Author(s)

Dror Cohen^1,2, Ze’evi Ma’or^2,3, Meital Portugal Cohen^2,4, Miriam Oron⁵, Ron Kohen^1*

¹The Myers Skin Research Laboratory, Faculty of Medicine, Institute for Drug Research, School of Pharmacy, Hebrew University of Jerusalem, Jerusalem, Israel.
²The Skin Research Institute, The Dead-Sea & Arava Science Center, Masada, Israel.
³Fosun Jinmei (Shanghai) Cosmetics Co., Ltd., Shanghai, China.
⁴AHAVA Dead Sea Laboratories, Lod, Israel.
⁵Miriam Oron Mingelgrin Consulting, Jerusalem, Israel.

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.

Nrf2 Pathway, Ionic Osmotic Stress, Dead Sea Water, Oxidative Stress, Human Skin Model

Cohen, D. , Ma’or, Z. , Cohen, M. , Oron, M. and Kohen, R. (2022) Nrf2 Pathway Involvement in the Beneficial Skin Effects of Moderate Ionic Osmotic Stress—The Case of The Dead Sea Water. Journal of Cosmetics, Dermatological Sciences and Applications, 12, 109-130. doi: 10.4236/jcdsa.2022.122010.