Cyanidin enriched diet delays Muscular Dystrophy progression in alpha-sarcoglycan knock-out mice

Muscular dystrophies (MDs) are clinically and molecularly heterogeneous genetic diseases, characterized by primary wasting of skeletal muscle that compromises patient mobility and, in the most severe cases, respiratory and cardiac functions, leading to wheelchair dependency, respiratory failure and premature death. Literature illustrates a tight relationship between oxidative stress and progression of muscular dystrophies due to the contractile function of the muscles. Several studies show also that the use natural antioxidants, as anthocyanins, displays protective effect in many chronic diseases. Using a bioactive compound as cyanidin (C3G), which is known to induce anti-inflammatory and antioxidant responses, can be resourceful in order to reduce the administration of drugs, reducing risks of severe side effects. In this study we show how a C3G enriched diet (RD) ameliorates morphologically and functionally the dystrophic muscles of the alpha-Sarcoglycan (a-SG) null mouse model. Furthermore muscles of a-SG null mice fed with the RD display a more oxidative metabolism and more slow Mysoin Heavy Chain (MyHC) positive muscle fibers, which are known to be more protected from dystrophic injury. Mice fed with RD display a reduction in inflammatory markers caused by the exclusion of the transcription factor NF-kB from nucleus. Also we show that the protection from the oxidative injury is due to the transcription factor Nrf-2, which upon C3G stimuli, translocates into the nucleus and transcribes for typical protective enzymes.