{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:30:25Z","timestamp":1790947825720,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T00:00:00Z","timestamp":1705449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hesperetin (HST) is a flavonoid compound naturally occurring in citrus fruits and is widespread in various traditional medicinal herbs such as grapefruit peel, orange peel, and tangerine peel. These plant materials are commonly used in traditional Chinese medicine to prepare herbal remedies. The study aimed to investigate the potential molecular mechanisms through which HST reduces ferroptosis in human umbilical vein endothelial cells (HUVECs) and promotes angiogenesis and wound healing. We employed network pharmacology to predict the downstream targets affected by HST. The expression of markers related to ferroptosis was assessed through Western blot (WB) and polymerase chain reaction. Intracellular levels of ferroptosis\u2010related metabolism were examined using glutathione\/oxidized glutathione (GSH\/GSSG) and malondialdehyde (MDA) assay kits. Mitochondrial status and iron levels within the cells were investigated through staining with Mitosox, FerroOrange, and JC1 staining. Potential downstream direct targets of HST were identified using molecular docking. Additionally, wound healing and neovascularization within the wound site were analyzed using various methods including HE staining, Masson's staining, immunohistochemistry, and Doppler hemodynamics assessment. HST effectively inhibits the elevated levels of intracellular ferroptosis stimulated by ERASTIN. Furthermore, we observed that HST achieves this inhibition of ferroptosis by activating SIRT3. In a diabetic rat wound model, HST significantly promotes wound healing, reducing levels of tissue ferroptosis, consistent with our in vitro findings. This study demonstrates that HST can inhibit the progression of ferroptosis and protect the physiological function of HUVECs by activating SIRT3. HST holds promise as a natural compound for promoting diabetic wound healing.<\/jats:p>","DOI":"10.1002\/ptr.8121","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T01:54:47Z","timestamp":1705542887000},"page":"1478-1493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Hesperetin promotes diabetic wound healing by inhibiting ferroptosis through the activation of\n                    <scp>SIRT3<\/scp>"],"prefix":"10.1002","volume":"38","author":[{"given":"Xianbin","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Orthopaedic The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Orthopaedics of Zhejiang Province  Wenzhou China"},{"name":"The Second School of Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province  Wenzhou China"},{"name":"Alberta Institute Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitian","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Orthopaedics of Zhejiang Province  Wenzhou China"},{"name":"The First School of Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjie","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Orthopaedics of Zhejiang Province  Wenzhou China"},{"name":"The Second School of Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhe","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Orthopaedics of Zhejiang Province  Wenzhou China"},{"name":"The Second School of Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqing","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Orthopaedics of Zhejiang Province  Wenzhou China"},{"name":"The Second School of Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Orthopaedics of Zhejiang Province  Wenzhou China"},{"name":"The Second School of Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9070-3655","authenticated-orcid":false,"given":"Shi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Orthopaedics of Zhejiang Province  Wenzhou China"},{"name":"The Second School of Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112838"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21466"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/1061186X.2022.2085729"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.14102"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.07.017"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32374-6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.01.012"},{"key":"e_1_2_10_9_1","article-title":"Ultra\u2010low concentration electrolyte enabling LiF\u2010rich SEI and dense plating\/stripping processes for lithium metal batteries","author":"Chen T.","year":"2022","journal-title":"Advanced Science (Weinheim, Baden\u2010Wurttemberg, Germany)"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2019.05.040"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.01.030"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-018-1702-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.943321"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa891"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2018.10.001"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100763"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.898657"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2018.1513608"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku293"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2018.1476964"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312726"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-019-1512-7"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-019-0223-y"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00324-8"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.09.022"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0FO02736G"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00042.2021"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.03.022"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2021.04.007"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111552"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110103"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11655-019-3064-0"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1816342"},{"key":"e_1_2_10_34_1","article-title":"GeneCards version 3: The human gene integrator","author":"Safran M.","year":"2010","journal-title":"Database (Oxford)"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2021.1875979"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.7b00589"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12101428"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1074"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01257-8"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.70194"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.10.011"},{"key":"e_1_2_10_43_1","doi-asserted-by":"crossref","DOI":"10.1093\/database\/baaa021","article-title":"FerrDb: A manually curated resource for regulators and markers of ferroptosis and ferroptosis\u2010disease associations","volume":"2020","author":"Zhou N.","year":"2020","journal-title":"Database: The Journal of Biological Databases and Curation"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102707"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2023.2200291"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.8121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T07:45:54Z","timestamp":1710315954000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.8121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,17]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/ptr.8121"],"URL":"https:\/\/doi.org\/10.1002\/ptr.8121","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,17]]},"assertion":[{"value":"2023-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}