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

Oxid Med Cell Longev. 2020 Jun 17:2020:4386562. doi: 10.1155/2020/4386562. eCollection 2020.

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.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Antioxidants / therapeutic use*
  • Autophagy / drug effects
  • Biological Products / therapeutic use*
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / psychology
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Inflammation
  • Janus Kinase 2 / metabolism
  • Male
  • Maze Learning / drug effects
  • Mice
  • Oxidative Stress / drug effects
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Streptozocin / adverse effects

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Biological Products
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Streptozocin
  • Jak2 protein, mouse
  • Janus Kinase 2