{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:08:22Z","timestamp":1789549702590,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["ORF\u20102026\u2010647"],"award-info":[{"award-number":["ORF\u20102026\u2010647"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Tumor necrosis factor\u2010alpha (TNF\u2010\u03b1) mediates inflammatory cytotoxicity in skeletal muscle, causing mitochondrial dysfunction, bioenergetic collapse, and ATPase\u2010dependent ion homeostasis disruption implicated in aging, cachexia, and inflammatory myopathy. Carvacrol (5\u2010isopropyl\u20102\u2010methylphenol), a monoterpenoid from\n                      <jats:italic>Origanum vulgare<\/jats:italic>\n                      and\n                      <jats:italic>Thymus vulgaris<\/jats:italic>\n                      , has antioxidant, anti\u2010inflammatory, and membrane\u2010stabilizing properties, but its modulation of TNF\u2010\u03b1\u2010induced toxicity, ROS, ATPase activities, \u0394\u03c8m, antioxidant enzymes, and stress\u2010responsive gene expression remains uncharacterized. This study aimed to examine the effect of carvacrol on TNF\u2010\u03b1\u2010induced oxidative and bioenergetic damage in L6 rat myoblasts. L6 rat myoblasts were exposed to TNF\u2010\u03b1 (10\u2009ng\/mL, 1\u2009h) to establish a validated model of inflammatory cytotoxicity, followed by carvacrol treatment (6.25\u2009\u00b5g\/mL, 24\u2009h). Cytotoxicity was evaluated by MTT assay and lactate dehydrogenase (LDH) release. Intracellular ROS were quantified fluorimetrically using DCFH\u2010DA. Oxidative stress markers included catalase and superoxide dismutase (SOD) activities, with \u0394\u03c8m assessed by flow cytometry (Muse MitoPotential kit). Ion\u2010dependent ATPase activities (Na\n                      <jats:sup>+<\/jats:sup>\n                      \/K\n                      <jats:sup>+<\/jats:sup>\n                      \u2010, Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010, Mg\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010dependent) were determined by inorganic phosphate release. SIRT1 and AMPK mRNA expression was quantified by RT\u2010qPCR ( method, GAPDH\u2010normalized). TNF\u2010\u03b1 exposure induced significant cytotoxicity, membrane damage, ROS accumulation, mitochondrial depolarization, suppression of ion\u2010dependent ATPase activities, and dysregulation of catalase and SOD. Post\u2010exposure carvacrol treatment significantly attenuated these effects: LDH release decreased from ~340 to ~73\u2009U\/mL, ROS generation was reduced, \u0394\u03c8m was partially restored, and ATPase activities and antioxidant enzyme activities were recovered toward control levels. Carvacrol significantly upregulated SIRT1 mRNA by 1.62\u2009\u00b1\u20090.18\u2010fold and AMPK mRNA by 2.04\u2009\u00b1\u20090.23\u2010fold relative to TNF\u2010\u03b1\u2010treated cells, consistent with activation of the SIRT1\/AMPK metabolic stress\u2010response axis. Carvacrol mitigates TNF\u2010\u03b1\u2010driven bioenergetic toxicity in L6 myoblasts through coordinated modulation of mitochondrial polarization, ROS burden, ion\u2010dependent ATPase function, antioxidant defenses, and SIRT1\/AMPK\u2010mediated transcriptional stress responses. These findings identify carvacrol as a multi\u2010target modulator of inflammatory skeletal muscle cell toxicity and provide mechanistic foundations for further investigation in differentiated muscle models and in vivo systems.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbt.71087","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:58:13Z","timestamp":1787759893000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Carvacrol Mitigates TNF\u2010\u03b1\u2010Driven Oxidative and Bioenergetic Impairment in L6 Rat Myoblasts"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0554-8721","authenticated-orcid":false,"given":"Ali M.","family":"Albarrati","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Sciences, College of Applied Medical Sciences King Saud University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8845-109X","authenticated-orcid":false,"given":"Rakan I.","family":"Nazer","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, College of Medicine King Saud University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-014-9915-y"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.12.012"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-S302"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3829"},{"key":"e_1_2_10_6_1","first-page":"9","article-title":"Elevated TNF\u2010\u03b1 Correlates With Sarcopenia in Older Adults: A Systematic Review and Meta\u2010Analysis","volume":"21","author":"Chen J.","year":"2024","journal-title":"Immunity & Ageing: IA"},{"key":"e_1_2_10_7_1","first-page":"5125","article-title":"TNF\u2010\u03b1\u2010Induced Mitochondrial Dysfunction in C2C12 Myoblasts: Implications for Aging Muscle","volume":"236","author":"Zhang Y.","year":"2021","journal-title":"Journal of Cellular Physiology"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/rr67"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2364com"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00371"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2017.07.009"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-017-0012-4"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00040.2012"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0230-3"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0b013e328328d0a4"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2011.12.005"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0019-2"},{"key":"e_1_2_10_18_1","first-page":"153","article-title":"Plants of the Genus Thymus: From Phytochemistry to Pharmacology","volume":"238","author":"Sharifi\u2010Rad M.","year":"2018","journal-title":"Food Chemistry"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M900255-JLR200"},{"issue":"1","key":"e_1_2_10_20_1","first-page":"6","article-title":"Antibacterial and Anti\u2010Inflammatory Properties of Carvacrol in Periodontal Disease","volume":"11","author":"Gursoy U. 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