{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:49:23Z","timestamp":1792511363120,"version":"4.5.0"},"reference-count":69,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["Food Science &amp; Nutrition"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Rheumatoid arthritis (RA) is a chronic inflammatory condition that affects millions of people globally, often leading to morbidity. Recent research highlights the potential of natural products in managing arthritis symptoms and modifying disease progression. Among these,\n                    <jats:italic>Melaleuca alternifolia<\/jats:italic>\n                    oil (MAO) has emerged as a promising therapeutic option due to its anti\u2010inflammatory and analgesic properties. A total of 36 Sprague\u2013Dawley rats weighing between 200 and 220\u2009g were divided into six groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096). On day 0, arthritis was induced by CFA. On day 8, treatment started and lasted till day 28. Paw edema and arthritic score were measured. Moreover, hematological, histological, and biochemical parameters were evaluated. The mRNA expression levels of anti\u2010inflammatory cytokine IL\u20104 and pro\u2010inflammatory cytokines such as TNF\u2010\u03b1, IL\u20106, NF\u2010\u03baB, and IL\u20101\u03b2 were measured using real\u2010time polymerase chain reaction (qPCR). ELISA was used to detect PGE2 levels. Network pharmacology was used to evaluate the hub genes between the phytocompounds and rheumatoid arthritis. Molecular docking and scoring calculations were done for the top matched hub genes for moderate confirmations between phytocompounds and targets. GC\u2013MS analysis was also performed to identify potential anti\u2010inflammatory constituents present in the plant oil. Treatment with MAO effectively reduced paw edema and swelling. Histopathological examinations demonstrated significant improvement in the treatment groups. Biochemical parameters such as creatinine, urea, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) did not significantly alter, and hematological parameters such as red blood cells (RBC), white blood cells (WBC), hemoglobin (Hb), and platelet count were restored in the treated group. The mRNA expression of anti\u2010inflammatory cytokines, including IL\u20104, was upregulated, and pro\u2010inflammatory biomarkers such as TNF\u2010\u03b1, IL\u20101\u03b2, IL\u20106, and NF\u2010\u03baB were significantly downregulated in the arthritic control group. Furthermore, treatment with MAO significantly reduced PGE2 levels. Network pharmacology indicated the hub genes and several biological processes, molecular functions, cellular components, and KEGG pathways that are involved in rheumatoid arthritis. Molecular docking was performed against hub genes such as AKT1, BCL\u20102, MAPK3, and MMP9 that are involved in various pro\u2010inflammatory cytokine formation and pathophysiology of rheumatoid arthritis. GC\u2013MS analysis of the plant's oil revealed the presence of numerous anti\u2010inflammatory and antirheumatic phytochemicals. MAO possesses considerable anti\u2010arthritic properties by downregulating pro\u2010inflammatory biomarkers such as IL\u20101\u03b2, NF\u2010\u03baB, IL\u20106, TNF\u2010\u03b1, and upregulating anti\u2010inflammatory IL\u20104. Further investigations are needed to explore its potential as a natural therapeutic option for treating RA.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.72328","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T10:08:07Z","timestamp":1790158087000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling the Anti\u2010Arthritic Potential of Bioactive Compounds From\n                    <i>Melaleuca alternifolia<\/i>\n                    Oil: Integrated In\u00a0Vivo, Molecular Docking, and Network Pharmacology Insights"],"prefix":"10.1002","volume":"14","author":[{"given":"Sana","family":"Sabir","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy The University of Lahore  Lahore 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Lahore  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1213-7886","authenticated-orcid":false,"given":"Kiran","family":"Mashaal","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy The University of Lahore  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3496-3684","authenticated-orcid":false,"given":"Esmael M.","family":"Alyami","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science King Khalid University  Abha Asir Saudi Arabia"},{"name":"Research Centre for Advanced Materials Science (RCAMS) King Khalid University  Abha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Alsolami","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science King Khalid University  Abha Asir Saudi 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M.Butt et\u00a0al.2023.\u201cAmelioration of Rheumatoid Arthritis in Rats by 4\u2010Allylanisole Through Modulation of Inflammatory Mediator.\u201dhttps:\/\/doi.org\/10.21203\/rs.3.rs\u20103235676\/v1.","DOI":"10.21203\/rs.3.rs-3235676\/v1"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.10.5227"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-017-1053-3"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-023-01374-y"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1279215"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.806075"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2024.2348575"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-024-01512-0"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-025-04153-4"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpbi.5"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0294236"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2006.11.039"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-024-01153-1"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-018-1713-x"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0324060"}],"container-title":["Food Science &amp; Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/fsn3.72328","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/fsn3.72328","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/fsn3.72328","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:21:17Z","timestamp":1792509677000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/fsn3.72328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":69,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/fsn3.72328"],"URL":"https:\/\/doi.org\/10.1002\/fsn3.72328","archive":["Portico"],"relation":{},"ISSN":["2048-7177","2048-7177"],"issn-type":[{"value":"2048-7177","type":"print"},{"value":"2048-7177","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2025-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72328"}}