Effects of Quercetin on Muscle Function during IL‐6‐induced Cancer Cachexia

Abstract

Cachexia is a devastating wasting condition that occurs secondary to chronic diseases including AIDS, COPD, and cancer. Characterized by a loss of body weight including adipose tissue and muscle atrophy, 20-50% of cancer patients are affected with an annual mortality rate of 80%. It is known that IL-6 drives cachexia in the male ApcMin/+ mouse. Quercetin, an anti-inflammatory flavonoid, has been shown to attenuate symptoms of cachexia. There is evidence that this occurs through the IL-6 pathway; however, this has not been directly tested. The purpose of this study was to determine whether quercetin could attenuate muscle function loss caused by systemic IL-6 over-expression in female ApcMin/+mice. Our hypothesis was that IL-6 over-expression would exacerbate muscle strength and endurance decrements, which would be attenuated by quercetin supplementation in cachectic female ApcMin/+ mice. Female ApcMin/+ mice (n=24) were divided into 4 groups at 15 weeks of age: 1) Control 2) IL-6 electroporation (50 μg plasmid in 50 μl PBS), 3) daily quercetin gavage (75 mg/kg body weight), 4) IL-6 electroporation + quercetin. Functional testing including voluntary grip strength, run to fatigue, and DEXA scan were performed before treatment and at time of sacrifice. Quercetin attenuated grip strength loss compared to control mice (p=0.02); however, this effect was abolished by the overexpression of IL-6 in addition to quercetin. Quercetin was unable to rescue muscle endurance loss. Further analysis will determine the pathways by which quercetin and IL-6 exert their effects on muscular strength and endurance in cachectic female ApcMin/+mice.