Abstract

Alzheimer's disease (AD) is an age‑associated dementia disorder characterized by Aβ plaques and neurofibrillary tangles. There is a strong link between cerebrovascular angiopathy, oxidative stress, inflammation, and glucose metabolism abnormalities with the development of AD. In this study, we investigated the therapeutic influences of artemisinin and TSP‑1‑human endometrial‑derived stem cells (TSP‑1‑hEDSCs) on the streptozocin‑induced model of AD and diabetes in rats. Hippocampal and intraperitoneal injections of streptozocin were used to induce AD and diabetes in male Wistar rats, followed by intranasal administration of a single dose of TSP‑1‑hEDSCs and intraperitoneal administration of artemisinin for 4 weeks. Hematoxylin together with eosin staining was performed for demonstrating Aβ plaque formation and for analyzing the influence of treatments on the pyramidal cells in the hippocampus. Biochemical analysis was used to assay the serum levels of glucose, MDA, ROS, and TAC. The expression of TNF‑α was measured using real‑time PCR. Streptozocin induced AD and diabetes via Aβ plaque formation and increasing blood glucose levels. It also increased the levels of ROS, MDA, and TNF‑α and decreased the levels of TAC. Simultaneous or separate administration of artemisinin and TSP‑1‑hEDSCs ameliorated this influence by considerably reducing Aβ plaque formation in the hippocampus, reducing glucose, MDA, ROS, and TNF‑α levels, and increasing TAC levels. It appears that artemisinin and TSP‑1‑hEDSCs improve the adverse features of AD in a rat model of AD and diabetes. Therefore, artemisinin and TSP‑1‑hEDSCs could be utilized as an adjunct treatment, as well as a protective agent, in AD patients.

Highlights

  • Alzheimer’s disease (AD) is one of the most com‐ mon types of age‐related dementia, characterized by irreversible and devastating neuronal degeneration

  • We showed that hippocampal and i.p. injections of STZ could induce AD and diabetes in male Wistar rats via aggregation of β‐amyloid pep‐tide (Aβ) plaque formation and in‐ creased blood glucose levels and neuronal cell death

  • The model was able to achieve a number of AD features, such as inducing oxidative stress, inflammation, hyperglycemia, aggregation of Aβ plaques, and neuronal cell death and degeneration

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Summary

Introduction

Alzheimer’s disease (AD) is one of the most com‐ mon types of age‐related dementia, characterized by irreversible and devastating neuronal degeneration. It slowly destroys memory, cognition, and eventually disrupts the ability to perform the simplest daily ac‐ tivities (Alzheimer’s Association, 2014). 2007; Rubio‐Perez and Morillas‐Ruiz, 2012; Saido, 2013; Belluti et al, 2013). It is a potent pro‐inflammatory cy‐ tokine that plays a key role in initiating inflammation events. The accumulation of plaques leads to ongoing neoangiogenesis, increased vascular perme‐ ability, and further hypervascularization (Jefferies et al, 2013), and it plays a considerable role in the patho‐ genesis of AD and tissue injury

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