Antia, a Natural Antioxidant Product, Attenuates Cognitive Dysfunction in Streptozotocin-Induced Mouse Model of Sporadic Alzheimer's Disease by Targeting the Amyloidogenic, Inflammatory, Autophagy, and Oxidative Stress Pathways.

Nesrine S El Sayed,Mamdooh H Ghoneum

doi:10.1155/2020/4386562

Abstract

Background Many neurodegenerative diseases such as Alzheimer's disease are associated with oxidative stress. Therefore, antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases. Objective We investigated the ability of the antioxidant Antia to exert a protective effect against sporadic Alzheimer's disease (SAD) induced in mice. Antia is a natural product that is extracted from the edible yamabushitake mushroom, the gotsukora and kothala himbutu plants, diosgenin (an extract from wild yam tubers), and amla (Indian gooseberry) after treatment with MRN-100. Methods Single intracerebroventricular (ICV) injection of streptozotocin (STZ) (3 mg/kg) was used for induction of SAD in mice. Antia was injected intraperitoneally (i.p.) in 3 doses (25, 50, and 100 mg/kg/day) for 21 days. Neurobehavioral tests were conducted within 24 h after the last day of injection. Afterwards, mice were sacrificed and their hippocampi were rapidly excised, weighed, and homogenized to be used for measuring biochemical parameters. Results Treatment with Antia significantly improved mice performance in the Morris water maze. In addition, biochemical analysis showed that Antia exerted a protective effect for several compounds, including GSH, MDA, NF-κB, IL-6, TNF-α, and amyloid β. Further studies with western blot showed the protective effect of Antia for the JAK2/STAT3 pathway. Conclusions Antia exerts a significant protection against cognitive dysfunction induced by ICV-STZ injection. This effect is achieved through targeting of the amyloidogenic, inflammatory, and oxidative stress pathways. The JAK2/STAT3 pathway plays a protective role for neuroinflammatory and neurodegenerative diseases such as SAD.

Highlights

Age-related neurodegenerative diseases like Alzheimer’s disease (AD) are on the rise
We studied the effect of Antia on mice induced with sporadic Alzheimer’s disease (SAD) via intracerebroventricular (ICV) injection of streptozotocin (STZ); this is a well-established animal model of SAD based on brain resistance to insulin [37] and imitates the age-related pathology of SAD in humans such as memory impairment, oxidative stress, neuroinflammation, and neurodegeneration [38]
The study of the effect of Antia on the time mice spent in the target quadrant of the Morris water maze (Figure 2(b)) showed that STZ-treated mice spent only 25.4% of the time in the quadrant in comparison with sham control mice, while treatment of STZinjected mice with 25, 50, and 100 mg/kg of Antia spent 72.5%, 75.8%, and 85.4% of the time, respectively, in comparison with sham control mice

Summary

Introduction

Age-related neurodegenerative diseases like Alzheimer’s disease (AD) are on the rise. The brain’s neurons have high rates of energy production and oxygen consumption, making them extremely sensitive to excessive generation of reactive oxygen species (ROS) Many neurodegenerative diseases such as Alzheimer’s disease are associated with oxidative stress. We investigated the ability of the antioxidant Antia to exert a protective effect against sporadic Alzheimer’s disease (SAD) induced in mice. Biochemical analysis showed that Antia exerted a protective effect for several compounds, including GSH, MDA, NF-κB, IL-6, TNF-α, and amyloid β. Antia exerts a significant protection against cognitive dysfunction induced by ICV-STZ injection. This effect is achieved through targeting of the amyloidogenic, inflammatory, and oxidative stress pathways. The JAK2/STAT3 pathway plays a protective role for neuroinflammatory and neurodegenerative diseases such as SAD

Methods

Results

Conclusion