Hippophae rhamnoides has been extensively used in oriental traditional medicines for treatment of asthma, skin diseases, gastric ulcers, and lung disorders. In this study, we isolated casuarinin from the leaves of H. rhamnoides and examined the effect of casuarinin on the TNF-alpha-induced ICAM-1 expression in a human keratinocytes cell line HaCaT. Pretreatment with casuarinin inhibited TNF-alpha-induced protein and mRNA expression of ICAM-1 and subsequent monocyte adhesiveness in HaCaT cells. Casuarinin significantly inhibited TNF-alpha-induced NF-kappa B activation. In addition, casuarinin inhibited activation of ERK and p38 MAPK in a dose-dependent manner. Furthermore, pretreatment with casuarinin decreased TNF-alpha-induced pro-inflammatory mediators, such as IL-1 beta, IL-6, IL-8, and MCP-1. These results demonstrated that casuarinin exerts its anti-inflammatory activity by suppressing TNF-alpha-induced expression of ICAM-1 and pro-inflammatory cytokines/chemokines via blockage of activation of NF-kappa B and ERK/p38 MAPK and can be used as a therapeutic agent against inflammatory skin diseases. (C) 2011 Elsevier Inc. All rights reserved.