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.
