Curcumin Supplementation Suppresses Ubiquitin Proteasome System Activity Following Exercise-Induced Muscle Damage In Humans

Abstract

PURPOSE: Curcumin is a natural polyphenolic compound with profound antioxidant and anti-inflammatory properties. Moreover, combined curcumin and piperine supplementation has shown improved curcumin bioavailability by 2000%. Multiple studies have demonstrated that exposure to curcumin leads to dysregulation of the ubiquitin-proteasome system (UPS) in cell culture. However, to date, no data has investigated curcumin’s ability to influence UPS activity in a human model. Therefore, the purpose of this study was to investigate the effects of curcumin and piperine supplementation on markers of UPS activity following exercise-induced muscle damage in human skeletal muscle. METHODS: Twenty-three recreationally active male and female participants were randomized into a curcumin + piperine (CUR; n=11); or placebo + piperine (PLA; n=12). Both groups were instructed to consume 2g of their respective supplement and 20mg of piperine for 11 consecutive days. Following 8 consecutive days of supplementation, participants performed a 45-min eccentrically-biased muscle damaging treadmill protocol at 60% VO2max. Muscle Biopsies and delayed muscle soreness (DOMS) analyses were performed 30 minutes prior and 3-, 24-, 48-, and 72-hours post exercise-induced muscle damage. Muscle ubiquitin, MAFbx, ubiquitin specific peptidase 19 (USP19), and chymotrypsin-like protease (CLP) concentrations were measured using ELISA kits. A 2x5 repeated measures ANOVA with pairwise comparisons was conducted with significance set at p<0.05. RESULTS: Both groups had a significant time effect for DOMS (p < .001). Pairwise comparisons indicated DOMS was significantly greater from baseline at all time points except 72 hours post muscle damage. No significant differences were found for CLP or USP19 across any time points. Regardless of time, there was a significant group effect for ubiquitin (p = .012) and MAFbx (p = .016) where CUR was significantly lower than PLA. CONCLUSION: Curcumin appears to attenuate muscle ubiquitin and MAFbx in response to a muscle damaging protocol. As key markers of protein degradation, this implies decreased ubiquination and a subsequent reduction in proteasomal activity. Therefore, curcumin supplementation potentially plays a role in preserving skeletal muscle mass through decreased muscle breakdown.