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Total flavones from <jats:italic>Abelmoschus manihot<\/jats:italic> (TFA), a natural extract that extensively used in patients with chronic kidney disease, has been used for treatment of renal tubular injury in DKD; however, whether TFA alleviates DT and its potential mechanisms remain unclear. Hence, we investigated the effects of TFA, compared to dapagliflozin, in DT management both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>, using a DKD rat model and the NRK\u201052\u2009E cells. Following modeling, the DKD rats received TFA, dapagliflozin, or vehicle for 6\u2009weeks. For the <jats:italic>in vitro<\/jats:italic> research, the NRK\u201052\u2009E cells were exposed to advanced glycation end products (AGEs) plus ferrostatin\u20101 (Fer\u20101), dapagliflozin, or TFA. Changes in biochemical parameters and renal tubular injury were analyzed <jats:italic>in vivo<\/jats:italic>, while changes in ferroptosis of renal tubular cells and the ferroptosis\u2010related proteins expression were analyzed both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. We found that TFA and dapagliflozin improved biochemical parameters, renal tubular injury, and ferroptosis in the DKD rats. Moreover, TFA and dapagliflozin inhibited ferroptosis by ameliorating iron deposition, lipid peroxidation capacity, and ferroptosis\u2010related proteins expression <jats:italic>in vitro<\/jats:italic>, which was similar to the effects of Fer\u20101. Collectively, this study demonstrated that TFA treated DT in a manner similar to dapagliflozin by inhibiting ferroptosis of renal tubular cells via improving iron deposition and antioxidant capacity. Our findings provide new pharmacological evidence for TFA application in DT treatment.<\/jats:p>","DOI":"10.1002\/ar.25123","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T06:00:47Z","timestamp":1669615247000},"page":"3199-3213","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Inhibition of ferroptosis of renal tubular cells with total flavones of <i>Abelmoschus manihot<\/i> alleviates diabetic tubulopathy"],"prefix":"10.1002","volume":"306","author":[{"given":"Mei\u2010Zi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Institute of Chinese Medicine, Nanjing University  Nanjing China"},{"name":"Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University 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