Abstract
Bicyclic monoterpene diols (BMTd) stimulate nitric oxide synthesis in melanoma and neuronal cells, representing cell types arising from embryonic neural crest tissue. This study shows that an equimolar mixture of the BMTd's 2,3-cis/exo-pinanediol and 2,3-cis/exo-camphanediol stimulates nitric oxide synthesis in epithelial cells of the skin, specifically normal human epidermal keratinocytes (NHEK) and normal human microvascular endothelial cells (HMVEC). A 1 mM mixture increased nitric oxide 3-fold in HMVEC in the first 24 h after treatment, and a 2 mM mixture produced an equivalent increase in NHEK. We hypothesized that an increase in nitric oxide in skin would lead to an increase in microcirculation, thereby increasing skin temperature. We found that twice daily application of 1mM BMTd lotion significantly increased arm skin temperature by 0.5 degrees C in 14 days compared to placebo, while a 2 mM mixture significantly increased skin temperature by 0.3 degrees C in 7 days (P < or = 0.05; ANOVA). A single application of a 2 mM BMTd mixture applied 30 min before a 30 min cold challenge (6 degrees C), maintained facial skin temperature 1.4 degrees C above untreated control sites (P < or = 0.05; ANOVA). We also tested whether BMTd...Continue Reading
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