title: Emodin suppression of ocular surface inflammatory reaction.
abstract: OBJECTIVE
  To determine whether a Chinese herbal medicine component, emodin, suppresses inflammatory/fibrogenic reaction in cultured subconjunctival fibroblasts and reduces injury-induced increases in ocular surface inflammation in mice.
  
  
  METHODS
  Effects of emodin were measured in human subconjunctival fibroblasts on proliferation and migration with colorimetry and scratch wound assay, respectively. Neovascularization was evaluated using an endothelial cell-fibroblast coculture model. Proinflammatory mediator and extracellular matrix component gene and protein expression was characterized with real-time reverse transcription-polymerase chain reaction, enzyme immunoassay, and immunocytochemistry, respectively. Western blotting and immunohistochemistry evaluated the activation of nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK). In a mouse corneal alkali-burn model, the effects of emodin on ocular surface inflammation and fibrosis were evaluated.
  
  
  RESULTS
  Emodin suppressed tumor necrosis factor alpha (TNF-alpha)-induced fibroblast migration and fibronectin deposition in vitro. VEGF induced neovascularization but did not affect cell proliferation and collagen type 1 production. Monocyte/macrophage-chemoattractant protein-1 gene and protein expression declined. Emodin inhibited TNF-alpha-induced NF-kappaB p65 and JNK activation but did not affect transforming growth factor beta1-induced Smad2/3 signaling. In vivo, emodin inhibited proinflammatory and fibrogenic reactions.
  
  
  CONCLUSIONS
  Emodin suppressed in vitro TNF-alpha-induced stimulation of proinflammatory reaction. In a mouse ocular alkali burn model, this herbal component lessened inflammation and scarring. Additional studies are warranted to evaluate the therapeutic potential of emodin in lessening ocular tissue inflammation and resultant fibrosis after injury.
authors.affiliation: Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. aikitano@wakayama-med.ac.jp
authors.forename: Ai
authors.initials: A
authors.lastname: Kitano
authors.forename: Shizuya
authors.initials: S
authors.lastname: Saika
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamanaka
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ikeda
authors.forename: Yuka
authors.initials: Y
authors.lastname: Okada
authors.forename: Kumi
authors.initials: K
authors.lastname: Shirai
authors.forename: Peter S
authors.initials: PS
authors.lastname: Reinach
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D024042:Collagen Type I / Q000378:metabolism; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003233:Conjunctivitis, Allergic / Q000517:prevention & control*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004642:Emodin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D024042:Collagen Type I; D004365:Drugs, Chinese Herbal; D005353:Fibronectins; D016328:NF-kappa B; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D048670:MAP Kinase Kinase 4; D004642:Emodin