Interestingly, the combination exerted more favorable actions in all measured parameters and histological findings than the solo-treated groups.<h4>Conclusion</h4>This study revealed the superiority of the combined therapy, compared to solo treatments, in alleviation of AlCl<sub>3</sub>-induced AD in rats, via adjustment of the Nrf2/HO-1, P38 MAPK/JNK/NF-κB/JAK-2/STAT-3, PI3K/AKT/GSK-3β/CREB, AMPK/SIRT-1, PERK/CHOP, and apoptotic hubs. This evidence concerns the gene MAPK8 and Alzheimer disease.