{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T18:13:15Z","timestamp":1760551995330,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LG Household &amp; Health Care"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Abnormal inactivation of the Wnt\/\u03b2-catenin signaling pathway is involved in skin diseases like androgenetic alopecia, vitiligo and canities, but small-molecule activators are rarely described. In this study, we investigated the stimulatory effects of escin on the canonical Wnt\/\u03b2-catenin signaling pathway in cultured human dermal papilla cells (hDPCs). Escin stimulated Wnt\/\u03b2-catenin signaling, resulting in increased \u03b2-catenin and lymphoid enhancer-binding factor 1 (LEF1), the accumulation of nuclear \u03b2-catenin and the enhanced expression of Wnt target genes in cultured hDPCs. Escin drastically reduced the protein level of glycogen synthase kinase (GSK)-3\u03b2, a key regulator of the Wnt\/\u03b2-catenin signaling pathway, while the presence of the proteasome inhibitor MG-132 fully restored the GSK-3\u03b2 protein level. The treatment of secreted frizzled-related proteins (sFRPs) 1 and 2 attenuated the activity of escin in Wnt reporter assays. Our data demonstrate that escin is a natural agonist of the canonical Wnt\/\u03b2-catenin signaling pathway and downregulates GSK-3\u03b2 protein expression by facilitating the proteasomal degradation of GSK-3\u03b2 in cultured hDPCs. Our data suggest that escin likely stimulates Wnt signaling through direct interactions with frizzled receptors. This study underscores the therapeutic potential of escin for Wnt-related diseases such as androgenetic alopecia, vitiligo and canities.<\/jats:p>","DOI":"10.3390\/cimb45070373","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T01:06:36Z","timestamp":1689555996000},"page":"5902-5913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Escin Activates Canonical Wnt\/\u03b2-Catenin Signaling Pathway by Facilitating the Proteasomal Degradation of Glycogen Synthase Kinase-3\u03b2 in Cultured Human Dermal Papilla Cells"],"prefix":"10.3390","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7692-1111","authenticated-orcid":false,"given":"Jae Young","family":"Shin","sequence":"first","affiliation":[{"name":"LG Household & Health Care (LG H&H) R&D Center, 70, Magokjoongang 10-ro, Gangseo-gu, Seoul 07795, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4785-7090","authenticated-orcid":false,"given":"Jaeyoon","family":"Kim","sequence":"additional","affiliation":[{"name":"LG Household & Health Care (LG H&H) R&D Center, 70, Magokjoongang 10-ro, Gangseo-gu, Seoul 07795, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7920-3411","authenticated-orcid":false,"given":"Yun-Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"LG Household & Health Care (LG H&H) R&D Center, 70, Magokjoongang 10-ro, Gangseo-gu, Seoul 07795, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanghwa","family":"Lee","sequence":"additional","affiliation":[{"name":"Innovo Therapeutics Inc., 507 38, Mapo-daero, Mapo-gu, Seoul 04174, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nae-Gyu","family":"Kang","sequence":"additional","affiliation":[{"name":"LG Household & Health Care (LG H&H) R&D Center, 70, Magokjoongang 10-ro, Gangseo-gu, Seoul 07795, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.cell.2012.05.012","article-title":"Wnt\/beta-catenin signaling and disease","volume":"149","author":"Clevers","year":"2012","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.devcel.2009.06.016","article-title":"Wnt\/beta-catenin signaling: Components, mechanisms, and diseases","volume":"17","author":"MacDonald","year":"2009","journal-title":"Dev. 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