title: Citrus hallabong [(Citrus unshiu × C. sinensis) × C. reticulata)] exerts potent anti-inflammatory properties in murine splenocytes and TPA-induced murine ear oedema model.
abstract: BACKGROUND
  Hallabong [(Citrus unshiu × C. sinensis) X C. reticulata)] (Rutaceae) is a hybrid citrus cultivated in temperate regions of South Korea. Its fruit is well-known for pharmacological properties.
  
  
  OBJECTIVE
  This study examined the anti-inflammatory effect of 80% ethanol extract of Hallabong (HE) on concanavalin A (Con A)-stimulated splenocytes and mouse oedema model induced by 12-O-tetradecanoylphorbal acetate (TPA).
  
  
  METHODS
  Murine splenocytes treated with HE were stimulated with Con A (10 μg/mL, for 24 h) were evaluated for T-cell population and production of inflammatory cytokines IL-2, IL-4 and IFN-γ. Anti-inflammatory effect of topically applied HE (100 μg/20 μL) on TPA (4 μg/20 μL/ear)-induced ear oedema was investigated in mouse model.
  
  
  RESULTS
  HE-treated Con A-stimulated murine splenocytes showed a marked decrease in CD44/CD62L+memory T-cell population, an important marker for anti-inflammatory activity, and a significant inhibition in the production of IL-2 and IFN-γ. HE treatment had reduced the mouse skin oedema (47%) and myeloperoxidase (MPO) activity significantly (40%) in TPA-challenged tissues. More importantly, immunohistochemical localization revealed the suppressed (p < 0.05) expression of inducible nitric oxide (iNOS), cyclooxygenase-2 (COX2). HE decreased the infiltration of CD3+T cells and F4/80+macrophages to the site of inflammation and a topical application of HE significantly suppressed the expression of TNF-α (20.2%).
  
  
  CONCLUSIONS
  A topical application of HE can exert a potential anti-inflammatory effect and HE can be explored further as a putative alternative therapeutic agent for inflammatory oedema.
authors.affiliation: a Department of Veterinary Medicine and Veterinary Medical Research Institute , Jeju National University , Jeju , Korea.
authors.forename: Kalahe Hewage Iresha Nadeeka Madushani
authors.initials: KH
authors.lastname: Herath
authors.affiliation: a Department of Veterinary Medicine and Veterinary Medical Research Institute , Jeju National University , Jeju , Korea.
authors.forename: So Jin
authors.initials: SJ
authors.lastname: Bing
authors.affiliation: a Department of Veterinary Medicine and Veterinary Medical Research Institute , Jeju National University , Jeju , Korea.
authors.forename: Jinhee
authors.initials: J
authors.lastname: Cho
authors.affiliation: b Department of Advanced Convergence Technology & Science , Jeju National University , Jeju , Korea.
authors.forename: Areum
authors.initials: A
authors.lastname: Kim
authors.affiliation: c Jeju Diversity Research Institute, Jeju Technopark , Seogwipo , Korea.
authors.forename: Gi-Ok
authors.initials: GO
authors.lastname: Kim
authors.affiliation: c Jeju Diversity Research Institute, Jeju Technopark , Seogwipo , Korea.
authors.forename: Jong-Chul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: a Department of Veterinary Medicine and Veterinary Medical Research Institute , Jeju National University , Jeju , Korea.|b Department of Advanced Convergence Technology & Science , Jeju National University , Jeju , Korea.
authors.forename: Youngheun
authors.initials: Y
authors.lastname: Jee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002957:Citrus; D032084:Citrus sinensis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004423:Ear; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D013154:Spleen / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
chemical_list: D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D013755:Tetradecanoylphorbol Acetate
keywords: Anti-inflammation; ear skin oedema; pro-inflammatory cytokines; pro-inflammatory mediators