{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:50:03Z","timestamp":1791273003392,"version":"4.1.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2026,10]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n A natural sesquiterpene lactone compound Eupalinolide B protected against diabetic kidney disease.<\/jats:p>\n <\/jats:list-item>\n \n Eupalinolide B targeted cell division cycle 37 protein and disrupted the interaction between cell division cycle 37 and heat shock protein 90.<\/jats:p>\n <\/jats:list-item>\n \n The renoprotective effects of Eupalinolide B were dependent on cell division cycle 37\u2013mediated inflammatory pathways in diabetic kidney disease.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n \n Diabetic kidney disease (DKD) is a major complication of diabetes, driven by chronic inflammation throughout its initiation and progression. Developing effective novel therapeutics is urgently needed. Eupalinolide B, a natural small compound derived from\n Eupatorium lindleyanum DC<\/jats:italic>\n ., has multiple bioactive properties, notably antitumor and anti-inflammatory activities. However, the therapeutic potential of Eupalinolide B for DKD remains unclear. This study was to investigate the potential effects, direct targets, and pharmacologic mechanisms of Eupalinolide B against DKD, and discover novel therapeutic targets in the progression of DKD.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The therapeutic effects of Eupalinolide B were assessed in high glucose\u2013induced rat mesangial (HBZY-1) cells and\n db\/db<\/jats:italic>\n diabetic mice. Targeting and binding site engagement of Eupalinolide B was validated through activity-based protein profiling technology, pull-down assay, surface plasmon resonance analysis, and high-resolution mass spectrometry analysis. The target protein was knocked down to investigate its role in DKD-related inflammation and determine whether Eupalinolide B's renoprotective effects depend on the protein. The impact of Eupalinolide B on protein\u2013protein interactions was examined using immunoblotting, immunohistochemistry, immunofluorescence, and coimmunoprecipitation assays.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Eupalinolide B was observed to ameliorate the glomerular filtration dysfunction and histopathologic damage in\n db\/db<\/jats:italic>\n mice and suppress NF-\u03baB and mitogen-activated protein kinase proinflammatory pathways in both high glucose\u2013induced HBZY-1 cells and\n db\/db<\/jats:italic>\n mice. In addition, we found that Eupalinolide B directly bound to cysteine 64 and 234 residues of cell division cycle 37 (CDC37), the essential cochaperone of heat shock protein 90 (HSP90). Mechanistically, by targeting CDC37, Eupalinolide B disrupted the interaction between CDC37 and HSP90, consequently blocking downstream proinflammatory signaling upon high glucose induction in HBZY-1 cells.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Eupalinolide B was identified as a novel CDC37-targeting agent with renoprotective and anti-inflammatory effects against DKD that functions by inhibiting CDC37\u2013HSP90 interaction.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000001122","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T16:04:55Z","timestamp":1778515495000},"page":"2146-2161","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Eupalinolide B Ameliorates Diabetic Kidney Disease via Inhibition of Cell Division Cycle 37\u2013Mediated Inflammatory Pathways"],"prefix":"10.1681","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9926-3129","authenticated-orcid":false,"given":"Huiying","family":"Li","sequence":"first","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, China"},{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China"},{"name":"Department of Biochemistry, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9477-3155","authenticated-orcid":false,"given":"Guanjun","family":"Li","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, China"},{"name":"Department of Nephrology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People\u2019s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Huang","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, China"},{"name":"Department of Nephrology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People\u2019s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6770-924X","authenticated-orcid":false,"given":"Tianyun","family":"Fan","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3471-037X","authenticated-orcid":false,"given":"Junzhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3770-5261","authenticated-orcid":false,"given":"Liwei","family":"Gu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyou","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4772-9483","authenticated-orcid":false,"given":"Huan","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5530-5042","authenticated-orcid":false,"given":"Yali","family":"Song","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, China"},{"name":"Department of Reproductive Medicine, Dongguan State Key Laboratory of Integrated Traditional Chinese and Western Medicine for the Diagnosis and Treatment of Infertility, Dongguan Institute of Reproductive and Genetic Research, Dongguan Maternal and Child Health Care Hospital, Dongguan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingming","family":"Luo","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, China"},{"name":"Department of Reproductive Medicine, Dongguan State Key Laboratory of Integrated Traditional Chinese and Western Medicine for the Diagnosis and Treatment of Infertility, Dongguan Institute of Reproductive and Genetic Research, Dongguan Maternal and Child Health Care Hospital, Dongguan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0575-0105","authenticated-orcid":false,"given":"Jigang","family":"Wang","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, China"},{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China"},{"name":"Department of Nephrology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People\u2019s Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China"},{"name":"Department of Reproductive Medicine, Dongguan State Key Laboratory of Integrated Traditional Chinese and Western Medicine for the Diagnosis and Treatment of Infertility, Dongguan Institute of Reproductive and Genetic Research, Dongguan Maternal and Child Health Care Hospital, Dongguan, China"},{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"issue":"1","key":"B1-20261005","doi-asserted-by":"crossref","first-page":"15018","DOI":"10.1038\/nrdp.2015.18","article-title":"Diabetic kidney disease","volume":"1","author":"Thomas","year":"2015","journal-title":"Nat Rev Dis Primers."},{"issue":"5","key":"B2-20261005","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41581-021-00393-8","article-title":"Pathophysiology of diabetic kidney disease: impact of SGLT2 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Nephrol."},{"issue":"2","key":"B6-20261005","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.kint.2022.10.030","article-title":"Targeting inflammation to treat diabetic kidney disease: the road to 2030","volume":"103","author":"Rayego-Mateos","year":"2023","journal-title":"Kidney Int."},{"issue":"11","key":"B7-20261005","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/s41580-023-00640-9","article-title":"Structural and functional complexity of HSP90 in cellular homeostasis and disease","volume":"24","author":"Chiosis","year":"2023","journal-title":"Nat Rev Mol Cell Biol."},{"issue":"1","key":"B8-20261005","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/med.21807","article-title":"Targeting the HSP90-CDC37-kinase chaperone cycle: a promising therapeutic strategy for cancer","volume":"42","author":"Wang","year":"2022","journal-title":"Med Res 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GSK-3\u03b2\/\u03b2-catenin pathway","volume":"235","author":"Wang","year":"2025","journal-title":"Biochem Pharmacol."},{"key":"B31-20261005","doi-asserted-by":"crossref","first-page":"109148","DOI":"10.1016\/j.intimp.2022.109148","article-title":"Eupalinolide B attenuates lipopolysaccharide-induced acute lung injury through inhibition of NF-\u03baB and MAPKs signaling by targeting TAK1 protein","volume":"111","author":"Yang","year":"2022","journal-title":"Int Immunopharmacol."},{"issue":"6293","key":"B32-20261005","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1126\/science.aaf5023","article-title":"Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase","volume":"352","author":"Verba","year":"2016","journal-title":"Science."},{"issue":"2","key":"B33-20261005","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.molcel.2016.04.005","article-title":"Molecular mechanism of protein kinase recognition and sorting by the 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English)."},{"issue":"16","key":"B36-20261005","doi-asserted-by":"crossref","first-page":"5017","DOI":"10.1073\/pnas.1505244112","article-title":"A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for RIP3 activation during necroptosis","volume":"112","author":"Li","year":"2015","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"3","key":"B37-20261005","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1007\/s10753-023-01789-3","article-title":"Inhibition of Cdc37 ameliorates arthritis in collagen-induced arthritis rats by inhibiting synoviocyte proliferation and migration through the ERK pathway","volume":"46","author":"Sun","year":"2023","journal-title":"Inflammation."},{"issue":"44","key":"B38-20261005","doi-asserted-by":"crossref","first-page":"32311","DOI":"10.1074\/jbc.M705785200","article-title":"Signal responsiveness of I\u03baB kinases is determined by Cdc37-assisted transient interaction with Hsp90","volume":"282","author":"Hinz","year":"2007","journal-title":"J Biol Chem."},{"issue":"2","key":"B39-20261005","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S1097-2765(02)00450-1","article-title":"TNF-induced recruitment and activation of the IKK complex require CDC37 and HSP90","volume":"9","author":"Chen","year":"2002","journal-title":"Mol Cell."},{"issue":"51","key":"B40-20261005","doi-asserted-by":"crossref","first-page":"35381","DOI":"10.1074\/jbc.M109.051532","article-title":"Characterization of celastrol to inhibit Hsp90 and Cdc37 interaction","volume":"284","author":"Zhang","year":"2009","journal-title":"J Biol Chem."},{"issue":"4","key":"B41-20261005","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/s41401-021-00737-x","article-title":"Okicamelliaside targets the N-terminal chaperone pocket of HSP90 disrupts the chaperone protein interaction of HSP90-CDC37 and exerts antitumor activity","volume":"43","author":"Cheng","year":"2022","journal-title":"Acta Pharmacol Sin."},{"issue":"11","key":"B42-20261005","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1002\/1873-3468.14080","article-title":"The CDC37\u2010HSP90 chaperone complex co\u2010translationally degrades the nascent kinase\u2010dead mutant of HIPK2","volume":"595","author":"M\u00fcller","year":"2021","journal-title":"FEBS Lett."},{"issue":"17","key":"B43-20261005","doi-asserted-by":"crossref","first-page":"e2414673","DOI":"10.1002\/advs.202414673","article-title":"Autophagy related 5 promotes mitochondrial fission and inflammation via HSP90\u2010HIF\u20101\u03b1\u2010Mediated glycolysis in kidney fibrosis","volume":"12","author":"Hu","year":"2025","journal-title":"Adv Sci."}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:00:41Z","timestamp":1791230441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,11]]},"references-count":43,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.0000001122","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,11]]},"assertion":[{"value":"2025-06-25","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-06","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}