消渴草粗萃物對高脂飲食及STZ誘發高血糖大鼠胰島素阻抗及肝臟解毒功能之影響

Abstract

研究指出攝取高脂飲食會造成周邊組織胰島素阻抗，並且增加罹患第二型糖尿病及非酒精性脂肪肝的風險。消渴草(Ruellia tuberosa L.)屬於爵床科蘆莉草屬，東方國家中將之作為治療糖尿病的民間草藥。本研究探討消渴草改善高脂飲食合併STZ腹腔注射誘發之第二型糖尿病大鼠高血糖及肝臟解毒酵素系統的效果。細胞試驗方面，以33mM高葡萄糖誘導clone 9大鼠肝臟細胞株胰島素阻抗，並將消渴草水萃物或醇萃物與螢光葡萄糖2-NBDG共同培養，偵測2-NBDG的攝入量以評估抗胰島素阻抗能力；動物試驗方面，以高脂飲食合併腹腔注射STZ誘導雄性Wistar大鼠成第二型糖尿病後，每日管餵每公斤體重100或400毫克的消渴草萃取物連續4周，並評估其降血糖與改善肝臟解毒酵素的效果。結果顯示，消渴草水萃物及醇萃物分別在800mg/L的劑量下均分別可顯著地增加胰島素阻抗clone 9大鼠肝臟細胞40%及18%的葡萄糖攝入能力。消渴草水及醇萃取物均能使第二型糖尿病大鼠的血糖值、糖化血色素及果糖胺值顯著地降低，並增加肝臟中SOD、CAT和GPx抗氧化酵素的活性。聚合酶鏈鎖反應結果顯示，消渴草水萃物或醇萃物能夠對 CYP 2E1、CYP 3A2、CYP 4A2、UGT 1A7、GST M1 和 SULT 1A1顯著地恢復至正常水平。綜合以上結果，消渴草具有降低第二型糖尿病大鼠之高血糖、改善肝臟胰島素阻抗及解毒酵素系統的能力。

Studies suggest that individuals with high fat intake may adversely affect insulin resistance in the periphery tissues and result in increased risk of bothType 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ruellia tuberosa L. (RTL) belongs to the Acanthaceae family. In folk medicine, it has been used for curing diabetes in East Asia. The present work was to investigate the effect of RTL on anti-hyperglycemia and detoxification enzymes system of liver in high-fat diet plus streptozotocin (STZ) induced T2DM rats. The clone 9 rat hepatocytes were treated with 33nM glucose for the induction of insulin resistance. These cells were then co-incubated with water or ethanol extract from RTL. The uptake of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy -d-glucose (2-NBDG) in insulin-resistant clone 9 cells was used as a platform for screening extracts with the anti-insulin resistance potential. The male Wistar rats fed with high-fat diet followed by intraperitoneal injection of STZ to induced T2DM were subsequently orally administered with extract from RTL once a day at a dosage of 100 or 400 mg/kg bw for 4 weeks. The effect of RTL on anti-hyperglycemia and detoxification in T2DM rats were analyzed. The results show that water or ethanol extract from RTL (800mg/L) increases 40% and 18%, respectively, glucose uptake ability in insulin-resistant clone 9 rat hepatocytes. The plasma glucose and glycemic marker, such as HbA1C and fructosamine, levels were significantly decreased, and hepatic anti-oxidant enzymes, including SOD, CAT and GPx, activity were significantly increased in both water and ethanol extract treated T2DM rats. The results from real-time PCR analysis suggest that water or ethanol extract from RTL significantly normalized the expressions of phase I and II detoxification enzymes, including CYP 2E1, CYP 3A2, CYP 4A2, UGT 1A7, GST M1 and SULT 1A1, in T2DM rats (p< 0.05). In conclusion, RTL may alleviate hypoglycemia and hepatic insulin resistance, and ameliorate detoxification function in high-fat diet plus STZ induced T2DM rats.