# Mechanistic insights into the lipotropic and atheroprotective effects of rosuvastatin-loaded glycerosomes in dyslipidemic rats

## TL;DR

This study explores how a drug-loaded formulation protects against liver and heart diseases in rats with high cholesterol.

## Contribution

The study reveals new mechanistic pathways through which rosuvastatin-loaded glycerosomes exert protective effects in dyslipidemic rats.

## Key findings

- ROS-GLY downregulated hepatic lncRNA-H19 and upregulated miR-130a, reducing PPAR-γ levels.
- ROS-GLY upregulated the aortic PPAR-γ/LXRα/ABCA1 pathway, improving lipid metabolism.
- Molecular docking confirmed strong binding of rosuvastatin to key proteins like PPAR-γ and LXR-α.

## Abstract

Dyslipidemia is a major risk factor for the development of NAFLD, atherosclerosis and cardiovascular diseases. Rosuvastatin (ROS) is a lipid-lowering drug that protects against the development of NAFLD and atherosclerosis. However, the mechanism of this protection remains obscure. Therefore, the current study aims to explore the mechanism by which ROS-loaded glycerosomes (ROS-GLY) protect against NAFLD and atherosclerosis. Hence, for this purpose, hepatic lncRNA-H19/miR-130a/PPAR-γ and aortic PPAR-γ/LXRα/ABCA1 signaling pathways were assessed. In addition, these target pathways were predicted using molecular docking analysis. Thirty-five male Sprague Dawley rats were separated into control, dyslipidemic (poloxamer 407 (P 407)), P 407+ROS-GLY, P 407+NC, and P 407+ROS-GLY+NC groups. ROS-GLY improved lipid profile, hepatic MDA, SOD, catalase and total antioxidant capacity (TAC) in compared to P 407 group. In the dyslipidemic group, ROS-GLY downregulated hepatic lncRNA-H19 expression which leads to an upregulate of the miR-130a level and subsequent reduction of the PPAR-γ level. Consequently, the hepatic expression level of lipogenic genes such as, ACC-1, FASN and SCD-1 was significantly downregulated in the ROS-GLY group than the dyslipidemic one. Aortic PPAR-γ/LXRα/ABCA1 signaling pathway was significantly upregulated in the ROS-GLY group compared to the dyslipidemic group. Furthermore, ROS-GLY modulated IL-6 and IL-10 immunoprotein expression in hepatic and aortic tissues. Interestingly, ROS showed a substantial binding affinity with PPAR-γ, LXR-α, and FASN, according to a molecular docking study. The current study indicated that ROS-GLY protected against the progression of NAFLD and atherosclerosis in dyslipidemic rats via modulation of lipid profile, oxidative stress, pro-/anti-inflammatory cytokines, hepatic lncRNA-H19/miR-130a/PPAR-γ, and aortic PPAR-γ/LXRα/ABCA1 signaling pathways.

The online version contains supplementary material available at 10.1038/s41598-025-34918-z.