Nrf2 Pathway Involvement in the Beneficial Skin Effects of Moderate Ionic Osmotic Stress—The Case of The Dead Sea Water

Objectives: Exposing skin to moderate ionic osmotic stress (MIOS) triggers several biochemical responses. The objective of this work is to reveal the mechanism triggered by MIOS on the skin surface. Furthermore, this work aims to study the involvement of the Nrf2 (nuclear factor erythroid-2-related factor 2) pathway, activated by MIOS, and its beneficial effect in protecting skin against stress via the stimulation of phase II enzymes. Methods: HaCaT cells and human skin organ culture were exposed to Dead Sea Water (DSW) as MIOS inducers and the induction of internal ROS elevation, Nrf2 translocation, mRNA gene expressions of the phase II enzymes, heme-oxygenase 1 (HO1), and Catalase (CAT) were determined. Results: Skin exposure to MIOS increases Nrf2 translocation to the nucleus, leading to increased levels of ROS, HO1, and CAT. Furthermore, exposing skin to MIOS promotes protection against UVB-related risks. This is demonstrated by attenuation of the expression of biomarkers, related to UVB-induced damage, Caspase-3, IL-8, and IL-1β. Conclusions: Skin exposure to MIOS leads to the activation of Nrf2 skin defense pathway and, therefore, could present beneficial advantages to human skin health, as demonstrated on human skin models. The beneficial effects of MIOS, induced by DSW are significantly superior to eq. NaCl brine, suggests that MIOS protection of skin against stress is partially related to specific mineral combinations.

Dead Sea Minerals-Induced Positive Stress as an Innovative Resource for Skincare Actives

Objective: Exposure to certain stresses in small doses might lead to a protective effect by improving resistance to other stressors. Dead Sea (DS) minerals can be a relevant source to induce positive stress due to their high salinity and unique mineral combination. This concept could be further optimized using advanced unique cell biotechnology. The purpose of this study was to elucidate the innovative concept of DS minerals (water extract and black mud) supplementation in small amount to Pichia pastoris yeast growth media as a positive stress by testing the capability of accepted fermentation compounds to affect the appearance of skin. Methods: Skin equivalents were topically applied with different Pichia pastoris fermentations (Metabiotics?). Skin elasticity biomarkers were tested, since loss of elasticity and suppleness is a natural skin aging process leading to deeper wrinkles and loss of firmness. A preliminary screening at the gene level using DNA microarray was performed and subsequently, the following proteins were detected using ELISA or immunoblotting assays: elastin, fibulin-1, lysyl oxidase (LOX), metalloproteinase 3 (MMP-3), E-cadherin, claudin 4, tight junction protein (TJP)-1 and TJP-2. UVB irradiation was selected as a stressor. Results: Fermentation compounds generated in the presence of small doses of DS minerals affected the expression of various elasticity-related genes in skin. Moreover, they significantly attenuated the abnormal UVB-induced alterations, the proteins elastin, fibulin-1, LOX, MMP-3, E-cadherin and TJP-2. Conclusions: The observations clearly demonstrate that when DS Metabiotics? compounds are topically applied, significant alterations in several biomarkers that contribute to skin elasticity occur. Thus, these novel compounds have the potential to serve as skincare actives.

A Dead Sea Water-Enriched Body Cream Improves Skin Severity Scores in Children with Atopic Dermatitis

Dead Sea (DS) mud and water are known for their unique composition of minerals, and for their therapeutic properties on inflammatory skin diseases. The objective of the study was to evaluate the efficacy of an emollient cream enriched with DS water in children with atopic dermatitis (AD). Eighty six AD children were randomized in a double-blind controlled study to receive twice-daily topical treatment with a body cream enriched with DS minerals (TP) compared to two types of control: 1) DM, DS minerals with lower DS water concentrations than TP, and 2) an emollient (E) with no DS minerals. Efficacy was assessed by a change in clinical skin severity scores: SCORing Atopic Dermatitis (SCORAD), investigator’s global assessment (IGA) and patient global assessment (PGA) as well as by objective physiological parameters: transepidermal water loss (TEWL), stratum corneum hydration (SCH), affected body surface area (BSA) and Objective Severity Assessment of Atopic Dermatitis (OSAAD). The total length of the trial was 12 weeks divided to 6 visits at weeks 0, 2, 4, 6, 8, 12. The study showed that both TP and DM creams improved OSAAD scores. Only TP improved TEWL and SCH. TP was the most effective regarding TEWL, SCH and OSAAD compared to DM and E. Treatment with E decreased more significantly IGA score compared to TP. Although within each treatment group significant improvements in SCH, BSA, SCORAD, IGA and PGA were observed, the reduction in BSA, SCORAD and PGA was not significantly different among the groups. Our results clearly show the benefits of TP as a leave on-skin emulsion enrich with DS water in terms of skin barrier function. Thus, TP can serve as an effective adjuvant treatment for AD skin as well as for its maintenance.