biostudies-literatureHeo HGyeonggido Business & Science AcceleratorNational Research Foundation of KoreaKorea Research Institute of Bioscience and Biotechnology13983https://www.ebi.ac.uk/biostudies/studies/S-EPMC9385628biostudies-literatureUnknown12(1)There is still an unmet need for development of safer antimelanogenic or melanin-degrading agents for skin hyperpigmentation, induced by intrinsic or extrinsic factors including aging or ultraviolet irradiation. Owing to the relatively low cytotoxicity compared with other chemical materials, several studies have explored the role of 2'-fucosyllactose (2'-FL), the most dominant component of human milk oligosaccharides. Here, we showed that 2'-FL reduced melanin levels in both melanocytic cells and a human skin equivalent three-dimensional in vitro model. Regarding the cellular and molecular mechanism, 2'-FL induced LC3I conversion into LC3II, an autophagy activation marker, followed by the formation of LC3II⁺/PMEL⁺ autophagosomes. Comparative transcriptome analysis proScientific reportsHuman milk oligosaccharide 2'-fucosyllactose promotes melanin degradation via the autophagic AMPK-ULK1 signaling axis.PMC9385628KGM5422113MSIT 2019005607Lee MGPark GPark JHJang DBin BHKwak BMHeo HPark CCha BfalseHuman milk oligosaccharide 2'-fucosyllactose promotes melanin degradation via the autophagic AMPK-ULK1 signaling axis.There is still an unmet need for development of safer antimelanogenic or melanin-degrading agents for skin hyperpigmentation, induced by intrinsic or extrinsic factors including aging or ultraviolet irradiation. Owing to the relatively low cytotoxicity compared with other chemical materials, several studies have explored the role of 2'-fucosyllactose (2'-FL), the most dominant component of human milk oligosaccharides. Here, we showed that 2'-FL reduced melanin levels in both melanocytic cells and a human skin equivalent three-dimensional in vitro model. Regarding the cellular and molecular mechanism, 2'-FL induced LC3I conversion into LC3II, an autophagy activation marker, followed by the formation of LC3II⁺/PMEL⁺ autophagosomes. Comparative transcriptome analysis pro2022-01-01T00:00:00Z2022 Aug2025-04-18T15:23:32.343Z2025-02-19T01:38:14.463ZS-EPMC93856283597796610.1038/s41598-022-17896-4