Anti-inflammation activity of brazilin in TNF-\u03b1 induced human psoriasis dermatitis skin model

Da Hee Choi,Hyung Seo Hwang

doi:10.1186/s13765-019-0455-z

Da Hee Choi, Hyung Seo Hwang

Open Access

https://doi.org/10.1186/s13765-019-0455-z

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Abstract

Psoriasis is a chronic inflammatory skin disease that causes erythema, scale, and invasion due to excessive proliferation of keratinocyte and vascular deformation of the upper part of the dermis. Recently, it has been reported that brazilin, an active compound of Caesalpinia sappan L., possesses anti-inflammatory activity in mouse macrophage. However, little is known about its effect or anti-inflammatory activity on psoriasis dermatitis. Thus, the objective of this study was to determine anti-inflammatory activity of brazilin in TNF-α-induced human keratinocyte (HaCaT) widely used as a model of psoriatic dermatitis. First, CCK-8 assay was performed to determine cytotoxicity of brazilin in HaCaT cells and cytotoxicity was not observed up to 7 μg/mL concentrations. Brazilin decreased mRNA expression levels of inflammatory cytokines such as IL-1α, IL-1β, IL-6, IL-8 and TNF-α in a concentration dependent manner. Brazilin also significantly reduced phosphorylation of I-κB, Akt, and MAPKs such as ERK, JNK, p38 and STAT3 in immortalized human keratinocytes (HaCaT) induced by TNF-α. In addition, inflammation causes the weakness of the skin barrier structure and increase cell permeability, stimulating serious problems in skin moisturizing. Thus, we observed changes of skin permeability in TNF-α induced inflammatory condition through transepithelial electrical resistance (TEER) assay. While TNF-α induced inflammation caused reduction of TEER value (ohm (Ω) × cm2), it was recovered by treatment with brazilin in a concentration-dependent manner. These results strongly imply that brazilin can reinforce the skin barrier due to its anti-inflammatory activity. Therefore, brazilin could be a promising candidate for treating psoriasis dermatitis.

Highlights

Inflammation is innate immunity reaction that protects human bodies from external pathogens or tissue damage [1]
We have studied on diverse effects of Caesalpinia sappan L. extract and brazilin with human skin cells [27,28,29,30]
Human keratinocytes induce an inflammatory reaction by secreting various types of inflammatory cytokines such as TNF-α, IL-1, IL-6, IL-7, IL-8, IL-17, and IL-21 due to external stimulus

Summary

Introduction

Inflammation is innate immunity reaction that protects human bodies from external pathogens or tissue damage [1]. When TNF-α binds to TNFR (Tumor Necrosis Factor Receptor) in keratinocyte, Akt (Protein kinase B) and IKK (I-κB kinase) protein is activated to phosphorylate I-κB (Inhibitors kappa B), which activates NF-kB. This consequentially accelerates expression of inflammatory cytokines such as IL-1α, IL-1β, IL-6, IL-8, and TNF-α [19,20,21,22]. Due to activation of TNF-α signal, ERK, JNK, and p38 proteins are phosphorylated and overexpressed in psoriasis dermatitis [23,24,25,26]

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