{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:08:00Z","timestamp":1793142480839,"version":"4.5.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Cisplatin-induced acute kidney injury (AKI) increases the patient mortality dramatically and results in an unfavorable prognosis. A strong correlation between AKI and ferroptosis, which is a notable type of programmed cell death, was found in recent studies. Myricitrin is a natural flavonoid compound with diverse pharmacological properties. To investigate the protective effect of myricitrin against cisplatin induced human tubular epithelium (HK-2) cell injury and the underlying anti-ferroptic mechanism by this study. Firstly, a pharmacology network analysis was proposed to explore the myricitrin\u2019s effect. HK-2 cells were employed for <jats:italic>in vitro<\/jats:italic> experiments. Ferroptosis was detected by cell viability, quantification of iron, malondialdehyde, glutathione, lipid peroxidation fluorescence, and glutathione peroxidase (GPX4) expression. Ferritinophagy was detected by related protein expression (NCOA4, FTH, LC3II\/I, and SQSTM1). In our study, GO enrichment presented that myricitrin might be effective in eliminating ferroptosis. The phenomenon of ferroptosis regulated by ferritinophagy was observed in cisplatin-activated HK-2 cells. Meanwhile, pretreatment with myricitrin significantly rescued HK-2 cells from cell death, reduced iron overload and lipid peroxidation biomarkers, and improved GPX4 expression. In addition, myricitrin downregulated the expression of LC3II\/LC3I and NCOA4 and elevated the expression of FTH and SQTM. Furthermore, myricitrin inhibited ROS production and preserved mitochondrial function with a lower percentage of green JC-1 monomers. However, the protection could be reserved by the inducer of ferritinophagy rapamycin. Mechanically, the Hub genes analysis reveals that AKT and NF-\u03baB are indispensable mediators in the anti-ferroptic process. In conclusion, myricitrin ameliorates cisplatin induced HK-2 cells damage by attenuating ferritinophagy mediated ferroptosis.<\/jats:p>","DOI":"10.3389\/fphar.2024.1372094","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T19:15:41Z","timestamp":1718133341000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Myricitrin inhibited ferritinophagy-mediated ferroptosis in cisplatin-induced human renal tubular epithelial cell injury"],"prefix":"10.3389","volume":"15","author":[{"given":"Jiawen","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Sui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingcheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1681\/ASN.2017070765","article-title":"Clinical decision support for in-hospital AKI","volume":"29","author":"Al-Jaghbeer","year":"2018","journal-title":"J. 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