{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:59:52Z","timestamp":1792605592918,"version":"4.5.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Melanocyte (MC) death represents the basic pathological change of vitiligo. Kaempferol (Kae) is one of the main active ingredients of Tribulus terrestris, which is a commonly used Chinese medicine in the treatment of vitiligo. However, it remains unclear whether Kae can improve MC death, and hence relevant mechanisms need to be further explored. Therefore, we aimed to investigate the effect of Kae on MC death and relevant mechanisms. The targets of Kae and the differential genes of vitiligo were screened based on different databases. Besides, the protein-protein interaction (PPI) network of the common target of Kae and vitiligo was constructed to further identify the \u201ckeycluster\u201d genes of the drug-disease interaction (DDI) network. In addition, the enrichment analysis based on Gene Ontology (GO), Disease Ontology (DO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed on the \u201ckeycluster\u201d genes. Based on the network pharmacological results, it was found that Kae may ameliorate MC death through the ferroptosis pathway. Hence, the ferroptosis model of human primary epidermal melanocyte 1 (HEM-1) was induced by RAS-selective lethal 3 (RSL3) and then co-cultured with Kae. Moreover, the role of Kae in MC ferroptosis was investigated by detecting the changes in mitochondrial morphology and functions, the levels of reactive oxygen species (ROS) and iron ions, the protein expression of glutathione peroxidase 4 (GPX4), and antioxidant activities. Finally, si-GPX4 was used to silence the ferroptosis core protein GPX4 to re-examine the above indicators, thus verifying relevant mechanisms. The network pharmacology results showed that Kae was responsive to oxidative stress and ROS. The treatment of vitiligo by Kae mainly involved pigmentation, melanin metabolic processes, and such signaling pathways as melanogenesis, ferroptosis, and tyrosine metabolism. The in vitro experiment results indicated that Kae can effectively improve RSL3-induced HEM-1 ferroptosis, including alleviating mitochondrial damage, decreasing the level of ROS and iron ions, and up-regulating the expression of GPX4 and antioxidants. After silencing GPX4, the protective effect of Kae against HEM-1 ferroptosis was attenuated. Our study concluded that Kae can reduce RSL3-induced ferroptosis in HEM-1, and its mechanism is related to the regulation of the expression of the ferroptosis pathway protein GPX4. These findings are expected to provide novel insights into the treatment of vitiligo.<\/jats:p>","DOI":"10.1038\/s41598-025-91905-0","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T14:17:47Z","timestamp":1741789067000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An investigation into the mechanism for Kaempferol improving melanocyte death based on network Pharmacology and experimental verification"],"prefix":"10.1038","volume":"15","author":[{"given":"Jinming","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeqiang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"91905_CR1","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1146\/annurev-immunol-100919-023531","volume":"38","author":"ML Frisoli","year":"2020","unstructured":"Frisoli, M. 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