title: Protective effect of betulinic acid on early atherosclerosis in diabetic apolipoprotein-E gene knockout mice.
abstract: 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.
authors.affiliation: College of Oriental Medicine and Professional Graduate School of Oriental Medicine bHanbang Body-fluid Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: Jung Joo
authors.initials: JJ
authors.lastname: Yoon
authors.affiliation: College of Oriental Medicine and Professional Graduate School of Oriental Medicine bHanbang Body-fluid Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: College of Oriental Medicine and Professional Graduate School of Oriental Medicine bHanbang Body-fluid Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: Byung Hyuk
authors.initials: BH
authors.lastname: Han
authors.affiliation: College of Oriental Medicine and Professional Graduate School of Oriental Medicine bHanbang Body-fluid Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: Eun Sik
authors.initials: ES
authors.lastname: Choi
authors.affiliation: College of Oriental Medicine and Professional Graduate School of Oriental Medicine bHanbang Body-fluid Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: Min Chul
authors.initials: MC
authors.lastname: Kho
authors.affiliation: College of Oriental Medicine and Professional Graduate School of Oriental Medicine bHanbang Body-fluid Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: Ji Hun
authors.initials: JH
authors.lastname: Park
authors.affiliation: College of Oriental Medicine and Professional Graduate School of Oriental Medicine bHanbang Body-fluid Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: You Mee
authors.initials: YM
authors.lastname: Ahn
authors.affiliation: College of Oriental Medicine and Professional Graduate School of Oriental Medicine bHanbang Body-fluid Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Republic of Korea.
authors.forename: Hye Yoom
authors.initials: HY
authors.lastname: Kim
authors.affiliation: College of Oriental Medicine and Professional Graduate School of Oriental Medicine bHanbang Body-fluid Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Republic of Korea. Electronic address: dgkang@wku.ac.kr.
authors.forename: Dae Gill
authors.initials: DG
authors.lastname: Kang
authors.affiliation: College of Oriental Medicine and Professional Graduate School of Oriental Medicine bHanbang Body-fluid Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Republic of Korea. Electronic address: host@wku.ac.kr.
authors.forename: Ho Sub
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics*; D050197:Atherosclerosis / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D055786:Gene Knockout Techniques; D006949:Hyperlipidemias / Q000150:complications; D006973:Hypertension / Q000150:complications; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D009569:Nitric Oxide; D000094062:Betulinic Acid
keywords: ApoE KO mice; Atherosclerosis; Betulinic acid; Insulin resistance; Vascular dysfunction