Autophagy-mediated regulation of psoriasis biomarkers by Dead Sea and magnetized saline waters: An in vitro study.

BACKGROUND: Dysregulated autophagy is linked to abnormal keratinocyte differentiation and persistent psoriatic inflammation. Smart fluids, such as Dead Sea Water (DSW) and saline magnetized water (MW), have emerged as potential non-pharmacological autophagy activators. This study evaluates their effects on psoriasis-like keratinocytes, focusing on calcitonin gene-related peptide (CGRP), a neuropeptide involved in pruritus and inflammation, and secreted frizzled-related protein 4 (SFRP4), whose reduced expression contributes to epidermal hyperplasia. The role of autophagy in mediating these effects was also investigated. METHODS: Polycytokine-stimulated HaCaT keratinocytes were treated with DSW or saline MW. CGRP and SFRP4 expression levels were assessed alongside autophagy markers beclin-1 and LC3B. The involvement of autophagy was confirmed using wortmannin, an autophagy inhibitor. RESULTS: Both DSW (4.7 ± 1.9 a.u.) and saline MW (3.6 ± 1.6 a.u.) significantly reduced CGRP expression compared to controls (non-magnetized saline: 7.5 ± 2.3 a.u.; distilled water: 7.6 ± 2.5 a.u.; all p< 0.001). While both fluids enhanced SFRP4 expression equally (p = 0.78), saline MW showed superior CGRP inhibition (p< 0.001). Both fluids mitigated polycytokine-induced reductions in beclin-1 and LC3B levels (all p< 0.001), with saline MW showing more pronounced effects (p< 0.05). Wortmannin impaired the effects of both fluids on CGRP and SFRP4, indicating autophagy mediation. CONCLUSIONS: DSW and saline MW show promise as sustainable active ingredients for topical formulations targeting psoriatic inflammation via autophagy activation.