桑葉多酚減少肝臟脂肪堆積之作用

Mulberry Leaf Polyphenol Extracts Reduced Accumulation of Lipid in Hepatocytes

陳書郡(Shu-Chun Chen)

指導教授 ： 王朝鐘 ； 張雲菁

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2009年)

https://doi.org/10.6834/CSMU.2009.00135

摘要

當脂肪過度堆積在肝時會增加肝臟疾病之風險，與肥胖、脂血代謝異常、高血壓、胰島素抗性及糖尿病等有極高之關聯性，但因病狀容易遭到忽略而進展成更嚴重的脂肪性肝炎，所以降低肝臟脂肪堆積之化學藥品或是天然萃取物開發，已經成為當前治療脂肪肝性疾病一項重要的課題。來自乾燥桑葉 (Morus spp.)中的桑葉多酚萃取物 (MLPE) 被證實具有降血糖、降血脂、對抗粥狀動脈硬化等心血管疾病危險因子，然MLPE是否具備抑制肝臟脂肪堆積之功效仍有待確認，故本論文以細胞模式和動物模式探討MLPE 減少肝臟脂肪堆積之作用與機制，並分別以油酸和高油脂飲食 (high fat diet, HFD) 誘導兩種模式中肝臟脂肪堆積。結果發現MLPE可降低血液和肝臟脂質 (三酸甘油酯、膽固醇、脂肪酸) 堆積的現象，並使高油脂飲食組動物體重減輕。同時還發現MLPE可以減少脂質生成酵素，例如：FAS (fatty acid synthase)、ACC (Acetyl-CoA carboxylase)、HMGCR (HMG-CoA reductase) 及其相關轉錄因子 (SREBP1，SREBP2，PPARγ) 之蛋白表現。此外，MLPE主要是透過AMPK (AMP-activating kinase) 之傳訊路徑調控上述這些蛋白質，達到降低肝臟脂肪堆積之效果。此研究證實MLPE可以有效降低血液和肝臟中脂質含量，且無肝腎毒性之不良副作用，對於抑制脂肪肝確有不錯之開發潛力，然而，今後仍需進行更深入研究證實MPLE促進脂質代謝之作用。

關鍵字

桑葉多酚 ； 脂肪肝 ； 油酸 ； 高油脂飲食

並列摘要

Fat accumulation in the liver increases the risk of developing progressive liver injuries, and may have implication abount obesity, dyslipidemia, hypertension, insulin resistance and diabetes. It is a very important to develop specific pharmacological or nutritional agents to reduce lipid content and prevent the development of more severe forms of liver disease. Mulberry leaf polyphenol extracts (MLPEs) were extracted from dry mulberry leaves (Morus spp.), which have been known to modulate serum fasting glucose, lipid and antiatherosclerosis. However, the effect of MLPEs on regulating hepatic lipid metabolism is unclear. This study was evaluate the effects and mechanisms of MLPEs in reducing hepatic lipid accumulation when administered in fat overload conditions both in cell culture and in an animal experimental model. We found that MLPEs could regulate serum and hepatic lipid contents (e.g. triglyceride, cholesterol, and free faty acid) and about range of weight gain was also reduced in HFD (high-fat diet) mice. Furthermore, numerous lipogenic enzymes, such as FAS (fatty acid synthetase), ACC (acetyl-CoA carboxylase), HMGCR (HMG-CoA reductase) and associated-lipigenic transcriptional factors (SREBP1, SREBP2, and PPARγ) were suppressed by MLPEs. Our results show that MLPEs are able to reduce the hepatic lipid accumulation through the AMPK (AMP-activaing protein kinase) signaling pathway. And it may have potential therapeutic implications for human dyslipidemias. However, more evidences are still required to demonstrate the effects of MLPEs on lipid metabolism.

並列關鍵字

Mulberry leaf polyphenols ； fatty liver ； oleic acid ； high fat diet

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