Bay 11‐7082, an NF‐κB Inhibitor, Prevents Post‐Inflammatory Hyperpigmentation Through Inhibition of Inflammation and Melanogenesis

Abstract

Post‐inflammatory hyperpigmentation (PIH) is a very common disorder of cutaneous hyperpigmentation, which poses a persistent management challenge in the fields of dermatology and esthetics. This study was designed to explore the anti‐melanogenic and anti‐inflammatory effects of Bay 11‐7082, an NF‐κB inhibitor, using small‐molecule screening, to determine its potential application for PIH prevention. The molecular mechanisms were investigated in vitro and ex vivo in epidermis‐humanized mice using melanin content, RT‐PCR, and immunoblotting. Bay 11‐7082 suppressed proinflammatory cytokines and ameliorated 2,4‐dinitrofluorobenzene (DNFB)‐induced contact dermatitis on day 15. The suppression of melanin synthesis by Bay 11‐7082 was attributed to the reduction of MITF, which was induced by extracellular signal‐regulated kinase activation. Bay 11‐7082 reduced epidermal melanin accumulation in UVB‐stimulated ex vivo human epidermis as well as in the ear and tail skin of K14‐stem cell factor (SCF) transgenic mice. Topical administration of Bay 11‐7082 improved PIH on day 35 in the post‐DNFB dorsal skin of K14‐SCF transgenic mice. In conclusion, Bay 11‐7082 can be considered a promising candidate for the development of a preventive topical agent for PIH.