Zerumbone Treatment Upregulates Hyaluronic Acid Synthesis via the MAPK, CREB, STAT3, and NF-κB Signaling Pathways in HaCaT Cells

Hyaluronic acid (HA), a hydrophilic molecule and a natural skin moisturizer, is produced by the enzyme HA synthase (HAS). Appropriate HA levels are important to maintain the skin moisture content. HA also improves skin conditions by partially recovering the function of the damaged skin barrier. In this study, we investigated the expression and mechanism of action of moisturizing factors related to HA production by analyzing the moisturizing effect of zerumbone (ZER) treatment in human keratinocytes (HaCaT cells). Changes in the expression levels of aquaporin-3 (AQP3), HAS, and hyaluronidase (HYAL) mRNAs upon ZER treatment in HaCaT cells were examined using real-time PCR. In addition, changes in the HAS-related signaling pathways were analyzed using western blotting. ZER treatment increased HAS and AQP3 mRNA as well as HA levels in a dose-dependent manner while reducing UVB-induced HYAL levels. Further, HAS expression-related MAPK, STAT3, and CREB were phosphorylated as ZER concentration increased. We conclude that ZER treatment may help improve skin moisturization and aid in the recovery of the skin barrier by increasing HA levels in human keratinocyte cell lines.