Mechanisms of heparinoid-induced skin moisturizing effect: Influence on natural moisturizing factors

Abstract

The present study was conducted to clarify mechanisms underlying the skin moisturizing effect of a heparinoid as an active ingredient of Hirudoid® cream or lotion in hairless mice. Dry skin was experimentally induced on the back of animals by daily treatment with acetone/ether (1:1) followed by distilled water (A/E/W) for 8 days. From the day subsequent to initiation of A/E/W treatment, Hirudoid® Soft (w/o-type cream) or a base not containing heparinoid was daily (100 mg) applied to the back for 7 days immediately after A/E/W treatment. Throughout the A/E/W treatment, skin capacitance reflecting the water content of the stratum corneum was significantly decreased and transepidermal water loss (TEWL) was significantly increased, indicating attenuation of water-holding capacity and barrier function of the stratum corneum, respectively. The total content of free amino acids, major natural moisturizing factors (NMF), was significantly reduced in the stratum corneum obtained after termination of A/E/W treatment. A lack of lamellar bilayer structure was found within the intercellular spaces of the stratum corneum. Additionally, marked epidermal hyperplasia was provoked by A/E/W treatment. These changes induced by A/E/W were ameliorated by daily application of Hirudoid® Soft but not the base. Hirudoid® Soft significantly suppressed not only the A/E/W-induced decrease in skin capacitance, but also the increase in TEWL, and increased the total content of free amino acids in the stratum corneum. Many lamellar body-derived contents appeared within the intercellular spaces of the stratum corneum, suggesting that Hirudoid® Soft tended to repair the structure of the stratum corneum. Furthermore, A/E/W-induced epidermal hyperplasia was pronouncedly attenuated by Hirudoid® Soft. These results suggest that the heparinoid improved the impaired water-holding capacity and barrier function of the stratum corneum in experimentally-induced dry skin mainly based on an increase in NMF levels and partially the accelerated recovery of the intercellular lamellar structure.