Effects of Rosmarisnus officinalis and Methylphenidate on Protein Glycation in AlCl3-induced Mouse Model of Alzheimer’s Disease

Abstract

Alzheimer‟ disease (AD), the most common type of dementia, is a complex disorder characterized by memory loss and cognitive deficits. The amyloid β (Aβ) peptide accumulations and Tau protein hyper-phosphorylation lead to the formation of classical hallmarks of AD i.e., amyloid plaques and neurofibrillary tangles (NFTs). This abnormal deposition affects a range of cellular and molecular processes including protein expression and posttranslational modifications (PTMs). Protein glycation is a non enzymatic PTM that results in production of Advanced Glycation End products (AGEs). Emerging evidence indicates the involvement of AGEs in Aβ and tau aggregation in NFTs; however, their exact role and mechanism is not completely elaborate. Besides CNS, the circulating AGEs also affect liver and kidneys. The present study was aimed to investigate the role of protein glycation with a particular emphasis on the mRNA expression alterations of glycation associated genes; Receptor for AGEs (RAGE), Glyoxalase I (GLO1) and Glyoxalase II (GLO2); in AlCl3-treated mouse model of AD. The study focused on the protective effects of medicinal herb Rosmarinus officinalis and compared its effects with Donepezil and methylphenidate, a potent psychostimulant. Histopathological assessment of liver and kidney sections also revealed marked morphological and structural alterations; however, treatment with R. officinalis and MPH significantly reversed these deleterious effects. R. officinalis also significantly decreased the increased expression of RAGE, while also normalized the GLO1, GLO2 SOD1 and SOD2 expression. Therefore, it is suggested that R. officinalis has antiglycative as well as antioxidative effects when compared with MPH and donepezil. An in-silico docking analysis was also performed to assess the binding interactions of RAGE, GLO1, and 2 GLO2 with Donepezil, MPH, and R. officinalis bioactive compounds. The findings indicate that R. officinalis has potential protective and antiglycative effects, which are mainly associated with ursolic acid and genkwanin.