Bioassay-Guided Isolation of Neuroprotective Compounds fromUncaria rhynchophyllaagainst Beta-Amyloid-Induced Neurotoxicity

Abstract

Uncaria rhynchophyllais a component herb of many Chinese herbal formulae for the treatment of neurodegenerative diseases. Previous study in our laboratory has demonstrated that an ethanol extract ofUncaria rhynchophyllaameliorated cognitive deficits in a mouse model of Alzheimer’s disease induced by D-galactose. However, the active ingredients ofUncaria rhynchophyllaresponsible for the anti-Alzheimer’s disease activity have not been identified. This study aims to identify the active ingredients ofUncaria rhynchophyllaby a bioassay-guided fractionation approach and explore the acting mechanism of these active ingredients by using a well-established cellular model of Alzheimer’s disease, beta-amyloid- (Aβ-) induced neurotoxicity in PC12 cells. The results showed that six alkaloids, namely, corynoxine, corynoxine B, corynoxeine, isorhynchophylline, isocorynoxeine, and rhynchophylline were isolated from the extract ofUncaria rhynchophylla. Among them, rhynchophylline and isorhynchophylline significantly decreased Aβ-induced cell death, intracellular calcium overloading, and tau protein hyperphosphorylation in PC12 cells. These results suggest that rhynchophylline and isorhynchophylline are the major active ingredients responsible for the protective action ofUncaria rhynchophyllaagainst Aβ-induced neuronal toxicity, and their neuroprotective effect may be mediated, at least in part, by inhibiting intracellular calcium overloading and tau protein hyperphosphorylation.