Rizk_2024_Biochem.Biophys.Res.Commun_739_150971

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 (AlCl(3)) was employed to induce AD-like brain toxicity in rats. The rats were divided into four groups: Negative control, AlCl(3)-induced AD rats (100 mg/kg body weight, orally), AlCl(3)-AD induced rats treated with BF-7 (10 mg/kg body weight, orally), AlCl(3)-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 AlCl(3)-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.