{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:03:33Z","timestamp":1787069013730,"version":"build-2736575974"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82160735"],"award-info":[{"award-number":["82160735"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2025,8]]},"DOI":"10.1016\/j.jep.2025.120182","type":"journal-article","created":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T18:22:01Z","timestamp":1750530121000},"page":"120182","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Mechanistic analysis of anti-prostate cancer and toxicity-reducing effects of bufadienolides extracts: Comparative efficacy and safety with isolated bioactive compounds"],"prefix":"10.1016","volume":"352","author":[{"given":"Rong","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingmei","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Seon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daihong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenguang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9838-0990","authenticated-orcid":false,"given":"Juan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.jep.2025.120182_bib1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1186\/s12916-022-02457-3","article-title":"The lipidomic profile of the tumoral periprostatic adipose tissue reveals alterations in tumor cell's metabolic crosstalk","volume":"20","author":"Altuna-Coy","year":"2022","journal-title":"BMC Med."},{"key":"10.1016\/j.jep.2025.120182_bib2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jep.2016.03.049","article-title":"Venenum bufonis induces rat neuroinflammation by activiating NF-\u03baB pathway and attenuation of BDNF","volume":"186","author":"Bi","year":"2016","journal-title":"J. Ethnopharmacol."},{"issue":"6","key":"10.1016\/j.jep.2025.120182_bib3","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/S0024-3205(02)02302-0","article-title":"Effects of Chan Su, a traditional Chinese medicine, on the calcium transients of isolated cardiomyocytes: cardiotoxicity due to more than Na, K-ATPase blocking","volume":"72","author":"Bick","year":"2002","journal-title":"Life Sci."},{"key":"10.1016\/j.jep.2025.120182_bib4","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.phrs.2017.07.009","article-title":"Arenobufagin inhibits prostate cancer epithelial-mesenchymal transition and metastasis by down-regulating \u03b2-catenin","volume":"123","author":"Chen","year":"2017","journal-title":"Pharmacol. Res."},{"issue":"9","key":"10.1016\/j.jep.2025.120182_bib5","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1080\/15376516.2020.1805664","article-title":"Oxidative stress-mediated mitochondrial pathway-dependent apoptosis is induced by silica nanoparticles in H9c2 cardiomyocytes","volume":"30","author":"Cui","year":"2020","journal-title":"Toxicol. Mech. Methods"},{"key":"10.1016\/j.jep.2025.120182_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.tiv.2023.105566","article-title":"Bufadienolides from the Bufo viridis toad venom exert cytotoxic effects on cancer cells by inducing cell apoptosis and cell cycle arrest","volume":"89","author":"Dong","year":"2023","journal-title":"Toxicol. Vitro"},{"key":"10.1016\/j.jep.2025.120182_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2024.118751","article-title":"Study on the underlying mechanism of Huachansu capsule induced cardiotoxicity of normal rat by integrating transcriptomics, metabolomics and network toxicology","volume":"336","author":"Fan","year":"2025","journal-title":"J. Ethnopharmacol."},{"issue":"1","key":"10.1016\/j.jep.2025.120182_bib8","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1186\/s12944-024-02301-y","article-title":"Rod-shaped mesoporous silica nanoparticles reduce bufalin cardiotoxicity and inhibit colon cancer by blocking lipophagy","volume":"23","author":"Fan","year":"2024","journal-title":"Lipids Health Dis."},{"issue":"3","key":"10.1016\/j.jep.2025.120182_bib9","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.3892\/etm.2021.10447","article-title":"Effects of low-dose bufalin combined with hydroxycamptothecin on human castration-resistant prostate cancer xenografts in nude mice","volume":"22","author":"Gu","year":"2021","journal-title":"Exp. Ther. Med."},{"issue":"12","key":"10.1016\/j.jep.2025.120182_bib10","doi-asserted-by":"crossref","DOI":"10.3390\/ph17121696","article-title":"Bufadienolides from chansu injection synergistically enhances the antitumor effect of erlotinib by inhibiting the KRAS pathway in pancreatic cancer","volume":"17","author":"Guo","year":"2024","journal-title":"Pharmaceuticals"},{"issue":"1","key":"10.1016\/j.jep.2025.120182_bib11","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/s12967-018-1580-x","article-title":"Resibufogenin suppresses colorectal cancer growth and metastasis through RIP3-mediated necroptosis","volume":"16","author":"Han","year":"2018","journal-title":"J. Transl. Med."},{"issue":"1","key":"10.1016\/j.jep.2025.120182_bib12","doi-asserted-by":"crossref","DOI":"10.3390\/toxins11010014","article-title":"In vitro cytotoxicity induced by the bufadienolides 1\u03b1,2\u03b1-Epoxyscillirosidine and Lanceotoxin B on rat myocardial and mouse neuroblastoma cell lines","volume":"11","author":"Henn","year":"2019","journal-title":"Toxins"},{"issue":"5","key":"10.1016\/j.jep.2025.120182_bib13","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1021\/acschembio.4c00089","article-title":"Cytochrome P450 mining for bufadienolide diversification","volume":"19","author":"Lei","year":"2024","journal-title":"ACS Chem. Biol."},{"issue":"12","key":"10.1016\/j.jep.2025.120182_bib14","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1038\/s41590-019-0514-y","article-title":"IL-17 receptor-based signaling and implications for disease","volume":"20","author":"Li","year":"2019","journal-title":"Nat. Immunol."},{"issue":"7","key":"10.1016\/j.jep.2025.120182_bib15","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/pros.24117","article-title":"Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF-1 upregulation of TUBB2B beta-tubulin isoform","volume":"81","author":"Liotti","year":"2021","journal-title":"Prostate"},{"issue":"3","key":"10.1016\/j.jep.2025.120182_bib16","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/bjc.2012.283","article-title":"Prospective randomised evaluation of traditional Chinese medicine combined with chemotherapy: a randomised phase II study of wild toad extract plus gemcitabine in patients with advanced pancreatic adenocarcinomas","volume":"107","author":"Meng","year":"2012","journal-title":"Br. J. Cancer"},{"issue":"7","key":"10.1016\/j.jep.2025.120182_bib17","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1158\/1541-7786.MCR-21-0099","article-title":"NF-\u03baB blockade with oral administration of dimethylaminoparthenolide (DMAPT), delays prostate cancer resistance to Androgen Receptor (AR) inhibition and inhibits AR variants","volume":"19","author":"Morel","year":"2021","journal-title":"Mol. Cancer Res."},{"issue":"6","key":"10.1016\/j.jep.2025.120182_bib18","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1021\/np400034d","article-title":"Structure-activity relationship analysis of bufadienolide-induced in vitro growth inhibitory effects on mouse and human cancer cells","volume":"76","author":"Moreno","year":"2013","journal-title":"J. Nat. Prod."},{"issue":"3\u20134","key":"10.1016\/j.jep.2025.120182_bib19","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1142\/S0192415X92000254","article-title":"Pharmacological actions of \"kyushin,\" a drug containing toad venom: cardiotonic and arrhythmogenic effects, and excitatory effect on respiration","volume":"20","author":"Morishita","year":"1992","journal-title":"Am. J. Chin. Med."},{"key":"10.1016\/j.jep.2025.120182_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2022.116761","article-title":"A novel survivin dimerization inhibitor without a labile hydrazone linker induces spontaneous apoptosis and synergizes with docetaxel in prostate cancer cells","volume":"65","author":"Peery","year":"2022","journal-title":"Bioorg. Med. Chem."},{"issue":"1","key":"10.1016\/j.jep.2025.120182_bib21","doi-asserted-by":"crossref","DOI":"10.3390\/molecules27010051","article-title":"Novel strategies for solubility and bioavailability enhancement of bufadienolides","volume":"27","author":"Shao","year":"2021","journal-title":"Molecules"},{"key":"10.1016\/j.jep.2025.120182_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155914","article-title":"Multi-omics reveals bufadienolide Q-markers of Bufonis Venenum based on antitumor activity and cardiovascular toxicity in zebrafish","volume":"133","author":"Sun","year":"2024","journal-title":"Phytomedicine"},{"issue":"36","key":"10.1016\/j.jep.2025.120182_bib23","article-title":"Clinical efficacy and safety of Huachansu injection combination with platinum-based chemotherapy for advanced non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials","volume":"100","author":"Tan","year":"2021","journal-title":"Medicine (Baltim.)"},{"key":"10.1016\/j.jep.2025.120182_bib24","article-title":"Novel stereoselective bufadienolides reveal new insights into the requirements for Na(+), K(+)-ATPase inhibition by cardiotonic steroids","volume":"6","author":"Tang","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jep.2025.120182_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2023.116695","article-title":"Network pharmacology and metabolomics elucidate the underlying mechanisms of Venenum bufonis in the treatment of colorectal cancer","volume":"317","author":"Tao","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120182_bib26","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/546210","article-title":"Bufalin induces mitochondria-dependent apoptosis in pancreatic and oral cancer cells by downregulating hTERT expression via activation of the JNK\/p38 pathway","volume":"2015","author":"Tian","year":"2015","journal-title":"Evid Based Complement Alternat Med"},{"issue":"4","key":"10.1016\/j.jep.2025.120182_bib27","first-page":"532","article-title":"Induction of apoptosis by arsenic trioxide and hydroxy camptothecin in gastriccancer cells in vitro","volume":"6","author":"Tu","year":"2000","journal-title":"World J. Gastroenterol."},{"issue":"511","key":"10.1016\/j.jep.2025.120182_bib28","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.aao4910","article-title":"Structural principles of tumor necrosis factor superfamily signaling","volume":"11","author":"Vanamee","year":"2018","journal-title":"Sci. Signal."},{"issue":"5","key":"10.1016\/j.jep.2025.120182_bib29","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1158\/0008-5472.CAN-13-2939","article-title":"Bufalin is a potent small-molecule inhibitor of the steroid receptor coactivators SRC-3 and SRC-1","volume":"74","author":"Wang","year":"2014","journal-title":"Cancer Res."},{"issue":"11","key":"10.1016\/j.jep.2025.120182_bib30","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0113272","article-title":"Resibufogenin and cinobufagin activate central neurons through an ouabain-like action","volume":"9","author":"Wang","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.jep.2025.120182_bib31","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jep.2019.03.042","article-title":"Venenum bufonis: an overview of its traditional use, natural product chemistry, pharmacology, pharmacokinetics and toxicology","volume":"237","author":"Wei","year":"2019","journal-title":"J. Ethnopharmacol."},{"issue":"9","key":"10.1016\/j.jep.2025.120182_bib32","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1111\/j.2042-7158.1983.tb04337.x","article-title":"Comparison of digoxin-induced cardiac toxicity in resistant and sensitive species","volume":"35","author":"Weinhouse","year":"1983","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.jep.2025.120182_bib33","article-title":"Resibufogenin suppresses triple-negative breast cancer angiogenesis by blocking VEGFR2-Mediated signaling pathway","volume":"12","author":"Yang","year":"2021","journal-title":"Front. Pharmacol."},{"issue":"7","key":"10.1016\/j.jep.2025.120182_bib34","doi-asserted-by":"crossref","first-page":"4895","DOI":"10.1007\/s00210-023-02916-5","article-title":"Arenobufagin regulates the p62-Keap1-Nrf2 pathway to induce autophagy-dependent ferroptosis in HepG2 cells","volume":"397","author":"Yang","year":"2024","journal-title":"Naunyn-Schmiedebergs Arch Pharmacol"},{"issue":"7","key":"10.1016\/j.jep.2025.120182_bib35","doi-asserted-by":"crossref","DOI":"10.3390\/molecules29071571","article-title":"Isolation, identification and chemical modification of bufadienolides from Bufo melanostictus schneider and their cytotoxic activities against prostate cancer cells","volume":"29","author":"Ye","year":"2024","journal-title":"Molecules"},{"key":"10.1016\/j.jep.2025.120182_bib36","doi-asserted-by":"crossref","DOI":"10.3389\/fchem.2023.1137547","article-title":"Toad venom-derived bufadienolides and their therapeutic application in prostate cancers: current status and future directions","volume":"11","author":"Ye","year":"2023","journal-title":"Front. Chem."},{"key":"10.1016\/j.jep.2025.120182_bib37","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2023.1274336","article-title":"An overview of the past decade of bufalin in the treatment of refractory and drug-resistant cancers: current status, challenges, and future perspectives","volume":"14","author":"Ye","year":"2023","journal-title":"Front. Pharmacol."},{"issue":"1","key":"10.1016\/j.jep.2025.120182_bib38","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s40164-021-00243-0","article-title":"19-Hydroxybufalin inhibits non-small cell lung cancer cell proliferation and promotes cell apoptosis via the Wnt\/\u03b2-catenin pathway","volume":"10","author":"Yu","year":"2021","journal-title":"Exp. Hematol. Oncol."},{"issue":"5","key":"10.1016\/j.jep.2025.120182_bib39","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1111\/cas.14345","article-title":"Bufalin reverses multidrug resistance by regulating stemness through the CD133\/nuclear factor-\u03baB\/MDR1 pathway in colorectal cancer","volume":"111","author":"Zhan","year":"2020","journal-title":"Cancer Sci."},{"issue":"2","key":"10.1016\/j.jep.2025.120182_bib40","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s11306-022-01968-7","article-title":"Multi-omics profiling of PC-3 cells reveals bufadienolides-induced lipid metabolic remodeling by regulating long-chain lipids synthesis and hydrolysis","volume":"19","author":"Zhang","year":"2023","journal-title":"Metabolomics"},{"key":"10.1016\/j.jep.2025.120182_bib41","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.freeradbiomed.2022.01.009","article-title":"Bufotalin induces ferroptosis in non-small cell lung cancer cells by facilitating the ubiquitination and degradation of GPX4","volume":"180","author":"Zhang","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.jep.2025.120182_bib42","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1479-5876-12-57","article-title":"Bufalin attenuates the stage and metastatic potential of hepatocellular carcinoma in nude mice","volume":"12","author":"Zhang","year":"2014","journal-title":"J. Transl. Med."},{"issue":"1","key":"10.1016\/j.jep.2025.120182_bib43","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1038\/s41467-019-09601-3","article-title":"Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation","volume":"10","author":"Zheng","year":"2019","journal-title":"Nat. Commun."}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874125008712?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874125008712?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T07:49:23Z","timestamp":1771832963000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874125008712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":43,"alternative-id":["S0378874125008712"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2025.120182","relation":{},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mechanistic analysis of anti-prostate cancer and toxicity-reducing effects of bufadienolides extracts: Comparative efficacy and safety with isolated bioactive compounds","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2025.120182","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"120182"}}