A topical heparinoid‐containing product improves epidermal permeability barrier homeostasis in mice

Abstract

Because of the importance of epidermal functions, including stratum corneum hydration and maintenance of permeability barrier homeostasis, in the pathogenesis of a variety of cutaneous and systemic disorders, a wide range of products has been developed to improve epidermal functions. However, the underlying mechanisms whereby certain products, including heparinoid‐containing product, are far little understood. In the present study, we assessed the impact of a heparinoid‐containing product, Hirudoid® cream, on epidermal permeability barrier function and expression levels of a panel of epidermal mRNA related to the formation/maintenance of the permeability barrier in mouse skin. Our results showed that while the baseline levels of transepidermal water rates remained unchanged, treatment with Hirudoid® cream twice daily for 7 days significantly accelerated permeability barrier recovery and increased stratum corneum hydration. In parallel, expression levels of epidermal mRNA for certain differentiation marker‐related proteins, lipid synthetic enzymes, keratinocyte proliferation and antimicrobial peptides also increased significantly. Together, these results provide the underlying mechanisms by which topical Hirudoid® cream improves epidermal permeability barrier and antimicrobial function. Because of its benefits for epidermal functions, heparinoid‐containing product could be more useful in the management of skin conditions, characterized by abnormal permeability barrier and antimicrobial function.

Topical Applications of a Heparinoid-Containing Product Attenuate Glucocorticoid-Induced Alterations in Epidermal Permeability Barrier in Mice

“…Transepidermal water loss (TEWL) rates, stratum corneum hydration, and skin surface pH were measured 18 h after the last treatment, using respective probes connected to an MPA5 physiology monitor (Courage + Khazaka electronic GmbH, Cologne, Germany) [28]. Permeability barrier recovery rates were assessed 4 h after tape stripping [28]. Skinfold thickness was measured with a digital caliper (Mitutoyo, Tokyo, Japan) by folding the flank skin with the thumb and the index figures [22].…”

“…Skinfold thickness was measured with a digital caliper (Mitutoyo, Tokyo, Japan) by folding the flank skin with the thumb and the index figures [22]. Data are expressed as percentage of untreated normal control (setting normal controls as 100%) [28].…”

“…Although these approaches can prevent some of the GC-induced side effects, their benefits for stratum corneum hydration and antimicrobial peptide expression have not been demonstrated in GC-treated skin. However, our recent study demonstrated that topical applications of a heparinoid-containing product improved both antimicrobial peptide expression and stratum corneum hydration, in addition to accelerating epidermal permeability barrier recovery, likely via upregulating the expression levels of mRNA for keratinocyte proliferation, differentiation, and lipid production [28], which all can be downregulated by GCs. Therefore, we determined here whether topical heparinoid-containing product could prevent GC-induced abnormalities in epidermal function.…”

Mutations in 3β‐hydroxysteroid‐δ8, δ7‐isomerase paradoxically benefit epidermal permeability barrier homeostasis in mice

“…Percentage of barrier recovery rates was calculated as described previously. 14 Irritant and allergic contact dermatitis were induced as previously described 15,16 in TD and WT mice, using phorbol 12-myristate 13-acetate (TPA, Sigma-Aldrich, St. Louis, MO) and 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (oxazolone, OX, Sigma-Aldrich, St. Louis, MO), respectively. TPA (0.001% in acetone) was applied once to the inner and outer surface of the ear.…”

“…TEWL rates were measured immediately, 2 and 4 h after tape‐stripping, using a TM300 probe connected to an MPA5 (Courage & Khazaka, Germany). Percentage of barrier recovery rates was calculated as described previously 14 …”