Zeaxanthin Exhibits Protective Effects in Myocardial Injury by Inhibiting TGF-β/Smad2/3 and p38MAPK/NF-κB Signaling Pathways
Abstract Background: Zeaxanthin is a newly discovered natural product in β-carotenoid family with multiple bioactivities. Recently, it has been shown that zeaxanthin may have cardioprotective effects in several studies, but its mechanisms have not been fully investigated. Herein, we explored the role and mechanism of zeaxanthin in myocardial injury.Methods and Results: In this study, three different models were used to investigate the mechanism by which zeaxanthin alleviates myocardial injury. H9C2 Cardiomyocyte injury models were induced by H2O2. TUNEL assay, Flow cytometry, and Western blot analysis showed that treatment with zeaxanthin significantly decreased cardiomyocyte apoptosis and apoptosis-related protein expression. And reactive oxygen species (ROS) measurement analysis and Western blot analysis showed that treatment with zeaxanthin also could reduce the production of ROS and affect the expression of p38-Mitogen activated protein kinase/nuclear factor-κ gene bindin (p38MAPK/NF-κB) signaling pathway. Transforming Growth Factor-β1 (TGF-β1) was used to establish the fibrosis model in cardiac fibroblasts (CFs). QRT-PCR and Western blot analysis showed that treatment with zeaxanthin significantly decreased the expression of fibrosis markers in CFs. Myocardial injury animal models were induced by high-fat diet (HFD). Our results demonstrated that zeaxanthin improved fibrosis damage and cardiomyocyte apoptosis in HFD mice. Furthermore, Western blot analysis showed that TGF-β/Drosophila mothers against decapentaplegic2/3 (TGF-β/Smad2/3) signaling pathway related protein p-Smad2/3, Smad2/3, and TGF-β1 were significantly downregulated by zeaxanthin treatment.Conclusions: Zeaxanthin may alleviate HFD and H2O2-induced heart injury by regulating TGF-β/Smad2/3 and p38MAPK/NF-κB signaling pathways, which is of immense clinical significance in the treatment of cardiovascular disease.