Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Spermidine Protects against Oxidative Stress in Inflammation Models Using Macrophages and Zebrafish

  • Jeong, Jin-Woo (Anti-Aging Research Center and Department of Biochemistry, Dongeui University College of Korean Medicine) ;
  • Cha, Hee-Jae (Departments of Parasitology and Genetics, Kosin University College of Medicine) ;
  • Han, Min Ho (Natural products Research Team, Marine Biodiversity Institute of Korea) ;
  • Hwang, Su Jung (Department of Pharmacy, College of Pharmacy, Inje University) ;
  • Lee, Dae-Sung (Natural products Research Team, Marine Biodiversity Institute of Korea) ;
  • Yoo, Jong Su (Natural products Research Team, Marine Biodiversity Institute of Korea) ;
  • Choi, Il-Whan (Department of Microbiology, College of Medicine, Inje University) ;
  • Kim, Suhkmann (Department of Chemistry, College of Natural Sciences, Pusan National University) ;
  • Kim, Heui-Soo (Department of Biological Sciences, College of Natural Sciences, Pusan National University) ;
  • Kim, Gi-Young (Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University) ;
  • Hong, Su Hyun (Anti-Aging Research Center and Department of Biochemistry, Dongeui University College of Korean Medicine) ;
  • Park, Cheol (Department of Molecular Biology, College of Natural Sciences & Human Ecology, Dongeui University) ;
  • Lee, Hyo-Jong (Department of Pharmacy, College of Pharmacy, Inje University) ;
  • Choi, Yung Hyun (Anti-Aging Research Center and Department of Biochemistry, Dongeui University College of Korean Medicine)
  • Received : 2016.12.11
  • Accepted : 2017.01.18
  • Published : 2018.03.01
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Abstract

Spermidine is a naturally occurring polyamine compound that has recently emerged with anti-aging properties and suppresses inflammation and oxidation. However, its mechanisms of action on anti-inflammatory and antioxidant effects have not been fully elucidated. In this study, the potential of spermidine for reducing pro-inflammatory and oxidative effects in lipopolysaccharide (LPS)-stimulated macrophages and zebrafish was explored. Our data indicate that spermidine significantly inhibited the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$), and cytokines including tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$ in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects of spermidine accompanied by a marked suppression in their regulatory gene expression at the transcription levels. Spermidine also attenuated the nuclear translocation of $NF-{\kappa}B$ p65 subunit and reduced LPS-induced intracellular accumulation of reactive oxygen species (ROS) in RAW 264.7 macrophages. Moreover, spermidine prevented the LPS-induced NO production and ROS accumulation in zebrafish larvae and was found to be associated with a diminished recruitment of neutrophils and macrophages. Although more work is needed to fully understand the critical role of spermidine on the inhibition of inflammation-associated migration of immune cells, our findings clearly demonstrate that spermidine may be a potential therapeutic intervention for the treatment of inflammatory and oxidative disorders.

Keywords

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