Protective Activity of Alpha-Mangostin against UVB-Induced Injury in HaCaT Cells by Modulating the Ceramide and MAPK and NF-B Signaling Pathways

This study investigated the potential protective effects of alpha-mangostin (alpha-MG) on ultraviolet B (UVB)-induced damage in HaCaT cells. The results showed that alpha-MG less than 10 mu M had no significant cytotoxicity and exposure to UVB (50 mJ/cm(2)) reduced cell viability by approximately 50% compared with the control. The 2 mu M alpha-MG upregulated cell viability and downregulated the expression of metal matrix proteases (MMPs). The results of flow cytometry, real-time quantitative PCR (RT-qPCR), and immunoblotting manifested that alpha-MG relieved the extent of apoptosis and reduced the levels of apoptosis-associated mRNAs and proteins, respectively. The results of RT-qPCR and ELISA indicated that alpha-MG suppressed the generation of IL-6 and TNF-alpha. Furthermore, alpha-MG effectively downregulated activation of the UVB-induced nuclear factor kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPK) signaling pathways. Finally, lipidomics profiling demonstrated that alpha-MG significantly reduced UVB radiation-increased ceramide. Overall, these results demonstrated that alpha-MG has beneficial effects against photoaging by reducing the ceramide content and inhibiting MAPK and NF-kappa B signaling pathways.