Abstract
It has long been believed that histamine is associated with cutaneous melanogenesis. Specifically, H2-receptor antagonists reportedly inhibit melanogenesis, but H1-receptor antagonists, which are some of the most commonly prescribed medicines in dermatology, have not been studied to determine whether and how they regulate melanogenesis. Therefore, we screened H1-receptor antagonists to determine whether they inhibit melanogenesis and found that loratadine was particularly effective, in this regard without compromising cellular viability. Loratadine downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase in melanocytes. To determine the intracellular signaling pathways, Akt was consistently activated by loratadine. PI3K/Akt pathway inhibitor, LY294002, restored the reduced melanin content that was induced by loratadine. In addition, phospho-GSK-3β also was found to be increased following loratadine treatment. Loratadine reduced the amount of PKC-βII in the membrane fraction, thereby decreasing its activity. Taken together, our data indicate that loratadine regulates melanogenesis via Akt/MITF and PKC-βII signaling, thereby leading to the inhibition of melanogenic proteins. The antimelanogenic effects of loratadine have potentially significant and useful roles in dermatologic practice, although further clinical studies will be required to test this.
Highlights
Hyperpigmentary skin disorders are a major issue of concern for people with dark skin
Antihistamines were considered histamine receptor antagonists, but they work as inverse agonists by binding to histamine receptors, thereby returning cellular equilibrium and reducing allergic property [10]
H1 and H2 receptors exist on the surface of human melanocytes and melanoma cells [11]
Summary
Hyperpigmentary skin disorders are a major issue of concern for people with dark skin. Clinicians have attempted to treat hyperpigmentary disorders using various therapeutic modalities, including hypopigmenting agents, but the results have been discouraging. We recently reported the inflammatory features of melasma in Korean women and that mast cells are frequently found in the dermis of melasma lesions [1]. We proposed the association between increased dermal mast cells and clinical features of hyperpigmentation and telangiectasia in photodamaging process [2]. Inflammatory mediators such as histamine, prostaglandins, and nitric oxide have been identified as possible therapeutic approaches for hyperpigmentary skin disorders [3]
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