Therapeutic Effect of Rosolic Acid against Endothelial Dysfunction in Diabetic Wistar Rats

Introduction: Endothelial dysfunction (ED) results from impaired vascular endothelial cell function, disrupting key processes such as hemostasis, vascular tone regulation, vasculogenesis, angiogenesis, and inflammation. These processes are mediated by a complex signaling network involving hormones, cytokines, and chemokines. ED is recognized as a major contributor to the onset and progression of several micro- and macrovascular diseases, including diabetes. Our previous study demonstrated that the polyphenol Rosolic acid (RA) protects against ER stress-induced ED in vitro by activating nuclear factor erythroid 2-related factor 2 (Nrf2). Additionally, RA enhanced the proliferation and survival of pancreatic β-cells in a co-culture model with endothelial cells under ER stress conditions. Methods: In this study, we investigated RA's protective effects against diabetes-induced ED using high-fat diet (HFD)-fed and streptozotocin-induced type-2 diabetic rat models. We evaluated RA’s impact on vascular function and metabolic parameters in these models. objective: To evaluate the protective effects of Rosolic acid (RA) on endothelial dysfunction (ED) in high-fat diet (HFD)-fed and streptozotocin-induced type-2 diabetic rat models. To assess the impact of RA on vascular function in diabetic rats by analyzing key markers of endothelial dysfunction, including ICAM-1, VCAM-1, and Endothelin-1. To investigate the effects of RA on metabolic parameters, such as glucose tolerance and lipid profiles, in diabetic conditions. To examine the role of RA in modulating Nrf2 and its downstream target genes involved in oxidative stress and endothelial function in aortic tissues. To compare the therapeutic efficacy of RA with the standard anti-diabetic drug Gliclazide in protecting against diabetes-induced endothelial dysfunction. Results: RA significantly mitigated diabetes-induced ED in the aortic tissues of HFDfed diabetic Wistar rats. RA treatment improved glucose tolerance and reduced hyperlipidemia, showing efficacy comparable to the anti-diabetic drug Gliclazide. Moreover, RA elevated Nrf2 levels and its downstream target genes in aortic tissues while reducing ED markers such as ICAM-1, VCAM-1, and endothelin-1. Conclusion: These findings highlight RA as a promising therapeutic agent for diabetes and its associated vascular complications, with potential for broader clinical applications.