Regulatory effects of Ishige okamurae extract and Diphlorethohydroxycarmalol on skin barrier function

Abstract

Ethnopharmacological relevance: The pharmacological potential of marine organisms remains largely unexplored. Ishige Okamurae, commonly known as Pae, is extensively distributed over Asia. Its antioxidant, antibacterial, antiobesity, and anti-inflammatory properties are also being investigated. Aim of the study: In most cases of atopic dermatitis, the stratum corneum, the outermost layer of the epidermis, is damaged, causing symptoms such as dryness and hyperproliferation of the epidermis. In particular, the disruption of cell junctions leads to damage of the skin barrier, exacerbating the disease and becoming a target for therapeutic development. Our study aims to investigate of Ishige okamurae extract (IOE) and a major compound derived from it, called Diphlorethohydroxycarmalol (DPHC), can help strengthen the skin barrier in animals with atopic dermatitis induced by 2,4-dinitrochlorobenzene (DNCB). Materials and methods: In keratinocyte cell lines, HaCaT cells, the cytotoxicity of IOE and DPHC was assessed by MTT analysis. The gene expression of skin barrier factors and tight junctions were determined by real-time PCR in tumor necrosis factor-α/interferon-γ-stimulated HaCaT cells. In addition, JAK/STAT signaling pathway was performed to evaluating the mechanism of drugs by Western blot. Next, we studied the effects of IOE and DPHC on the skin of animals with DNCB-induced atopic dermatitis. We measured the expression of genes related of the skin barrier and tight junctions in their ear tissue. Results: As a result, IOE and DPHC confirmed that the expression of skin barrier proteins (thymic stromal lymphopoietin, filaggrin, loricrin, and involucrin) was improved in the DNCB-induced atopic dermatitis model and HaCaT cells. In addition, the expression of tight junction-related proteins (claudin, occludin, and tight junction protein-1) were improved. Conclusion: IOE and DPHC ameliorated the atopic dermatitis lesions through alleviating the pro-inflammatory responses and tight junction protein destruction. Our results suggest that IOE and DPHC could be promising candidates for enhancing skin barrier function.