Protective effect of betulinic acid on early atherosclerosis in diabetic apolipoprotein-E gene knockout mice

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• 作者：Jung Joo Yoon ; Yun Jung Lee ; Byung Hyuk Han ; Eun Sik Choi ; Min Chul Kho ; Ji Hun Park ; You Mee Ahn ; Hye Yoom Kim ; Dae Gill Kang ; ^{dgkang@wku.ac.kr} ; Ho Sub Lee ; ^{host@wku.ac.kr}
• 关键词：Betulinic acid ; ApoE KO mice ; Atherosclerosis ; Vascular dysfunction ; Insulin resistance
• 刊名：European Journal of Pharmacology
• 出版年：2017
• 出版时间：5 February 2017
• 年：2017
• 卷：796
• 期：Complete
• 页码：224-232
• 全文大小：985 K
• 卷排序：796

文摘

Atherosclerosis, a chronic and progressive disease, is a leading cause of endothelial dysfunction, diabetes mellitus, hypertension, and hypercholesterolemia. Betulinic acid (BA), a pentacyclic triterpene, has been reported to have a variety of biological effects, including anti-inflammatory and immunomodulatory properties. This study was designed to determine whether BA could prevent atherosclerosis in diabetic apolipoprotein-E gene knockout (ApoE KO) mice. The mice were treated with BA for 12 weeks to examine its beneficial effects on atherosclerosis in ApoE KO mice. Male ApoE KO mice and age-matched control group mice (C57BL/6Jms) were used as experimental systems and their systolic blood pressure, insulin resistance, and vascular inflammation were measured. BA-treated ApoE KO mice showed lowered systolic blood pressure. The metabolic parameter showed that BA decreased blood urea nitrogen, triglyceride, and total cholesterol levels. Blood glucose, insulin, glucose tolerance results, and the homeostasis model assessment of insulin resistance (HOMA-IR) index were found to be better in BA-treated ApoE KO mice than untreated ApoE KO mice. Consistent with the change in lipid profiles, oil red O and H&E staining revealed that treatment with BA reduced atherosclerotic lesions such as roughened endothelial layers. BA ameliorated the reduction of endothelial nitric oxide synthase (eNOS) expression, leading to the inhibition of intracellular adhesion molecule 1 (ICAM-1) and endothelin 1 (ET-1) expression. These results suggest that BA may be useful in the treatment and prevention of early atherosclerosis via the attenuation of endothelial dysfunction in diabetic ApoE KO mice.