The novel therapeutic strategy of myricetin/chitooligosaccharide/astaxanthin, as potent multi-target-directed ligands for the potential treatment of Alzheimer's disease with comorbid depression

Objective The mixed particles of Myricetin (MYR)/Chitooligosaccharide (COS)/Astaxanthin (AST) had not study to therapeutic effects on Alzheimer's disease (AD) combined with depression. In this study, the mixed particles of MYR/COS/AST were investigate the inhibitory activities against cholinesterase (ChE) and monoamine oxidase (MAO), possessing good activity were further assayed to inhibit β-amyloid1-42 (Aβ 1-42 ) aggregation, beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), the neuroprotective activity and cytotoxicity. Materials and methods ChE and MAO inhibitory activities by Ellman and Holts method. Aβ aggregation were evaluated by thioflavin T assay, BACE1 inhibition used the fluorescence resonance energy transfer (FRET)-based. The protective effect were tested by against L-Glutamate (L-Glu)-induced HT22 cell damage, Cu 2+ - and Fe 3+ -induced neuronal damage, the cytotoxicity were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. The antidepressant activities were measured by the forced swimming test (FST). Results The results showed that the mass ratio of the mixed particles MYR/COS/AST was 10:10:3, which exhibited the best inhibitory activities on AChE, MAO, also exhibited inhibition against Aβ 1-42 aggregation, BACE-1, Aβ 1-42 disaggregation, exerted protective effects L-Glu-induced HT22 cell damage and on the cells against Cu 2+ and Fe 3+ -induced damage in BV-2 cells. In the FST, the mixed particles of MYR/COS/AST (10:10:1) exhibited good antidepressant effect. None of three substances showed cytotoxicity against L929 cells. The molecular docking revealed important interactions between the active three substances and amino acid residues. Conclusions These studies provide the technical data for ensuring potential treatment of AD combined with depression of the mixed particles of MYR/COS/AST (10:10:3).