Rosiridin Protects Against Aluminum Chloride-Induced Memory Impairment via Modulation of BDNF/NFκB/PI3K/Akt Pathway in Rats

Medicina (Kaunas). 2024 Nov 4;60(11):1812. doi: 10.3390/medicina60111812.

Abstract

Background and Objectives: Rosiridin is a monoterpene with outstanding monoamine inhibitory activity that is useful to treat depressive episodes and rapid-onset dementia. The current investigation aims to evaluate the neurologically protective impact of rosiridin, which opposes aluminum chloride (AlCl3) and causes memory dysfunction in rats. Materials and Methods: Memory impairment was developed in Wistar rats by administering AlCl3 (100 mg/kg p.o.) orally for 42 days and then supplemented with rosiridin at 10 and 20 mg/kg/p.o. Upon completion of the investigation, the behavior factor was performed utilizing the Y-maze, Morris Water Maze, and open field tests. Estimating numerous biological factors, such as nitric oxide (NO), oxidative stress (malondialdehyde MDA), acetylcholinesterase (AChE), butyrylcholinesterase levels (BuChE), antioxidants (glutathione GSH, catalase CAT, and superoxide dismutases SODs) and neurotransmitter (serotonin-5HT, dopamine-DA, acetylcholine-Ach) in the brain. Furthermore, interleukin-6 (IL-6), IL-1β, tumor necrosis factor (TNF-α), brain-derived neurotrophic factor (BNDF), nuclear factor kappa B (NFᴋB), phosphatidylinositol 3-kinase (PI3K), and pAkt were assessed in the diffused brain cells. Results: The rosiridin-treated group significantly improved in terms of behavioral parameters, including in the Y-maze, Morris Water Maze, and open field tests. Further, rosiridin restored biochemical parameters, including NO, oxidative stress AChE, BuChE, antioxidants, neurotransmitters, IL-6, IL-1β, TNF-α, BNDF, NFᴋB, PI3K, and pAkt compared to AlCl3. Conclusions: The current investigation reveals that rosiridin could ameliorate the impairment of memory that AlCl3 causes in rats via improvements in behavioral and restored biochemical parameters.

Keywords: Alzheimer’s disease; aluminum chloride; brain-derived neurotrophic factor; cognitive impairment.

MeSH terms

  • Aluminum Chloride*
  • Animals
  • Brain-Derived Neurotrophic Factor* / analysis
  • Brain-Derived Neurotrophic Factor* / drug effects
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Disease Models, Animal
  • Male
  • Maze Learning / drug effects
  • Memory Disorders* / chemically induced
  • Memory Disorders* / drug therapy
  • NF-kappa B* / metabolism
  • Oxidative Stress / drug effects
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Rats
  • Rats, Wistar*
  • Signal Transduction / drug effects

Substances

  • Aluminum Chloride
  • Brain-Derived Neurotrophic Factor
  • NF-kappa B
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases

Grants and funding

The authors extend their sincere gratitude to King Saud University for funding this research project number (RSPD2024939).