Metabolic Alterations and the Protective Effect of Punicalagin Against Glutamate-Induced Oxidative Toxicity in HT22 Cells

• Published in: Neurotoxicity research Vol. 31; no. 4; pp. 521 - 531
• Main Authors: Pathakoti, Kavitha, Goodla, Lavanya, Manubolu, Manjunath, Tencomnao, Tewin
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-05-2017
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Death - drug effects; Cells, Cultured; Glutamic Acid - toxicity; Hydrolyzable Tannins - pharmacology; Membrane Potential, Mitochondrial - drug effects; Metabolome - drug effects; Mice; Neurobiology; Neurochemistry; Neurology; Neurons - metabolism; Neuroprotective Agents - pharmacology; Neurosciences; Original Article; Oxidative Stress - drug effects; Pharmacology/Toxicology; Reactive Oxygen Species - metabolism; Multivariate analyses; Oxidative stress; HT22 cells; Punicalagin; Glutamate; Metabolite profiling
• ISSN: 1029-8428; 1476-3524
• DOI: 10.1007/s12640-016-9697-2

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.