Biomol Ther.  2018 Mar;26(2):146-156. 10.4062/biomolther.2016.272.

Spermidine Protects against Oxidative Stress in Inflammation Models Using Macrophages and Zebrafish

Affiliations
  • 1Anti-Aging Research Center and Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 47227, Republic of Korea. choiyh@deu.ac.kr
  • 2Departments of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267, Republic of Korea.
  • 3Natural products Research Team, Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea.
  • 4Department of Pharmacy, College of Pharmacy, Inje University, Gimhae 50834, Republic of Korea.
  • 5Department of Microbiology, College of Medicine, Inje University, Busan 47392, Republic of Korea.
  • 6Department of Chemistry, College of Natural Sciences, Pusan National University, Busan 46241, Republic of Korea.
  • 7Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Republic of Korea.
  • 8Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea.
  • 9Department of Molecular Biology, College of Natural Sciences & Human Ecology, Dongeui University, Busan 47340, Republic of Korea.

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 E2 (PGE2), and cytokines including tumor necrosis factor-α and interleukin-1β 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-κB 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.

Keyword

Spermidine; Macrophages; Zebrafish; Anti-Inflammation; Anti-Oxidant

MeSH Terms

Antioxidants
Cytokines
Dinoprostone
Genes, Regulator
Inflammation*
Larva
Macrophages*
Necrosis
Neutrophils
Nitric Oxide
Oxidative Stress*
Reactive Oxygen Species
Spermidine*
Zebrafish*
Antioxidants
Cytokines
Dinoprostone
Nitric Oxide
Reactive Oxygen Species
Spermidine
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