The Haoqin-Huaban formula alleviates UVB-induced skin damage through HOXA11-AS-mediated stabilization of EZH2.

Exposure of skin to ultraviolet B (UVB) irradiation induces oxidative damage, immune suppression, inflammation, and skin cancer. Recently, an increase in the use of traditional Chinese medicine decoction with antioxidant properties has emerged as protection for skin tissues against UVB-induced damage. The aim of this study was to investigate mechanisms of the protective effect of the Haoqin-Huaban formula (HQHB) on UVB-induced skin damage. First, cell survival, apoptosis, and oxidative stress were evaluated upon UVB irradiation in the presence of HQHB using HaCaT cells and mice as model systems. Subsequently, bioinformatic analyses, RNA pulldown assays, RNA immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation were conducted to verify the regulation among HQHB, hypoxia-inducible factor 1α (HIF-1α), HOXA11-AS and enhancer of zeste homolog 2 (EZH2) in HaCaT cells. In this study, we found that administration of HQHB inhibited, in a dose-dependent manner, UVB-induced skin damage by eliminating oxidative stress. HQHB was found to upregulate HOXA11-AS expression by activating HIF-1α. Furthermore, HOXA11-AS stabilized the EZH2 protein by inhibiting its ubiquitination and proteasomal degradation. Consequently, rescue assays demonstrated that HOXA11-AS promoted proliferation and inhibited apoptosis in HaCaT cells by reducing oxidative stress. Taken together, our results help to elucidate the function and regulatory mechanism of HQHB in reducing UVB-induced skin damage.