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) × cm 2 ), 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. which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Rebaudioside A is a natural sweetener isolated from Stevia rebaudiana Bertoni, one of the glycosides based on steviol. Recent studies have shown that rebaudioside A inhibits the inflammatory response by inhibiting cytokines secretion such as interleukin-1α/1β in activated RAW264.7 mouse macrophage cells by LPS. However, the inhibitory mechanism of inflammation by rebaudioside A in the presence of LPS has not been fully elucidated. Therefore, in this study, we tried to investigate the antiinflammatory activity of rebaudioside A at the protein level when RAW264.7 cells were stimulated by LPS. The inducible nitric oxide synthase protein expression level was reduced in the group treated with 250 μM rebaudioside A compared to the LPS-treated group. In addition, the mRNA expression level of NF-κB, which is a representative nuclear transcription factor by inflammatory signal, was also decreased as compared with that of LPS-treated group. In addition, NF-κB and inhibitor-κB (I-κB) complexes that are known to be dissociated by I-κB phosphorylation and ubiquitination were less phosphorylated than LPS treated group in the presence rebaudioside A. Finally, we could find that rebaudioside A was involved in the NF-κB pathway through reducing extracellular signal-regulated kinase1/2 phosphorylation in a concentration-dependent manner. These results suggest that rebaudioside A might suppress inflammatory reaction through MAPK and NF-κB regulation in LPS-stimulated RAW264.7.

Taxifolin, a bioactive flavonoid, has been attracting attention as a beneficial and valuable phytochemical due to its antioxidant, anticancer, and anti-inflammatory properties. Recently, an improvement effect of taxifolin against psoriasis has been reported in an animal experimental model. However, its exact mechanism of action at molecular and cellular levels is not known. Thus, the purpose of this study was to verify the anti-inflammatory effect of taxifolin on psoriasis at cellular/molecular level using HaCaT human keratinocytes. First, a CCK-8 assay was performed to evaluate cytotoxicity of taxifolin. Results revealed that taxifolin was a relatively safe material, showing no cytotoxicity at concentrations up to 300 μg/mL. In TNF-α-induced HaCaT cells, taxifolin significantly inhibited mRNA expression levels of pro-inflammatory cytokines (IL-1α, IL-1-β, and IL-6) and chemokines (CXCL8 and CCL20). The ability of taxifolin to regulation expression of inflammatory cytokine genes was associated with phosphorylation of IκB/STAT3 protein. In addition, taxifolin inhibited expression levels of IL-1α/β, IL-6, CXCL8, and CCL20 by inhibiting IκB/STAT3 protein phosphorylation upon stimulation of TNF-α, IL-17A, and IFN-γ. These results show that taxifolin has the potential to be developed as a treatment for psoriasis and skin inflammation.

Psoriasis is an autoimmune skin disease that is accompanied by hyper proliferation of the epidermis, erythema of various sizes, and ulceration. However, the mechanism of the development of psoriasis dermatitis is unclear. Recently, it is known that the inflammatory cytokines and Th17 cells as well as chemokine (CC motif) ligand 20 (CCL20) are involved in the process of keratinocytes hyper-differentiation, which is common in psoriasis dermatitis. Therefore, we studied the effects of yakuchinone-A, an active ingredient of Alpinia oxyphylla Miquel known for its anti-inflammatory activity, to improve psoriasis dermatitis. First, cytotoxicity of yakuchinone-A was observed in cell counting kit-8 assay and not observed in 10 μg/mL concentration on the human keratinocyte HaCaT cells. Yakuchinone-A in the presence of tumor necrosis factor-alpha (TNF-α) on HaCaT cells inhibited mRNA expression of IL-6, IL-8, and TNF-α by up to 61.4±7.5, 23.6±1.5, 46.0±4.8%. CCL20, a chemokine that attracts immune cells such Th17 cells to the inflammation location, was also significantly suppressed by yakuchinone-A. In addition, IκB and STAT3 phosphorylation involved in the CCL20 expression was inhibited by yakuchinone-A in a concentration-dependent manner up to the level of 79.1±5.0, 80.8±2.3%. Furthermore, yakuchinone-A downregulated CCL20 mRNA expression level on IL-17A-activated HaCaT cells as a concentration-dependent manner. Based on these results, yakuchinone-A is expected to be developed as a new material for improving psoriasis dermatitis in the future.

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