title: Dietary zerumbone prevents mouse cornea from UVB-induced photokeratitis through inhibition of NF-κB, iNOS, and TNF-α expression and reduction of MDA accumulation.
abstract: OBJECTIVE
  Ultraviolet B (UVB) irradiation activates nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) in the cornea, resulting in inflammatory responses and malondialdehyde (MDA) accumulation. This study aims to determine the effect of zerumbone, a potent NF-κB inhibitor and inflammation modulators, on UVB-induced corneal damages in a mouse model.
  
  
  METHODS
  Fifty female imprinting control region (ICR) mice were randomly divided into five groups. The mice were anaesthetized with their ocular surfaces exposed to UVB light (0.72J/cm(2)/daily), followed by daily dietary zerumbone supplements at 0, 1, 10, and 100 mg/kg of bodyweight. Mice without zerumbone supplements were used as treatment controls and mice without UVB irradiation as blank controls. Corneal surface damages were graded according to smoothness, opacity, and the extent of lissamine green staining. Histopathological changes were also examined, along with the expression of NF-κB, iNOS, and tumor necrosis factor-α (TNF-α). MDA accumulation and the levels of two antioxidant enzymes, glutathione (GSH) and GSH reductase (GR) were also examined.
  
  
  RESULTS
  UVB irradiation caused significant damages to cornea, including sustained inflammation, apparent corneal ulcer, and severe epithelial exfoliation, leading to thinning of corneal epithelial layer, and infiltration of polymorphonuclear leukocytes. NF-κB expression was highly activated with nuclear translocation. The expression of iNOS and TNF-α were increased. MDA accumulation was also increased in both the corneal epithelial layer and the stroma. With dietary zerumbone, corneal damages were ameliorated in a dose-dependent manner. NF-κB activation and its nuclear translocation were blocked with decreased expression of iNOS and TNF-α. Infiltration of polymorphonuclear leukocytes was also blocked by dietary zerumbone. Besides, MDA accumulation was reduced with concomitant increase of GSH and GR levels.
  
  
  CONCLUSIONS
  Dietary zerumbone prevents UVB-induced corneal damages by inhibition of NF-κB, iNOS, and TNF-α, with concomitant reduction of MDA accumulation and increase of GSH and GR levels in the mouse model. Results of this study suggest that dietary zerumbone may be used as a prophylactic agent against UVB-induced photokeratitis.
authors.affiliation: School of Optometry, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Bo-Yie
authors.initials: BY
authors.lastname: Chen
authors.forename: David Pei-Cheng
authors.initials: DP
authors.lastname: Lin
authors.forename: Chia-Yung
authors.initials: CY
authors.lastname: Wu
authors.forename: Mei-Ching
authors.initials: MC
authors.lastname: Teng
authors.forename: Chi-Yun
authors.initials: CY
authors.lastname: Sun
authors.forename: Yuan-Ting
authors.initials: YT
authors.lastname: Tsai
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Su
authors.forename: Soo-Ray
authors.initials: SR
authors.lastname: Wang
authors.forename: Han-Hsin
authors.initials: HH
authors.lastname: Chang
mesh_terms: D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D019781:Corneal Topography; D004035:Diet Therapy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression; D005978:Glutathione / Q000032:analysis / Q000096:biosynthesis; D005980:Glutathione Reductase / Q000032:analysis; D007634:Keratitis / Q000178:diet therapy* / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008086:Lissamine Green Dyes / Q000032:analysis; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D008086:Lissamine Green Dyes; D016328:NF-kappa B; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; C403304:zerumbone; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; D005980:Glutathione Reductase; D005978:Glutathione