title: 1β-Hydroxyalantolactone, a sesquiterpene lactone from Inula japonica, attenuates atopic dermatitis-like skin lesions induced by 2,4-dinitrochlorobenzene in the mouse.
abstract: BACKGROUND
  1β-Hydroxyalantolactone (IJ-5) is a sesquiterpene lactone compound isolated from Inula japonica Thunb (Asteraceae). Sesquiterpene lactones have been shown to modulate many processes that influence inflammatory reactions.
  
  
  OBJECTIVE
  The present study examines the protective effect of IJ-5 on atopic dermatitis (AD) in a mouse model induced by 2,4-dinitrochlorobenzene (DNCB).
  
  
  METHODS
  AD-like skin lesions were induced in Balb/c mice by sensitizing once with painting 100 μL of 5% DNCB on their shaved back skin and then challenging with 20 μL of 0.2% DNCB five times on their right ears at 3 d interval starting on day 5 post-sensitization. IJ-5 was administrated intraperitoneally at 10 mg/kg 1 h before each DNCB challenge.
  
  
  RESULTS
  IJ-5 treatment attenuated DNCB-induced dermatitis severity and right ear swelling. The serum levels of IgE, IL-4, and IL-6 in IJ-5-treated mice were reduced by 54.7, 56.5, and 53.0%, respectively, while the mRNA levels of TNFα, IL-1, IL-4, and IL-6 in back skin lesions of IJ-5-treated mice were reduced by 47.7, 61.5, 57.5, and 58.5%, respectively, compared with untreated controls. Histopathological examination showed that IJ-5 treatment decreased DNCB-induced hypertrophy, hyperkeratosis, and infiltration of inflammatory cells in both ear and back skins. Moreover, IJ-5 suppressed the expression of TNFα, IL-1, and IL-6 with IC50 values of 6.58, 9.48, and 7.01 μM, respectively, and inhibited the activation of NF-κB pathway in TNFα-stimulated HaCat cells.
  
  
  CONCLUSIONS
  The present study demonstrates the protective effects of IJ-5 against AD-like skin inflammation and highlights IJ-5 as a potential therapeutic agent for AD.
authors.affiliation: a School of Pharmacy, the Second Military Medical University , Shanghai , China.
authors.forename: Guochao
authors.initials: G
authors.lastname: Lin
authors.affiliation: a School of Pharmacy, the Second Military Medical University , Shanghai , China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Gao
authors.affiliation: a School of Pharmacy, the Second Military Medical University , Shanghai , China.
authors.forename: Jinli
authors.initials: J
authors.lastname: Cheng
authors.affiliation: a School of Pharmacy, the Second Military Medical University , Shanghai , China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Li
authors.affiliation: a School of Pharmacy, the Second Military Medical University , Shanghai , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shan
authors.affiliation: a School of Pharmacy, the Second Military Medical University , Shanghai , China.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000818:Animals; D003876:Dermatitis, Atopic / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D004137:Dinitrochlorobenzene / Q000633:toxicity*; D038143:Inula; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000627:therapeutic use*
chemical_list: C000599362:1-hydroxyalantolactone; D004137:Dinitrochlorobenzene; D010936:Plant Extracts; D012717:Sesquiterpenes
keywords: Cytokine; HaCat cells; NF-κB; inflammation