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

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.

References: 1. Kayed, R. et al. (2003) Science 300: 486–489. 2. Selkoe, D. J. (1994) Annu. Rev. Cell Biol. 10: 373–403. 3. Nunan, J., Small, D. H. (2000) FEBS Lett. 483: 6–10. 4. Estus, S. et al. (1997)J. Neurosci. 17: 7736–7745.