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.
Original language | English (US) |
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Pages (from-to) | 177-188 |
Number of pages | 12 |
Journal | Skin Pharmacology and Physiology |
Volume | 28 |
Issue number | 4 |
DOIs | |
State | Published - Jun 9 2015 |
Bibliographical note
Publisher Copyright:© 2015 S. Karger AG, Basel.
Keywords
- Caspase14
- Cell proliferation
- Delphinidin
- Differentiation
- Filaggrin
- Inducible nitric oxide synthase
- Inflammation
- Ki67
- Koebnerisin
- Loricrin
- Normal human and psoriatic skin equivalent model
- Proliferating cell nuclear antigen procaspase-3, -7, -9
- Psoriasin
- Psoriasis