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

Planta Med. 2008 Jun;74(8):828-33. doi: 10.1055/s-2008-1074548. Epub 2008 Jun 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Cell Line
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Monoterpenes / pharmacology*
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Signal Transduction
  • Tropolone / analogs & derivatives*
  • Tropolone / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Anti-Infective Agents
  • Monoterpenes
  • NF-kappa B
  • PDK1 protein, human
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Tumor Necrosis Factor-alpha
  • Tropolone
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • beta-thujaplicin