title: Phytochemical Ginkgolide B Attenuates Amyloid-β1-42 Induced Oxidative Damage and Altered Cellular Responses in Human Neuroblastoma SH-SY5Y Cells.
abstract: Oxidative stress is an upsurge in reactive oxygen/nitrogen species (ROS/RNS), which aggravates damage to cellular components viz. lipids, proteins, and nucleic acids resulting in impaired cellular functions and neurological pathologies including Alzheimer's disease (AD). In the present study, we have examined amyloid-β (Aβ)-induced oxidative stress responses, a major cause for AD, in the undifferentiated and differentiated human neuroblastoma SH-SY5Y cells. Aβ1-42-induced oxidative damage was evaluated on lipids by lipid peroxidation; proteins by protein carbonyls; antioxidant status by SOD and GSH enzyme activities; and DNA and RNA damage levels by evaluating the number of AP sites and 8-OHG base damages produced. In addition, the neuro-protective role of the phytochemical ginkgolide B (GB) in countering Aβ1-42-induced oxidative stress was assessed. We report that the differentiated cells are highly vulnerable to Aβ1-42-induced oxidative stress events as exerted by the deposition of Aβ in AD. Results of the current study suggest that the pre-treatment of GB, followed by Aβ1-42 treatment for 24 h, displayed neuro-protective potential, which countered Aβ1-42-induced oxidative stress responses in both undifferentiated and differentiated SH-SY5Y neuronal cells by: 1) hampering production of ROS and RNS; 2) reducing lipid peroxidation; 3) decreasing protein carbonyl content; 4) restoring antioxidant activities of SOD and GSH enzymes; and 5) maintaining genome integrity by reducing the oxidative DNA and RNA base damages. In conclusion, Aβ1-42 induces oxidative damage to the cellular biomolecules, which are associated with AD pathology, and are protected by the pre-treatment of GB against Aβ-toxicity. Taken together, this study advocates for phytochemical-based therapeutic interventions against AD.
authors.affiliation: Centre for Animal Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab, India.
authors.forename: Iqbal
authors.initials: I
authors.lastname: Gill
authors.affiliation: Centre for Biochemistry and Microbial Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab, India.
authors.forename: Sukhchain
authors.initials: S
authors.lastname: Kaur
authors.affiliation: Centre for Animal Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab, India.
authors.forename: Navrattan
authors.initials: N
authors.lastname: Kaur
authors.affiliation: Centre for Biochemistry and Microbial Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab, India.
authors.forename: Monisha
authors.initials: M
authors.lastname: Dhiman
authors.affiliation: Centre for Animal Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mantha
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D046934:Ginkgolides / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*; D064209:Phytochemicals / Q000494:pharmacology*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D046934:Ginkgolides; D007783:Lactones; D010446:Peptide Fragments; D064209:Phytochemicals; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D009569:Nitric Oxide; D014212:Tretinoin; D006861:Hydrogen Peroxide; C045856:ginkgolide B; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: Aβ1-42; DNA/RNA base damage; amyloid-beta; antioxidants; ginkgolide B; neuronal differentiation; oxidative stress