Glycyrrhizin protects human melanocytes from H2O2-induced oxidative damage via the Nrf2-dependent induction of HO-1

摘要

Oxidative stress serves a critical role in melanocyte death and is considered to be a major cause of vitiligo. The nuclear factor E2-related factor 2 (Nrf2) signaling pathway has an important role in the antioxidative stress mechanisms of melanocytes. Glycyrrhizin (GR) is a derivative of herbal medicines used to treat hepatitis and allergic disease due to its antiviral and anti-allergy effects. GR also activates Nrf2 and induces the expression of heme oxygenase (HO)-1 in macrophages. Whether GR can protect human melanocytes from oxidative stress remains unknown. The present study investigated the potential protective effects of GR against oxidative stress in human melanocytes and the mechanisms involved. Following exposure to 0.5 mM hydrogen peroxide (H2O2), human primary melanocytes were treated with 1 mM GR. Cell viability was determined using a Cell Counting Kit-8 assay, and apoptosis was evaluated by flow cytometry. GR treatment significantly improved cell viability, reduced the apoptotic rate of melanocytes and reduced the level of reactive oxygen species in human melanocytes. Furthermore, GR induced the nuclear translocation of Nrf2 and induced the expression of HO-1 in melanocytes. The knockdown of Nrf2 by small interfering RNA or the inhibition of HO-1 by ZnPP reversed the protective effect of GR on melanocytes against H2O2-induced cytotoxicity and apoptosis. These data demonstrate that GR protects human melanocytes from H2O2-induced oxidative damage via the Nrf2-dependent induction of HO-1, providing evidence for the application of GR in the treatment of vitiligo.