title: Topical application of delphinidin reduces psoriasiform lesions in the flaky skin mouse model by inducing epidermal differentiation and inhibiting inflammation.
abstract: BACKGROUND
  Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation and aberrant keratinocyte differentiation. We have shown that treatment of reconstituted human skin with delphinidin, an anthocyanidin, present in pigmented fruits and vegetables, increased the expression and processing of caspase-14, which is involved in cornification. Delphinidin also increases the expression of epidermal differentiation marker proteins.
  
  
  OBJECTIVE
  To determine whether topical application of delphinidin can modulate pathological markers of psoriasiform lesions in flaky skin mice and if this is associated with increased epidermal differentiation and a reduction in proliferation and inflammation.
  
  
  METHODS
  Five-week-old female homozygous flaky skin mice (fsn/fsn) were treated topically with delphinidin (0·5 mg cm(-2) and 1 mg cm(-2) skin areas, respectively), five times a week, up to 14 weeks of age.
  
  
  RESULTS
  Treatment of flaky skin mice with delphinidin resulted in a reduction in (i) pathological markers of psoriasiform lesions; (ii) infiltration of inflammatory cells; and (iii) mRNA and protein expression of inflammatory cytokines. Delphinidin treatment also increased the expression and processing of caspase-14, and expression of filaggrin, loricrin, keratin-1 and keratin-10. Furthermore, there was a decrease in the expression of markers for cell proliferation (proliferating cell nuclear antigen and keratin-14) and modulation of tight junction proteins (occludin and claudin-1). In addition, delphinidin treatment increased the expression of activator protein-1 transcription factor proteins (JunB, JunD, Fra1 and Fra2).
  
  
  CONCLUSIONS
  Delphinidin could be a promising agent for treatment of psoriasis and other hyperproliferative skin disorders.
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, 1670 University Blvd, Birmingham, 35294, AL, U.S.A.
authors.forename: H C
authors.initials: HC
authors.lastname: Pal
authors.forename: J C
authors.initials: JC
authors.lastname: Chamcheu
authors.forename: V M
authors.initials: VM
authors.lastname: Adhami
authors.forename: G S
authors.initials: GS
authors.lastname: Wood
authors.forename: C A
authors.initials: CA
authors.lastname: Elmets
authors.forename: H
authors.initials: H
authors.lastname: Mukhtar
authors.forename: F
authors.initials: F
authors.lastname: Afaq
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000008:administration & dosage / Q000494:pharmacology*; D053456:Caspase 14 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D062445:Claudin-1 / Q000378:metabolism; D003879:Dermatologic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004817:Epidermis / Q000187:drug effects; D005260:Female; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008822:Mice, Transgenic; D062793:Occludin / Q000378:metabolism; D011565:Psoriasis / Q000517:prevention & control*
chemical_list: D000872:Anthocyanins; D062445:Claudin-1; D003879:Dermatologic Agents; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D062793:Occludin; C064554:loricrin; D053456:Caspase 14; C017185:delphinidin