title: Anti-septic effects of pelargonidin on HMGB1-induced responses in vitro and in vivo.
abstract: A certain nucleosomal protein-high mobility group box-1 (HMGB1)-has recently been established as a late mediator of sepsis, with a relatively wide therapeutic window for pharmacological intervention. Pelargonidin (PEL) is a well-known red pigment found in plants; it has important biological activities that are potentially beneficial for human health. In the present study, we investigated whether PEL can modulate HMGB1-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. The anti-inflammatory activities of PEL were determined by measuring permeability, leukocyte adhesion and migration, and activation of pro-inflammatory proteins in HMGB1-activated HUVECs and mice, as well as the beneficial effects of PEL on survival rate in the mouse sepsis model. The data showed that PEL had effectively inhibited lipopolysaccharide (LPS)-induced release of HMGB1 and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. Furthermore, PEL inhibited the HMGB1-mediated production of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), as well as the activation of nuclear factor-κB (NF-κB) and extracellular signal-regulated kinases 1 and 2 (ERK1/2). Collectively, these results indicate that PEL could be used to treat various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.
authors: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, 80 Dahak-ro, Buk-Gu, Daegu, 41566, Republic of Korea.
authors: Gahee
authors: G
authors: Min
authors: Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan, 38610, Republic of Korea.
authors: Sae-Kwang
authors: SK
authors: Ku
authors: National Institute of Fisheries Science, 397-68, Sanyangilju-ro, Sanyang-eup, TongYeong-si, Gyeongsangnam-do, 53085, Republic of Korea.
authors: Mi Seon
authors: MS
authors: Park
authors: School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
authors: Tae-Joo
authors: TJ
authors: Park
authors: ABRC, CMRI, School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, Republic of Korea.
authors: Hyun-Shik
authors: HS
authors: Lee
authors: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, 80 Dahak-ro, Buk-Gu, Daegu, 41566, Republic of Korea. baejs@knu.ac.kr.
authors: Jong-Sup
authors: JS
authors: Bae
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000891:Anti-Infective Agents, Local / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D024243:HMGB1 Protein / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010860:Pigments, Biological / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000872:Anthocyanins; D000891:Anti-Infective Agents, Local; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D010860:Pigments, Biological; C066957:pelargonidin
keywords: HMGB1; HUVEC; Inflammation; Pelargonidin; Sepsis