Pycnogenol ® protects neurons from amyloid-β peptide-induced apoptosis

Abstract

Neuronal apoptosis is one of the pathological features of Alzheimer’s disease (AD). Morphological pathology reveals that neuronal apoptosis is associated with senile plaques containing amyloid-β peptide (Aβ) in AD brains. Reactive oxygen species (ROS) has been proposed to be involved in the apoptotic mechanism of Aβ-mediated neurotoxicity. In the present study, using a rat pheochromocytoma (PC12) cell line, we investigated the effect of Pycnogenol ® (PYC), a potent antioxidant and ROS scavenger, on Aβ 25–35-induced apoptosis and ROS generation. We used vitamin E, a known antioxidant agent, to verify the effect of PYC. Aβ 25–35-induced apoptosis in PC12 cells was demonstrated by: (1) a dose-dependent loss of cell viability; (2) a time- and dose-dependent increase in the apoptotic cells; (3) an induction of DNA fragmentation; and (4) an increase in caspase-3 activity and cleavage of poly (ADP-ribose) polymerase (PARP). Our data showed that a significant increase in ROS formation preceded apoptotic events after PC12 cells were exposed to Aβ 25–35. We further found that PYC not only suppressed the generation of ROS but also attenuated caspase-3 activation, DNA fragmentation, PARP cleavage, and eventually protected against Aβ-induced apoptosis. Vitamin E also suppressed cell death and caspase-3 activation induced by Aβ 25–35. Taken together, these results suggest that ROS may be involved in Aβ-induced apoptosis in PC12 cells. They further suggest that PYC can reduce apoptosis, possibly by decreasing free radical generation in PC12 cells.