PMID- 24262867 OWN - NLM STAT- MEDLINE DCOM- 20140912 LR - 20140113 IS - 1873-6971 (Electronic) IS - 0367-326X (Linking) VI - 92 DP - 2014 Jan TI - Vascular barrier protective effects of pellitorine in LPS-induced inflammation in vitro and in vivo. PG - 177-87 LID - S0367-326X(13)00301-8 [pii] LID - 10.1016/j.fitote.2013.11.006 [doi] AB - Pellitorine (PT), an active amide compound, is well known to possess insecticidal, antibacterial and anticancer properties. In this study, we first investigated the possible barrier protective effects of pellitorine against pro-inflammatory responses induced by lipopolysaccharide (LPS) and the associated signaling pathways in vitro and in vivo. The barrier protective activities of PT were determined by measuring permeability, monocyte adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated human umbilical vein endothelial cells (HUVECs) and in mice. We found that PT inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of monocytes to human endothelial cells. PT also suppressed LPS-induced hyperpermeability and leukocyte migration in vivo. Further studies revealed that PT 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 PT resulted in reduced LPS-induced lethal endotoxemia. These results suggest that PT protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Lee, Wonhwa AU - Lee W AD - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea. FAU - Ku, Sae-Kwang AU - Ku SK AD - Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715, Republic of Korea. FAU - Min, Byung-Woon AU - Min BW AD - Department of BioMedical Clinical Pathology, Hanlyo University, Gwangyang 545-704, Republic of Korea. FAU - Lee, Sangkyu AU - Lee S AD - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. FAU - Jee, Jun-Goo AU - Jee JG AD - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. FAU - Kim, Jeong Ah AU - Kim JA AD - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. FAU - Bae, Jong-Sup AU - Bae JS AD - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: baejs@knu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131118 PL - Netherlands TA - Fitoterapia JT - Fitoterapia JID - 16930290R RN - 0 (Cell Adhesion Molecules) RN - 0 (Fatty Acids, Unsaturated) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-6) RN - 0 (NF-kappa B) RN - 0 (Plant Extracts) RN - 0 (Polyunsaturated Alkamides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 8IS5231171 (pellitorine) SB - IM MH - Animals MH - Asarum/*chemistry MH - Cell Adhesion/drug effects MH - Cell Adhesion Molecules/metabolism MH - Cell Movement/drug effects MH - Endothelial Cells/drug effects/metabolism MH - Endothelium, Vascular/cytology/drug effects/metabolism MH - Fatty Acids, Unsaturated/pharmacology/*therapeutic use MH - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism MH - Humans MH - Inflammation/chemically induced/drug therapy/*metabolism MH - Inflammation Mediators/*metabolism MH - Interleukin-6/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Monocytes/metabolism MH - NF-kappa B/metabolism MH - Permeability MH - Phytotherapy MH - Plant Extracts/*pharmacology/therapeutic use MH - Polyunsaturated Alkamides/pharmacology/*therapeutic use MH - Tumor Necrosis Factor-alpha/metabolism MH - Vascular Diseases/chemically induced/drug therapy/*metabolism OTO - NOTNLM OT - Barrier integrity OT - Endothelium OT - Inflammation OT - Lipopolysaccharide OT - Pellitorine EDAT- 2013/11/23 06:00 MHDA- 2014/09/13 06:00 CRDT- 2013/11/23 06:00 PHST- 2013/08/22 00:00 [received] PHST- 2013/11/06 00:00 [revised] PHST- 2013/11/09 00:00 [accepted] PHST- 2013/11/23 06:00 [entrez] PHST- 2013/11/23 06:00 [pubmed] PHST- 2014/09/13 06:00 [medline] AID - S0367-326X(13)00301-8 [pii] AID - 10.1016/j.fitote.2013.11.006 [doi] PST - ppublish SO - Fitoterapia. 2014 Jan;92:177-87. doi: 10.1016/j.fitote.2013.11.006. Epub 2013 Nov 18.