Therapeutic impact of a benzofuran derivative on Aluminium chloride-induced Alzheimer's disease-like neurotoxicity in rats via modulating apoptotic and Insulin 1 genes

Biochem Biophys Res Commun. 2024 Dec 20:739:150971. doi: 10.1016/j.bbrc.2024.150971. Epub 2024 Nov 9.

Abstract

Neurodegenerative disorders such as Alzheimer's disease (AD) are age-related and are fatal in advanced cases. There is a limited efficacy of drugs used for the management of these diseases. Herein, the neurotherapeutic efficacy of a benzofuran-derivative-7 (BF-7) was investigated. Aluminum chloride (AlCl3) was employed to induce AD-like brain toxicity in rats. The rats were divided into four groups: Negative control, AlCl3-induced AD rats (100 mg/kg body weight, orally), AlCl3-AD induced rats treated with BF-7 (10 mg/kg body weight, orally), AlCl3-AD-induced rats treated with the standard drug "Donepezil" (10 mg/kg body weight, orally). The behavioral performance was tested using a beam-balance test. Brain and serum acetylcholinesterase (AChE) activities and the brain levels of norepinephrine, dopamine (DA), and serotonin (5-HT) were measured. The genetic expression of Bcl-2, Bax, caspase-3, and insulin 1 were assayed. The histopathological imaging and the immunohistochemical evaluation of Glial Fibrillary Acidic Protein (GFAP) were investigated in the cerebral cortex. Treatment of AD-rats with BF-7 mitigated AlCl3-induced neurotoxicity by improving motor functions, counteracting apoptosis, and exerting cholinergic functions. In addition, the genetic expression of Insulin 1 was upregulated significantly in AD-induced rats treated with BF-7. This compound could be used as a promising candidate for neurotherapeutic drug discovery against AD or any other toxic brain disorders.

Keywords: 3-((3-acetylphenyl) amino)-1-(benzofuran-2-yl) prop-2-en-1-one (7); Acetylcholinesterase; Alzheimer's disease; Apoptotic genes; Insulin 1; Neurotoxicity.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Aluminum Chloride*
  • Aluminum Compounds* / toxicity
  • Alzheimer Disease* / chemically induced
  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Animals
  • Apoptosis* / drug effects
  • Benzofurans* / pharmacology
  • Benzofurans* / therapeutic use
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Chlorides* / toxicity
  • Insulin
  • Male
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Rats
  • Rats, Wistar

Substances

  • Aluminum Chloride
  • Benzofurans
  • Chlorides
  • Aluminum Compounds
  • Neuroprotective Agents
  • Insulin
  • Acetylcholinesterase