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 N1-methylspermidine (N1-MeSpd). N1-MeSpd was confirmed to be a metabolically stable compound, with a half life of 90 h. 0.5 µM N1-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. N1-MeSpd also reduced lactate dehydrogenase activity in the culture supernatant, a parameter of cell death and cell lysis. N1-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 N1-MeSpd may be mediated by anti-oxidative and anti-inflammatory effects. These additional properties of N1-MeSpd could be clinically important for the treatment of inflammatory alopecias and inflammatory scalp diseases.
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