Curcumin mitigates high glucose-induced cardiac oxidative stress via Notch1 pathway activation

This study aims to investigate the protective effects of curcumin (CUR) in high glucose (HG)-induced oxidative stress and apoptosis of primary cardiomyocytes by activating the Notch1 signaling pathway. CUR is a natural polyphenol isolated from turmeric rhizomes and is known for its antioxidant, anti-apoptotic, and anti-inflammatory effects, particularly relevant in diabetes.Therefore, we used neonatal rat cardiomyocytes exposed to HG conditions, followed by treatment with CUR and DAPT, respectively. We detected and assessed myocardial cells viability and antioxidant enzyme activity by CCK-8 reagent and antioxidant enzyme kit. Apoptosis was detected by flow cytometry. The production of reactive oxygen species was detected by fluorescence labeling, and the expression of related genes and proteins was detected by qRT-PCR and Western blot. HG-induced primary rat cardiomyocytes not only increased apoptosis and ROS production, but also decreased the activity of antioxidant enzymes and the expression of Notch1 and Hes1 proteins. After pre-treatment by CUR, surprisingly, we found that CUR markedly improved viability of HG-treated cardiomyocytes. The results showed that CUR could inhibit the apoptosis of rat cardiomyocytes, inhibit the production of intracellular ROS, and increase the activity of antioxidant enzymes. Further, we found that CUR can upregulate the expression of Notch1 and Hes1 proteins and related genes, suggesting that the protective effect of CUR on HG-induced damage involves the Notch1/Hes1 signaling. These results suggest that CUR protects cardiomyocytes from HG-induced oxidative stress by activating Notch1 and its downstream target genes.