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.

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.

Astragalus membranaceus (AM) has been used for anti-oxidative, anti-inflammatory, anti-cancer, and immunomodulatory activities. In this study, we confirmed that the anti-oxidative and anti-inflammatory effects of AM were enhanced after it was fermented by Lactiplantibacillus plantarum. The anti-oxidative effect was measured by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical levels, total phenolic contents (TPC), reducing power, and H₂O₂ levels. AM-LP MG5145 and MG5276 showed higher free radical scavenging activity than AM-NF (51.22%). In addition, AM-LP MG5145 and MG5276 showed higher TPC (49.11 mg GAE/mL), reducing power (OD₇₀₀ = 0.37), and H₂O₂ (1.71 µM) than AM-NF. The calycosin contents determined to AM-NF (17.24 ng/mL), AM-LP MG5145 (139.94 ng/mL), and MG5276 (351.01 ng/mL) using UPLC-ESI-MS/MS. Anti-inflammatory effects were analyzed by investigating the inhibitory effects of fermented AM on cytotoxicity, NO production, and mRNA expression of COX-2, iNOS, NF-κB, and TNF-α in LPS-induced RAW 264.7 cells. AM-LP MG5145 and MG5276 showed no cytotoxicity. AM-LP MG5145 (50.86%) and MG5276 (51.66%) inhibited NO production in LPS-induced RAW 264.7 cells. Moreover, AM-LP MG5145 and MG5276 downregulated macrophage iNOS, COX2, TNF-α, and NF-κB expression. In conclusion, A. membranaceus fermented by L. plantarum MG5145 and MG5276 can be used in cosmetics and health foods as natural antioxidant compounds.