Protective properties of quercetin and luteolin from Petasites japonicus leaves against Aβ (25–35)-induced neurotoxicity in B103 cells

Alzheimer's disease (AD) is a neurodegenerative disorder clinically characterized by progressive dementia that inevitably leads to incapacitation and death [1]. A pathologic hallmark of AD is the formation of extracellular senile plaques composed of 40–42 amino acid Aβ peptides, a product of amyloid precursor protein (APP) proteolysis [2]. Aβ fragments have shown to induce oxidative stress and inflammation in the brain, which are postulated to play important roles in the pathogenesis of AD [3]. In the course of screening anti-dementia agents from natural products, two compounds with the potent protective activity toward Aβ (25–35)-induced neurotoxicity were isolated from the ethyl acetate soluble fraction of Petasites japonicus leaves. Open column chromatographic separation with silica gel (Merck Art.7734, CH₂Cl₂-CH₃OH=10:1 to 4:1) afforded two active principles. By means of ¹H-NMR, ¹³C-NMR and LC/MS spectral analyses, they were identified as luteolin (1) and quercetin (2). At the concentration range of 1–50µM, 1 and 2 remarkably raised survival rate of the Aβ (25–35)-treated B103 neuroblastoma cells in both 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. 1 and 2 also completely inhibited Aβ (25–35)-induced reactive oxygen species (ROS) generation in B103 cells at 50µM. These results suggested that 1 and 2 might be a starting point for rational natural products-based drug design and be useful reagents for studying mechanism of Alzheimer's disease.

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