Inhibition of lipopolysaccharide-induced interleukin-1beta and tumor necrosis factor-alpha production by menthone through nuclear factor-kappaB signaling pathway in HaCat cells.

Menthone, the Chinese old remedy extracted from genus Mentha, has been widely used as a cooling agent, a counterirritant for pain relief, and for the treatment of pruritus. However, its detail mechanisms for interfering inflammatory reaction remain unknown. In this study, we found that menthone can suppress the lipopolysaccharide (LPS)-induced proinflammatory cytokines, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), as well as nuclear factor kappaB (NF-kappaB) activity induced by LPS and other inflammatory agents, including 12-O-tetradecanoylphorbol-13-acetate, hydrogen peroxide, okadaic acid, and ceramide. Furthermore, our data also demonstrated that the translocation of NF-kappaB activated by LPS into the nucleus was suppressed by menthone, and I-kappaB and beta-transducin repeat containing protein (beta-TrCP) were both involved in this suppression. To sum up, this study has provided molecular evidence for menthone effect on the LPS-induced cytokine production, NF-kappaB activation, and the involvement of I-kappaB and beta-TrCP.