Effects of Methanol Extract of Cratoxylum formosum (Jack) Benth. & Hook.f. ex Dyer Stem on Acetylcholinesterase Activity and Amyloid Precursor Protein metabolism in Neuronal Cells

Cratoxylum formosum (Jack) Benth. & Hook.f. ex Dyer has been traditionally used in Asia to treat wounds, fever, cough, and food poisoning. This study aimed to evaluate the inhibitory effects of the methanol extract of Cratoxylum formosum stem (CFM) on amyloid-beta (Aβ) secretion, its potential modulation of amyloid precursor protein (APP) processing, and its acetylcholinesterase (AChE) inhibitory activity. CFM was tested on APPswe-transfected neuroblastoma cells. At a concentration of 100 μg/mL, CFM significantly reduced Aβ₁₋₄₂ and Aβ₁₋₄₀ secretion by 48.8% and 57.8%, respectively. Treatment with CFM also enhanced the secretion of soluble amyloid precursor protein-alpha (sAPPα), a metabolite of non-amyloidogenic APP processing pathway, suggesting the activation of α-secretase. Additionally, levels of α-carboxy-terminal fragments (CTFs) of APP were increased, suggesting a potential inhibition of β-secretase activity and consequent reduction in Aβ production. Moreover, CFM exhibited a significant acetylcholinesterase (AChE) inhibitory activity, with inhibition rates of 68.5% and 79.9% observed at concentrations of 25 and 50 μg/mL, respectively. These findings highlight the potential of CFM as a natural therapeutic agent for Alzheimer’s disease by suppressing Aβ production and AChE activity, thus mitigating two key pathological features of the disease.