Biomolecules & Therapeutics  
Spermidine Protects against Oxidative Stress in Inflammation Models Using Macrophages and Zebrafish
Jin-Woo Jeong1,†, Hee-Jae Cha2,†, Min Ho Han3, Su Jung Hwang4, Dae-Sung Lee3, Jong Su Yoo3, Il-Whan Choi5, Suhkmann Kim6, Heui-Soo Kim7, Gi-Young Kim8, Su Hyun Hong1, Cheol Park9, Hyo-Jong Lee4 and Yung Hyun Choi1,*
1Anti-Aging Research Center and Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 47227,
2Departments of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267,
3Natural products Research Team, Marine Biodiversity Institute of Korea, Seocheon 33662,
4Department of Pharmacy, College of Pharmacy, Inje University, Gimhae 50834,
5Department of Microbiology, College of Medicine, Inje University, Busan 47392,
6Department of Chemistry, College of Natural Sciences, Pusan National University, Busan 46241,
7Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241,
8Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 63243,
9Department of Molecular Biology, College of Natural Sciences & Human Ecology, Dongeui University, Busan 47340, Republic of Korea
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The first two authors contributed equally to this work.
Received: December 11, 2016; Revised: December 25, 2016; Accepted: January 18, 2017; Published online: April 6, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

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.
Keywords: Spermidine, Macrophages, Zebrafish, Anti-Inflammation, Anti-Oxidant

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