Panax notoginseng flower protects against diabetic cardiomyopathy by regulating the ACSL4/ALOX15 pathway

Background Panax notoginseng (Burk.) F. H. Chen flower (SQH), a common traditional Chinese medicine and edible food, has long been shown to protect against diabetes. However, the protective effects of SQH against diabetic cardiomyopathy (DbCM) and its potential mechanisms are not yet understood. Aim of the Study This study aimed to analyze the therapeutic effects of the flowers of Panax notoginseng (SQH) on DbCM and elucidate its molecular mechanisms. Materials and Methods The in vitro model of DbCM was established using palmitate-treated H9c2 cardiomyocyte. A high-fat diet (HFD) in conjunction with streptozotocin (STZ)-induced DbCM mouse model was utilized to validate the cardioprotective effects and mechanism of SQH. Transcriptomic analysis was used to examine the potential mechanisms, followed by both in vitro and in vivo validation of key protein expression levels in the ACSL4/ALOX15 signaling pathway. Results In vitro , SQH treatment significantly protected H9c2 cells from palmitic acid (PA)-induced injury by reducing lipid peroxidation and improving mitochondrial membrane function. Transcriptomic data indicated that SQH influenced ferroptosis-related pathways. Moreover, SQH suppressed the ACSL4/ALOX15 pathway, leading to decreased levels of the key lipid peroxidation product 12-HETE and upregulation of GPX4. In DbCM mice, SQH administration improved glucose homeostasis, attenuated cardiac dysfunction, and reduced myocardial lipid peroxidation. Conclusion This study demonstrated that SQH ameliorated DbCM injury primarily by inhibiting ACSL4/ALOX15-mediated ferroptosis. These findings not only highlight Panax notoginseng flower as a promising therapeutic candidate for the early intervention of DbCM but also reveal the underlying mechanism of SQH’s protective effect.