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 Aβ_1-42, 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.

Alzheimer’s disease (AD) is a neurodegenerative condition characterized by a gradual decline in cognitive function, for which few effective treatments exist. This study investigated the neuroprotective potential of Oroxylum indicum root extract and its key constituents (baicalein, chrysin, oroxylin A) against AD hallmarks. The extract and its constituents exhibited antioxidant activity in the DPPH assay. They inhibited β-amyloid aggregation as measured by the thioflavin T assay and acetylcholinesterase activity using the Ellman method. In cell culture models, O. indicum extract showed an ability to protect neurons from the toxic effects of H₂O₂. Western blot analysis revealed the extract and its major active component, baicalein, downregulated pro-apoptotic markers (cleaved caspase-3, and BAX) upon H₂O₂ exposure. Furthermore, they reduced the expression of amyloidogenic proteins (BACE1) and phosphorylated tau. These findings suggest that O. indicum root extract, particularly baicalein, possesses multifaceted neuroprotective properties, targeting various aspects of AD pathogenesis, including oxidative stress, cholinergic dysfunction, β-amyloid formation, aggregation, and apoptosis. O. indicum root thus warrants further investigation as a promising source of therapeutic agents for AD.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and neuronal death. The pathophysiology of AD includes cholinergic nerve damage, neuroinflammation, oxidative stress, and misfolding of amyloid-beta protein (Aβ). Current AD drug development focuses on a single target, whereas the AD mechanism is multifactorial, originating from the Aβ cascade, so intervention in Aβ is necessary. Flavonoid compounds are known to have many neuroprotective activities. Quercetin, an easily found flavonoid, can be used against AD. This research aimed to evaluate quercetin’s neuroprotective effect in inhibiting AD progression. In the in-vitro test, quercetin was assessed for its impact on inhibiting monomeric Aβ1-42 aggregation and inducing the disintegration of Aβ1-42 fibrils. Quercetin was also evaluated for its toxicity on differentiated human cholinergic cells (SH-SY5Y). Next, the neuroprotective effect of quercetin was tested in the same cells as Aβ1-42 induction. In-silico methods (Molecular docking and Molecular dynamics) were carried out to explain the molecular mechanism of drug action. In addition, druglikeness and ADMET parameters of flavonoids were predicted using SwissADME and pKCSM software. Quercetin is known to have a dual effect as an inhibitor of monomeric Aβ1-42 aggregation and a disintegrator of Aβ1-42 fibrils at concentrations of 10 µM – 200 µM. In molecular docking analysis, it is known that quercetin can bind to the hydrophobic part of Aβ1-42. Tests using molecular dynamics increasingly confirm that quercetin can disrupt the stability of Aβ1-42. In cell culture tests, quercetin was found to have a neuroprotective effect at an effective dose of 1-10 µM. ADMET parameters can also predict Quercetin and fulfill the Lipinski-Veber rule for predicting drug-likeness parameters. Quercetin has the potential to be developed as an anti-Alzheimer’s drug candidate with multi-target activity in the Aβ cascade.