title: Barrier protective effects of piperlonguminine in LPS-induced inflammation in vitro and in vivo.
abstract: 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-α (TNF-α) or Interleukin (IL)-6 and activation of nuclear factor-κB (NF-κB) 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.
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Lee
authors.forename: Hayoung
authors.initials: H
authors.lastname: Yoo
authors.forename: Jeong Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Sangkyu
authors.initials: S
authors.lastname: Lee
authors.forename: Jun-Goo
authors.initials: JG
authors.lastname: Jee
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.forename: You-Mie
authors.initials: YM
authors.lastname: Lee
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004148:Dioxolanes / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D010881:Piperidones
chemical_list: D004148:Dioxolanes; D048049:Extracellular Signal-Regulated MAP Kinases; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C498077:piperlongumine; D010881:Piperidones
keywords: Barrier integrity; Endothelium; Inflammation; Lipopolysaccharide; Piperlonguminine