Silybin as an anti-inflammatory and anti-fibrotic agent in cancer cachexia

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Unintentional body weight loss (cachexia) in chronic diseases, such as cancer can lead to the deterioration of quality of life, lack of response to treatment, and ultimately death. Cancer cachexia is characterized by systemic inflammation, muscle and fat loss, and reduced physical function. Tissue fibrosis or scarring has been observed in cancer cachectic patients. Muscle fibrosis is one of the most consistent findings among people with reduced muscle function due to myopathies, neuromuscular disorders, trauma, and sarcopenia. Blocking inflammation and fibrosis in the pre-cachectic and cachectic stages is critical to positively impact muscle health, locomotion, and performance. Silybin, one of the active compounds of the medicinal plant Silybum marianum has shown anti-inflammatory and anti-fibrotic properties in cardiac and liver disorders. Since there are no approved therapies for cancer cachexia and silybin has been associated to improve factors associated with cachexia, we propose to assess whether silybin reduces skeletal muscle fibrosis. Furthermore, we will determine if TGF-􀈕 is involved in initiating or maintaining loss of muscle mass and function. Our findings could lead to the discovery of a new mechanism and novel strategies to prevent and/or treat cachexia.