Comprehensive analysis of protective effects of <i>Loranthus tanakae</i> Franch. and Sav. on ovalbumin-induced atopic dermatitis in mice and TNF-<i>α</i>/INF-<i>γ</i>-stimulated HaCaT cells.

Abstract

<i>Loranthus tanakae</i> Franch. and Sav. is a traditional herbal remedy with anti-inflammatory and antioxidative properties, used to treat joint and respiratory inflammation. In this study, we investigated the therapeutic effects of <i>L. tanakae</i> ethanol extract (LTE) on atopic dermatitis (AD). An ovalbumin (OVA)-induced AD animal model and a human keratinocyte cell line, HaCaT, were used to assess LTE treatment effects on AD. An <i>in vitro</i> experiment showed that LTE treatment significantly decreased the production of regulated upon activation, normal T cell expressed and secreted (RANTES) cytokines and macrophage-derived chemokines (MDC) in tumor necrosis factor-alpha (TNF-<i>α</i>)/interferon-gamma (IFN-<i>γ</i>) (TNF-<i>α</i>/IFN-<i>γ</i>)-stimulated HaCaT cells in a concentration-dependent manner. In addition, treatment with LTE markedly reduced the translocation of signal transducer and activator transcription 1 (STAT1) protein to the nucleus and the phosphorylation of Janus kinase 2 (JAK2) in TNF-<i>α</i>/IFN-<i>γ</i>-stimulated HaCaT cells. In the <i>in vivo</i> experiment, administration of LTE significantly decreased the levels of immunoglobulin E (IgE) and interleukin-13 (IL-13) of OVA-induced AD mice, which was supported by histological evidence. Moreover, LTE treatment markedly reduced inflammatory cell infiltration and edema in the OVA-induced AD mice's damaged lesions. In addition, applying LTE notably inhibited the phosphorylation of JAK2 and STAT1 in the OVA-induced AD mice, supported by <i>in vitro</i> results. In conclusion, LTE effectively alleviated the AD-induced skin inflammation in the OVA-induced AD animal model and TNF-<i>α</i>/IFN-<i>γ</i>-stimulated HaCaT cells; this was related to the suppression of JAK2 and STAT1 phosphorylation. These findings suggest that LTE has potential as a therapeutic agent for AD management.