{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T12:27:04Z","timestamp":1785932824070,"version":"3.56.0"},"reference-count":64,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003627","name":"Cooperative Research Program for Agriculture Science and Technology Development","doi-asserted-by":"publisher","award":["PJ016400"],"award-info":[{"award-number":["PJ016400"]}],"id":[{"id":"10.13039\/501100003627","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Hair loss remains a significant problem that is difficult to treat; therefore, there is a need to identify safe natural materials that can help patients with hair loss. We evaluated the hair anagen activation effects of limonin, which is abundant in immature citrus fruits. Limonin increased the proliferation of rat dermal papilla cells (rDPC) by changing the levels of cyclin D1 and p27, and increasing the number of BrdU-positive cells. Limonin increased autophagy by decreasing phosphorylated mammalian target of rapamycin levels and increasing the phospho-Raptor, ATG7 and LC3B. Limonin also activated the Wnt\/\u03b2-catenin pathway by increasing phospho-\u03b2-catenin levels. XAV939, a Wnt\/\u03b2-catenin inhibitor, inhibited these limonin-induced changes, including induced autophagy, BrdU-positive cells, and cell proliferation. Limonin increased the phosphorylated AKT levels in both two-dimensional cultured rDPC and three-dimensional spheroids. Treatment with the PI3K inhibitor wortmannin inhibited limonin-induced proliferation, and disrupted other limonin-mediated changes, including decreased p27, increased BrdU-positive cells, induced autophagy, and increased ATG7 and LC3B levels. Wortmannin also inhibited limonin-induced cyclin D1 and LC3 expression in spheroids. Collectively, these results indicate that limonin can enhance anagen signaling by activating autophagy via targeting the Wnt\/\u03b2-catenin and\/or PI3K\/AKT pathways in rDPC, highlighting a candidate nutrient for hair loss treatment.<\/jats:p>","DOI":"10.3390\/nu14245358","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T07:59:21Z","timestamp":1671436761000},"page":"5358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Limonin, a Component of Immature Citrus Fruits, Activates Anagen Signaling in Dermal Papilla Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Jung-Il","family":"Kang","sequence":"first","affiliation":[{"name":"Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6576-5547","authenticated-orcid":false,"given":"Youn Kyoung","family":"Choi","sequence":"additional","affiliation":[{"name":"Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Chul","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Gyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok Won","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungeun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemistry & Cosmetics, Jeju National University, Jeju 63243, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Applied Life Science, SARI, Jeju National University, Jeju 63243, Republic of Korea"},{"name":"Subtropical\/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3403-3762","authenticated-orcid":false,"given":"Jin Won","family":"Hyun","sequence":"additional","affiliation":[{"name":"Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea"},{"name":"Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Sook","family":"Yoo","sequence":"additional","affiliation":[{"name":"Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea"},{"name":"Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Kyoung","family":"Kang","sequence":"additional","affiliation":[{"name":"Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea"},{"name":"Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","first-page":"95","article-title":"Review of the current understanding of the effect of ultraviolet and visible radiation on hair structure and options for photoprotection","volume":"55","author":"Signori","year":"2004","journal-title":"J. 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