Neuroprotective effect of garlic compounds in amyloid-beta peptide-induced apoptosis in vitro.
Med Sci Monit. 2002 Aug;8(8):BR328-37. PMID: 12165737
Division of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
BACKGROUND: Neuronal apoptosis is one of the pathological features of Alzheimer's disease (AD) and is associated with senile plaques containing amyloid-b peptide (Abeta). Reactive oxygen species (ROS) are proposed to be involved in the apoptotic mechanism of Abeta-mediated neurotoxicity. The purpose of this study was to determine the effects of aged garlic extract (AGE) and S-allyl cysteine (SAC) on Abeta(25-35)-induced apoptosis and ROS generation in a rat pheochromocytoma (PC12) cell line.
MATERIAL/METHODS: PC12 cells were grown in RPMI 1640 medium containing 5% fetal calf serum and 10% horse serum. Cells were incubated with AGE or SAC for 24 h prior to exposure to Abeta(25-35) for various times. Cell viability, DNA fragmentation, number of apoptotic cells, caspase activity and generation of ROS were determined.
RESULTS: Abeta(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 apoptotic cells; 3) An induction of DNA fragmentation; and 4) An increase in caspase-3 activity and cleavage of poly (ADP-ribose) polymerase (PARP). After exposing PC12 cells to Abbeta(25-35), a significant increase in ROS preceded apoptotic events. AGE and SAC not only suppressed the generation of ROS but also attenuated caspase-3 activation, DNA fragmentation, PARP cleavage and eventually protected against Ab-induced apoptosis.
CONCLUSIONS: Our data suggest that ROS may be involved in Ab-induced apoptosis in PC12 cells. They further suggest that garlic compounds can reduce apoptosis, possibly by enhancing the endogenous antioxidant defenses.