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

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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.

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Acknowledgements

This study was financially supported by Chulalongkorn University (RES560530255-AS). We are also thankful to the SAIF/CRNTS Department, IIT, Bombay (India) for providing the analytical facility. The author KP is thankful to Chulalongkorn University (Rachadapisek Sompot Fund) for providing a senior postdoctoral fellowship.

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Author notes

  1. Kavitha Pathakoti

    Present address: Department of Biology, Jackson State University, Jackson, MS, 39217, USA

Authors and Affiliations

  1. Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Kavitha Pathakoti & Tewin Tencomnao

  2. 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

    Lavanya Goodla

  3. Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, OH, 43210, USA

    Manjunath Manubolu

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  1. Kavitha Pathakoti
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  2. Lavanya Goodla
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  4. Tewin Tencomnao
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Correspondence to Tewin Tencomnao.

Electronic supplementary material

Figure S1

HPLC chromatograms for amino acids (A) Standard (B) Control (C) Glutamate group (D) PC-GLU group (GIF 78 kb)

High resolution (TIFF 1152 kb)

Figure S2

GC-MS chromatograms for Methanol fraction (A) Control (B) Glutamate group (C) PC-GLU group (GIF 92 kb)

High resolution (TIFF 587 kb)

Figure S3

GC-MS chromatograms for chloroform fraction (A) Control (B) Glutamate group (C) PC-GLU group (GIF 80 kb)

High resolution (TIFF 546 kb)

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Pathakoti, K., Goodla, L., Manubolu, M. et al. Metabolic Alterations and the Protective Effect of Punicalagin Against Glutamate-Induced Oxidative Toxicity in HT22 Cells. Neurotox Res 31, 521–531 (2017). https://doi.org/10.1007/s12640-016-9697-2

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  • DOI: https://doi.org/10.1007/s12640-016-9697-2

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