title: Barrier protective effects of 2,4,6-trihydroxy-3-geranyl acetophenone on lipopolysaccharides-stimulated inflammatory responses in human umbilical vein endothelial cells.
abstract: 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA), is a phloroglucinol compound found naturally in Melicope ptelefolia. Melicope ptelefolia has been used traditionally for centuries as natural remedy for wound infections and inflammatory diseases.
  
  
  OBJECTIVE
  Endothelial barrier dysfunction is a pathological hallmark of many diseases and can be caused by lipopolysaccharides (LPS) stimulation. Therefore, this study aims to investigate the possible barrier protective effects of tHGA upon LPS-stimulated inflammatory responses in human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  HUVECs were pretreated with tHGA prior to LPS stimulation, where inflammatory parameters including permeability, monocyte adhesion and migration, and release of pro-inflammatory mediators were examined. Additionally, the effect of tHGA on F-actin rearrangement and adhesion protein expression of LPS-stimulated HUVECs was evaluated.
  
  
  RESULTS
  It was found that pretreatment with tHGA inhibited monocyte adhesion and transendothelial migration, reduced endothelial hyperpermeability and secretion of prostaglandin E2(PGE2). Additionally, tHGA inhibited cytoskeletal rearrangement and adhesion protein expression on LPS-stimulated HUVECs.
  
  
  CONCLUSIONS
  As the regulation of endothelial barrier dysfunction can be one of the therapeutic strategies to improve the outcome of inflammation, tHGA may be able to preserve vascular barrier integrity of endothelial cells following LPS-stimulated dysfunction, thereby endorsing its potential usefulness in vascular inflammatory diseases.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43300, Malaysia.
authors.forename: Yi Joong
authors.initials: YJ
authors.lastname: Chong
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43300, Malaysia.
authors.forename: Nazmi Firdaus
authors.initials: NF
authors.lastname: Musa
authors.affiliation: Faculty of Science, Universiti Putra Malaysia, Serdang 43300, Malaysia.
authors.forename: Chean Hui
authors.initials: CH
authors.lastname: Ng
authors.affiliation: Faculty of Science, Universiti Putra Malaysia, Serdang 43300, Malaysia.
authors.forename: Khozirah
authors.initials: K
authors.lastname: Shaari
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43300, Malaysia.
authors.forename: Daud Ahmad
authors.initials: DA
authors.lastname: Israf
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43300, Malaysia. Electronic address: chauling@upm.edu.my.
authors.forename: Chau Ling
authors.initials: CL
authors.lastname: Tham
mesh_terms: D000098:Acetophenones / Q000737:chemistry / Q000494:pharmacology*; D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D018920:Coculture Techniques; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C000616900:2,4,6-trihydroxy-3-geranylacetophenone; D000098:Acetophenones; D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C573420:ICAM1 protein, human; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D010696:Phloroglucinol; D015232:Dinoprostone
keywords: 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA); Barrier protective effect; Endothelial dysfunction; Lipopolysaccharides; Melicope ptelefolia; Phloroglucinol