{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:37:37Z","timestamp":1792654657780,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":293,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe inflammatory lung disorders associated with high morbidity and mortality. Dysregulation of the renin\u2013angiotensin system (RAS) and proinflammatory pathways play an indispensable role in ALI progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aimed to investigate the protective potential of nobiletin (NOB) in mitigating ALI and hyperinflammatory lung injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>The study enrolled 32 male albino rats allocated into four groups: (Control, NOB, lipopolysaccharide [LPS], and NOB\u2009+\u2009LPS groups). Rats received NOB 20\u2009mg\/kg by oral gavage for 1 week; on the seventh day, a single dose of 15\u2009mg\/kg LPS was given by intranasal instillation. After 24\u2009h of LPS administration, plasma and lung tissue samples were analyzed for inflammatory cytokines, mitochondrial complex\u2010I, oxidative stress markers, and molecular signaling pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>NOB administration significantly downregulated miR\u2010200 expression, associated with ACE2 activation and attenuated AT1R\u2010mediated inflammatory responses. It also decreased NF\u2010\u03baB and p38 MAPK signaling, reducing pulmonary and systemic levels of tumor necrosis factor\u2010alpha (TNF\u2010\u03b1), interleukin\u20106 (IL\u20106), granulocyte monocyte\u2010colony stimulating factor (GM\u2010CSF), and interleukin\u201017A (IL\u201017A). Additionally, NOB improved the high mobility group box 1 (HMGB1)\/NF\u2010\u03baB\/mammalian target of rapamycin (mTOR) pathway, and increased mitochondrial complex\u2010I may be consistent with improved tissue preservation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NOB exerts protective effects against ALI by improving inflammatory cytokine, oxidative stress, miRNA\u2010200, mitochondrial complex\u2010I, and ACE2, highlighting its potential as a protective candidate for ALI and hyperinflammatory\u2010associated lung injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/omcl\/3253224","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:38:18Z","timestamp":1792651098000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["New Mechanistic Insights Into Nobiletin\u2019s Protective Effects Against LPS\u2010Induced Hyperinflammatory Acute Lung Injury in Rats: Targeting miR\u2010200, AT1R\/p38 MAPK, and HMGB1\/NF\u2010\u03baB mTOR Pathways"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8564-0722","authenticated-orcid":false,"given":"Rehab Ahmed Ahmed","family":"El-Shaer","sequence":"first","affiliation":[{"name":"Physiology Department Faculty of Medicine Tanta University  Tanta Egypt  tanta.edu.eg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9816-5556","authenticated-orcid":false,"given":"Sarah","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Basic Science Department Al-Rayan National College of Medicine  Al Madinah Al Munawwarah Saudi Arabia"},{"name":"Human Anatomy and Embryology Department Faculty of Medicine Tanta University  Tanta Egypt  tanta.edu.eg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4814-8421","authenticated-orcid":false,"given":"Norhan Ahmed","family":"AbuoHashish","sequence":"additional","affiliation":[{"name":"Pharmacology Department Faculty of Medicine Tanta University  Tanta Egypt  tanta.edu.eg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0222-1846","authenticated-orcid":false,"given":"Amira K.","family":"Eltokhy","sequence":"additional","affiliation":[{"name":"Medical Biochemistry Department Faculty of Medicine Tanta University  Tanta Egypt  tanta.edu.eg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7987-5111","authenticated-orcid":false,"given":"Heba Bassiony","family":"Ghanem","sequence":"additional","affiliation":[{"name":"Medical Biochemistry Department Faculty of Medicine Tanta University  Tanta Egypt  tanta.edu.eg"},{"name":"Clinical Laboratory 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