新型水溶性姜黄素衍生物对实验性 1 型糖尿病（短期研究）的影响。
Effect of novel water soluble curcumin derivative on experimental type- 1 diabetes mellitus (short term study).
机构信息
Unit of Biochemistry and Molecular Biology, the Medical Biochemistry Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
出版信息
Diabetol Metab Syndr. 2012 Jul 4;4(1):30. doi: 10.1186/1758-5996-4-30.
BACKGROUND
Diabetes mellitus type 1 is an autoimmune disorder caused by lymphocytic infiltration and beta cells destruction. Curcumin has been identified as a potent inducer of heme-oxygenase-1 (HO-1), a redoxsensitive inducible protein that provides protection against various forms of stress. A novel water soluble curcumin derivative (NCD) has been developed to overcome low in vivo bioavailability of curcumin. The aim of the present work is to evaluate the anti diabetic effects of the "NCD" and its effects on diabetes-induced ROS generation and lipid peroxidation in experimental type- 1 diabetes mellitus. We also examine whether the up regulation of HO-1 accompanied by increased HO activity mediates these antidiabetic and anti oxidant actions.
MATERIALS AND METHODS
Rats were divided into control group, control group receiving curcumin derivative, diabetic group, diabetic group receiving curcumin derivative and diabetic group receiving curcumin derivative and HO inhibitor ZnPP. Type-1 diabetes was induced by intraperitoneal injection of streptozotocin. Curcumin derivative was given orally for 45 days. At the planned sacrification time (after 45 days), fasting blood samples were withdrawn for estimation of plasma glucose, plasma insulin and lipid profile . Animals were sacrificed; pancreas, aorta and liver were excised for the heme oxygenase - 1 expression, activity and malondialdehyde estimation.
RESULTS
NCD supplementation to diabetic rats significantly lowered the plasma glucose by 27.5% and increased plasma insulin by 66.67%. On the other hand, the mean plasma glucose level in the control group showed no significant difference compared to the control group receiving the oral NCD whereas, NCD supplementation to the control rats significantly increased the plasma insulin by 47.13% compared to the control. NCD decreased total cholesterol, triglycerides, LDL cholesterol and increased HDL cholesterol levels. Also, it decreased lipid peroxides (malondialdehyde) in the pancreas, aorta and liver.
CONCLUSION
The (NCD) by its small dose possesses antidiabetic actions and that heme oxygenase induction seems to play an important role in its anti-diabetic effects. NCD also improves the lipid profile and oxidative status directly, proved by decreasing lipid peroxides (malondialdehyde) in pancreas, liver & aorta. The new water soluble curcumin derivative still retains the essential potencies of natural curcumin.
背景
1 型糖尿病是一种由淋巴细胞浸润和β细胞破坏引起的自身免疫性疾病。姜黄素已被确定为血红素加氧酶-1（HO-1）的有效诱导剂，HO-1 是一种氧化还原敏感的诱导蛋白，可提供针对各种形式应激的保护。已经开发出一种新型水溶性姜黄素衍生物（NCD）来克服姜黄素体内生物利用度低的问题。本研究旨在评估“NCD”的抗糖尿病作用及其对实验性 1 型糖尿病中 ROS 生成和脂质过氧化的影响。我们还检查了 HO-1 的上调是否伴随着 HO 活性的增加介导这些抗糖尿病和抗氧化作用。
材料和方法
大鼠分为对照组、对照组给予姜黄素衍生物、糖尿病组、糖尿病组给予姜黄素衍生物和糖尿病组给予姜黄素衍生物和 HO 抑制剂 ZnPP。通过腹腔注射链脲佐菌素诱导 1 型糖尿病。姜黄素衍生物口服给予 45 天。在计划的牺牲时间（45 天后），抽取空腹血样以测定血浆葡萄糖、血浆胰岛素和血脂谱。动物被处死；取出胰腺、主动脉和肝脏，用于测定血红素加氧酶-1 的表达、活性和丙二醛的测定。
结果
NCD 补充剂可使糖尿病大鼠的血浆葡萄糖降低 27.5%，使血浆胰岛素增加 66.67%。另一方面，与接受口服 NCD 的对照组相比，对照组的平均血浆葡萄糖水平无显著差异，而 NCD 补充剂可使对照组大鼠的血浆胰岛素增加 47.13%。NCD 降低了总胆固醇、甘油三酯、LDL 胆固醇并增加了 HDL 胆固醇水平。此外，它还降低了胰腺、主动脉和肝脏中的脂质过氧化物（丙二醛）。
结论
NCD 以小剂量具有抗糖尿病作用，血红素加氧酶诱导似乎在其抗糖尿病作用中发挥重要作用。NCD 还通过降低胰腺、肝脏和主动脉中的脂质过氧化物（丙二醛）直接改善血脂谱和氧化状态。新型水溶性姜黄素衍生物仍保留天然姜黄素的基本功效。
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