Fucoxanthin alleviates myocardial fibrosis in diabetic mice by suppressing oxidative stress in cardiac fibroblasts via Prdx4 regulation

Cardiac fibrosis is a serious pathological manifestation of diabetic cardiomyopathy (DCM), which can damage cardiac function and eventually lead to heart failure. This study demonstrated that fucoxanthin (FX), the most abundant carotenoid in the marine environment, significantly ameliorated cardiac dysfunction and reduced fibrosis levels in mice with DCM. FX was found to decrease the expression levels of both collagen type I (Col1) and collagen type III (Col3), which are key markers of fibrosis. Additionally, in vitro experiments further revealed that FX potently inhibited the proliferation and transformation of cardiac fibroblasts, accompanied by a notable downregulation of Col1 and Col3 expression. Furthermore, our results indicated that FX elevated mitochondrial membrane potential and decreased reactive oxygen species (ROS) levels in cardiac fibroblasts exposed to high glucose (HG) conditions. At the mechanistic level, FX was observed to markedly upregulate the expression of the antioxidant protein peroxiredoxin 4 (Prdx4) in these cells. Silencing of Prdx4 attenuated the suppressive effects of FX on both proliferation and oxidative stress in cardiac fibroblasts. In summary, FX mitigates HG-induced oxidative stress, cellular proliferation, and transformation within cardiac fibroblasts, with Prdx4 playing a critical role in mediating these effects, ultimately contributing to the alleviation of diabetic myocardial fibrosis. These findings demonstrate the pivotal role of FX in the prevention and treatment of myocardial fibrosis in diabetic mice, and have characterized Prdx4 as a crucial mediator in the FX-induced prevention of myocardial fibrosis in mice with DCM.