The effects of oleanolic acid on atherosclerosis in different animal models.
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.
Jiangsu Key Laboratory of Drug Screening and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing 210009, China.
Hanqiong
H
Luo
Jiangsu Key Laboratory of Drug Screening and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing 210009, China.
Jine
J
Liu
Jiangsu Key Laboratory of Drug Screening and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing 210009, China.
Qiong
Q
Ouyang
Jiangsu Key Laboratory of Drug Screening and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing 210009, China.
Chunxiao
C
Xuan
Jiangsu Key Laboratory of Drug Screening and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing 210009, China.
Lanlan
L
Wang
Jiangsu Key Laboratory of Drug Screening and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing 210009, China.
Tingting
T
Li
Jiangsu Key Laboratory of Drug Screening and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing 210009, China.
Jun
J
Liu
D000818:Animals; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D050356:Lipid Metabolism / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000737:chemistry / Q000494:pharmacology*; D047495:PPAR gamma / Q000235:genetics; D011817:Rabbits; D054419:Receptors, Adiponectin / Q000235:genetics; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D047495:PPAR gamma; D054419:Receptors, Adiponectin; D011973:Receptors, LDL; D009828:Oleanolic Acid; D002784:Cholesterol
animal model; atherosclerosis; oleanolic acid