{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:13:20Z","timestamp":1788502400547,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":245,"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"}],"funder":[{"DOI":"10.13039\/501100015690","name":"Universitas Padjadjaran","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015690","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Canadian Journal of Gastroenterology and Hepatology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Iron overload\u2013induced liver fibrosis involves interconnected pathological drivers: ferroptosis\u2010like oxidative injury and dysregulated macrophage polarization. Although\n                    <jats:italic>Caesalpinia sappan<\/jats:italic>\n                    L. possesses well\u2010characterized antioxidant and anti\u2010inflammatory properties, its efficacy against this dual pathological axis has not been experimentally established. This study investigated the hepatoprotective effects of\n                    <jats:italic>C. sappan<\/jats:italic>\n                    wood extract (SWE) in an iron dextran\u2013induced rat model of liver fibrosis. Male Wistar rats received intraperitoneal iron dextran (cumulative dose of 180\u2009mg\/kg BW over 39\u2009days) to induce hepatic iron overload, followed by 28\u2010day oral administration of SWE (25, 50, 75, or 100\u2009mg\/kg BW\/day) or deferasirox (20\u2009mg\/kg BW\/day). Hepatic iron concentration, liver function markers, oxidative stress parameters (MDA, SOD, and GPx4), macrophage polarization markers (CD86 and CD163), inflammatory and fibrogenic mediators (IL\u20106, IL\u201010, TGF\u2010\u03b21, and MMP\u201012), and fibrosis severity were assessed through biochemical, immunohistochemical, and histopathological analyses. SWE was standardized to 25.12% w\/w brazilin by HPLC\u2013PDA. SWE showed dose\u2010related effects with optimal efficacy at intermediate doses, reducing hepatic iron burden, restoring GPx4 activity, suppressing lipid peroxidation, and enhancing antioxidant defense, collectively attenuating ferroptosis\u2010like oxidative injury. Concurrently, SWE reduced M1 macrophage activation (decreased CD86 and IL\u20106) while promoting M2 polarization (increased CD163 and IL\u201010), suppressed TGF\u2010\u03b21\u2010driven fibrogenesis, and restored MMP\u201012\u2013mediated matrix remodeling, resulting in significant reductions in collagen deposition and fibrotic area. SWE performed comparably to deferasirox across most endpoints, with superior MMP\u201012 recovery. SWE simultaneously attenuates ferroptosis\u2010like oxidative injury and restores macrophage polarization balance, establishing it as a mechanistically coherent multitarget candidate for iron overload\u2013induced liver fibrosis with translational potential beyond that of iron chelation alone.\n                  <\/jats:p>","DOI":"10.1155\/cjgh\/3174951","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:38:25Z","timestamp":1788500305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Caesalpinia Sappan<\/i>\n                    Wood Extract Alleviates Ferroptosis\u2010Like Oxidative Injury and Restores Macrophage Polarization Balance in Iron Overload\u2013Induced Liver Fibrosis in Rats"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9392-8374","authenticated-orcid":false,"given":"Mohammad","family":"Ghozali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2626-1579","authenticated-orcid":false,"given":"Jeri Nobia","family":"Purnama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0055-9907","authenticated-orcid":false,"given":"Desak Made","family":"Malini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3856-2071","authenticated-orcid":false,"given":"Erick","family":"Khristian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0640-1273","authenticated-orcid":false,"given":"Ratu","family":"Safitri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v16.i5.671"},{"key":"e_1_2_12_2_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.5152\/tjg.2018.17330","article-title":"Liver Fibrosis","volume":"29","author":"Bataller R.","year":"2018","journal-title":"Turkish Journal of Gastroenterology"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-018-9897-3"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjbs.2017.08.007"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.2147\/jbm.s470177"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2022.11.003"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.08.056"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1155\/cjgh\/1200073"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.11.029"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102892"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu12092784"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.3a0318-108r"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.16092"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ircmb.2022.04.006"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110357"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apjtm.2015.05.014"},{"key":"e_1_2_12_17_2","first-page":"2589","article-title":"Sappan Wood Ethanol Extract (Caesalpinia sappan L.) as Adjuvant and Substitute of Iron Chelator in Acute Iron Overload Rat Model","volume":"10","author":"Pitaloka R. 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