Osthole relieves skin damage and inhibits chronic itch through modulation of Akt/ZO-3 pathway in atopic dermatitis

Eur J Pharmacol. 2023 Mar 13:175649. doi: 10.1016/j.ejphar.2023.175649. Online ahead of print.ABSTRACTAtopic dermatitis (AD) is the most prevalent chronic inflammatory skin condition and significantly reduces quality of life. Tight junction (TJ), which is located directly beneath the stratum corneum, maintains skin barrier function and aids in the identification of the cell's "territory". We evaluated seventeen TJ related genes to explore AD related alterations of TJ. Remarkably, we found that the expression of ZO-3, a gene that had not been linked to the development of TJ in AD, was significantly down-regulated in the skin of AD mice and patients. siRNA mediated knock-down of ZO-3 significantly decreased transepithelial electrical resistance in HaCaT cells, demonstrating that ZO-3 is essential to epidermal barrier function. In addition to ZO-3 downregulation, protein kinase B (Akt) phosphorylation was increased in the skin of AD mice. We further confirmed an inverse relationship between Akt phosphorylation and ZO-3 expression in AD using HaCaT cells and mouse models. Finally, we tested the efficacy of osthole as a treatment for AD in mice and HaCaT cells. Osthole inhibits Akt phosphorylation, and thereby enhances ZO-3 expression in mouse models of AD, resulting in greatly lessened AD associated skin damage chronic itch, and osthole also increased the expression of ZO-3 in HaCaT cells by inhibiting the phosphorylation of Akt. Together, we established that ZO-3 is essential fo...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research