title: Prodifferentiation, anti-inflammatory and antiproliferative effects of delphinidin, a dietary anthocyanidin, in a full-thickness three-dimensional reconstituted human skin model of psoriasis.
abstract: BACKGROUND
  Psoriasis is a chronic inflammatory disorder of skin and joints for which conventional treatments that are effective in clearing the moderate-to-severe disease are limited due to long-term safety issues. This necessitates exploring the usefulness of botanical agents for treating psoriasis. We previously showed that delphinidin, a diet-derived anthocyanidin endowed with antioxidant and anti-inflammatory properties, induces normal epidermal keratinocyte differentiation and suggested its possible usefulness for the treatment of psoriasis [1].
  
  
  OBJECTIVE
  To investigate the effect of delphinidin (0-20 μM; 2-5 days) on psoriatic epidermal keratinocyte differentiation, proliferation and inflammation using a three-dimensional reconstructed human psoriatic skin equivalent (PSE) model.
  
  
  METHODS
  PSEs and normal skin equivalents (NSEs) established on fibroblast-contracted collagen gels with respective psoriatic and normal keratinocytes and treated with/without delphinidin were analyzed for histology, expression of markers of differentiation, proliferation and inflammation using histomorphometry, immunoblotting, immunochemistry, qPCR and cultured supernatants for cytokine with a Multi-Analyte ELISArray Kit.
  
  
  RESULTS
  Our data show that treatment of PSE with delphinidin induced (1) cornification without affecting apoptosis and (2) the mRNA and protein expression of markers of differentiation (caspase-14, filaggrin, loricrin, involucrin). It also decreased the expression of markers of proliferation (Ki67 and proliferating cell nuclear antigen) and inflammation (inducible nitric oxide synthase and antimicrobial peptides S100A7-psoriasin and S100A15-koebnerisin, which are often induced in psoriatic skin). ELISArray showed increased release of psoriasis-associated keratinocyte-derived proinflammatory cytokines in supernatants of the PSE cultures, and this increase was significantly suppressed by delphinidin.
  
  
  CONCLUSIONS
  These observations provide a rationale for developing delphinidin for the management of psoriasis.
authors.affiliation: Department of Dermatology, University of Wisconsin-Madison, Madison, Wisc., USA.
authors.forename: Jean Christopher
authors.initials: JC
authors.lastname: Chamcheu
authors.forename: Harish C
authors.initials: HC
authors.lastname: Pal
authors.forename: Imtiaz A
authors.initials: IA
authors.lastname: Siddiqui
authors.forename: Vaqar M
authors.initials: VM
authors.lastname: Adhami
authors.forename: Seyoum
authors.initials: S
authors.lastname: Ayehunie
authors.forename: Brendan T
authors.initials: BT
authors.lastname: Boylan
authors.forename: Felicite K
authors.initials: FK
authors.lastname: Noubissi
authors.forename: Naghma
authors.initials: N
authors.lastname: Khan
authors.forename: Deeba N
authors.initials: DN
authors.lastname: Syed
authors.forename: Craig A
authors.initials: CA
authors.lastname: Elmets
authors.forename: Gary S
authors.initials: GS
authors.lastname: Wood
authors.forename: Farrukh
authors.initials: F
authors.lastname: Afaq
authors.forename: Hasan
authors.initials: H
authors.lastname: Mukhtar
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D000091344:Filaggrin Proteins; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D000893:Anti-Inflammatory Agents; D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C510475:S100A7A protein, human; C064554:loricrin; C032253:involucrin; D020169:Caspases; C017185:delphinidin