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However, renal adverse effects limit its clinical application. We previously reported that organic anion transporters (OATs) facilitated the renal transport of Imp and contributed its nephrotoxicity. Natural flavonoids exhibited renal protective effect. Here, we aimed to develop potent OAT inhibitors from traditional Chinese medicines (TCMs) and to evaluate its protective effect against Imp\u2010induced nephrotoxicity. Among 50 TCMs, <jats:italic>Tribuli Fructus<\/jats:italic>, <jats:italic>Platycladi Cacumen<\/jats:italic>, and <jats:italic>Lycopi Herba<\/jats:italic> exhibited potent inhibition on OAT1\/3. After screening their main components, Apigenin strongly inhibited Imp uptake by OAT1\/3\u2010HEK293 cells with IC50 values of 1.98 \u00b1\u20090.36 \u03bcM (OAT1) and 2.29 \u00b1\u20090.88 \u03bcM (OAT3). Moreover, Imp exhibited OAT1\/3\u2010dependent cytotoxicity, which was alleviated by Apigenin. Furthermore, Apigenin ameliorated Imp\u2010induced nephrotoxicity in rabbits, and reduced the renal secretion of Imp. Apigenin inhibited intracellular accumulation of Imp and sequentially decreased the nephrocyte toxicity in rabbit primary proximal tubule cells (rPTCs). Apigenin, a flavone widely distributed in TCMs, was a potent OAT1\/3 inhibitor. Through OAT inhibition, at least in part, Apigenin decreased the renal exposure of Imp and consequently protected against the nephrotoxicity of Imp. Apigenin can be used as a promising agent to reduce the renal adverse reaction of Imp in clinic.<\/jats:p>","DOI":"10.1002\/ptr.6727","type":"journal-article","created":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T03:05:17Z","timestamp":1590721517000},"page":"2998-3010","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Targeting renal <scp>OATs<\/scp> to develop renal protective agent from traditional Chinese medicines: Protective effect of Apigenin against Imipenem\u2010induced nephrotoxicity"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4056-7987","authenticated-orcid":false,"given":"Xiaokui","family":"Huo","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, College of Pharmacy Dalian Medical University  Dalian China"},{"name":"College (Institute) of Integrative Medicine Dalian Medical University  Dalian China"},{"name":"Provincial Key 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