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

Ethnopharmacological relevance: 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. Materials and methods: We investigated the effectiveness of IVE in tumor necrosis factor-alpha (TNF-alpha)/interferon-gamma (IFN-gamma)-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. Results: IVE inhibited the expression of TNF-alpha/IFN-gamma-induced mRNA and protein expression of thymus and activation-regulated chemokine (TARC/CCL17), macrophage-derived chemokine (MDC/CCL22), interleukin (1L)-6, and 1L-1 beta. Furthermore, IVE decreased TNF-alpha/IFN-gamma-induced mRNA expression of intercellular adhesion molecule-1 (ICAM-1). IVE inhibited nuclear factor (NF)-kappa B translocation into the nucleus, as well as phosphorylation and degradation of I kappa B alpha. IVE inhibited TNF-alpha/IFN-gamma-induced NF-kappa B and signal transducer and activator of transcription (STAT)1 activation in a dose-dependent manner. In addition, 1VE 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. Conclusions: IVE exerts anti-inflammatory effects by suppressing the expression of TNF-alpha/IFN-gamma-induced chemokines, pro-inflammatory cytokines, and adhesion molecules via blockade of NF-kappa B, STAT1, MAPK, and Akt activation, suggesting that IVE may be a useful therapeutic candidate for inflammatory skin diseases, such as atopic dermatitis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.