Nepetin, a Flavonoid Derived From Saussureae Involucratae, Suppresses The LPS-Induced Inflammatory Response in Cultured Human Keratinocytes

Abstract Background: Saussureae Involucratae Herba, known as “snow lotus” in Uyghur and/or Chinese medicines, is the dried aerial part of Saussurea involucrata (Kar. et Kir.) Sch.-Bip. (Asteraceae). One of the known pharmacological applications of this herb is to suppress chronic inflammation. Nepetin is considered as a bioactive flavonoid of Saussureae Involucratae Herba. Here, we are probing the efficacy of nepetin in modulating lipopolysaccharide (LPS)-stimulated inflammatory responses in cultured human keratinocytes.Results: In cultured keratinocytes, applied nepetin prevented the LPS-induced cell death. In parallel, the productions of inflammatory mediators, i.e. iNOS, COX-2，PGES2 and NO, were declined after nepetin challenge in LPS-treated keratinocytes. Besides, the treatment of nepetin in LPS-induced cultures suppressed the expressions of cytokines, i.e. IL-1β, IL-6 and TNF-α, in a dose-dependent manner. The productions of inflammatory modulators and/or cytokines could be accounted by nepetin-mediated NF-kB translocation from cytosol to nucleus within the inflammatory activated keratinocytes. In accord to this notion, the formation of ROS, as induced by LPS, could be reduced by nepetin challenge.Conclusions: The aforementioned results suggested that nepetin could account the anti-inflammatory properties of Saussureae Involucratae Herba, at least during the skin inflammation, e.g. atopic dermatitis.