Title:Therapeutic Effect of Rosolic Acid against Endothelial Dysfunction in
Diabetic Wistar Rats
Volume: 33
Issue: 1
Author(s): Karan Naresh Amin and Kunka Mohanram Ramkumar*
Affiliation:
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur,
603203, Chennai, Tamilnadu, India
Keywords:
Endothelial dysfunction, diabetes, rosolic acid, Nrf2, small molecules, vascular complications.
Abstract:
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 endoplasmic reticulum (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.
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 Intercellular Adhesion Molecule 1 (ICAM1), vascular cell adhesion
molecule 1 (VCAM1), 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.
