{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:09:18Z","timestamp":1793041758336,"version":"4.5.0"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA0910500"],"award-info":[{"award-number":["2021YFA0910500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U22A20380"],"award-info":[{"award-number":["U22A20380"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Chronic kidney disease (CKD) is a disease that affects more than 850 million people. Acute kidney injury (AKI) is a common cause of CKD, and blocking the AKI\u2013CKD transition shows promising therapeutic potential. Herein, we found that butyrolactone I (BLI), a natural product, exerts significant nephroprotective effects, including maintenance of kidney function, inhibition of inflammatory response, and prevention of fibrosis, in both folic acid\u2010 and ureteral obstruction\u2010induced AKI\u2013CKD transition mouse models. Notably, BLI showed greater blood urea nitrogen reduction and anti\u2010inflammatory effects than telmisartan. Bioinformatics analysis and target confirmation assays suggested that BLI directly binds to JAK1, and kinase inhibition assay confirmed it is a potent JAK1inhibitor with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 0.376\u00a0\u00b5M. Experiments in JAK1\u2010knockdown mice also proved that BLI targets JAK1 to work. Furthermore, BLI demonstrated nephroprotective effects and safety comparable to ivarmacitinib, the well\u2010known JAK1 inhibitor. Mechanistically, BLI targets JAK1 and inhibits its phosphorylation and JAK\u2010STAT activation, subsequently regulating the downstream signaling pathways to inhibit reactive oxygen species production, inflammation, and ferroptosis, thereby preventing the occurrence of kidney fibrosis and blocking the AKI\u2013CKD transition process. This study demonstrates for the first time that BLI is a JAK1 inhibitor and a promising candidate for delaying CKD progression, which warrants further investigation.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70064","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T01:55:39Z","timestamp":1737510939000},"source":"Crossref","is-referenced-by-count":11,"title":["Butyrolactone I blocks the transition of acute kidney injury to chronic kidney disease in mice by targeting JAK1"],"prefix":"10.1002","volume":"6","author":[{"given":"Zijun","family":"Zhang","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of Pharmacy Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of Pharmacy Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxing","family":"Qi","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of Pharmacy Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of Pharmacy Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of Pharmacy Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjuan","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Function of Natural Medicine Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zou","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Process Hubei Province Key Laboratory of Occupational Hazard Identification and Control School of Medicine Wuhan University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Process Hubei Province Key Laboratory of Occupational Hazard Identification and Control School of Medicine Wuhan University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianghu","family":"Gu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of Pharmacy Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of Pharmacy Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Huang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of Pharmacy Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Xiang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of Pharmacy Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantai","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Function of Natural Medicine Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7713-7230","authenticated-orcid":false,"given":"Qingyi","family":"Tong","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of Pharmacy Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of Pharmacy Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00519-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00284-z"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.10.016"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2022.100438"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-13-8871-2_1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30045-3"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kisu.2021.11.003"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222011253"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05969-9"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/np070341r"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(98)00381-4"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2016.06.040"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02403-3"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2184.2009.00584.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2022.07.050"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201901061R"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/md18110526"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27238367"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00114-z"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.9b01285"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-019-0095-5"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1538\/expanim.54.319"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202104034"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-022-04223-6"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12121581"},{"key":"e_1_2_10_27_1","article-title":"Pharmacological targeting macrophage phenotype via gut\u2010kidney axis ameliorates renal fibrosis in mice","volume":"178","author":"Xie Y","year":"2022","journal-title":"Pharmacol Res"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242216152"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3762"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2298-2"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015121376"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04137-1"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2117396119"},{"key":"e_1_2_10_34_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2020.101670","article-title":"Hypoxia inhibits ferritinophagy, increases mitochondrial ferritin, and protects from ferroptosis","volume":"36","author":"Fuhrmann DC","year":"2020","journal-title":"Redox Biol"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2021.10.024"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202305563"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-019-0380-z"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.10.042"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.12.007"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910040106"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo4363"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05716-0"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-043021-032816"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10010189"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-023-01047-8"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2022.8308"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16272"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1039\/B403052D"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10020275"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000079"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.174121"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1233259"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.08.007"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.935937"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12194"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00199.2018"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-52961-5"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12194"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0248-y"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfx377"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.4.110807.092205"}],"container-title":["MedComm"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.70064","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:52:18Z","timestamp":1739494338000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mco2.70064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,21]]},"references-count":60,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/mco2.70064"],"URL":"https:\/\/doi.org\/10.1002\/mco2.70064","archive":["Portico"],"relation":{},"ISSN":["2688-2663","2688-2663"],"issn-type":[{"value":"2688-2663","type":"print"},{"value":"2688-2663","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,21]]},"article-number":"e70064"}}