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Neurochem Res ; 49(6): 1592-1602, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38305960

RESUMO

In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100 µg·mL- 1) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (→3-α-L-fucp(2-SO3-)-1→4-α-L-fucp(2,3-SO3-)-1→section), SFcup showed a best inhibitory efficacy against AChE with IC50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results.


Assuntos
Acetilcolinesterase , Doença de Alzheimer , Inibidores da Colinesterase , Simulação de Acoplamento Molecular , Oligossacarídeos , Sargassum , Sargassum/química , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/química , Inibidores da Colinesterase/uso terapêutico , Camundongos , Acetilcolinesterase/metabolismo , Oligossacarídeos/farmacologia , Oligossacarídeos/química , Oligossacarídeos/isolamento & purificação , Masculino , Sulfatos/química , Sulfatos/farmacologia , Butirilcolinesterase/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Relação Dose-Resposta a Droga
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