PHYTOCHEMICAL GINKGOLIDE B PROTECTS CULTURED NEUROBLASTOMA SH-SY5Y CELLS AGAINST Aβ(25-35) INDUCED OXIDATIVE STRESS RESPONSES BY MAINTAINING THE MITOCHONDRIAL INTEGRITY

Alzheimer’s disease is associated with oxidative stress induced by accumulation of Aβ peptide, by disrupting the mitochondrial function. In this study, the oxidative stress responses induced by Aβ(25-35) and protective effects of diterpenoid phytochemical Ginkgolide B (GB) were evaluated by the determination of cellular oxidant/antioxidant status, oxidative DNA base damage and repair capacity of cells through evaluation of mitochondrial BER pathway status and the multifunctional enzyme APE1 in human neuroblastoma SH-SY5Y cells, and evaluation of mitochondrial membrane potential and changes in apoptotic pathway. It was found that Aβ(25-35) treatment increased ROS/RNS production, increased the activities of antioxidant SOD and Catalase enzymes, decreased the expression of mitochondrial SOD (SOD2), induced oxidative DNA base damage, might be altered the repair capacity as analyzed by the transcriptional and translational expression of APE1 and other BER pathway enzymes in the mitochondria, disrupted the mitochondrial membrane potential and induced apoptosis as a result of these responses. Phytochemical modulation by the pre-treatment of GB for 3 hr followed by the treatment of Aβ(25-35) for a period of 24 hr caused decrease in ROS/RNS, increase in activities of antioxidant enzymes and expression of SOD2, decreased oxidative DNA base damage and increased transcriptional and translational expression of APE1, increased/restored expression of APE1 and polymerase gamma (γ) in the mitochondria, restored mitochondrial membrane potential and rescued the SH-SY5Y cells from mitochondrial-mediated apoptosis against Aβ(25-35) induced oxidative stress responses. Taken together, GB showed neuroprotection by restoring cellular antioxidant defense system, repair capacity of cells and restoring mitochondrial integrity (genome and membrane potential), thus rescuing the SH-SY5Y cells from Aβ(25-35) induced oxidative stress responses.