Department of Biochemistry, Faculty of Science, University of Yaoundé 1, P. O. Box 812, Yaoundé, Cameroon; Center of Nutrition and Functional Foods, P.O. Box 8024, Yaoundé, Cameroon.
Department of Biochemistry, Faculty of Science, University of Yaoundé 1, P. O. Box 812, Yaoundé, Cameroon.
J Ethnopharmacol. 2024 Dec 5;335:118653. doi: 10.1016/j.jep.2024.118653. Epub 2024 Jul 31.
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.
The present research study investigated the neuroprotective effects of TeMac™ on Alzheimer-like pathology induced by aluminum chloride (AlCl) in diabetic rats.
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 AlCl (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.
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.
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.
ETHNOPHARMACOLOGICAL 相关性：阿尔茨海默病是最常见的神经退行性疾病，治疗方法有限。胰岛素抵抗在阿尔茨海默病的进展中起作用。目前正在研究调节胰岛素分泌和信号转导以及大脑氧化应激的疗法，以探索其在预防阿尔茨海默病（AD）中的潜在作用。Terminalia macroptera（Combretaceae）是一种植物，其不同部位传统上用于治疗代谢和神经疾病。先前的研究表明，粗提取物具有抗糖尿病作用。此外，该植物是单宁、酚酸、类黄酮、三萜的丰富来源。然而，目前尚无关于其在糖尿病大鼠 AD 生化改变中的保护作用的研究。
本研究旨在探讨 TeMac™对氯化铝（AlCl）诱导的糖尿病大鼠阿尔茨海默病样病理的神经保护作用。
对 TeMac™进行植物化学分析以定量单宁。通过其抑制β-分泌酶（EC 3.4.23.46）、单胺氧化酶 A（EC 1.4.3.4）和 Aβ 纤维形成的能力，研究 TeMac™的单宁富集部分（TEF）预防老年斑形成的潜在作用。通过单次腹腔注射链脲佐菌素（STZ，35 mg/kg BW）从雌性 Wistar 大鼠中诱导糖尿病模型。之后，测量血糖水平以确认糖尿病的诱导。诱导后 3 天，动物单独接受 AlCl（75 mg/kg BW）（AD 对照）或同时接受 400 mg/kg BW 的 TeMac™的 TEF 或 5 mg/kg BW Daonil，每天灌胃 42 天。实验结束时，处死大鼠，采集血液和大脑。评估大脑中淀粉样纤维、葡萄糖、白蛋白和 DPP4、β-分泌酶和磷酸酶的活性以及氧化应激标志物的水平。
TeMac™的 TEF 显示出抑制β-分泌酶、单胺氧化酶和 Aβ 纤维形成的潜在能力。TeMac™的 TEF 治疗显着抑制 DPP4 和 BACE1 活性，降低大脑葡萄糖和淀粉样纤维水平，提高大脑白蛋白水平并调节氧化应激标志物。
我们的研究结果表明，TeMac™的 TEF 可预防与胰岛素抵抗相关的阿尔茨海默病样病理。TeMac™的 TEF 可能是治疗糖尿病相关认知障碍的潜在候选药物。
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