Cited by 34Cholesterol and Lipid MetabolismAtherosclerosis and Cardiovascular DiseasesLipoproteins and Cardiovascular Health

The effects of oleanolic acid on atherosclerosis in different animal models

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Luo, Hanqiong, Liu, Jine, Ouyang, Qiong, Xuan, Chunxiao, Wang, Lanlan, Li, Tingting, Liu, Jun·2017·Acta Biochimica et Biophysica Sinica

Abstract

In the present study, three animal models, including C57BL/6J mice, low-density lipoprotein receptor knockout (LDLR-/-) mice, and rabbit that mimicked atherosclerosis, were established to investigate the inhibitory effect of oleanolic acid (OA) on atherosclerosis. In rabbit model, serum total cholesterol (TC), triglyceride, low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were measured. Carotid artery lesions were isolated for histological analysis. The red oil O and hematoxylin-eosin staining in liver were examined. The messenger ribonucleicacid (mRNA) levels of PPARγ, AdipoR1, and AdipoR2 related to lipid metabolism were determined. Compared with model group, OA and atorvastatin significantly lowered the levels of TC and LDL-C. The result of red oil O staining showed that OA and atorvastatin had similar effect on reducing the accumulation of lipid. Histological result demonstrated that OA reduced the thickness of intima. AdipoR1 was markedly increased, while AdipoR2 was remarkably decreased in OA group compared with that in the control group of the rabbit model. In LDLR-/- mouse model, lipid parameters in blood and mRNA levels of PPARγ, AdipoR1, and AdipoR2 were measured. It was found that OA exhibited similar effects as atorvastatin including reduced TG, LDL-C, and enhanced HDL-C. Notably, OA elevated the levels of AdipoR1 and PPARγ. At the same time, OA decreased TC and LDL-C in C57BL/6J mice model. Our results in three different animal models all revealed that OA retarded the development of atherosclerosis by influencing serum lipid levels, lipid accumulation in liver and intimal thickening of artery. And the underlying mechanism of OA on atherosclerosis may involve in lipid metabolism genes: PPARγ, AdipoR1, and AdipoR2.

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  • Trials in several animal models have reported reductions in serum TC, TG, LDL-C or VLDL-C and/or increased HDL-C concentrations following oral administration of different doses of MA, OA or high but not low doses of ursolic acid.

    “Trials in several animal models have also reported reductions in serum TC, TG, LDL-C or VLDL-C and/or increased HDL-C concentrations following oral administration of different doses (15–100 mg/kg/d) of MA [reviewed in 26], OA (5–25 mg/kg/d) [25–29] or high (200 mg/kg/d) but not low (50 mg/kg/d) doses of ursolic acid (UA) [30].”

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  1. Skaggs BJ, Hahn BH, McMahon M. The role of the immune system in atherosclerosis: molecules, mechanisms and implications for management of cardiovascular risk and disease in patients with rheumatic diseases. Nat Rev Rheumatol 2012, 8: 214-223.

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Authors
Luo, H., Liu, J., Ouyang, Q., Xuan, C., Wang, L., Li, T., & Liu, J.
Affiliations
China Pharmaceutical University (CN)
Corresponding author
Liu, Jun
Venue
Acta Biochimica et Biophysica Sinica
Published
2017-04-01
Volume
49
Issue
4
Pages
349-354
ISSN
1672-9145 (ISSN-L)
OpenAlex
W2592398276
Cited by
34
References
34
Citations by year
2026: 4 · 2025: 4 · 2024: 5 · 2022: 7 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 5
FWCI
3.64
Type
journal article
Language
en
Open access
Locations
  • Acta Biochimica et Biophysica Sinica (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81673443)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
oleanolic acid, atherosclerosis, Ldlr knockout mice, rabbit atherosclerosis model, atorvastatin, PPARγ, AdipoR1, AdipoR2, lipid metabolism, serum cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, hepatic lipid accumulation, intimal thickening, carotid artery lesions
MeSH terms
Animals, Cholesterol, Disease Models, Animal, Cholesterol, HDL, Cholesterol, LDL, Mice, Inbred C57BL, Oleanolic Acid, Rabbits, Receptors, LDL, Species Specificity, Molecular Structure, Gene Expression, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, PPAR gamma, Atherosclerosis, Lipid Metabolism, Receptors, Adiponectin

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