title: Effects of Hovenia dulcis Thunb. extract and methyl vanillate on atopic dermatitis-like skin lesions and TNF-α/IFN-γ-induced chemokines production in HaCaT cells.
abstract: OBJECTIVE
  Here, we hypothesized that Hovenia dulcis branch extract (HDB) and its active constituents ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis (AD)-like skin lesions by modulating the T helper Th1/Th2 balance in NC/Nga mice and TNF-α- and IFN-γ-induced production of thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in HaCaT cells.
  
  
  METHODS
  HaCaT cells were stimulated by TNF-α/IFN-γ in the presence of HDB and its constituents. TARC and MDC were measured by ELISA and RT-PCR. For the in-vivo study, oral feeding of HDB was performed for 5 weeks with 2,4-dinitrochlorobenzene (DNCB) treatment every other day. The efficacy of HDB on parameters of DNCB-induced AD was evaluated morphologically, physiologically and immunologically.
  
  
  RESULTS
  In-vitro studies showed that HDB and its constituents suppressed TNF-α/IFN-γ-induced production of TARC and MDC in HaCaT cells by inhibiting MAPK signalling. In-vivo studies showed that HDB regulated immunoglobulin (Ig) E and immunoglobulin G2a (IgG2a) levels in serum and the expression of mRNA for Th1- and Th2-related mediators in skin lesions. Histopathological analyses revealed reduced epidermal thickness and reduced infiltration of skin lesions by inflammatory cells.
  
  
  CONCLUSIONS
  These results suggest that HDB inhibits AD-like skin diseases by regulating Th1 and Th2 responses in NC/Nga mice and in HaCaT cells.
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Korea.|Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology, Gangneung, Korea.
authors.forename: Sue Ji
authors.initials: SJ
authors.lastname: Lim
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Korea.|Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology, Gangneung, Korea.
authors.forename: Myungsuk
authors.initials: M
authors.lastname: Kim
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Korea.|Department of Biological Chemistry, Korea University of Science and Technology, Daejeon, Korea.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Randy
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Korea.|Department of Biological Chemistry, Korea University of Science and Technology, Daejeon, Korea.
authors.forename: Eui Jeong
authors.initials: EJ
authors.lastname: Nam
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Korea. cwnho@kist.re.kr.|Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology, Gangneung, Korea. cwnho@kist.re.kr.
authors.forename: Chu Won
authors.initials: CW
authors.lastname: Nho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D054414:Chemokine CCL17 / Q000378:metabolism; D054422:Chemokine CCL22 / Q000378:metabolism; D018925:Chemokines / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D004137:Dinitrochlorobenzene; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D027823:Rhamnaceae / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D058408:Th1-Th2 Balance / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014641:Vanillic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; C106230:CCL17 protein, human; C515482:CCL22 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D018925:Chemokines; D004137:Dinitrochlorobenzene; D007074:Immunoglobulin G; D010936:Plant Extracts; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C000618837:methyl vanillate; D007073:Immunoglobulin E; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases; D014641:Vanillic Acid
keywords: 
  Hovenia dulcis
  ; NC/Nga mice; Th1-/Th2-related mediators; atopic dermatitis; immunoglobulin E; immunoglobulin G2a