Investigation of therapeutic effect of curcumin α and β glucoside anomers against Alzheimer's disease by the nose to brain drug delivery

Abstract

Alzheimer's disease (AD) is one of the greatest geriatric medicinal challenges of our century and is the main disease leading to dementia. Despite extensive scientific research advances, available disease-modifying treatment strategies remained limited; thus, increasing demand for new drugs. In recent years, medicinal plants attracted attention due to their potential role in dementia. In the present study, α and β anomers of curcumin glucosides (CGs) were synthesized and evaluated for Alzheimer's treatment. CGs were synthesized by fusion reaction as a novel and easy method with more advantages (high yield, short reaction time, and low chemicals), and the products were characterized using HNMR. Wistar male rats were used to administer different treatments. They divided into control, sham, Alzheimer, and test groups (Alzheimer + α anomer and Alzheimer + β anomer). Animals received normal saline, Scopolamine (1 mg/kg), high dose anomers, scopolamine, and two doses (12.5 and 25 mg/kg) of anomers, respectively, for 10 days. Then the Morris Water Maze (MWM) test was performed on all animals. Finally, the animals' brains were extracted and homogenized for glutathione, acetylcholine esterase activity, protein carbonyl, and lipid peroxide level detection. The escape latency and the distance towards the hidden platform in Morris water maze in the Alzheimer group were significantly higher than both the control and test groups. Besides, there were no significant differences between sham and control groups in all tests. Both anomers led to a significant increase in glutathione, and acetylcholine levels while they caused a decrease in lipid peroxidation and protein carbonyl levels in brain tissue. It seems that intranasal administration of both anomers positively influenced maze learning in scopolamine receiving subjects. Although both anomers resulted in similar biochemistry tests, a higher dose of β anomer indicated better results than α anomer not only in behavioral tests but also in biochemical tests.

Keywords: Alzheimer's disease; Curcumin; Fusion reactions; Glucoside; Glucosylation; Intranasal.