{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T10:31:48Z","timestamp":1793269908351,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82474473"],"award-info":[{"award-number":["82474473"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20241042"],"award-info":[{"award-number":["BK20241042"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Isoquercitrin (IQ) is a natural flavonoid compound with potent anti\u2010inflammatory and antioxidant effects; its role and mechanism of action in diabetic kidney disease (DKD) are unclear. This study clarified the role of IQ in delaying DKD and regulating tubular epithelial cell lipid metabolism.\n                    <jats:italic>db\/db<\/jats:italic>\n                    mice were randomly divided into DKD, low\u2010dose IQ, high\u2010dose IQ, and dapagliflozin groups. C57BL\/6J mice were used as controls. NRK\u201052E cells and connexin 43 (Cx43) knockdown (\n                    <jats:italic>Cx43<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) cells were incubated with IQ and bovine serum albumin (BSA) in\u00a0vitro. A cell counting kit\u20108 (CCK\u20108) was used to assess cell viability and a reactive oxygen species (ROS) detection kit was used to detect oxidative stress levels. Mitochondrial function was assessed using transmission electron microscopy, fluorescence staining, and an ATP assay. Western blotting was used to assess the levels of relevant proteins. IQ ameliorated renal dysfunction in\n                    <jats:italic>db\/db<\/jats:italic>\n                    mice, and proteomic analysis indicates its mechanism involves the regulation of lipid metabolism and mitochondrial function. BSA increased ROS generation, enhanced fluorescence, decreased ATP content, and increased the expression of phosphorylated extracellular signal\u2010regulated kinase (p\u2010ERK), Cx43, and cluster of differentiation 36 (CD36) in NRK\u201052E cells; these effects were ameliorated by IQ. After\n                    <jats:italic>Cx43<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    NRK cells were incubated with BSA, the ROS\/O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2013<\/jats:sup>\n                    fluorescence intensity and p\u2010ERK expression were lower than those in wildtype NRK\u201052E cells. IQ delayed the occurrence and development of DKD by modulating mitochondrial lipid metabolism through the inhibition of Cx43 expression and ERK phosphorylation. This study provides valuable insights for the pharmacological treatment of DKD.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70307","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:04:06Z","timestamp":1774591446000},"page":"4988-5004","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Isoquercitrin Improves Renal Tubular Epithelial Cell Mitochondrial Dysfunction by Regulating Extracellular Signal\u2010Regulated Kinase\/Reactive Oxygen Species Signaling and Connexin 43 Expression in Diabetic Kidney Disease"],"prefix":"10.1002","volume":"40","author":[{"given":"Qi","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Physiology, School of the Basic Medicine Xuzhou Medical University  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupeng","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of the Basic Medicine Xuzhou Medical University  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchen","family":"Sun","sequence":"additional","affiliation":[{"name":"First Clinical Medical College Xuzhou Medical University  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijing","family":"Li","sequence":"additional","affiliation":[{"name":"First Clinical Medical College Xuzhou Medical University  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Liu","sequence":"additional","affiliation":[{"name":"First Clinical Medical College Xuzhou Medical University  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buhui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of the Basic Medicine Xuzhou Medical University  Xuzhou 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