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

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. •AlCl3 can stimulate Alzheimer's disease (AD)-like neurotoxicity in rats.•AlCl3-induced neurotoxicity is mediated by apoptosis, disruption of neurotransmitters, and insulin deficiency.•BF-7 alleviated AlCl3-induced neurotoxicity via inhibiting AChE activity and regulating neurotransmission.•BF-7 mitigated neurotoxicity through upregulating Insulin 1 expression and Bcl2 and downregulating Bax and caspase-3.