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Current Medicinal Chemistry

Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Research Article

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

Author(s): Karan Naresh Amin and Kunka Mohanram Ramkumar*

Volume 33, Issue 1, 2026

Published on: 24 February, 2025

Page: [232 - 249] Pages: 18

DOI: 10.2174/0109298673358006250213053647

Price: $65

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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.

Keywords: Endothelial dysfunction, diabetes, rosolic acid, Nrf2, small molecules, vascular complications.

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