N(1)-methylspermidine, a stable spermidine analog, prolongs anagen and regulates epithelial stem cell functions in human hair follicles

Arch Dermatol Res. 2015 Nov;307(9):841-7. doi: 10.1007/s00403-015-1592-9. Epub 2015 Jul 28.


Spermidine (Spd), the prototypic polyamine, has been shown to be essential for hair follicle (HF) growth. However, Spd can be readily converted into other polyamines, and is physiologically unstable. Therefore, to assess its individual functions on HFs, we used the metabolically stable Spd analog N(1)-methylspermidine (N(1)-MeSpd). N(1)-MeSpd was confirmed to be a metabolically stable compound, with a half life of 90 h. 0.5 µM N(1)-MeSpd strongly prolonged anagen and decreased cell apoptosis in HFs in culture after 6 days, accompanied by specific stimulation of the expression of the epithelial stem cell-associated keratin, K15. N(1)-MeSpd also reduced lactate dehydrogenase activity in the culture supernatant, a parameter of cell death and cell lysis. N(1)-MeSpd diminished intracellular reactive oxygen species production in cultured keratinocytes, and reduced tumor necrosis factor-α, interleukin (IL)-1β and IL-6 gene and protein expression after lipopolysaccharide stimulation. This suggests that some effects of N(1)-MeSpd may be mediated by anti-oxidative and anti-inflammatory effects. These additional properties of N(1)-MeSpd could be clinically important for the treatment of inflammatory alopecias and inflammatory scalp diseases.

Keywords: Alopecia; Hair; Inflammation; Polyamines; Spermidine; TNF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Proliferation
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Hair Follicle / cytology
  • Hair Follicle / metabolism*
  • Humans
  • Inflammation / pathology
  • Interleukin-1beta / biosynthesis
  • Interleukin-1beta / genetics
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Keratin-15 / biosynthesis
  • Keratin-19 / biosynthesis
  • Keratinocytes / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Loose Anagen Hair Syndrome / genetics
  • Loose Anagen Hair Syndrome / pathology*
  • RNA, Messenger / biosynthesis
  • Reactive Oxygen Species / metabolism
  • Spermidine / analogs & derivatives*
  • Spermidine / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Tumor Necrosis Factor-alpha / biosynthesis


  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • KRT15 protein, human
  • Keratin-15
  • Keratin-19
  • RNA, Messenger
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • L-Lactate Dehydrogenase
  • Spermidine