Tranexamic Acid Inhibits 17β-Estradiol-Induced Melanogenesis Through PKA-CREB-MITF Pathway

Abstract

Tranexamic acid (TXA), a well-known anti-fibrinolytic agent, has been proven effective in the treatment of hyperpigmentation, particularly melasma. Oestrogen is known as an important cause of melasma and has been reported to induce pigmentation through the oestrogen receptor or the G protein-coupled oestrogen receptor. Although various mechanisms by which TXA improves skin pigmentation have been reported, its effect on oestrogen (17 beta-estradiol, E2)-induced pigmentation has not yet been elucidated. In this study, we investigated the effect of TXA on melanogenesis induced by 17 beta-estradiol. Cell viability was assessed in primary human epidermal melanocytes treated with 17 beta-estradiol or TXA. The effect of TXA on pigmentation was evaluated by western blot analysis, measuring the protein levels of phosphorylated CREB (p-CREB), MITF, and tyrosinase following treatment with 17 beta-estradiol. First, 17 beta-estradiol increases melanin production through the induction of the protein expressions of melanogenesis-associated molecules, including p-CREB, MITF, and tyrosinase. Our findings demonstrate that TXA inhibits 17 beta-estradiol-induced melanogenesis by downregulating the cAMP-PKA pathway. Given that TXA also reduces alpha-MSH-induced pigmentation via decreased phospho-PKA levels, our results suggest that TXA likely inhibits E2-induced melanogenesis by modulating the cAMP-PKA-CREB-MITF axis, contributing to its depigmenting effect.