Fucoxanthin ameliorated myocardial fibrosis in STZ-induced diabetic rats and cell hypertrophy in HG-induced H9c2 cells by alleviating oxidative stress and restoring mitophagy.

Diabetic cardiomyopathy (DCM) is one of the leading causes of death in diabetic patients, and is accompanied by increased oxidative stress and mitochondrial dysfunction. Fucoxanthin (FX), as a marine carotenoid, possesses strong antioxidant activity. The main purpose of our study was to explore whether FX could attenuate experimental cardiac hypertrophy by affecting mitophagy and oxidative stress. We found that FX improved lipid metabolism, myocardial damage, myocardial fibrosis and hypertrophy in the myocardial tissue of STZ-induced diabetic rats. Additionally, FX upregulated Nrf2 signaling to reduce the level of reactive oxygen species (ROS). FX also promoted Bnip3/Nix signaling to improve mitochondrial function and reduced the levels of mitochondrial and intracellular ROS, thereby reversing HG-induced H9c2 cell hypertrophy. However, treatment with the autophagy inhibitor CQ abolished the anti-hypertrophic effect of FX, accompanied by impaired mitochondrial function and increased ROS levels. In conclusion, we found that FX reduced the accumulation of TGF-β1, FN and α-SMA to relieve myocardial fibrosis in STZ-induced diabetic rats, and FX up-regulated Bnip3/Nix to promote mitophagy and enhanced Nrf2 signaling to alleviate oxidative stress, thereby inhibiting hypertrophy in HG-induced H9c2 cells. These results imply that FX may be developed as a functional food for DCM.