{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:01:45Z","timestamp":1787868105439,"version":"build-2784847793"},"reference-count":60,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T00:00:00Z","timestamp":1731715200000},"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":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Methotrexate (MTX) is commonly employed in cancer treatment, but its clinical use is restricted due to the MTX\u2010associated renal injury. This study investigates the combined potential of <jats:italic>Rhus coriaria<\/jats:italic> (sumac) and bone marrow mesenchymal stem cells (BMMSCs) against MTX\u2010induced nephrotoxicity in rats. The high\u2010resolution\u2010liquid chromatography\u2010mass spectrometry (HR\u2010LC\u2010MS) of sumac extract tentatively identified 22 phytochemicals, mostly flavonoids, anthocyanins, and steroids. Preparation of sumac liposomes attained a suitable particle size of 3041.33\u2009\u00b1\u2009339.42\u2009nm, a polydispersity index of 0.208\u2009\u00b1\u20090.086, and an encapsulation efficiency of 84.92\u2009\u00b1\u20093.47%. Rat BMMSCs were injected into the tail vein of the experimental rats (0.5\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> cells, intravenous [iv]) of seven treated groups. The experimental design relies on either pre\u2010 or posttreatment of rats with intraperitoneal (IP) sumac liposomes (SL) (200\u2009mg\/kg, daily with a dose of MTX (300\u2009\u00b5g\/kg\/14 days). The histopathological examination and serum analysis of creatinine and urea revealed good results, besides regulating levels of oxidative stress and inflammatory markers. Additionally, a significant decrease in the gene expression levels of B\u2010Cell Lymphoma 2 (Bcl\u20102) and caspases\u20103 and \u22129, a remarkable increase in the Bcl\u20102 Associated X\u2010Protein (Bax), nuclear factor erythroid 2\u2010related factor 2 (Nrf2), and heme\u2010oxygenase 1 expression, and a downregulation of Kelch\u2010like ECH\u2010associated protein 1 (Keap1). Collectively, the coadministration of SL with BMMSCs might be a potent therapeutic strategy for attenuation of MTX\u2010induced renal damage. The network pharmacology analysis identified the involved key hub genes as KEAP1, Nrf2, HMOX1, mitogen\u2010activated protein kinase (MAPK1), nuclear factor\u2010kappa B (NF\u2010KB), interleukin\u20101 beta (IL\u20101B), and caspase\u20103. The docking results revealed strong binding affinities of 7\u2010<jats:italic>O<\/jats:italic>\u2010methyl\u2010cyanidin\u20103\u2010<jats:italic>O<\/jats:italic>\u2010(2\u2033\u2010galloyl)\u2010galactoside with Keap1 and amentoflavone with MAPK. These insights pave the way for future experimental validation and therapeutic development of sumac\u2010based phytoconstituents against MTX\u2010induced nephrotoxicity.<\/jats:p>","DOI":"10.1002\/ardp.202400684","type":"journal-article","created":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T12:05:35Z","timestamp":1731758735000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Sumac liposomes\/mesenchymal stem cells fight methotrexate\u2010induced nephrotoxicity in rats via regulating Nrf\u20102\/Keap\u20101\/HO\u20101 and apoptotic signaling pathways"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5517-082X","authenticated-orcid":false,"given":"Eman Maher","family":"Zahran","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy Deraya University New Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reham H.","family":"Mohyeldin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Deraya University New Minia Egypt"},{"name":"Deraya Center for Scientific Research Deraya University New Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham","family":"Refaat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6993-3325","authenticated-orcid":false,"given":"Hesham A.","family":"Abou\u2010Zied","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy Deraya University Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai H.","family":"ElNaggar","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy Kafrelsheikh University Kafrelsheikh Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4545-3954","authenticated-orcid":false,"given":"Ghada M.","family":"Abbas","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy Horus University\u2010 Egypt (HUE) New Damietta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif A.","family":"Maher","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy New Valley University El\u2010kharga City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Entesar Ali","family":"Saber","sequence":"additional","affiliation":[{"name":"Department of Medical Science (Histology and Cell Biology), Faculty of Pharmacy Deraya University Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0526-6268","authenticated-orcid":false,"given":"Mohamed A.","family":"Zarka","sequence":"additional","affiliation":[{"name":"Department of College of Pharmacy The Islamic University Najaf Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud A.","family":"Elrehany","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Deraya University Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-6922","authenticated-orcid":false,"given":"Usama Ramadan","family":"Abdelmohsen","sequence":"additional","affiliation":[{"name":"Deraya Center for Scientific Research Deraya University New Minia Egypt"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy Minia University Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232112794"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8641026"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb43030123"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S237107"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/md21060336"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00060.2011"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S298900"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-38390-5"},{"key":"e_1_2_9_10_1","first-page":"11","volume":"14","author":"Rayne S.","year":"2007","journal-title":"Nat. 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