AUTHOR=Polouliakh Natalia, Ludwig Vanessa, Meguro Akira, Kawagoe Tatsukata, Heeb Oliver, Mizuki Nobuhisa TITLE=Alpha-Arbutin Promotes Wound Healing by Lowering ROS and Upregulating Insulin/IGF-1 Pathway in Human Dermal Fibroblast JOURNAL=Frontiers in Physiology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/articles/10.3389/fphys.2020.586843 DOI=10.3389/fphys.2020.586843 ISSN=1664-042X ABSTRACT=Alpha-arbutin (4-hydroxyphenyl alpha-glucopyranoside) is a known inhibitor of tyrosinase in keratinocytes; however, its effect on other genes and pathways in other skin cells has not been thoroughly investigated. In this study, we investigate the mechanism of alpha-arbutin activity in human dermal fibroblast cultures for 48 h. Results showed that the oxidative stress pathway was activated as alpha-arbutin reduced reactive oxygen species. In addition, we found a high possibility of wound healing and the upregulation of the insulin-like growth factor 1 receptor (IFG1R) pathway. We also investigated the role of the NRF2 gene in mediating the alpha-arbutin response. In silico comparative genomics analysis conducted using our original tool, SHOE, suggested transcription factors with a role in tumor suppression and toxicity response as candidates for regulating the alpha-arbutin–mediated pathway.