muscle regeneration in vivo after trauma are greatly enha nced following systemic administration of curcumin, a pharmacological inhib itor of the transcription factor NF-kappa B. Biochemical and histological a nalyses indicate an effect of curcumin after only 4 days of daily intraperi toneal injection compared with controls that require >2 wk to restore norma l tissue architecture. Curcumin can act directly on cultured muscle precurs or cells to stimulate both cell proliferation and differentiation under app ropriate conditions. Other pharmacological and genetic inhibitors of NF-kap pa B also stimulate muscle differentiation in vitro. Inhibition of NF-kappa B-mediated transcription was confirmed using reporter gene assays. We conc lude that NF-kappa B exerts a role in regulating myogenesis and that modula tion of NF-kappa B activity within muscle tissue is beneficial for muscle r epair. The striking effects of curcumin on myogenesis suggest therapeutic a pplications for treating muscle injuries.