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( Seongdo Jeong ),( Sae Kwang Ku ),( Gahee Min ),( Hyukaje Choi ),( Dong Ho Park ),( Jong Sup Bae ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-
Diketopiperazine is a natural products found from bacteria, fungi, marine sponges, gorgonian and red algae. They are cyclic dipeptides possessing relatively simple and rigid structures with chiral nature and various side chains. The compounds in this structure class have been known to possess diverse bio-activities including antibiotic activity, anti-cancer activity, neuroprotective activity, and anti-inflammatory activity. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate (PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of diketopiperazine and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Diketo-piperazine suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-ell. tumor necrosis factor-a, and interleukin-6. Furthermore, diketopiperazine demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of diketopiperazine on various systemic inflammatory dis-eases, such as sepsis or septic shock.
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