Details

Autor(en) / Beteiligte

• Arsito, Puguh Novi
• Waiwut, Pornthip
• Yenjai, Chavi
• Arthan, Supakorn
• Monthakantirat, Orawan
• Nualkaew, Natsajee
• Takomthong, Pitchayakarn
• Boonyarat, Chantana

Titel

Multifunctional effect of flavonoids from Millettia brandisiana against Alzheimer's disease pathogenesis

Ist Teil von

• Heliyon, 2023-11, Vol.9 (11), p.e21894-e21894, Article e21894

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 (Aβ) 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 Aβ 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-Aβ aggregation. Flavonoids with the 6″,6″-dimethylchromeno- [2″,3″:7,8]-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 Aβ1-42, potential flavonoids can attach to the central hydrophobic region and the C terminal hydrophobic and interfere with Aβ 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. [Display omitted]