Hinokitiol, a natural tropolone derivative, inhibits TNF-alpha production in LPS-activated macrophages via suppression of NF-kappaB.

In this study, we examined the modulatory effect of hinokitiol (HK) on the production of tumor necrosis factor (TNF)-alpha, a critical factor involved in skin inflammation and hair follicle apoptosis. HK effectively suppressed TNF-alpha production in lipopolysaccharide (LPS)-activated, macrophage-like (RAW264.7) cells. This compound also diminished mRNA synthesis of TNF-alpha, indicating that HK-mediated inhibition may occur at the transcriptional level. Moreover, this compound down-regulated the phosphorylation of PDK1, Akt/PKB, and ERK, resulting in a loss of nuclear factor (NF)-kappaB activation, which is detectable by immunoblotting and reporter gene assays. Therefore, these results suggest that HK may cure hair loss by suppressing factors that promote follicular apoptosis, such as TNF-alpha, in addition to stimulating new hair growth.