{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:25:06Z","timestamp":1787315106716,"version":"build-2736575974"},"reference-count":72,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["ASSAY and Drug Development Technologies"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">\n                      Colon cancer ranks among the most prevalent malignancies worldwide and contributes substantially to cancer-related mortality. This study employed an integrated approach to evaluate the chemopreventive effects of Boeravinone B (BB) and Resveratrol (REV), administered individually and in combination, in the azoxymethane (AOM)-induced rat model of colon cancer, with particular emphasis on cytokine signaling pathways and mitochondrial regulation of apoptosis. The combination of BB (15 mg\/kg) and REV (8 mg\/kg) exhibited greater efficacy than either treatment alone. These combined treatments (BB + REV) significantly reduced pro-inflammatory cytokines (IL-1\u03b2, IL-6, tumor necrosis factor-alpha [TNF-\u03b1]), nitro-oxidative stress indicators (NO, iNOS), and histological damage, while promoting mitochondria-mediated apoptosis via modulation of BAX and BCL2. Network analysis revealed that centrality metrics (betweenness, closeness, degree, and stress centrality), identified STAT3, SOCS3, JAK2, BAX, and BCL2 as key hub proteins involved in cytokine signaling and apoptotic pathways. These nodes exhibited the highest centrality values (betweenness: 0.046667 for STAT3\/SOCS3\/JAK2; degree: 10 for all five proteins), indicating their pivotal roles as therapeutic targets. Molecular docking revealed favorable binding affinities of BB for SOCS3 (\u22129.0 kcal\/mol), BAX (\u22129.0 kcal\/mol), JAK2 (\u22128.1 kcal\/mol), and STAT3 (\u22127.8 kcal\/mol). In comparison, REV exhibited its highest binding affinities for SOCS3 (\u22127.2 kcal\/mol) and BAX (\u22127.0 kcal\/mol). These findings identify SOCS3, BAX, JAK2, and STAT3 as potential molecular targets mediating the combined treatment\u2019s anti-inflammatory and pro-apoptotic effects. This integrated\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                      study showed that combined BB and REV exerted a stronger chemopreventive effect against AOM-induced colon cancer via complementary mechanisms: restoring mitochondrial adenosine triphosphate synthase (ATPase) activity, suppressing biomarkers of inflammation, nitro-oxidative stress, and apoptosis, with strong binding affinities. These findings support repurposing BB and REV as a multitargeted combination therapy against colon cancer.\n                    <\/jats:italic>\n                  <\/jats:p>","DOI":"10.1177\/1540658x261467596","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:16:58Z","timestamp":1784798218000},"page":"560-581","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated\n                    <i>In Vivo<\/i>\n                    and\n                    <i>In Silico<\/i>\n                    Approaches for Targeting JAK2\/STAT3\/SOCS3: Repurposing Boeravinone B and Resveratrol as Chemopreventive Agents in Colon Cancer"],"prefix":"10.1177","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8414-5498","authenticated-orcid":false,"given":"Shabnoor","family":"Iqbal","sequence":"first","affiliation":[{"name":"AMITD Department of Pharmacology, School of Clinical Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa."},{"name":"Department of Physiology, Government College University Faisalabad, Faisalabad, Pakistan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usman","family":"Khan","sequence":"additional","affiliation":[{"name":"National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"e_1_3_4_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/GO.22.00429"},{"key":"e_1_3_4_3_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2018.0021"},{"key":"e_1_3_4_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_3_4_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare13131512"},{"key":"e_1_3_4_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/10781552231178293"},{"key":"e_1_3_4_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-025-01676-0"},{"key":"e_1_3_4_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ans.18046"},{"key":"e_1_3_4_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyae013"},{"key":"e_1_3_4_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0126-x"},{"key":"e_1_3_4_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00412.2025"},{"key":"e_1_3_4_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1218046"},{"key":"e_1_3_4_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu9060572"},{"key":"e_1_3_4_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/0118715206354948250226103832"},{"key":"e_1_3_4_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2014.07.007"},{"key":"e_1_3_4_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12476"},{"key":"e_1_3_4_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods14071091"},{"key":"e_1_3_4_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods9030340"},{"key":"e_1_3_4_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.150186"},{"key":"e_1_3_4_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/837042"},{"key":"e_1_3_4_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-1486"},{"key":"e_1_3_4_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26144367"},{"key":"e_1_3_4_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2022.121605"},{"issue":"12","key":"e_1_3_4_24_1","first-page":"4183","article-title":"Boeravinone B a natural rotenoid exerts anticancer activity via inducing internalization and degradation of inactivated EGFR and ErbB2 in human colon cancer cells","volume":"10","author":"Huang Y","year":"2018","unstructured":"23.Huang Y, , Sun Y, , Wang WW, et al. Boeravinone B a natural rotenoid exerts anticancer activity via inducing internalization and degradation of inactivated EGFR and ErbB2 in human colon cancer cells. Am J Transl Res 2018;10(12):4183\u20134192.","journal-title":"Am J Transl Res"},{"key":"e_1_3_4_25_1","doi-asserted-by":"publisher","DOI":"10.21037\/jgo-22-733"},{"key":"e_1_3_4_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24244506"},{"key":"e_1_3_4_27_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2023-0054"},{"key":"e_1_3_4_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05870.x"},{"key":"e_1_3_4_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1287505"},{"key":"e_1_3_4_30_1","volume-title":"Guide for the care and use of laboratory animals","author":"National Research Council","year":"2011","unstructured":"29.National Research Council. Guide for the care and use of laboratory animals, 8th ed. National Academies Press; 2011; doi: 10.17226\/12910","edition":"8"},{"key":"e_1_3_4_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-50947-y"},{"key":"e_1_3_4_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers4030673"},{"key":"e_1_3_4_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb45020057"},{"key":"e_1_3_4_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutos.2022.01.008"},{"key":"e_1_3_4_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apjtm.2017.03.026"},{"key":"e_1_3_4_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/07482337211034711"},{"key":"e_1_3_4_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-3247-5_7"},{"key":"e_1_3_4_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11091401"},{"key":"e_1_3_4_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327120930125"},{"key":"e_1_3_4_40_1","doi-asserted-by":"publisher","DOI":"10.1177\/09603271231178015"},{"key":"e_1_3_4_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-8-S4-S11"},{"key":"e_1_3_4_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.24309"},{"key":"e_1_3_4_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjbs.2022.103458"},{"key":"e_1_3_4_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-822312-3.00019-9"},{"key":"e_1_3_4_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030535"},{"key":"e_1_3_4_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27306"},{"key":"e_1_3_4_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-024-12715-7"},{"key":"e_1_3_4_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-76825-9"},{"issue":"4","key":"e_1_3_4_49_1","first-page":"348","article-title":"Polyphenols, dietary sources and bioavailability","volume":"43","author":"D\u2019archivio M","year":"2007","unstructured":"48.D\u2019archivio M, , Filesi C, , DI Benedetto R, et al. Polyphenols, dietary sources and bioavailability. Ann Ist Super Sanita 2007;43(4):348\u2013361.","journal-title":"Ann Ist Super Sanita"},{"key":"e_1_3_4_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2014.04.004"},{"key":"e_1_3_4_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules20022728"},{"key":"e_1_3_4_52_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026621666211105093658"},{"key":"e_1_3_4_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu8080515"},{"key":"e_1_3_4_54_1","article-title":"Non-canonical nitric oxide signalling and DNA methylation: Inflammation induced epigenetic alterations and potential drug targets","author":"Switzer CH","year":"2023","unstructured":"53.Switzer CH. Non-canonical nitric oxide signalling and DNA methylation: Inflammation induced epigenetic alterations and potential drug targets. Br J Pharmacol 2023.","journal-title":"Br J Pharmacol"},{"issue":"2","key":"e_1_3_4_55_1","first-page":"153","article-title":"Endothelial Nitric Oxide Synthase (eNOS) and the cardiovascular system: In physiology and in disease states","volume":"15","author":"Tran N","year":"2022","unstructured":"54.Tran N, , Garcia T, , Aniqa M, et al. Endothelial Nitric Oxide Synthase (eNOS) and the cardiovascular system: In physiology and in disease states. Am J Biomed Sci Res 2022;15(2):153\u2013177.","journal-title":"Am J Biomed Sci Res"},{"key":"e_1_3_4_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.806470"},{"key":"e_1_3_4_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sajb.2024.09.011"},{"key":"e_1_3_4_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16620"},{"key":"e_1_3_4_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22138"},{"key":"e_1_3_4_60_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.119.018440"},{"key":"e_1_3_4_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2015.01.013"},{"key":"e_1_3_4_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnesp.2022.01.004"},{"key":"e_1_3_4_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0731-6"},{"key":"e_1_3_4_64_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109048"},{"key":"e_1_3_4_65_1","doi-asserted-by":"publisher","DOI":"10.3390\/diseases9040079"},{"key":"e_1_3_4_66_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.2c00651"},{"key":"e_1_3_4_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-72577-8"},{"key":"e_1_3_4_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-012-9570-1"},{"key":"e_1_3_4_69_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6CP01555G"},{"key":"e_1_3_4_70_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules191117154"},{"key":"e_1_3_4_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05842.x"},{"key":"e_1_3_4_72_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712799945085"},{"issue":"3","key":"e_1_3_4_73_1","first-page":"e1353","article-title":"Resveratrol-loaded nanomedicines for cancer applications","volume":"4","author":"Annaji M","year":"2021","unstructured":"72.Annaji M, , Poudel I, , Boddu SHS, et al. Resveratrol-loaded nanomedicines for cancer applications. Cancer Rep (Hoboken) 2021;4(3):e1353.","journal-title":"Cancer Rep (Hoboken)"}],"container-title":["ASSAY and Drug Development Technologies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1540658X261467596","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1540658X261467596","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1540658X261467596","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:46:37Z","timestamp":1787312797000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1540658X261467596"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":72,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,10,1]]}},"alternative-id":["10.1177\/1540658X261467596"],"URL":"https:\/\/doi.org\/10.1177\/1540658x261467596","relation":{},"ISSN":["1540-658X","1557-8127"],"issn-type":[{"value":"1540-658X","type":"print"},{"value":"1557-8127","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]}}}