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.

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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