Curcumin Improves Exercise Performance of Mice with Coronary Artery Ligation Induced HFrEF: Nrf2 and Antioxidant Mechanisms in Skeletal Muscle

A hallmark of chronic heart failure with low ejection fraction (HFrEF) is exercise intolerance. We hypothesized that reduced expression of nuclear factor E2-related factor 2 (Nrf2) in skeletal muscle contributes to impaired exercise performance. We further hypothesized that curcumin (Cur), a Nrf2 activator, would preserve or increase exercise capacity in HF. Experiments were carried out in mice with coronary artery ligation-induced HFrEF. Cur was deliveried by a subcutaneous osmotic minipump at a dose of 50 mg/kg/day for 8 weeks. In vivo, in situ, and in vitro experiments were employed to evaluate exercise capacity, muscle function, and molecular mechanisms. We found that: (1) the maximal speed, running distance to exhaustion, and limb grip force were significantly lower in HFrEF mice compared to sham. Cur-treated HF mice displayed enhanced exercise performance compared to vehicle-treated HF mice; (2) Both soleus (Sol) and extensor digitorum longus (EDL) muscles of HFrEF mice exhibited reduced force and r...