Syringin from Fraxinus rhynchophylla Hance inhibit the apoptotic neuronal cell death induced by Aβ25–35

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive degeneration and loss of neuronal cells in the brain. β-Amyloid peptide (Aβ) is produced by proteolysis of amyloid precursor protein (APP), and its accumulation in the senile plaque is the major hallmark of AD pathogenesis [1, 2, 3]. Various experimental evidence support that Aβ plaque can induce neurotoxic effect on neuronal cells [4]. In the course of screening of anti-dementia agents from medicinal plants, the ethanolic extract of Fraxinus rhynchophylla Hance showed neuroprotective effect against Aβ25–35-induced cytotoxicity in cultured B103 cells. The extract was partitioned with dichloromethane (CH2Cl2), n-butanol (n-BuOH), and water, successively. The repeated chromatographic separation afforded an active compound, and its chemical structure was elucidated as syringin by 1H- and 13C-NMR and LC-MS. Its effects on apoptotic cell death were determined by MTT, H2DCF-DA and caspase-3 activity assay. As results, syringin significantly increased B103 cell viability up to 79.16% at 20µM in the presence of 12.5µM of Aβ25–35, and it remarkably decreased Aβ25–35-induced reactive oxygen species (ROS) generation up to 92.87% at the same concentration. In addition, the activity of caspase-3, an enzymatic major marker of apoptosis, was decreased up to 39.75% at 25µM. These results indicate that syringin and ethanolic extracts from Fraxinus rhynchophylla Hance could be a promising agent for anti-dementia.