Aluminum-induced molecular neurodegeneration: The protective role of genistein and chickpea extract

Abstract

Neurotoxicity of Al is well established and linked to oxidative damage and neurodegeneration. This study investigated the protective role of genistein (Gen) and chickpea extract (CPE) against AlCl3-induced neurodegeneration. HPLC analysis revealed that biochanin A-7-O-β-D-glucoside and biochanin A are the major components of the CPE. Gene expression of TNF-α, APP, BACE1, PSEN-2 and ER-β were assessed in brain extract using RT-PCR. Also, NF-кB subunit P65 and COX-2 expression were evaluated by western blotting. The cholinergic function, histological examination and oxidative status were also estimated. The AlCl3 significantly up regulated the expression of the NF-кB subunit P65, COX-2, TNF- α, BACE1and APP while it significantly down regulated PSEN-2 and ER-β expression. The activity of acetyl cholinesterase (AChE) and the oxidative stress parameters as well as the histological examination confirmed the deleterious effect of AlCl3. The administration of either CPE or Gen attenuated the expression of inflammatory cytokines, inhibited the amyloidogenesis and restored both the AChE activity and ER-β expression. Gen and CPE also inhibited the oxidative stress and ameliorated the histological alterations. Accordingly, the present study provides an insight on the molecular role of Gen and CPE as protective agents against neuronal injury.