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

Abstract

Introduction: Either systemic or topical glucocorticoids (GCs) can cause significant adverse effects on cutaneous structure and function. Although some products and ingredients can improve GC-induced abnormalities in epidermal permeability barrier, the efficacy is moderate. Prior studies in normal mice showed that topical applications of a heparinoid-containing product, Hirudoid® cream, improve epidermal barrier function by upregulation of epidermal proliferation, expression of mRNA for epidermal differentiation, and lipid production. Objective: The objective of this study was to assess whether topical applications of this product could prevent GC-induced changes in epidermal function in murine skin. Materials and Methods: One group of C57BL/6J mice was treated topically with 0.05% clobetasol propionate twice daily for 6 days, while another group was treated topically with Hirudoid® cream 30 min after each application of clobetasol propionate. Untreated mice served as normal controls. Transepidermal water loss (TEWL) rates, stratum corneum hydration, and skin surface pH were measured using respective probes connected to an MPA5 physiology monitor. qPCR was used to measure the expression levels of mRNA for keratinocyte differentiation-related proteins and lipid synthetic enzymes. Results: Co-applications of Hirudoid® cream with GC minimally, but significantly, increased skin thickness in comparison to GC treatment alone (p < 0.05), in parallel with increased expression levels of mRNA for PCNA in both the dermis and the epidermis. Moreover, Hirudoid® cream largely prevented GC-induced elevation in basal TEWL (p < 0.001) and delay in barrier recovery (p < 0.05), accompanied by upregulation in the expression levels of mRNA for epidermal involucrin, HMGCoA, and SPT1. However, both stratum corneum hydration and skin surface pH were comparable in the skin treated with GC alone versus GC + Hirudoid® cream. Conclusion: Topical heparinoid-containing product can partially prevent GC-induced alterations in some epidermal functions.

The Effects of Mucopolysaccharide Polysulfate on Steroid-Induced Tight Junction Barrier Dysfunction in Human Epidermal Keratinocytes and a 3D Skin Model

“…In our previous report [31], MPS increased the protein levels of claudin-1 and ZO-1, a TJ constituent, in normal HEKa. Wen et al [32] reported that topical MPS-containing products increased mRNA expressions of epidermal differentiation markers and lipid synthetic enzymes in clobetasol propionate-containing product-induced skin barrier impairment in mice. Indeed, the abnormal cell morphology of keratinocytes induced by CP also tended to normalize after 72 h of coadministration of 1 μg/mL MPS (data not shown).…”

“…The interaction of hyaluronic acid with its receptor CD44 has also been reported to inhibit CP-induced skin atrophy [29], and in the CD44 knockout keratinocytes, claudin-1 expression is reduced and TJ barrier formation is delayed [37]. Recently, it has been reported that MPS-containing creams suppress CP-induced skin atrophy in mice and show efficacy against CP-induced impairment of the epidermal permeability barrier [32] and that treatment of keratinocytes with MPS increases TJ-related proteins such as claudin-1 and ZO-1 [31]. In consideration of these reports, it is suggested that CD44 activation may be involved in the increased expression of TJ-related proteins in MPS, but the relationship with CD44 signaling needs to be examined in future studies.…”

Efficacy and safety of 1565‐nm nonablative fractional laser combined with mucopolysaccharide polysulfate cream for erythematous acne scars

“…Finally, MPS cream might improve the appearance of acne scars by promoting epidermal proliferation and improving epidermal barrier function. Topical heparinoids raised the levels of mRNA expression in mouse skin for proteins involved in epidermal differentiation (filaggrin and involucrin), lipid synthesis (HMGCoA and SPT1), and epidermal proliferation 30,31 . In addition to the respective effects of the two treatments themselves, part of the reason for the superior efficacy of the combined therapy may be that the laser promoted drug delivery via the skin, which enhanced the penetration and absorption of MPS cream so that it could better exert its effects 32 …”

Efficacy and Safety of Mucopolysaccharide Polysulfate Cream for Non-Exudative Eczema: A Systematic Review and Meta-Analysis

“…It not only elevated the expression levels of epidermal mRNA for lipid production, such as HMGCoA, fatty acid synthase (FAS), and serine palmitoyltransferase 1 (SPT1), but also increased the expression levels of some skin proteins, including filaggrin, involucrin, and loricrin (37,38). Furthermore, when combined with TCS, MPS cream could largely prevent TCS-induced elevation in TEWL in comparison to TCS alone (39), which was also consistent with the result of this meta-analysis (21). Second, MPS cream also showed some anti-inflammatory effects.…”