Curcumin improves exercise performance of mice with coronary artery ligation-induced HFrEF

Nrf2 and antioxidant mechanisms in skeletal muscle

Ahmed M. Wafi, Juan Hong, Tara L. Rudebush, Li Yu, Bryan Hackfort, Hanjun Wang, Harold D Schultz, Irving H Zucker, Lie Gao

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A hallmark of chronic heart failure (HF) 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, a Nrf2 activator, would preserve or increase exercise capacity in HF. Experiments were carried out in mice with coronary artery ligation-induced HFrEF. Curcumin was deliveried by a subcutaneous osmotic minipump at a dose of 50 mg·kg 1 ·day 1 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 with sham. Curcumin-treated HF mice displayed enhanced exercise performance compared with vehicle-treated HF mice; 2) both soleus (Sol) and extensor digitorum longus (EDL) muscles of HFrEF mice exhibited reduced force and rapid fatigue, which were ameliorated by curcumin; and 3) protein expression of Nrf2, hemeoxygenase-1, SOD2, myogenin, and MyoD were significantly lower, but total ubiquitinated proteins, MURF1, and atrogen-1 were higher in Sol and EDL of HFrEF compared with sham mice, whereas these alterations in Nrf2 signaling and antioxidant defenses in HFrEF were attenuated by curcumin, which had no effect on cardiac function per se in mice with severe HFrEF. These data suggest that impaired Nrf2 signaling intrinsic to skeletal muscle contributes to exercise intolerance in HFrEF. Skeletal muscle Nrf2 should be considered as a novel therapeutic target in severe HF.

Original languageEnglish (US)
Pages (from-to)477-486
Number of pages10
JournalJournal of Applied Physiology
Volume126
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

NF-E2-Related Factor 2
Curcumin
Ligation
Coronary Vessels
Skeletal Muscle
Antioxidants
Heart Failure
Ubiquitinated Proteins
Myogenin
Muscles
Heme Oxygenase-1
Hand Strength
Running
Fatigue
Extremities

Keywords

  • Exercise intolerance
  • HFrEF
  • Myopathy
  • Oxidative stress

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Curcumin improves exercise performance of mice with coronary artery ligation-induced HFrEF : Nrf2 and antioxidant mechanisms in skeletal muscle. / Wafi, Ahmed M.; Hong, Juan; Rudebush, Tara L.; Yu, Li; Hackfort, Bryan; Wang, Hanjun; Schultz, Harold D; Zucker, Irving H; Gao, Lie.

In: Journal of Applied Physiology, Vol. 126, No. 2, 01.02.2019, p. 477-486.

Research output: Contribution to journalArticle

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