背景:阿尔茨海默病是最常见的神经退行性疾病,具有治疗局限性。胰岛素抵抗在阿尔茨海默病的进展中起作用。调节胰岛素分泌和信号传导的疗法,以及大脑中的氧化应激,目前正在研究它们在预防阿尔茨海默病(AD)中的潜在作用。大翅目(Combretaceae)是一种植物,传统上已将其不同部分用于治疗代谢和神经系统疾病。先前的研究已经表明粗提取物表现出抗糖尿病性质。此外,这种植物是单宁的丰富来源,酚酸,黄酮类化合物,三萜。然而,目前尚无关于其对糖尿病大鼠AD生化改变的保护作用的研究。
目的:本研究探讨了TeMac™对糖尿病大鼠氯化铝(AlCl3)诱导的阿尔茨海默样病理的神经保护作用。
方法:进行TeMac™的植物化学分析以定量单宁。TeMac™的单宁富集部分(TEF)预防老年斑形成的潜在作用是通过其抑制β-分泌酶活性的能力进行的(EC3.4.23.46),和单胺氧化酶A(EC1.4.3.4)以及抑制Aβ的纤维化。通过单次腹膜内注射链脲佐菌素(STZ,35mg/kgBW)。之后,测量血糖水平以确认糖尿病的诱导。诱导三天后,动物单独接受AlCl3(75mg/kgBW)(AD对照)或同时接受400mg/kgBW的TeMac™TEF或5mg/kgBWDaonil,每天灌胃42天。实验结束时,老鼠被处死,收集血液和大脑。淀粉样纤维的水平,葡萄糖,白蛋白和DPP4,β-分泌酶和磷酸酶的活性,并评估了大脑中氧化应激的标志物。
结果:TeMac™的TEF显示出抑制β-分泌酶和单胺氧化酶活性的潜在能力,和Aβ纤颤。TeMac™TEF治疗显著抑制DPP4和BACE1活性,降低脑葡萄糖和淀粉样蛋白原纤维水平,和改善脑白蛋白水平和调节氧化应激标志物。
结论:我们的研究结果表明,TeMac™的TEF可以预防与大鼠胰岛素抵抗相关的阿尔茨海默型病理。TeMac™的TEF可能是治疗糖尿病相关认知障碍的潜在候选药物。
BACKGROUND: Alzheimer\'s disease is the most common neurodegenerative disease with therapeutic limitations. Insulin resistance plays a role in the progression of Alzheimer\'s disease. Therapies that modulate insulin secretion and signaling, as well as oxidative stress in the brain are now being investigated for their potential role in the prevention of Alzheimer\'s disease (AD). Terminalia macroptera (Combretaceae) is a plant that different parts have been used traditionally for the treatment of metabolic and neurological conditions. Previous study has indicated that the crude extract exhibit anti-diabetic property. In addition, the plant is a rich source of tannins, phenolic acids, flavonoids, triterpenes. However, there is no study on its protective effect against biochemical alterations of AD in diabetic rats.
OBJECTIVE: The present research study investigated the neuroprotective effects of TeMac™ on Alzheimer-like pathology induced by aluminum chloride (AlCl3) in diabetic rats.
METHODS: A phytochemical analysis of TeMac™ was carried out to quantify tannins. The potential effect of the tannins-enriched fraction (TEF) of TeMac™ to prevent the formation of senile plaques was conducted by its ability to inhibit the activities of β-secretase (EC 3.4.23.46), monoamine oxidase A (EC 1.4.3.4) and the fibrillation of Aβ. A diabetic model was induced from female Wistar rats by a single intraperitoneal injection of
streptozotocin (STZ, 35 mg/kg BW). After that, the blood glucose level was measured to confirm the induction of diabetes. Three days after induction, animals received AlCl3 (75 mg/kg BW) alone (AD control) or concomitantly with 400 mg/kg BW of TEF of TeMac™ or 5 mg/kg BW Daonil by daily gavage for 42 days. At the end of the experiment, rats were sacrificed, blood and brains were collected. The levels of amyloid fibrils, glucose, albumin and the activities of DPP4, β-secretase and phosphatase, and markers of oxidative stress in the brain were assessed.
RESULTS: TEF of TeMac™ displays a potential ability to inhibit the activities of β-secretase, monoamine oxidase, and Aβ fibrillation. Treatment with TEF of TeMac™ significantly inhibited DPP4 and BACE1 activities and reduced brain glucose and amyloid fibril levels, and improved cerebral albumin levels and modulated oxidative stress markers.
CONCLUSIONS: Our findings indicate that TEF of TeMac™ prevents Alzheimer\'s-type pathology linked to insulin resistance in rats. TEF of TeMac™ may be a potential drug candidate for the treatment of diabetes-associated cognitive impairment.