Illicium verum extract inhibits TNF-α- and IFN-γ-induced expression of chemokines and cytokines in human keratinocytes

Illicium verum Hook. f. (star anise) has been used in traditional medicine for treatment of skin inflammation, rheumatism, asthma, and bronchitis. This study investigated the anti-inflammatory effects of Illicium verum extract (IVE) in the human keratinocyte HaCaT cell line. We investigated the effectiveness of IVE in tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-induced human keratinocytes. To measure the effects of IVE on chemokine and pro-inflammatory cytokine expression in HaCaT cells, we used the following methods: cell viability assay, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, and luciferase reporter assay. IVE inhibited the expression of TNF-α/IFN-γ-induced mRNA and protein expression of thymus and activation-regulated chemokine (TARC/CCL17), macrophage-derived chemokine (MDC/CCL22), interleukin (IL)-6, and IL-1β. Furthermore, IVE decreased TNF-α/IFN-γ-induced mRNA expression of intercellular adhesion molecule-1 (ICAM-1). IVE inhibited nuclear factor (NF)-κB translocation into the nucleus, as well as phosphorylation and degradation of IκBα. IVE inhibited TNF-α/IFN-γ-induced NF-κB and signal transducer and activator of transcription (STAT)1 activation in a dose-dependent manner. In addition, IVE significantly inhibited activation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and Akt. Furthermore, IVE contained 2.14% trans-anethole and possessed significant anti-inflammatory activities. IVE exerts anti-inflammatory effects by suppressing the expression of TNF-α/IFN-γ-induced chemokines, pro-inflammatory cytokines, and adhesion molecules via blockade of NF-κB, STAT1, MAPK, and Akt activation, suggesting that IVE may be a useful therapeutic candidate for inflammatory skin diseases, such as atopic dermatitis.