Resumo

Objectives: The aim of our studies was to establish the safety and efficacy of novel, high-potency Hyaluronidase Inhibitors when topically applied to facial skin. We hypothesized that inhibiting the enzymatic breakdown of HA by inhibiting Hyaluronidase activity would increase the amount of High Molecular Weight (HMW) HA, resulting in a kind of “moisturizing from within” that would enhance skin texture and appearance. Furthermore, Low Molecular Weight (LMW), degraded HA is highly inflammatory and is seen at high levels in aging skin and especially in inflammatory conditions like Rosacea. Introduction: While many Hyaluronidase inhibitors have been described, their use as topical cosmeceuticals is limited by their lack of bioavailability or by toxicity. Through a large screening effort, using biochemistry, cell models and explants of human facial skin, we identified a mix of botanical extracts that was highly inhibitory and showed potent activity in our skin models. Here, the authors describe the histologic effects of testing creams containing the active botanicals and assess the results of a clinical study of 130 patients with mild/moderate Rosacea. Materials / method: To study the effects on living skin, creams containing the extracts were applied to one side of the face only for up to 3 weeks by patients who had scheduled facelifts. The skin samples were processed for Histology and stained for HA. 130 patients with diagnosed mild to moderate Rosacea/Erythema were treated for 12 weeks with creams containing different concentrations of the active botanical extracts Photographic records of each patient compared the Rosacea severity before and after treatment and were assessed by a physician. Results: Validating the results from our laboratory studies, the facelift patients showed significantly increased HMW HA in the Epidermis on the side of the face to which they had applied the cream. The epidermis and dermis appeared thicken and improved cellularity. Patients reported improvements in skin texture and moisturization on the treated sides. In the Rosacea studies, 78% of patients showed significant reduction in facial redness after 12 weeks. The effect was concentration dependent – ranging from 48% positive at lowest tested dose to 86% positive responses at the highest dose. Conclusion: We have identified safe, effective and topically active natural product inhibitors of HA degradation in human skin. In normally aged skin, we see increased epidermal cellularity and a marked increase in epidermal HA content in treated versus control skin. These effects contribute to skin rejuvenation and moisturization. Furthermore, our anti-Hyaluronidase botanicals act to decrease the presence of inflammatory LMW HA fragments, inhibit mast cell degranulation and effectively reduce facial redness in mild to moderate Rosacea. No significant adverse events were seen with this treatment.