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Neurotoxicity Research

, Volume 31, Issue 4, pp 521–531 | Cite as

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

  • Kavitha Pathakoti
  • Lavanya Goodla
  • Manjunath Manubolu
  • Tewin TencomnaoEmail author
ORIGINAL ARTICLE

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.

Keywords

Glutamate Oxidative stress HT22 cells Punicalagin Metabolite profiling Multivariate analyses 

Notes

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.

Supplementary material

12640_2016_9697_Fig7_ESM.gif (78 kb)
Figure S1

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

12640_2016_9697_MOESM1_ESM.tif (1.1 mb)
High resolution (TIFF 1152 kb)
12640_2016_9697_Fig8_ESM.gif (92 kb)
Figure S2

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

12640_2016_9697_MOESM2_ESM.tif (588 kb)
High resolution (TIFF 587 kb)
12640_2016_9697_Fig9_ESM.gif (81 kb)
Figure S3

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

12640_2016_9697_MOESM3_ESM.tif (546 kb)
High resolution (TIFF 546 kb)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Kavitha Pathakoti
    • 1
    • 2
  • Lavanya Goodla
    • 3
  • Manjunath Manubolu
    • 4
  • Tewin Tencomnao
    • 1
    Email author
  1. 1.Department of Clinical Chemistry, Faculty of Allied Health SciencesChulalongkorn UniversityBangkokThailand
  2. 2.Department of BiologyJackson State UniversityJacksonUSA
  3. 3.South China Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina
  4. 4.Division of Environmental Health Sciences, College of Public HealthThe Ohio State UniversityColumbusUSA

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