{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T07:43:56Z","timestamp":1785743036319,"version":"3.56.0"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"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":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetic nephropathy constitutes the leading cause for end\u2010stage kidney disease. Ginkgetin is a common natural non\u2010toxic biflavone and fulfills pleiotropic pharmacological characterizations, such as anti\u2010inflammation and kidney injury. Nevertheless, its efficacy in diabetic nephropathy remains elusive. Here, ginkgetin exhibited little cytotoxicity in glomerular mesangial cells. Of note, ginkgetin restrained high glucose (HG)\u2010induced mesangial cell proliferation and oxidative stress by inhibiting ROS and malonaldehyde levels, but enhancing antioxidant SOD activity. Additionally, ginkgetin suppressed HG\u2010evoked transcript and release of inflammatory cytokine TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u20106. Concomitantly, the increased extracellular matrix (ECM) deposition in HG\u2010treated glomerular mesangial cells was attenuated by ginkgetin via decreasing expression of collagen IV, fibronectin, and laminin. Intriguingly, ginkgetin\u2010restored HG\u2010impaired autophagy; whereas blocking autophagy by its inhibitor 3\u2010MA overturned ginkgetin function against HG\u2010evoked mesangial cell dysfunction. Mechanistically, ginkgetin\u2010mediated AMPK\/mTOR axis accounted for HG\u2010impaired autophagy. Importantly, blockage of AMPK signaling reversed ginkgetin\u2010restored autophagy and its protective efficacy against HG\u2010induced dysfunction in mesangial cells. Thus, these findings highlight that ginkgetin may attenuate HG\u2010evoked mesangial cell hyperplasia, oxidative stress, inflammation, and ECM accumulation by activating AMPk\/mTOR\u2010mediated autophagy pathway. Therefore, ginkgetin may alleviate the progression of diabetic nephropathy by regulating glomerular mesangial cell dysfunction, supporting a promising therapeutic agent against diabetic nephropathy.<\/jats:p>","DOI":"10.1111\/cbdd.13915","type":"journal-article","created":{"date-parts":[[2021,6,20]],"date-time":"2021-06-20T11:14:03Z","timestamp":1624187643000},"page":"620-630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Ginkgetin alleviates high glucose\u2010evoked mesangial cell oxidative stress injury, inflammation, and extracellular matrix (ECM) deposition in an AMPK\/mTOR\u2010mediated autophagy axis"],"prefix":"10.1111","volume":"98","author":[{"given":"Lin","family":"Wei","sequence":"first","affiliation":[{"name":"Departments of General Medicine The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Jian","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang","family":"Erjiong","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Qihan","sequence":"additional","affiliation":[{"name":"Departments of Endocrinology The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2020.111642"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2018.11.027"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11020483"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-017-0569-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3181\/0705-MR-134"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-017-0879-y"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2010.02.004"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2018.1553608"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.03.107"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.29.1046"},{"key":"e_1_2_9_12_1","first-page":"3182","article-title":"The activity and role of autophagy in the pathogenesis of diabetic nephropathy","volume":"22","author":"Liu W. J.","year":"2018","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2015.08.010"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2018.1538352"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2009.07.021"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0061"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.09.003"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/pop.2015.0181"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004110970"},{"key":"e_1_2_9_20_1","first-page":"6250","article-title":"Effect of miR\u201029c on renal fibrosis in diabetic rats via the AMPK\/mTOR signaling pathway","volume":"23","author":"Shao H.","year":"2019","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-019-1133-6"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-016-1488-4"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2017.10.026"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20120198"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12462"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2015.1032958"},{"key":"e_1_2_9_27_1","volume-title":"Preventive and therapeutic effect of ginkgetin on kidney damage of rat by carboplatin","author":"Xiao\u2010Gang T. U.","year":"2006"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.29680"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1159\/000481758"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.03700417"},{"key":"e_1_2_9_31_1","article-title":"Ginkgetin aglycone attenuates the apoptosis and inflammation response through nuclear factor\u2010kB signaling pathway in ischemic\u2010reperfusion injury","author":"Zhang L.","year":"2018","journal-title":"Journal of Cellular Biochemistry"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.01.001"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2019.153060"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.13915","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cbdd.13915","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.13915","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T13:11:04Z","timestamp":1692882664000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.13915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1111\/cbdd.13915"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.13915","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7]]},"assertion":[{"value":"2021-03-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}