PMID- 23619565 OWN - NLM STAT- MEDLINE DCOM- 20140305 LR - 20231213 IS - 1873-6351 (Electronic) IS - 0278-6915 (Linking) VI - 58 DP - 2013 Aug TI - Barrier protective effects of piperlonguminine in LPS-induced inflammation in vitro and in vivo. PG - 149-57 LID - S0278-6915(13)00270-6 [pii] LID - 10.1016/j.fct.2013.04.027 [doi] AB - Piperlonguminine (PL), an important component of Piper longum fruits, is well known to possess potent anti-hyperlipidemic, anti-platelet and anti-melanogenesis activities. In this study, we first investigated the possible barrier protective effects of piperlonguminine against proinflammatory responses induced by lipopolysaccharide (LPS) and the associated signaling pathways in vitro and in vivo. The barrier protective activities of PL were determined by measuring permeability, monocytes adhesion and migration, and activation of proinflammatory proteins in LPS-activated human umbilical vein endothelial cells (HUVECs) and in mice. We found that PL inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of monocytes to human endothelial cells. PL also suppressed LPS-induced hyperpermeability and leukocytes migration in vivo. Further studies revealed that PL suppressed the production of tumor necrosis factor-alpha (TNF-alpha) or Interleukin (IL)-6 and activation of nuclear factor-kappaB (NF-kappaB) or extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, treatment with PL resulted in reduced LPS-induced septic mortality. Collectively, these results suggest that PL protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Lee, Wonhwa AU - Lee W AD - College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. FAU - Yoo, Hayoung AU - Yoo H FAU - Kim, Jeong Ah AU - Kim JA FAU - Lee, Sangkyu AU - Lee S FAU - Jee, Jun-Goo AU - Jee JG FAU - Lee, Min Young AU - Lee MY FAU - Lee, You-Mie AU - Lee YM FAU - Bae, Jong-Sup AU - Bae JS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130422 PL - England TA - Food Chem Toxicol JT - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JID - 8207483 RN - 0 (Dioxolanes) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - SGD66V4SVJ (piperlongumine) SB - IM MH - Animals MH - Capillary Permeability/drug effects MH - Cells, Cultured MH - Dioxolanes/*pharmacology MH - Endothelium, Vascular/drug effects MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Humans MH - In Vitro Techniques MH - Inflammation/chemically induced/*prevention & control MH - Interleukin-6/biosynthesis MH - Lipopolysaccharides/*toxicity MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B/metabolism MH - Tumor Necrosis Factor-alpha/biosynthesis OTO - NOTNLM OT - Barrier integrity OT - Endothelium OT - Inflammation OT - Lipopolysaccharide OT - Piperlonguminine EDAT- 2013/04/27 06:00 MHDA- 2014/03/07 06:00 CRDT- 2013/04/27 06:00 PHST- 2013/01/13 00:00 [received] PHST- 2013/03/27 00:00 [revised] PHST- 2013/04/12 00:00 [accepted] PHST- 2013/04/27 06:00 [entrez] PHST- 2013/04/27 06:00 [pubmed] PHST- 2014/03/07 06:00 [medline] AID - S0278-6915(13)00270-6 [pii] AID - 10.1016/j.fct.2013.04.027 [doi] PST - ppublish SO - Food Chem Toxicol. 2013 Aug;58:149-57. doi: 10.1016/j.fct.2013.04.027. Epub 2013 Apr 22.