Floralozone alleviates doxorubicin-induced cardiac senescence and fibrosis by inhibiting the VEGFR1

Floralozone(FL) is a medicinal compound with potential cardiovascular protective effects. Vascular endothelial growth factor receptor 1 (VEGFR1) signaling has been implicated in cardiovascular dysfunction. This study investigated whether floralozone ameliorates heart failure (HF) through regulation of VEGFR1. HF was induced in rats by intraperitoneal injection of doxorubicin (DOX) for six weeks. VEGFR1 expression was analyzed by immunofluorescence and Western blotting. Oxidative stress was determined by DHE staining of myocardial ROS and serum MDA and SOD assays. Senescence associated β-galactosidase (SA-β-gal) staining was performed to evaluate the degree of myocardial aging. HE staining was used to observe cardiac morphology. Masson, argyrophilic and orcein staining were applied to detect the degree of myocardial fibrosis, and echocardiography was conducted to assess cardiac function in each group. Floralozone (FL) modulated VEGFR1 expression and alleviated DOX-induced oxidative stress, cardiac aging, myocardial fibrosis, and cardiac dysfunction in HF rats. The protective effects of FL on oxidative stress, cardiac aging, myocardial fibrosis, cardiac function, and VEGFR1 expression were attenuated by pharmacological activation of VEGFR1 with placental growth factor (PLGF), supporting the involvement of VEGFR1 signaling in the cardioprotective effects of FL. These findings suggest that floralozone exerts cardioprotective effects against DOX induced heart failure, at least in part, through modulation of VEGFR1 associated signaling and oxidative stress. Floralozone modulated VEGFR1 expression and was associated with reduced oxidative stress, cardiac aging, and myocardial fibrosis, ultimately improving cardiac dysfunction. However, the precise causal relationship between VEGFR1 signaling and oxidative stress remains to be determined. These findings suggest that floralozone may have therapeutic potential for DOX induced cardiac injury through modulation of VEGFR1 associated pathological processes.