{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T04:53:03Z","timestamp":1781153583019,"version":"3.54.1"},"reference-count":71,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>This study aimed to assess whether <jats:styled-content style=\"fixed-case\"><jats:italic>Melissa officinalis<\/jats:italic><\/jats:styled-content> (MO) or lemon balm could counteract the detrimental effects of diclofenac (DIC) on the liver and kidneys in male albino rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Forty adult male Wistar rats were randomly assigned to four groups (<jats:italic>n<\/jats:italic>\u2009=\u200910 per group): control, DIC (10\u2009mg\/kg intraperitoneally), DIC\u2009+\u2009MO (10\u2009mg\/kg DIC IP\u2009+\u2009200\u2009mg\/kg lemon balm orally), and MO only (200\u2009mg\/kg orally) for 28\u2009days. Biochemical, molecular, and histopathological evaluations were conducted to assess organ function and tissue integrity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>DIC significantly impaired hepatic and renal function (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), evidenced by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alpha\u2010fetoprotein (AFP). Oxidative stress increased, as shown by higher malondialdehyde levels and reduced antioxidants, including glutathione and catalase (CAT). Inflammatory cytokines such as tumor necrosis factor\u2010alpha (TNF\u2010\u03b1) and interleukin\u20106 (IL\u20106) were also elevated. Histopathological analysis indicated severe tissue damage and cell death in the liver and kidneys from DIC. However, adding MO alongside DIC mitigated these effects, improving both biochemical and histopathological parameters in the liver and kidneys. Gene expression analysis revealed upregulation of STAT3 and TNF\u2010\u03b1 and downregulation of AMP\u2010activated protein kinase (<jats:italic>AMPK<\/jats:italic>), sirtuin 1 (<jats:italic>SIRT1<\/jats:italic>), and nuclear factor erythroid 2\u2013related factor 2 (<jats:italic>Nrf2<\/jats:italic>). Coadministration of MO significantly reversed these alterations (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), improved tissue architecture, and restored antioxidant and anti\u2010inflammatory balance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MO provided substantial protection against oxidative damage and functional disturbances induced by DIC in liver and kidney tissues.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jat.4799","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T19:55:16Z","timestamp":1745870116000},"page":"1649-1663","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp><i>Melissa officinalis<\/i><\/scp> Attenuates Diclofenac\u2010Induced Hepatorenal Toxicity via AMPK\/SIRT1 and STAT3\/Nrf2 Pathways"],"prefix":"10.1002","volume":"45","author":[{"given":"Alyaa\u00a0R.","family":"Salama","sequence":"first","affiliation":[{"name":"Department of Clinical Pathology, Faculty of Veterinary Medicine Alexandria University  Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neveen\u00a0R.","family":"Ashoura","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Veterinary Medicine Alexandria University  Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kariman\u00a0A.","family":"Esmail","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Veterinary Medicine Alexandria University  Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossam\u00a0G.","family":"Tohamy","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine Alexandria University  Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2722-2466","authenticated-orcid":false,"given":"Mustafa","family":"Shukry","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Veterinary Medicine Kafrelsheikh University  Kafrelsheikh Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badriyah\u00a0S.","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy, Princess Nourah bint Abdulrahman University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa\u00a0A.","family":"Aboushouk","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Faculty of Veterinary Medicine Alexandria University  Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115794"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(08)60523-0"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2017.12.002"},{"issue":"1","key":"e_1_2_13_5_1","first-page":"971","article-title":"Negative Chronotropic and Antidysrhythmic Effects of Hydroalcoholic Extract of Lemon Balm (Melissa officinalis L.) on CaCl2\u2010Induced Arrhythmias in Rats","volume":"7","author":"Akhondali Z.","year":"2015","journal-title":"Electronic Physician"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1559325819899256"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathophys.2017.07.003"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crphys.2021.03.002"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000267723.65696.4a"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtumed.2019.10.002"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.22159\/ajpcr.2019.v12i3.30829"},{"key":"e_1_2_13_12_1","volume-title":"Theory and Practice of Histological Techniques","author":"Bancroft J. 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