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.

Share and Cite:

Portugal-Cohen, M. , Dominguez, M. , Oron, M. , Holtz, R. and Ma’or, Z. (2015) Dead Sea Minerals-Induced Positive Stress as an Innovative Resource for Skincare Actives. Journal of Cosmetics, Dermatological Sciences and Applications, 5, 22-35. doi: 10.4236/jcdsa.2015.51004.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Mattson, M.P. (2008) Hormesis Defined. Ageing Research Reviews, 7, 1-7.
[2] Mattson, M.P. and Cheng, A. (2006) Neurohormetic Phytochemicals: Low-Dose Toxins That Induce Adaptive Neuronal Stress Responses. Trends in Neurosciences, 29, 632-639.
[3] Sukenik, S., Buskila, D., Neumann, L., Kleiner-Baumgarten, A., Zimlichman, S. and Horowitz, J. (1990) Sulphur Bath and Mud Pack Treatment for Rheumatoid Arthritis at the Dead Sea Area. Annals of the Rheumatic Diseases, 49, 99-102.
[4] Moses, S.W., David, M., Goldhammer, E., Tal, A. and Sukenik, S. (2006) The Dead Sea, a Unique Natural Health Resort. Israel Medical Association Journal, 8, 483-488.
[5] Ma’or, Z., Henis, Y., Alon, Y., Orlov, E., Sorensen, K.B. and Oren, A. (2006) Antimicrobial Properties of Dead Sea Black Mineral Mud. International Journal of Dermatology, 45, 504-511.
[6] Even-Paz, Z. and Efron, D. (1996) The Dead Sea as a Spa Health Resort. Israel Journal of Medical Sciences, 32, S4-S8.
[7] Hodak, E., Gottlieb, A.B., Segal, T., Politi, Y., Maron, L., Sulkes, J. and David, M. (2003) Climatotherapy at the Dead Sea Is a Remittive Therapy for Psoriasis: Combined Effects on Epidermal and Immunologic Activation. Journal of the American Academy of Dermatology, 49, 451-457.
[8] Proksch, E., Nissen, H.P., Bremgartner, M. and Urquhart, C. (2005) Bathing in a Magnesium-Rich Dead Sea Salt Solution Improves Skin Barrier Function, Enhances Skin Hydration, and Reduces Inflammation in Atopic Dry Skin. International Journal of Dermatology, 44, 151-157.
[9] Portugal-Cohen, M., Afriat-Staloff, I., Soroka, Y., Frusic-Zlotkin, M., Schlippe, G., Voss, W. and Ma’or, Z. (2014) Protective Effects of a Novel Preparation Consists of Concentrated Dead Sea Water and Natural Plants Extracts against Skin Photo-Damage. Journal of Cosmetics, Dermatological Sciences and Applications, 4, 7-15.
[10] Portugal-Cohen, M., Soroka, Y., Ma’or, Z., Oron, M., Zioni, T., Bregegere, F.M., Neuman, R., Kohen, R. and Milner, Y. (2009) Protective Effects of a Cream Containing Dead Sea Minerals against UVB-Induced Stress in Human Skin. Experimental Dermatology, 18, 781-788.
[11] Soroka, Y., Ma’or, Z., Leshem, Y., Verochovsky, L., Neuman, R., Bregegere, F.M. and Milner, Y. (2008) Aged Keratinocyte Phenotyping: Morphology, Biochemical Markers and Effects of Dead Sea Minerals. Experimental Gerontology, 43, 947-957.
[12] Wineman, E., Portugal-Cohen, M., Soroka, Y., Cohen, D., Schlippe, G., Voss, W., Brenner, S., Milner, Y., Hai, N. and Ma’or, Z. (2012) Photo-Damage Protective Effect of Two Facial Products, Containing a Unique Complex of Dead Sea Minerals and Himalayan Actives. Journal of Cosmetic Dermatology, 11, 183-192.
[13] Molnar, K. and Farkas, E. (2010) Current Results on Biological Activities of Lichen Secondary Metabolites: A Review. Zeitschrift für Naturforschung C, 65, 157-173.
[14] Takema, Y., Yorimoto, Y., Kawai, M. and Imokawa, G. (1994) Age-Related Changes in the Elastic Properties and Thickness of Human Facial Skin. British Journal of Dermatology, 131, 641-648.
[15] Schwartz, E., Feinberg, E., Lebwohl, M., Mariani, T.J. and Boyd, C.D. (1995) Ultraviolet Radiation Increases Tropoelastin Accumulation by a Post-Transcriptional Mechanism in Dermal Fibroblasts. Journal of Investigative Dermatology, 105, 65-69.
[16] Starcher, B., Pierce, R. and Hinek, A. (1999) UVB Irradiation Stimulates Deposition of New Elastic Fibers by Modified Epithelial Cells Surrounding the Hair Follicles and Sebaceous Glands in Mice. Journal of Investigative Dermatology, 112, 450-455.
[17] Seo, J.Y., Lee, S.H., Youn, C.S., Choi, H.R., Rhie, G.E., Cho, K.H., Kim, K.H., Park, K.C., Eun, H.C. and Chung, J.H. (2001) Ultraviolet Radiation Increases Tropoelastin mRNA Expression in the Epidermis of Human Skin in Vivo. Journal of Investigative Dermatology, 116, 915-919.
[18] Roark, E.F., Keene, D.R., Haudenschild, C.C., Godyna, S., Little, C.D. and Argraves, W.S. (1995) The Association of Human Fibulin-1 with Elastic Fibers: An Immunohistological, Ultrastructural, and RNA Study. Journal of Histochemistry & Cytochemistry, 43, 401-411.
[19] Cox, T.R. and Erler, J.T. (2011) Remodeling and Homeostasis of the Extracellular Matrix: Implications for Fibrotic Diseases and Cancer. Disease Models & Mechanisms, 4, 165-178.
[20] Quan, T., Qin, Z., Xia, W., Shao, Y., Voorhees, J.J. and Fisher, G.J. (2009) Matrix-Degrading Metalloproteinases in Photoaging. Journal of Investigative Dermatology Symposium Proceedings, 14, 20-24.
[21] Rittie, L. and Fisher, G.J. (2002) UV-Light-Induced Signal Cascades and Skin Aging. Ageing Research Reviews, 1, 705-720.
[22] Chen, Z., Seo, J.Y., Kim, Y.K., Lee, S.R., Kim, K.H., Cho, K.H., Eun, H.C. and Chung, J.H. (2005) Heat Modulation of Tropoelastin, Fibrillin-1, and Matrix Metalloproteinase-12 in Human Skin in Vivo. Journal of Investigative Dermatology, 124, 70-78.
[23] Furukawa, F., Fujii, K., Horiguchi, Y., Matsuyoshi, N., Fujita, M., Toda, K., Imamura, S., Wakita, H., Shirahama, S. and Takigawa, M. (1997) Roles of E-and P-Cadherin in the Human Skin. Microscopy Research and Technique, 38, 343-352.<343::AID-JEMT2>3.0.CO;2-K
[24] Gruss, C. and Herlyn, M. (2001) Role of Cadherins and Matrixins in Melanoma. Current Opinion in Oncology, 13, 117-123.
[25] Fuller, L.C., Allen, M.H., Montesu, M., Barker, J.N. and Macdonald, D.M. (1996) Expression of E-Cadherin in Human Epidermal Non-Melanoma Cutaneous Tumours. British Journal of Dermatology, 134, 28-32.
[26] Hung, C.F., Chiang, H.S., Lo, H.M., Jian, J.S. and Wu, W.B. (2006) E-Cadherin and Its Downstream Catenins Are Proteolytically Cleaved in Human HaCaT Keratinocytes Exposed to UVB. Experimental Dermatology, 15, 315-321.
[27] Yuki, T., Hachiya, A., Kusaka, A., Sriwiriyanont, P., Visscher, M.O., Morita, K., Muto, M., Miyachi, Y., Sugiyama, Y. and Inoue, S. (2011) Characterization of Tight Junctions and Their Disruption by UVB in Human Epidermis and Cultured Keratinocytes. Journal of Investigative Dermatology, 131, 744-752.
[28] Yamamoto, T., Kurasawa, M., Hattori, T., Maeda, T., Nakano, H. and Sasaki, H. (2008) Relationship between Expression of Tight Junction-Related Molecules and Perturbed Epidermal Barrier Function in UVB-Irradiated Hairless Mice. Archives of Dermatological Research, 300, 61-68.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.