Multifunctional effect of flavonoids from Millettia brandisiana against Alzheimer's disease pathogenesis.
Heliyon
; 9(11): e21894, 2023 Nov.
Article
en En
| MEDLINE
| ID: mdl-38106662
ABSTRACT
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and neuronal death. Fifteen flavonoids from Millettia brandisiana were evaluated for the multifunctional effect against AD pathogenesis, including butyrylcholine esterase (BuChE) inhibition, anti-amyloid beta (Aß) aggregation and neuroprotection against hydrogen peroxide (H2O2) toxicity in differentiated human neuroblastoma SH-SY5Y cell. To understand the mechanism and structure-activity relationship, binding interactions between flavonoids and the BuChE and Aß were investigated in silico. Furthermore, drug-likeness properties and ADMET parameters were evaluated in silico using SwissADME and pKCSM tools. All flavonoids exhibit a good drug-likeness profile. Six flavonoids have potency in BuChE inhibition, and four flavonoids show potency in anti-Aß aggregation. Flavonoids with the 6â³,6â³-dimethylchromeno- [2â³,3â³7,8]-flavone structure show a favorable multifunctional effect. In silico analysis showed that flavonoids can bind in various positions to the catalytic triad, anionic site, and acyl pocket. In Aß1-42, potential flavonoids can attach to the central hydrophobic region and the C terminal hydrophobic and interfere with Aß interchain hydrogen binding. When compared together, it can inhibit multifunctional action with a favorable ADMET parameter and drug-likeness profile. In addition, candidine can prevent neuronal damage in differentiated SH-SY5Y neuroblastoma cells induced by H2O2 in a dose-dependent manner.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Heliyon
Año:
2023
Tipo del documento:
Article
País de afiliación:
Tailandia
Pais de publicación:
Reino Unido