Mulberry extract inhibits the development of atherosclerosis in cholesterol-fed rabbits 生科四甲 吳威儀

脂質的過氧化及低密度脂蛋白的氧化被證實是動脈粥狀硬 化發生過程的致病因子。利用抗氧化劑預防低密度脂蛋白 的氧化反應可能使是一種有效的抑制動脈粥狀硬化發生過 程的方法。利用桑椹豐富的天然抗氧化色素成分，我們期 待桑椹可抑制低密度脂蛋白氧化而達到預防動脈粥狀硬化 的發生。此外，並以高膽固醇飲食混合桑椹萃取物餵食之 動物實驗模式，觀察動物血脂變化及血管的病理變化，最 終以科學證據驗證桑椹具有抑制預防動脈粥狀硬化發生的 效果。 Abstract

名詞解釋  MWE → mulberry water extract  HCD → High cholesterol diet  Atherosclerosis → 動脈粥狀硬化  Anthocyanin → 花色素 ( 抗氧化物質 )  Foam cell → 泡沫細胞  Intima → 動脈血管內膜

低密度脂蛋白 (LDL)  LDL 富含膽固醇，人體總血清中約有 65% 的膽固醇 由 LDL 攜帶傳送至周圍組織，因此 LDL 的吸收與膽 固醇的代謝息息相關。若 LDL 無法有效的被細胞組 織吸收，而在血液循環系統中存在過多的 LDL 會增 加罹患心血管循環系統疾病的風險。  低密度脂蛋白 80% 可由肝吸收，另 20% 則由周圍 組織吸收，吸收方式是經由 LDL receptor 攝取， 藉由 receptor-mediated 途徑與 nonspecific endocytosis 方式進入細胞及肝臟中。 Introduction

Atherosclerosis

病程的中期 macrophage 會與 intima 中 T cell 作用而產生成 cytokines

Materials and methods  Preparation of MWE 桑椹果實 (100g)+ 飲用水 (200cc) 果汁機 濾網過濾去渣 離心機離心去渣 (3000rpm,15mins) -80c 冷凍； 12 小時 真空冷凍乾燥  Concentrations of anthocyanins in MWE >MWE contains about 2.5% anthocyanins

Animals and diets  Group1 rabbits were fed with standard chow.  Group2 rabbits were fed with standard chow with 1% MWE in the daily diet.  Group3 rabbits were fed with HCD diet(containing 3% lard oil and 1.3% cholesterol).  Group4 treated with HCD plus 0.5% MWE.  Group5 treated with HCD plus 1% MWE.

Growth and diet intake No significant difference in body weights was observed during the experimental period.

Result and Discussion This may indicate a specific inhibitory effect of MWE on fatty acid synthesis, especially triglycerides.

Effect of MWE on serum lipid levels Effect of MWE on plasma cholesterol levels in 10 week-period HCD-fed rabbits.

動物動脈組織切片之病理分析

The arrow( ) is shown for foam cell and ( ) for smooth muscle cell migration. Calcification core is shown as arrow ( ) in (c);

Pathological analysis Calcification 是指 foam cell apoptosis 後，細胞所流出的膽固 醇和脂質聚集而促使 Gruel 的形成。 Gruel 唯一種糜粥狀的油 脂聚合物，也是形成動脈粥狀硬化斑的主因。

動物動脈脂肪斑 (fatty streak) 染色 脂肪的堆積情形

主動脈損害程度

MWE 餵食下肝、腎之生化毒性分析  此表顯示 MWE 添加於飲食中並不會有生化毒性

Conclusion In this study, MWE was shown to decrease cholesterol and triglyceride and attenuate the development of atherosclerosis in HCD-fed rabbits. Additionally, MWE had no toxic effects on the liver or renal functions during the experimental period. Taken together, these data suggest a promising application of MWE in cardioprotection. MWE was shown to lower the serum cholesterol and triglyceride and repress progression of atherosclerosis in HCD-fed rabbits. This outcome might be attributed to the preventative effect of anthocyanins against LDL-oxidation in the arterial wall and supports the use of MWE for lowering the incidence of atherosclerosisand coronary heart disease.