Barrier protective effects of piperlonguminine in LPS-induced inflammation in vitro and in vivo.

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.
AuthorsWonhwa Lee, Hayoung Yoo, Jeong Ah Kim, Sangkyu Lee, Jun-Goo Jee, Min Young Lee, You-Mie Lee, Jong-Sup Bae
JournalFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 58 Pg. 149-57 (Aug 2013) ISSN: 1873-6351 [Electronic] England
PMID23619565 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Ltd. All rights reserved.
Chemical References
  • Dioxolanes
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Extracellular Signal-Regulated MAP Kinases
  • piperlonguminine
  • Animals
  • Capillary Permeability (drug effects)
  • Cells, Cultured
  • Dioxolanes (pharmacology)
  • Endothelium, Vascular (drug effects)
  • Extracellular Signal-Regulated MAP Kinases (metabolism)
  • Humans
  • In Vitro Techniques
  • Inflammation (chemically induced, prevention & control)
  • Interleukin-6 (biosynthesis)
  • Lipopolysaccharides (toxicity)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B (metabolism)
  • Tumor Necrosis Factor-alpha (biosynthesis)

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