PMID- 32218123 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2076-3921 (Print) IS - 2076-3921 (Electronic) IS - 2076-3921 (Linking) VI - 9 IP - 4 DP - 2020 Mar 25 TI - A Melanin-Related Phenolic Polymer with Potent Photoprotective and Antioxidant Activities for Dermo-Cosmetic Applications. LID - 10.3390/antiox9040270 [doi] LID - 270 AB - 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 effect 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 microg/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 muM), 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. FAU - Liberti, Davide AU - Liberti D AUID- ORCID: 0000-0003-1255-5030 AD - Department of Chemical Sciences, University of Naples "Federico II", Via Cintia 4, I-80126 Naples, Italy. FAU - Alfieri, Maria Laura AU - Alfieri ML AD - Department of Chemical Sciences, University of Naples "Federico II", Via Cintia 4, I-80126 Naples, Italy. FAU - Monti, Daria Maria AU - Monti DM AUID- ORCID: 0000-0002-1136-0576 AD - Department of Chemical Sciences, University of Naples "Federico II", Via Cintia 4, I-80126 Naples, Italy. FAU - Panzella, Lucia AU - Panzella L AUID- ORCID: 0000-0002-2662-8205 AD - Department of Chemical Sciences, University of Naples "Federico II", Via Cintia 4, I-80126 Naples, Italy. FAU - Napolitano, Alessandra AU - Napolitano A AUID- ORCID: 0000-0003-0507-5370 AD - Department of Chemical Sciences, University of Naples "Federico II", Via Cintia 4, I-80126 Naples, Italy. LA - eng PT - Journal Article DEP - 20200325 PL - Switzerland TA - Antioxidants (Basel) JT - Antioxidants (Basel, Switzerland) JID - 101668981 PMC - PMC7222206 OTO - NOTNLM OT - 5,6-dihydroxyindole-2-carboxylic acid OT - HaCaT cells OT - Nrf-2. OT - UVA OT - antioxidant OT - glutathione OT - melanins OT - photoprotection OT - reactive oxygen species COIS- The authors declare no conflict of interest. EDAT- 2020/03/29 06:00 MHDA- 2020/03/29 06:01 PMCR- 2020/03/25 CRDT- 2020/03/29 06:00 PHST- 2020/02/26 00:00 [received] PHST- 2020/03/16 00:00 [revised] PHST- 2020/03/23 00:00 [accepted] PHST- 2020/03/29 06:00 [entrez] PHST- 2020/03/29 06:00 [pubmed] PHST- 2020/03/29 06:01 [medline] PHST- 2020/03/25 00:00 [pmc-release] AID - antiox9040270 [pii] AID - antioxidants-09-00270 [pii] AID - 10.3390/antiox9040270 [doi] PST - epublish SO - Antioxidants (Basel). 2020 Mar 25;9(4):270. doi: 10.3390/antiox9040270.