Abstract
Numerous epidemiological findings have repeatedly established associations between Type 2 Diabetes Mellitus (T2DM) and Alzheimer’s disease. Targeting different pathways in the brain with T2DM-therapy offers a novel and appealing strategy to treat diabetes-related neuronal alterations. Therefore, here we investigated the capability of a natural compound, curcumin nanoparticle (CurNP), and a biomedical metal, zinc oxide nanoparticle (ZnONP), to alleviate hippocampal modifications in T2DM-induced rats. The diabetes model was induced in male Wistar rats by feeding a high-fat diet (HFD) for eight weeks followed by intraperitoneal injection of streptozotocin (STZ). Then model groups were treated orally with curcumin, zinc sulfate, two doses of CurNP and ZnONP, as well as metformin, for six weeks. HFD/STZ-induced rats exhibited numerous biochemical and molecular changes besides behavioral impairment. Compared with model rats, CurNP and ZnONP boosted learning and memory function, improved redox and inflammation status, lowered Bax, and upregulated Bcl2 expressions in the hippocampus. In addition, the phosphorylation level of the MAPK/ERK pathway was downregulated significantly. The expression of amyloidogenic-related genes and amyloid-beta accumulation, along with tau hyperphosphorylation, were lessened considerably. In addition, both nanoparticles significantly improved histological lesions in the hippocampus. Based on our findings, CurNP and ZnONP appear to be potential neuroprotective agents to mitigate diabetic complications-associated hippocampal toxicity.
Highlights
Academic Editors: Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria 21511, Egypt; Center of Excellency for Preclinical Study (CE-PCS), Pharmaceutical and Fermentation Industries
We examined the role of prepared nanoparticles on the MAPK/extracellular signal kinase (ERK) pathway in the hippocampus of Type 2 diabetes mellitus (T2DM)-induced rats to figure out the most effective and safe compound(s) among the current therapies and find the effective dose, and to support the rationale for using naturally occurring nanoparticles and metal oxide-based nanomaterials in clinical trials for preventing or treating T2DM and its complications, Alzheimer’s disease (AD)
TEM analysis displayed that zinc oxide nanoparticle (ZnONP) had a diameter between 11 and 22 nm while
Summary
Here we investigated the capability of a natural compound, curcumin nanoparticle (CurNP), and a biomedical metal, zinc oxide nanoparticle (ZnONP), to alleviate hippocampal modifications in T2DM-induced rats. The expression of amyloidogenicrelated genes and amyloid-beta accumulation, along with tau hyperphosphorylation, were lessened considerably. Both nanoparticles significantly improved histological lesions in the hippocampus. Type 2 diabetes mellitus (T2DM) is associated with an increased risk of neurocognitive dysfunction and Alzheimer’s disease (AD). Obese animal models have shown impaired insulin signaling before developing T2DM [5]. It has been documented those changes published maps and institutional affiliations. Pharmaceutics 2021, 13, 1937 in carbohydrate metabolism play an essential role in the pathophysiology of T2DM and act as an important contributor to the pathogenic mechanisms related to reduced cognitive performance [6,7]
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