番石榴葉萃出物對streptozotocin-nicotinamide誘發第二型糖尿病大白鼠血糖之影響

Abstract

糖尿病是現今常見的一種慢性代謝疾病，隨著生活品質的提昇及物質充裕，糖尿病病患的比例也日益增加。根據世界衛生組織預測，到西元 2025 年全球罹患糖尿病的人數將達到三億人。番石榴（Psidium guajava Linn.）屬桃金孃科（Myrtaceae），本省民間常將野生番石榴果實或葉片曬乾熬湯飲用，作為降火氣、清血、降血糖之用，是坊間盛行的糖尿病藥草療法。本研究係以低劑量 Streptozotocin（65 mg/Kg BW）與胰臟保護劑 Nicotinamide（230 mg/Kg BW）注射 Sprague-Dawley 大白鼠，使產生類似第二型糖尿病的動物模式，探討番石榴（Psidium guajava Linn.）葉部之水與乙醇萃取物的降血糖效果，及其對肝臟碳水化合物代謝之影響。結果顯示，在急性試驗中，番石榴葉水或醇萃物皆具有顯著延緩血糖上升的效果，且高劑量組（400 mg/Kg BW）效果優於低劑量組（200 mg/Kg BW）。而在長期灌食實驗中，期間於第四、六週進行口服葡萄糖耐受性試驗，結果顯示番石榴葉（灌食劑量 400 mg/Kg BW）水萃物或醇萃物均能明顯改善糖尿病鼠的葡萄糖耐受性；試驗動物於第六週犧牲後測其肝臟中碳水化合物代謝酵素活性變化，結果顯示長期灌食番石榴葉水萃物能活化肝臟 hexokinase（HKase）、phosphofructokinase（PFKase）、glucose-6-phosphate dehydrogenas（G6PDHase）活性及降低 fructose-1,6-bisphosphatase（F1,6BPase）、Glucose -6-phosphatase（G6Pase）活性，顯示其能促進葡萄糖進入 glycolysis pathway 及 pentose monophosphate shunt 並減少肝臟葡萄糖的釋放而降低血糖；灌食番石榴葉乙醇萃取物之糖尿病大鼠只有 HKase 與 G6PDHase 活性較糖尿病組高，而 PFKase、 F1,6BPase 及 G6Pase 活性與糖尿病組並沒有顯著差異（p<0.05）。分析管餵六週後，糖尿病大鼠的骨骼肌及肝臟細胞葡萄糖攝入能力及肝醣合成能力的變化，結果顯示管餵葉粗萃物並不會促進骨骼肌對葡萄糖的攝入能力，但能增加肝臟細胞對葡萄糖的攝入能力並促進肝醣合成。綜合所得的結果得知，番石榴葉萃出物具顯著的降血糖效果，且其降血糖效果乃是藉由改變其肝臟碳水化合物代謝酵素活性，並增強糖尿病大白鼠肝臟對葡萄糖的攝入及肝醣合成能力，因而降低糖尿病大白鼠的高血糖現象。

Diabetes mellitus (DM) is one of the major diseases that human being eagerly wants to overcome. In 2006, DM was the fourth of top ten causes of death in Taiwan and more than 95% are type 2 DM. Guava (Psidium guajava Linn.) is one of the most important economic fruit in Taiwan. Leaves and fruit of guava are believed to have hypoglycemic effects which have been popularly employed in traditional DM treatment in Taiwan. However, there is insufficient scientific evidence for guava to cure DM, especially type 2 DM. In the present study, we injected low-dose streptozotocin (STZ) plus nicotinamide (NA) into Sprague-Dawley (SD) rats to induce Type 2 diabetes and to evaluate the antihyperglycemic effect and the carbohydrate metabolism of water and ethanol extracts from guava leaves. The study contains two parts, the acute and the long term experiments. In the acute experiment, the water or ethanol extracts of guava leaves were prepared and in the oral glucose tolerance test (OGTT) was performed to evaluate the hypoglycemic effects. In the long term experiment, we investigated the effect of aqueous or ethanol extracts from guava leaves in STZ–NA induced diabetic rats daily administered for 6 weeks. Results of the acute experiment showed that plasma glucose levels of the diabetic rats administered with 200 or 400 mg/kg BW of aqueous or ethanol guava leaf extracts were lower than the diabetic control group (p<0.05). This indicated that aqueous or ethanol extracts from guava leaves could effectively delay the rise of plasma glucose after feeding in diabetic rats. Diabetic rats administered with 400 mg/kg BW of aqueous or ethanol guava leaf extracts significantly reduced plasma glucose than 200 mg/kg BW. Therefore, aqueous or ethanol extracts from guava leaves with dosage of 400 mg/kg BW were used to carry out the long term experiments. The result of the long term experiments, showed that the diabetes groups fed with 400 mg/kg BW of aqueous or ethanol guava leaf extracts presented a significantly reduction of blood sugar level comparing to diabetes and normal groups (both fed with saline) and could delay the elevation of plasma glucose during the OGTT test after the fourth and sixth weeks. The rats were sacrificed at the 6 weeks and the carbohydrate metabolism enzyme activities in liver were measured. The activities of hexokinase, phosphofructokinase, and glucose-6-phosphate dehydrogenas in diabetic rats fed with aqueous guava leaf extracts were higher than those of diabetic control rats (p<0.05), while the activity of fructose-1, 6-bisphosphatase and glucose-6-phosphatase was markedly lower than diabetic control rats (p<0.05). In addition, the activities of hexokinase and glucose-6-phosphate dehydrogenase in diabetic rats fed with ethanol guava leaf extracts were higher than diabetic control rats, while the activities of phosphofructokinase, fructose-1, 6-bisphosphatase, and glucose-6-phosphatase were no different with each group. The blood glucose reduction ability of extracts from guava leaves in diabetic rats may be related with the activity of hepatic carbohydrate metabolic enzymes. In additional, the abilities of glucose uptake and glycogen synthesis are significantly promoted in hepatocytes of diabetic rats treated with aqueous or ethanol extracts from guava leaves. These results indicate that extracts of guava leaves may regulate the plasma glucose in STZ–NA induced type 2 diabetic rats.