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].

OBJECTIVES:

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: Jean Christopher Chamcheu, Harish C Pal, Imtiaz A Siddiqui, Vaqar M Adhami, Seyoum Ayehunie, Brendan T Boylan, Felicite K Noubissi, Naghma Khan, Deeba N Syed, Craig A Elmets, Gary S Wood, Farrukh Afaq, Hasan Mukhtar
• Journal: Skin pharmacology and physiology (Skin Pharmacol Physiol) Vol. 28 Issue 4 Pg. 177-88 ( 2015) ISSN: 1660-5535 [Electronic] Switzerland
• PMID: 25620035 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Anthocyanins
• Anti-Inflammatory Agents
• Cytokines
• FLG protein, human
• Filaggrin Proteins
• Membrane Proteins
• Protein Precursors
• RNA, Messenger
• S100 Calcium Binding Protein A7
• S100 Proteins
• S100A7A protein, human
• loricrin
• involucrin
• Caspases
• delphinidin

Topics

• Anthocyanins (pharmacology)
• Anti-Inflammatory Agents (pharmacology)
• Caspases (genetics, metabolism)
• Cell Differentiation
• Cells, Cultured
• Cytokines (metabolism)
• Filaggrin Proteins
• Humans
• Keratinocytes (drug effects, metabolism)
• Membrane Proteins (genetics, metabolism)
• Models, Biological
• Protein Precursors (genetics, metabolism)
• Psoriasis (drug therapy, metabolism)
• RNA, Messenger (metabolism)
• S100 Calcium Binding Protein A7
• S100 Proteins (genetics)
• Skin (drug effects, metabolism)