山苦瓜改善血糖血脂代謝異常之效應探討

Abstract

代謝症候群指血糖調節異常 (胰島素抗性)、高血脂、中心型肥胖、高血壓等至少三項同時存在者，未經適當控制則具有極高之風險轉為第二型糖尿病及動脈粥狀硬化。PPARs (Peroxisome proliferators activated receptors) 為核受器家族的一員，受 ligand 活化後可啟動下游基因的轉錄，主調控葡萄糖及脂質代謝、運輸及貯存相關基因之表現。本實驗室在過去的研究中顯示，山苦瓜 (Momordica charantia L.) 乙酸乙酯萃物中含有可活化 PPARα 與 PPARγ 之成分，可調控其下游基因之表現。本研究先以高脂飲食誘發 C57BL/6J 小鼠產生血糖、血脂代謝異常現象，探討餵食山苦瓜全果凍乾粉末或其乙酸乙酯萃物，對小鼠體內葡萄糖及脂質代謝與肝臟 PPARα 相關基因表現之影響。分別餵食 C57BL/6J 小鼠含5% 大豆油 (B) 或30% 奶油 (C) 之實驗飼料 16 週後，C 組血糖、胰島素及血清中三酸甘油酯 (TG) 濃度顯著較 B 組高。再將 C 組小鼠隨機分為五組，一組維持原飼料，兩組分別更換為含有5% 山苦瓜全果凍乾粉末 (BGP) 及0.25% 山苦瓜乙酸乙酯萃物 (EAE) 之高油脂飼料，另外以含有0.5% clofibrate (CF) 或 0.004% rosiglitazone (R) 之高油脂飼料作為正對照組。繼續飼養四週後，BGP 組之血糖顯著低於 C 組 (p < 0.05)。飼養九週後，相較於 C 組，BGP 組體內葡萄糖耐受性顯著佳 (p < 0.05)。飼養 11 週後犧牲， BGP 組之體重增加量、血脂質、肝脂質皆顯著低於對照組C組。而 EAE 組在血脂、肝脂之部分指標顯著低於對照組 C 組。改以餵食 Wistar 大鼠含 5% 大豆油 (B) 或 30% 奶油 (C) 之實驗飼料 3 週後，C 組大鼠體重顯著高於 B 組。再將 C 組大鼠隨機分為六組，一組維持原飼料，三組分別更換為含有5% 山苦瓜全果凍乾粉末 (BGP)、1% 山苦瓜乙酸乙酯萃物 (EAE) 或 3% 山苦瓜酒精萃物之高油脂飼料，另外以含有1% clofibrate (CF) 或 0.01% rosiglitazone (R) 之高油脂飼料作為正對照組。飼養四週後，C 組出現口服葡萄糖耐受性較差，但 BGP 組則否 (p < 0.05)。飼養五週後犧牲，結果顯示 BGP 組之腹脂重量顯著低於對照組C 組，且山苦瓜全果凍乾粉末及其乙酸乙酯、酒精萃物可預防因高脂飲食造成的高血糖、高血清胰島素等症狀。此外，攝取山苦瓜全果凍乾粉末或其乙酸乙酯萃物能顯著誘發 β-oxidation 之關鍵酵素 acyl-CoA oxidase mRNA 之表現。綜合上述結果可知，5% 山苦瓜全果凍乾物可改善高脂飲食誘導之體重增加、高血糖、高血脂及葡萄糖不耐現象，可開發為調節血糖與血脂之功能性食品。

Metabolic syndrome, which develops as a result of insulin resistance, is characterized by obesity, glucose intolerance, hyperinsulinemia, dyslipidemia, and hypertension. Peroxisome proliferators-activated receptors (PPARs), ligand-dependent transcription factors that regulate the expression of genes involved in glucose and lipid homeostasis, are molecular targets of well-known therapeutic agents of hyperlipidemia and insulin resistance. Ethyl acetate (EA) extract of bitter gourd (momordica Charantia) has been found to active PPARα and PPARγ significantly. High-fat diet induced obesity rodent model was therefore employed in this study to investigate the effects of Momordica charantia L. on glucose and lipid metabolism. A few PPARα target gene expressions in liver were also examined. In experiment 1, C57BL/6J mice were prefed a high butterfat diet (30%) for 16 weeks for the development of hyperglycemia and hyperlipidemia. These animals were then assigned to 5 groups and respectively fed the high butter fat diet supplemented with none (the C diet group), 5% wild bitter ground powder (the BGP diet group), 0.25% of BGP ethyl acetate extract (the EAE diet group), 0.5% clofibrate (the CF diet group) or 0.004% rosiglitazone (the R group) for 11 weeks. A group of mice was simultaneously fed a basal diet (5% soybean oil, the B diet group) for a total of 27 weeks and serve as the normal control. Hyperglycemia, glucose intolerance, hypertriglyceridemia and hypercholesterolemia were observed in the C group but were significantly improved in the BGP group. In experiment 2, Wistar rats were respectively fed the basal diet (B), or the high butter fat diets for 3 weeks. The high fat fed groups were then assigned to 6 groups and respectively fed the high butterfat diet supplemented with none (C), 5% of bitter ground powder (BGP), 1% EA extract (EAE) or 3% ethanol extract (E) of bitter ground powder, 1% clofibrate (CF) or 0.01% rosiglitazone (R) for 5 weeks. Hyperinsulinemia and glucose intolerance were observed in the C group but not in the BGP, CF and R groups. Serum insulin of the EAE and E groups were also significantly lower than that of the C group. Up-regulation of PPARα target gene (ACO) mRNA expression were observed in rats fed the test diets containing 5% bitter ground powder (BGP) and 1% bitter ground powder EA extract (EAE). In conclusion, 5% wild bitter ground powder improved high fat diet-induced metabolic syndrome, such as hyperglycemia, hyperlipidemia, and glucose intolerance. These results provide evidence that wild bitter melon may potentially be developed as a functional food for ameliorating hyperglycemia and hyperlipidemia.