Ubiquitin Proteasome System Activity is Suppressed by Curcumin following Exercise-Induced Muscle Damage in Human Skeletal Muscle

Purpose: Curcumin is a polyphenolic compound that is suggested to dysregulate the ubiquitin-proteasome system (UPS). This study investigated the effects of curcumin supplementation on markers of UPS activity in response to muscle damage.

Methods: Twenty-three recreationally active male and females between the ages of 18-30 were randomized into a curcumin (CUR) or placebo (PLA) group. Both groups ingested 2 g of their respective supplement and 20 mg of piperine for 11 consecutive days. Following 8 consecutive days of supplementation, participants performed a 45-minute eccentrically-biased treadmill protocol at 60% VO2max. Muscle biopsies and delayed onset muscle soreness (DOMS) assessments were performed 30 minutes prior and 3, 24, 48, and 72 hours following exercise. Skeletal muscle ubiquitin, MAFbx/Atrogin-1, ubiquitin specific peptidase 19 (USP19), and chymotrypsin-like protease concentrations were measured using ELISA. A 3-way repeated measures ANOVA with pairwise comparisons was conducted with significance set at p ≤ 0.05.

Results: Compared to baseline, DOMS for both groups was significantly increased (p < 0.05) at all time points except 72 hours following exercise. No significant differences were found for USP19 between groups. Ubiquitin (p=.016) and MAFbx/Atrogin-1 (p=.006) were significantly lower for CUR compared to PLA. Additionally, MAFbx/Atrogin-1 was significantly greater for females (p=.013) compared to males. In males, curcumin resulted in significant reductions (p = .049) in chymotrypsin-like protease (p = .049).

Conclusion: While elevations in UPS activity were not observed in response to muscle damage, curcumin supplementation in humans does appear to dysregulate basal UPS activity in the presence of exercise-induced muscle damage.

Keywords: Diferuloylmethane; atrophy; muscle wasting; protein degradation; proteolysis.