**A Melanin-Related Phenolic Polymer with Potent Photoprotective and Antioxidant Activities for Dermo-Cosmetic Applications**

#### **Davide Liberti, Maria Laura Alfieri, Daria Maria Monti \*, Lucia Panzella \* and Alessandra Napolitano**

Department of Chemical Sciences, University of Naples "Federico II", Via Cintia 4, I-80126 Naples, Italy; davide.liberti@unina.it (D.L.); marialaura.alfieri@unina.it (M.L.A.); alesnapo@unina.it (A.N.)

**\*** Correspondence: mdmonti@unina.it (D.M.M.); panzella@unina.it (L.P.); Tel.: +39-081-679150 (D.M.M.); +39-081-674131 (L.P.)

Received: 26 February 2020; Accepted: 23 March 2020; Published: 25 March 2020

**Abstract:** Eumelanins, the dark variant of skin pigments, are endowed with a remarkable antioxidant activity and well-recognized photoprotective properties that have been ascribed to pigment components derived from the biosynthetic precursor 5,6-dihydroxyindole-2-carboxylic acid (DHICA). Herein, we report the protective e ffect of a polymer obtained starting from the methyl ester of DHICA (MeDHICA-melanin) against Ultraviolet A (UVA)-induced oxidative stress in immortalized human keratinocytes (HaCaT). MeDHICA-melanin was prepared by aerial oxidation of MeDHICA. At concentrations as low as 10 μg/mL, MeDHICA-melanin prevented reactive oxygen species accumulation and partially reduced glutathione oxidation in UVA-irradiated keratinocytes. Western blot experiments revealed that the polymer is able to induce the translocation of nuclear factor erythroid 2–related factor 2 (Nrf-2) to the nucleus with the activation of the transcription of antioxidant enzymes, such as heme-oxygenase 1. Spectrophotometric and HPLC analysis of cell lysate allowed to conclude that a significant fraction (ca. 7%), consisting mainly of the 4,4--dimer of MeDHICA (ca. 2 μM), was internalized in the cells. Overall these data point to the potential use of MeDHICA-melanin as an antioxidant for the treatment of skin damage, photoaging and skin cancers.

**Keywords:** melanins; 5,6-dihydroxyindole-2-carboxylic acid; antioxidant; photoprotection; UVA; HaCaT cells; reactive oxygen species; glutathione; Nrf-2
