{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T07:45:16Z","timestamp":1782632716862,"version":"3.54.5"},"reference-count":46,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Natural Science Foundation of Jiangsu Province, China","award":["BK20210077"],"award-info":[{"award-number":["BK20210077"]}]},{"name":"Basic Research Project of Xuzhou city","award":["KC22010"],"award-info":[{"award-number":["KC22010"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32302865"],"award-info":[{"award-number":["32302865"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Int Med Res"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Luteolin, a natural flavonoid, exhibits anticancer effects; however, its mechanisms of action are unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective computational study combined network pharmacology, molecular docking, and molecular dynamics simulation to explore luteolin\u2019s anticancer mechanisms in five types of cancers, including breast, lung, colorectal, gastric, and liver cancers. Network pharmacology helps uncover multi-target interactions in complex diseases. Public databases were used to build compound\u2013target, target\u2013disease, and protein\u2013protein interaction networks. Molecular docking and dynamics simulations validated luteolin\u2019s binding to AKT1. The Clinical Proteomic Tumor Analysis Consortium dataset and Human Protein Atlas database were used to assess AKT1 expression in cancer versus normal tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Topological analysis identified\n                      <jats:italic toggle=\"yes\">AKT1<\/jats:italic>\n                      (a PI3\u2005K\/AKT pathway kinase) as a hub gene linked to apoptosis, cell cycle, and tumor suppression. Molecular studies confirmed strong luteolin\u2013AKT1 binding. Clinical Proteomic Tumor Analysis Consortium and Human Protein Atlas data showed that compared with normal tissues, higher AKT1 expression was present in lung, gastric, and breast cancers and lower expression was observed in liver and colorectal cancers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The anticancer effects exerted by luteolin may involve AKT1 signaling modulation. Network pharmacology aids in revealing multi-target mechanisms of natural compounds, supporting further research on the therapeutic potential of luteolin.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03000605261460317","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:40:45Z","timestamp":1782369645000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Network pharmacology and bioinformatics analysis\u2013based strategy for exploring the mechanisms of luteolin in the treatment of five types of cancer: A retrospective computational study"],"prefix":"10.1177","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0608-3202","authenticated-orcid":false,"given":"Haixu","family":"Xu","sequence":"first","affiliation":[{"name":"Xuzhou University of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Xuzhou University of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chendong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Xuzhou University of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Xuzhou University of Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sha","sequence":"additional","affiliation":[{"name":"Xuzhou Central Hospital, Southeast University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26216452"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/0113816128313713240628063301"},{"key":"e_1_3_3_4_2","first-page":"14:","article-title":"Mechanism of luteolin against non-small-cell lung cancer: a study based on network pharmacology, molecular docking, molecular dynamics simulation, and in vitro experiments","author":"Zhang JH","year":"2024","unstructured":"Zhang JH, Li CL, Li WY, et al. Mechanism of luteolin against non-small-cell lung cancer: a study based on network pharmacology, molecular docking, molecular dynamics simulation, and in vitro experiments. Front Oncol 2024: 14: 1471109.","journal-title":"Front Oncol"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00702-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1039\/C8FO00033F"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26284"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-019-0238-y"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16568"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2021.05.019"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-017-1151-6"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.118"},{"key":"e_1_3_3_13_2","article-title":"Lead drug discover strategies from natural medicines based on network pharmacology","volume":"11","author":"Ma JH S","year":"2023","unstructured":"Ma JH S, Hou J, Liu S, et al. Lead drug discover strategies from natural medicines based on network pharmacology. Med Res Arch 2023; 11: 10.","journal-title":"Med Res Arch"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.2174\/0113816128328547240827045955"},{"key":"e_1_3_3_15_2","article-title":"An integrated approach of network pharmacology, molecular docking, and experimental verification uncovers kaempferol as the effective modulator of HSD17B1 for treatment of endometrial cancer","volume":"21","author":"Ruan GY","year":"2023","unstructured":"Ruan GY, Ye LX, Lin JS, et al. An integrated approach of network pharmacology, molecular docking, and experimental verification uncovers kaempferol as the effective modulator of HSD17B1 for treatment of endometrial cancer. J Transl Med 2023; 21: 204.","journal-title":"J Transl Med"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106657"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153714"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz382"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/02648725.2023.2193048"},{"key":"e_1_3_3_20_2","doi-asserted-by":"crossref","unstructured":"Stelzer GRN Rosen N Plaschkes I et al. The GeneCards suite: from gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics 2016; 54: 1.30.1\u20131.30.33.","DOI":"10.1002\/cpbi.5"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62407"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab953"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-010-9352-6"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.051"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.2c01504"},{"key":"e_1_3_3_26_2","doi-asserted-by":"crossref","unstructured":"Thiagarajan M. Abstract 2129: CPTAC: biospecimen accrual for proteogenomics. In: Conference: Proceedings: AACR Annual Meeting 2019 Atlanta Georgia March 29\u2013April 3 2019; Atlanta GA pp. 2129.","DOI":"10.1158\/1538-7445.AM2019-2129"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-147-8-200710160-00010"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-023-04084-8"},{"key":"e_1_3_3_29_2","article-title":"Identification of SRC, AKT1 and MAPK3 as therapeutic targets of apigenin and luteolin in colorectal and colon carcinoma through network pharmacology","volume":"67","author":"Hon KW","year":"2025","unstructured":"Hon KW, Nag S, Stany BK, et al. Identification of SRC, AKT1 and MAPK3 as therapeutic targets of apigenin and luteolin in colorectal and colon carcinoma through network pharmacology. Food Biosci 2025; 67: 106313.","journal-title":"Food Biosci"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-023-03046-x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1450847"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S386941"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/7765658"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7044"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph18111660"},{"key":"e_1_3_3_36_2","article-title":"Improving oral bioavailability of luteolin nanocrystals by surface modification of sodium dodecyl sulfate","author":"Liu JL","unstructured":"Liu JL, Sun YB, Cheng M, et al. Improving oral bioavailability of luteolin nanocrystals by surface modification of sodium dodecyl sulfate. AAPS PharmSciTech 2021; 22: 133.","journal-title":"AAPS PharmSciTech"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2019.04.044"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpta.2025.100833"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15061592"},{"key":"e_1_3_3_40_2","doi-asserted-by":"crossref","DOI":"10.1007\/s12032-021-01508-8","article-title":"Luteolin and cancer metastasis suppression: Focus on the role of epithelial to mesenchymal transition","volume":"38","author":"Hussain Y","year":"2021","unstructured":"Hussain Y, Cui JH, Khan H, et al. Luteolin and cancer metastasis suppression: Focus on the role of epithelial to mesenchymal transition. Med Oncol 2021; 38: 66.","journal-title":"Med Oncol"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00459"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-016-1933-1"},{"key":"e_1_3_3_43_2","first-page":"1025540","article-title":"Network pharmacology provides new methods and references for TCM research","volume":"13","author":"Zhang YaL X","year":"2022","unstructured":"Zhang YaL X, Wang H, Chen J. Network pharmacology provides new methods and references for TCM research. Front Pharmacol 2022; 13: 1025540.","journal-title":"Front Pharmacol"},{"key":"e_1_3_3_44_2","first-page":"345","article-title":"Luteolin inhibits the proliferation of lung cancer cells by binding to AR phosphorylation sites","volume":"355","author":"Qing YaF Y","year":"2023","unstructured":"Qing YaF Y, Hua G. Luteolin inhibits the proliferation of lung cancer cells by binding to AR phosphorylation sites. J Pharmacol Exp Ther 2023; 355: 345\u2013356.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_3_45_2","doi-asserted-by":"crossref","DOI":"10.1186\/s41065-025-00434-3","article-title":"The mechanism of Weiqi decoction treating gastric cancer: a work based on network pharmacology and experimental verification","volume":"162","author":"Huang X","year":"2025","unstructured":"Huang X, Pan ZH, Shen L, et al. The mechanism of Weiqi decoction treating gastric cancer: a work based on network pharmacology and experimental verification. Hereditas 2025; 162: 67.","journal-title":"Hereditas"},{"key":"e_1_3_3_46_2","article-title":"Luteolin enhances Transepithelial sodium transport in the lung alveolar model: integrating network pharmacology and mechanism study","author":"Chen L","year":"2023","unstructured":"Chen L, Yu T, Zhai YM, et al. Luteolin enhances Transepithelial sodium transport in the lung alveolar model: integrating network pharmacology and mechanism study. Int J Mol Sci 2023; 24: 10122.","journal-title":"Int J Mol Sci"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2022.2134426"}],"container-title":["Journal of International Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03000605261460317","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/03000605261460317","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03000605261460317","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T07:18:58Z","timestamp":1782631138000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/03000605261460317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1177\/03000605261460317"],"URL":"https:\/\/doi.org\/10.1177\/03000605261460317","relation":{},"ISSN":["0300-0605","1473-2300"],"issn-type":[{"value":"0300-0605","type":"print"},{"value":"1473-2300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"article-number":"03000605261460317"}}