{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T16:19:35Z","timestamp":1787674775250,"version":"build-2784847793"},"reference-count":56,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hepatomegaly in hemolytic disorders, including in thalassemia, is a common complication, primarily due to hemosiderosis and activation of extramedullary hematopoiesis. Globin chain imbalance leads to chronic hemolysis and ineffective erythropoiesis, which are associated with suppression of hepcidin expression. Reduced hepcidin levels may increase iron absorption and accumulation, contributing to oxidative stress and liver tissue damage. Iron chelation therapy, such as deferipron, is effective but has side effects, so safer alternatives are needed. Sappanwood (\n                      <jats:italic>Caesalpinia sappan<\/jats:italic>\n                      L.) contains the active compound brazilin, which chelates iron and exhibits antioxidant activity, potentially reducing oxidative stress, improving iron metabolism disorders, and reducing hepatomegaly. This study aims to evaluate the potential of sappanwood extract as a natural iron chelator and antioxidant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This experimental study used male Wistar rats (180\u2013250\u2009g) with a model of iron overload hemolytic anemia, which were divided into normal controls, negative controls (phenylhydrazine 40\u2009mg\/kg\u2009BW), positive controls (deferiprone 75\u2009mg\/kg\u2009BW), and sappanwood extract (SWE) treatment (50, 100, 200\u2009mg\/kg\u2009BW) for 14\u2009days. The parameters measured included iron metabolism, hepatomegaly, liver function, hepcidin\u2010related gene expression, and oxidative stress. Data were analyzed using ANOVA, with\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05 considered significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The results showed that administration of 100\u2009mg\/kg BW SWE provided optimal improvement (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), including reductions in hepatomegaly, SGPT, hemosiderin, lipid peroxidation, bilirubin, extramedullary hematopoiesis, and modulation in iron\u2010related gene expression, including\n                      <jats:italic>Hamp, Bmp6, Epo<\/jats:italic>\n                      , and\n                      <jats:italic>Ftl<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings confirm the potential of sappanwood as a potential therapeutic candidate for the management of iron overload in thalassemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70264","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T06:01:27Z","timestamp":1785996087000},"page":"1674-1689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sappanwood extract modulates hepatic structure\u2013function in hepatomegaly and hepcidin related iron regulatory pathways in a phenylhydrazine induced hemolytic anemia rat model relevant to thalassemia"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8606-8686","authenticated-orcid":false,"given":"Mohammad Indra","family":"Pratama","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Mathematics and Natural Sciences Universitas Padjadjaran  Jatinangor Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0640-1273","authenticated-orcid":false,"given":"Ratu","family":"Safitri","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Mathematics and Natural Sciences Universitas Padjadjaran  Jatinangor Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desak Made","family":"Malini","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Mathematics and Natural Sciences Universitas Padjadjaran  Jatinangor Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0452-4157","authenticated-orcid":false,"given":"Mas Rizky A. A.","family":"Syamsunarno","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine Universitas Padjadjaran  Jatinangor Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9392-8374","authenticated-orcid":false,"given":"Mohammad","family":"Ghozali","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine Universitas Padjadjaran  Jatinangor Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7470-1155","authenticated-orcid":false,"given":"Madihah","family":"Madihah","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Mathematics and Natural Sciences Universitas Padjadjaran  Jatinangor Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13051465"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.5812\/ijp.2004"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.29309\/tpmj\/2024.31.02.7729"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0b013e328337b52f"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241612654"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/26348535221103560"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.4621"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phoj.2022.11.001"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/thalassrep13030017"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.4084\/MJHID.2022.052"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1717"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-06-857995"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.15416\/pcpr.v1i3.15218"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16071016"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0211942"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.14740\/jh642"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-790121"},{"issue":"2","key":"e_1_2_13_19_1","first-page":"2023","article-title":"Review artikel: potensi Kayu Secang (Caesalpinia sappan L.) sebagai antihipertensi","volume":"1","author":"Sunusi PN","year":"2023","journal-title":"Makassar Nat Prod J"},{"key":"e_1_2_13_20_1","first-page":"1","article-title":"A potential use of Brazilin from Caesalpinia sappan L. heartwood as antioxidant, iron chelator and Jak2 inhibitor for thalassemia: a review","author":"Youngest R","year":"2024","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1355533"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e38213"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcme.2024.03.017"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.30476\/ijms.2024.103099.3629"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1159\/000072913"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202216525"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.121124"},{"issue":"10","key":"e_1_2_13_28_1","first-page":"808","article-title":"Quantitative study of iron metabolism\u2010related genes expression in rat","volume":"26","author":"Qin LY","year":"2013","journal-title":"Biomed Environ Sci"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368915X686850"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.8564265"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10245831"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.06.028"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12871-025-02988-1"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43162-024-00298-5"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.2147\/jbm.s7224"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v13.i11.1688"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.59779\/jiomnepal.1314"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.4137\/CMBD.S3969"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/15353702231191197"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci114934"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.961892"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4146.On-demand"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30117"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.03.033"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/BS9.0000000000000008"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/hs9.0000000000000035"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241310885"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115495"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.091991"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106386"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202050202"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.151621"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(97)00039-2"},{"key":"e_1_2_13_54_1","doi-asserted-by":"crossref","unstructured":"TortiFM TortiSV.Regulation of ferritin genes and protein.2002. [Online].http:\/\/ashpublications.org\/blood\/article\u2010pdf\/99\/10\/3505\/1684486\/h81002003505.pdf","DOI":"10.1182\/blood.V99.10.3505"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-025-02378-6"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.16576"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.4103\/joah.joah_63_22"}],"container-title":["Animal Models and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.70264","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ame2.70264","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.70264","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:25:50Z","timestamp":1787671550000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ame2.70264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":56,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/ame2.70264"],"URL":"https:\/\/doi.org\/10.1002\/ame2.70264","archive":["Portico"],"relation":{},"ISSN":["2576-2095","2576-2095"],"issn-type":[{"value":"2576-2095","type":"print"},{"value":"2576-2095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2026-03-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}