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Oleanolic acid protects against pathogenesis of atherosclerosis, possibly via FXR-mediated angiotensin (Ang)-(1-7)
Yunyun Pan1, Fenghua Zhou2, Zhenhua Song3
1Department of Pharmaceutical, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, China; Department of Clinical Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510080, China.
Abstract:
Atherosclerosis, the leading cause of cardiovascular diseases in the world, is a chronic inflammatory disorder characterized by the dysfunction of arteries. Oleanolic acid (OA) is a bioactive nature product which exists in various plants and herbs. Previous studies have demonstrated that OA was involved in numerous of biological processes, including atherosclerosis. However, the exact mechanisms of the anti-atherosclerosis effects of OA remain unknown. Here, in our study, we analyzed the effects and possible underlying mechanisms of OA in atherosclerosis depending a cell model and an animal model of atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL, 100 μg/mL) for 24 h to establish an atherosclerotic cell model. New Zealand white (NZW) rabbits were fed with high-fat (HF) diets for three months to establish an atherosclerotic animal model. Then, cell viability and expression of cytokines (ANG, NO, eNOS, IL-1β, TNF-α, and IL-6) were measured with CCK-8 assay and ELISA kits, cell apoptosis and cell cycle distribution were analyzed by flow cytometry in the atherosclerotic cell model. Results showed that ox-LDL induced effects of anti-proliferation, cytokines alterations, and cell apoptosis were abolished by the application of OA or Ang (1-7). Further study indicated that OA increased the expression of ANG by upregulating the FXR expression in the ox-LDL induced HUVECs arthrosclerosis model. And the in vivo experiment in the HF diet induced animal model suggested that OA may inhibit the development of atherosclerosis. The atherosclerosis of aortas was assessed by Hematoxylin Eosin (HE), Oil Red O and Picrosirius Red staining; the expression levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were determined by the fully automatic biochemical analyzer, in the atherosclerotic animal model. All the results showed that OA treatment improved the cell viability in the cell model, inhibited the atherosclerosis development in the animal model. OA play as an anti-atherosclerosis agent in both the cell model and animal model by upregulating the production of Angiotensin (Ang)-(1-7) through FXR.
Insights
Oleanolic acid (OA) demonstrates anti-atherosclerosis effects by upregulating Angiotensin-(1-7) production via FXR, improving cell viability and inhibiting disease progression in cell and animal models.
Area of Science:
- Cardiovascular Biology
- Pharmacology
- Natural Products Chemistry
Background:
- Atherosclerosis is a leading cause of cardiovascular disease, driven by chronic arterial inflammation.
- Oleanolic acid (OA), a plant-derived compound, shows potential in biological processes, including atherosclerosis.
- The precise anti-atherosclerosis mechanisms of OA require further elucidation.
Purpose of the Study:
- To investigate the anti-atherosclerosis effects of Oleanolic acid (OA).
- To elucidate the underlying mechanisms of OA's action in atherosclerosis.
- To evaluate OA in both in vitro and in vivo models of atherosclerosis.
Main Methods:
- Established an atherosclerotic cell model using human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL).
- Developed an atherosclerotic animal model in New Zealand white rabbits fed a high-fat (HF) diet.
- Assessed cell viability, cytokine expression, apoptosis, cell cycle, aortic pathology, and lipid profiles.
Main Results:
- OA treatment reversed ox-LDL-induced anti-proliferation, altered cytokine profiles, and apoptosis in HUVECs.
- OA increased Angiotensin (ANG) expression by upregulating Farnesoid X Receptor (FXR) in the cell model.
- OA treatment improved cell viability and inhibited atherosclerosis development in the animal model, as evidenced by histological and biochemical analyses.
Conclusions:
- Oleanolic acid (OA) exhibits significant anti-atherosclerosis properties in both cellular and animal models.
- OA functions as an anti-atherosclerosis agent by enhancing Angiotensin-(1-7) production through FXR activation.
- These findings highlight OA's therapeutic potential for managing atherosclerosis.
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