{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T21:59:13Z","timestamp":1776895153458,"version":"3.51.2"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":349,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p><jats:italic>Astragalus membranaceus<\/jats:italic> root has been widely used for repigmentation treatment in vitiligo, but its mechanism is poorly understood. We sought to investigate the effect of astragaloside IV (AS\u2010IV), a main active extract of the <jats:italic>Astragalus membranaceus<\/jats:italic> root, on melanin synthesis in normal human epidermal melanocytes (NHEMs) and to elucidate its underlying mechanisms. Melanin content, tyrosinase activity, qPCR, western blot, and immunofluorescence were employed. Specific inhibitors and small interfering RNA were used to investigate the possible pathway. AS\u2010IV stimulated melanin synthesis and upregulated the expression of melanogenesis\u2010related genes in a concentration\u2010dependent manner in NHEMs. AS\u2010IV could activate the aryl hydrocarbon receptor (AhR), and AS\u2010IV\u2010induced melanogenesis was inhibited in si\u2010AhR\u2010transfected NHEMs. In addition, we showed that AS\u2010IV enhanced the phosphorylation of AKT and GSK\u20103<jats:italic>\u03b2<\/jats:italic> and nuclear translocation of <jats:italic>\u03b2<\/jats:italic>\u2010catenin. AS\u2010IV\u2010induced MITF expression upregulation and melanin synthesis were decreased in the presence of <jats:italic>\u03b2<\/jats:italic>\u2010catenin inhibitor FH353. Furthermore, AhR antagonist CH223191 inhibited the activation of AKT\/GSK\u20103<jats:italic>\u03b2<\/jats:italic>\/<jats:italic>\u03b2<\/jats:italic>\u2010catenin signaling, whereas the expression of CYP1A1 (marker of AhR activation) was not affected by the AKT inhibitor in AS\u2010IV\u2010exposed NHEMs. Our findings show that AS\u2010IV induces melanogenesis through AhR\u2010dependent AKT\/GSK\u20103<jats:italic>\u03b2<\/jats:italic>\/<jats:italic>\u03b2<\/jats:italic>\u2010catenin pathway activation and could be beneficial in the therapy for depigmented skin disorders.<\/jats:p>","DOI":"10.1155\/2020\/8838656","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:35:07Z","timestamp":1608078907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Astragaloside IV Enhances Melanogenesis via the AhR\u2010Dependent AKT\/GSK\u20103<i>\u03b2<\/i>\/<i>\u03b2<\/i>\u2010Catenin 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