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

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.

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.

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.

DSW and saline MW show promise as sustainable active ingredients for topical formulations targeting psoriatic inflammation via autophagy activation.