title: Metabolic Alterations and the Protective Effect of Punicalagin Against Glutamate-Induced Oxidative Toxicity in HT22 Cells.
abstract: Oxidative stress is involved in many neurological diseases, including Alzheimer's disease. Punicalagin (PC) is a hydrolysable polyphenol derived from Punica granatum and a potent antioxidant. In this study, the neuroprotective effect of PC on glutamate-induced oxidative stress was evaluated in the mouse hippocampal cell line, HT22. PC treatment protected HT22 cells from glutamate-induced cell death in a concentration-dependent manner, potentially attenuated glutamate-induced intracellular reactive oxygen species (ROS) and restored the mitochondrial membrane depolarization. Metabolic alterations after glutamate-induced oxidative stress and the protective effect of PC were evaluated with HPLC and GC-MS profiling methods with multivariate statistical analyses. Alterations in ten metabolites were identified, including amino acids, aspartic acid, asparagine, threonine, anserine, cysteine, tryptophan, lysine, as well as fatty acids palmitic acid, stearic acid, and palmitoleic acid. Metabolic pathway analysis revealed the involvement of multiple affected pathways, such as cysteine and methionine metabolism, tryptophan metabolism, alanine, aspartate, and glutamate and fatty acid oxidation. These results clearly demonstrate that PC is a promising therapeutic agent for oxidative stress-associated diseases.
authors.affiliation: Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.|Department of Biology, Jackson State University, Jackson, MS, 39217, USA.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Pathakoti
authors.affiliation: South China Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kai Yuan Avenue, Science Park, Guangzhou, 510530, China.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Goodla
authors.affiliation: Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, OH, 43210, USA.
authors.forename: Manjunath
authors.initials: M
authors.lastname: Manubolu
authors.affiliation: Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand. tewin.t@chula.ac.th.
authors.forename: Tewin
authors.initials: T
authors.lastname: Tencomnao
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000633:toxicity*; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D055442:Metabolome / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D047348:Hydrolyzable Tannins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; C115642:punicalagin
keywords: Glutamate; HT22 cells; Metabolite profiling; Multivariate analyses; Oxidative stress; Punicalagin