{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:55:59Z","timestamp":1790016959840,"version":"4.0.1"},"reference-count":114,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["MOST 111-2321-B-255-001 and MOST 111-2320-B-038-040-MY3"],"award-info":[{"award-number":["MOST 111-2321-B-255-001 and MOST 111-2320-B-038-040-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Cadmium (Cd), a highly toxic heavy metal, is used in food and agricultural products while displaying nephrotoxicity to animals and humans. The genus <jats:italic><jats:italic>Syzygium<\/jats:italic><\/jats:italic> (Myrtle family) is rich in precious phenolic metabolites with various therapeutic values. This study investigated the phenolic content and the therapeutic potential of the defatted 80% aqueous methanol extract (DE) of <jats:italic><jats:italic>S. malaccense<\/jats:italic><\/jats:italic> and <jats:italic><jats:italic>S. samarangense<\/jats:italic><\/jats:italic> leaves against Cd-induced kidney injury in rats for the first time. High-performance liquid chromatography-Mass spectrometry (HPLC-MS), in addition to Folin-Ciocalteu and aluminium chloride colourimetric methods, depicted the phenolic metabolites, total phenolic content, and total flavonoid content, respectively. The nephroprotective effect was investigated using fifty-six female <jats:italic><jats:italic>Sprague Dawley<\/jats:italic><\/jats:italic> rats divided into eight groups: control group, CdCl<jats:sub>2<\/jats:sub>-treated group (3 mg\/kg\/i.p\/7 days), and three groups of each species treated with the DE (250, 500, and 1000 mg\/kg\/o.p., respectively). The phytochemical analysis revealed the richness of <jats:italic><jats:italic>S. samarangense<\/jats:italic><\/jats:italic> DE by phenolic and flavonoid content over <jats:italic><jats:italic>S. malaccense<\/jats:italic><\/jats:italic>. The HPLC-MS showed the tentative identification of sixty-two compounds, in positive and negative ionization modes, belonging to phenolic acids <jats:bold>(1\u22126<\/jats:bold>), flavonoids <jats:bold>(7\u221252),<\/jats:bold> and miscellaneous compounds <jats:bold>(53\u221262)<\/jats:bold>. Both extracts were considered safe up to 5 g\/kg. At the maximum tested dose (100 mg\/Kg), the DEs significantly (<jats:italic><jats:italic>p<\/jats:italic><\/jats:italic>\u2009&lt;\u20090.001) boosted the levels of antioxidant markers by 3.3\u20136 fold, lessened the inflammatory indicators by 66.8%\u221275.1%, and reduced the apoptotic parameters by 45.4\u201373.3%, compared to the CdCl<jats:sub>2<\/jats:sub>-treated group. Additionally, the DEs maintained the mitochondrial function and inhibited autophagy <jats:italic><jats:italic>via<\/jats:italic><\/jats:italic> decreasing adenosine monophosphate-activated protein kinase by 49.2%\u221250.6%, and baclin-1 by 49.5%\u221256.1%. Additionally, the DEs increased the mammalian target of rapamycin (mTOR) by 4.7\u20134.9 fold. Additionally, the DE ameliorated CdCl2-induced elevations in serum ALT and AST, indicating a protective effect against systemic toxicity. Ultimately, the DE of <jats:italic><jats:italic>S. malaccense<\/jats:italic><\/jats:italic> and <jats:italic><jats:italic>S. samarangense<\/jats:italic><\/jats:italic> protect against Cd-induced nephrotoxicity that may be correlated to their abundant phenolic content. However, selecting suitable formulations and implementing clinical studies are among the future directions.<\/jats:p>","DOI":"10.1371\/journal.pone.0329586","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T18:41:03Z","timestamp":1755196863000},"page":"e0329586","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["HPLC-MS profiling and protective potential of the defatted aqueous methanol extract of two Syzygium species against cadmium chloride-induced nephrotoxicity in rats"],"prefix":"10.1371","volume":"20","author":[{"given":"Fatma A.","family":"Moharram","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar 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