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.
School of Bioscience and Biotechnology, and the Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea.
Se Eun
SE
Byeon
Yong Gyu
YG
Lee
Jin-Chul
JC
Kim
Jae Gun
JG
Han
Hyeon Yong
HY
Lee
Jae Youl
JY
Cho
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D039821:Monoterpenes / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D015398:Signal Transduction; D014334:Tropolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000890:Anti-Infective Agents; D039821:Monoterpenes; D016328:NF-kappa B; C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D014409:Tumor Necrosis Factor-alpha; D014334:Tropolone; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C009479:beta-thujaplicin