{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T14:41:54Z","timestamp":1793976114613,"version":"4.8.0"},"reference-count":102,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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":["82574730"],"award-info":[{"award-number":["82574730"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008402","name":"Chengdu University of Traditional Chinese Medicine","doi-asserted-by":"publisher","award":["WXLH202405003"],"award-info":[{"award-number":["WXLH202405003"]}],"id":[{"id":"10.13039\/501100008402","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1016\/j.phymed.2026.157858","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:19:21Z","timestamp":1768868361000},"page":"157858","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Hydroxy Safflower Yellow A: A Natural Compound from Carthamus tinctorius L. with Potent Activity Against Liver Fibrosis and Cancer"],"prefix":"10.1016","volume":"153","author":[{"given":"Yuyan","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lvchen","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruotong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2026.157858_bib0001","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/6657639","article-title":"Bioactive Substances in Safflower Flowers and Their Applicability in Medicine and Health-Promoting Foods","volume":"2021","author":"Adamska","year":"2021","journal-title":"Int J Food Sci"},{"key":"10.1016\/j.phymed.2026.157858_bib0002","doi-asserted-by":"crossref","DOI":"10.1155\/2018\/8259280","article-title":"Hydroxysafflor Yellow A: A Promising Therapeutic Agent for a Broad Spectrum of Diseases","volume":"2018","author":"Ao","year":"2018","journal-title":"Evid Based Complement Alternat Med"},{"key":"10.1016\/j.phymed.2026.157858_bib0003","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ejrad.2018.01.025","article-title":"Diagnosis and staging of hepatocellular carcinoma (HCC): current guidelines","volume":"101","author":"Ayuso","year":"2018","journal-title":"Eur J Radiol"},{"issue":"2","key":"10.1016\/j.phymed.2026.157858_bib0004","article-title":"Antioxidant and Pro-Oxidant Properties of Carthamus Tinctorius","volume":"9","author":"Bacchetti","year":"2020","journal-title":"Hydroxy Safflor Yellow A, and Safflor Yellow A. Antioxidants (Basel)"},{"key":"10.1016\/j.phymed.2026.157858_bib0005","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2022.121918","article-title":"Hydroxy-safflower yellow A composites: An effective strategy to enhance anti-myocardial ischemia by improving intestinal permeability","volume":"623","author":"Bao","year":"2022","journal-title":"Int J Pharm"},{"issue":"5","key":"10.1016\/j.phymed.2026.157858_bib0006","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.cmet.2024.04.006","article-title":"Hepatic selective insulin resistance at the intersection of insulin signaling and metabolic dysfunction-associated steatotic liver disease","volume":"36","author":"Bo","year":"2024","journal-title":"Cell Metab"},{"key":"10.1016\/j.phymed.2026.157858_bib0007","article-title":"Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma","volume":"14","author":"Chen","year":"2023","journal-title":"Front Immunol"},{"key":"10.1016\/j.phymed.2026.157858_bib0008","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2022.112950","article-title":"Pharmacokinetic-pharmacodynamic modeling analysis for hydroxysafflor yellow A-calycosin in compatibility in normal and cerebral ischemic rats: A comparative study","volume":"150","author":"Chen","year":"2022","journal-title":"Biomed Pharmacother"},{"issue":"4","key":"10.1016\/j.phymed.2026.157858_bib0009","first-page":"2989","article-title":"Hydroxysafflor yellow A induces autophagy in human liver cancer cells by regulating Beclin 1 and ERK expression","volume":"19","author":"Chen","year":"2020","journal-title":"Exp Ther Med"},{"issue":"41","key":"10.1016\/j.phymed.2026.157858_bib0010","doi-asserted-by":"crossref","first-page":"11288","DOI":"10.1021\/acs.jafc.9b05079","article-title":"The Multifunctional Benefits of Naturally Occurring Delphinidin and Its Glycosides","volume":"67","author":"Chen","year":"2019","journal-title":"J Agric Food Chem"},{"key":"10.1016\/j.phymed.2026.157858_bib0011","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2024.1374680","article-title":"Genetic diversity, clinical uses, and phytochemical and pharmacological properties of safflower (Carthamus tinctorius L.): an important medicinal plant","volume":"15","author":"Cheng","year":"2024","journal-title":"Front Pharmacol"},{"issue":"2","key":"10.1016\/j.phymed.2026.157858_bib0012","doi-asserted-by":"crossref","first-page":"244","DOI":"10.2174\/1567201811666141021142606","article-title":"Self emulsifying drug delivery system (SEDDS) for phytoconstituents: a review","volume":"12","author":"Chouhan","year":"2015","journal-title":"Curr Drug Deliv"},{"issue":"41","key":"10.1016\/j.phymed.2026.157858_bib0013","doi-asserted-by":"crossref","first-page":"6304","DOI":"10.3748\/wjg.v26.i41.6304","article-title":"Efficacy and safety of anti-hepatic fibrosis drugs","volume":"26","author":"Damiris","year":"2020","journal-title":"World J Gastroenterol"},{"issue":"4","key":"10.1016\/j.phymed.2026.157858_bib101","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3109\/13880209.2013.840850","article-title":"Alteration of the ERK5 pathway by hydroxysafflor yellow A blocks expression of MEF2C in activated hepatic stellate cells in vitro","volume":"52","author":"Dong","year":"2014","journal-title":"J. Pharm. Biol."},{"issue":"7","key":"10.1016\/j.phymed.2026.157858_bib0014","doi-asserted-by":"crossref","first-page":"3957","DOI":"10.1021\/jf9025458","article-title":"Delphinidin induces necrosis in hepatocellular carcinoma cells in the presence of 3-methyladenine, an autophagy inhibitor","volume":"58","author":"Feng","year":"2010","journal-title":"J Agric Food Chem"},{"key":"10.1016\/j.phymed.2026.157858_bib0015","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.aca.2017.11.069","article-title":"Combination of chemical fingerprinting with bioassay, a preferable approach for quality control of Safflower Injection","volume":"1003","author":"Feng","year":"2018","journal-title":"Anal Chim Acta"},{"issue":"5","key":"10.1016\/j.phymed.2026.157858_bib0016","doi-asserted-by":"crossref","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int J Cancer"},{"issue":"1","key":"10.1016\/j.phymed.2026.157858_bib0017","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1080\/15548627.2021.1895658","article-title":"The m\u00e9nage \u00e0 trois of autophagy, lipid droplets and liver disease","volume":"18","author":"Filali-Mouncef","year":"2022","journal-title":"Autophagy"},{"issue":"21","key":"10.1016\/j.phymed.2026.157858_bib0018","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1056\/NEJM197111182852108","article-title":"Tumor angiogenesis: therapeutic implications","volume":"285","author":"Folkman","year":"1971","journal-title":"N Engl J Med"},{"issue":"14","key":"10.1016\/j.phymed.2026.157858_bib0019","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13143498","article-title":"Autophagy Inhibition in BRAF-Driven Cancers","volume":"13","author":"Foth","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"23","key":"10.1016\/j.phymed.2026.157858_bib0020","doi-asserted-by":"crossref","first-page":"19225","DOI":"10.1021\/acsomega.2c00457","article-title":"Oral Bioavailability-Enhancing and Anti-obesity Effects of Hydroxysafflor Yellow A in Natural Deep Eutectic Solvent","volume":"7","author":"Gao","year":"2022","journal-title":"ACS Omega"},{"issue":"5","key":"10.1016\/j.phymed.2026.157858_bib0021","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1097\/HEP.0000000000000182","article-title":"Hepatic fibrosis: Targeting peroxisome proliferator-activated receptor alpha from mechanism to medicines","volume":"78","author":"Gong","year":"2023","journal-title":"Hepatology"},{"issue":"1","key":"10.1016\/j.phymed.2026.157858_bib0022","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.yexcr.2010.10.005","article-title":"Cellular inhibitor of apoptosis 1 (cIAP-1) degradation by caspase 8 during TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis","volume":"317","author":"Guicciardi","year":"2011","journal-title":"Exp Cell Res"},{"issue":"1","key":"10.1016\/j.phymed.2026.157858_bib0023","doi-asserted-by":"crossref","DOI":"10.1097\/HC9.0000000000000612","article-title":"PPAR agonists for the treatment of cholestatic liver diseases: Over a decade of clinical progress","volume":"9","author":"Hayes","year":"2025","journal-title":"Hepatol Commun"},{"key":"10.1016\/j.phymed.2026.157858_bib0024","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.966759","article-title":"Mechanism of hydroxysafflor yellow A on acute liver injury based on transcriptomics","volume":"13","author":"Hou","year":"2022","journal-title":"Front Pharmacol"},{"issue":"1","key":"10.1016\/j.phymed.2026.157858_bib0025","doi-asserted-by":"crossref","first-page":"8875","DOI":"10.1038\/s41598-021-88339-9","article-title":"Safety of traditional Chinese medicine injection based on spontaneous reporting system from 2014 to 2019 in Hubei Province, China","volume":"11","author":"Huang","year":"2021","journal-title":"Sci Rep"},{"issue":"4","key":"10.1016\/j.phymed.2026.157858_bib0026","article-title":"Mechanism of Action of Cyanidin 3-O-Glucoside in Gluconeogenesis and Oxidative Stress-Induced","volume":"11","author":"Jia","year":"2022","journal-title":"Cancer Cell Senescence. Antioxidants (Basel)"},{"issue":"5","key":"10.1016\/j.phymed.2026.157858_bib0027","first-page":"2595","article-title":"Hydroxysafflor yellow A attenuates ischemia\/reperfusion-induced liver injury by suppressing macrophage activation","volume":"7","author":"Jiang","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"issue":"27","key":"10.1016\/j.phymed.2026.157858_bib0028","doi-asserted-by":"crossref","first-page":"6221","DOI":"10.1021\/acs.jafc.5b02181","article-title":"Cyanidin-3-O-\u03b2-glucoside Purified from Black Rice Protects Mice against Hepatic Fibrosis Induced by Carbon Tetrachloride via Inhibiting Hepatic Stellate Cell Activation","volume":"63","author":"Jiang","year":"2015","journal-title":"J Agric Food Chem"},{"issue":"8","key":"10.1016\/j.phymed.2026.157858_bib0029","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1039\/C7FO00265C","article-title":"Cyanidin-3-O-\u03b2-glucoside combined with its metabolite protocatechuic acid attenuated the activation of mice hepatic stellate cells","volume":"8","author":"Jiang","year":"2017","journal-title":"Food Funct"},{"issue":"7","key":"10.1016\/j.phymed.2026.157858_bib0030","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1016\/j.cgh.2022.04.013","article-title":"Fibrosis Stage-specific Incidence of Hepatocellular Cancer After Hepatitis C Cure With Direct-acting Antivirals: A Systematic Review and Meta-analysis","volume":"21","author":"Kim","year":"2023","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"3","key":"10.1016\/j.phymed.2026.157858_bib0031","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41575-020-00372-7","article-title":"Molecular and cellular mechanisms of liver fibrosis and its regression","volume":"18","author":"Kisseleva","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"5","key":"10.1016\/j.phymed.2026.157858_bib0032","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2020106700","article-title":"Cell death pathways: intricate connections and disease implications","volume":"40","author":"Kist","year":"2021","journal-title":"Embo j"},{"issue":"13","key":"10.1016\/j.phymed.2026.157858_bib0033","doi-asserted-by":"crossref","DOI":"10.3390\/cells14130942","article-title":"Molecular Regulation of SASP in Cellular Senescence: Therapeutic Implications and Translational Challenges","volume":"14","author":"Klepacki","year":"2025","journal-title":"Cells"},{"issue":"22","key":"10.1016\/j.phymed.2026.157858_bib100","doi-asserted-by":"crossref","first-page":"14281","DOI":"10.3390\/ijms232214281","article-title":"Integrating network pharmacology and transcriptomic strategies to explore the pharmacological mechanism of hydroxysafflor yellow a in delaying liver aging","volume":"23","author":"Kong","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phymed.2026.157858_bib0034","doi-asserted-by":"crossref","DOI":"10.1016\/j.addr.2021.113869","article-title":"Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis","volume":"176","author":"Kumar","year":"2021","journal-title":"Adv Drug Deliv Rev"},{"key":"10.1016\/j.phymed.2026.157858_bib0035","doi-asserted-by":"crossref","DOI":"10.1016\/j.foodchem.2025.144353","article-title":"Enzymatic fatty acid acylation of cyanidin-3-O-glucoside extracted from black rice bran: thermostability, lipophilicity, cytotoxicity and absorption studies","volume":"484","author":"Leonarski","year":"2025","journal-title":"Food Chem"},{"issue":"5","key":"10.1016\/j.phymed.2026.157858_bib0036","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.ejps.2012.03.003","article-title":"Hydroxysafflor yellow A induces apoptosis in activated hepatic stellate cells through ERK1\/2 pathway in vitro","volume":"46","author":"Li","year":"2012","journal-title":"Eur J Pharm Sci"},{"key":"10.1016\/j.phymed.2026.157858_bib0037","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jep.2014.12.068","article-title":"Pharmacokinetic profiles of hydroxysafflor yellow A following intravenous administration of its pure preparations in healthy Chinese volunteers","volume":"162","author":"Li","year":"2015","journal-title":"J Ethnopharmacol"},{"issue":"1","key":"10.1016\/j.phymed.2026.157858_bib0038","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12943-024-02213-6","article-title":"Tailoring traditional Chinese medicine in cancer therapy","volume":"24","author":"Li","year":"2025","journal-title":"Mol Cancer"},{"issue":"1","key":"10.1016\/j.phymed.2026.157858_bib0039","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3892\/mmr.2016.5965","article-title":"Restorative effects of hydroxysafflor yellow A on hepatic function in an experimental regression model of hepatic fibrosis induced by carbon tetrachloride","volume":"15","author":"Li","year":"2017","journal-title":"Mol Med Rep"},{"key":"10.1016\/j.phymed.2026.157858_bib0040","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2023.1303012","article-title":"Research progress of traditional Chinese medicine in improving hepatic fibrosis based on inhibiting pathological angiogenesis","volume":"14","author":"Li","year":"2023","journal-title":"Front Pharmacol"},{"issue":"11","key":"10.1016\/j.phymed.2026.157858_bib0041","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1016\/j.molp.2024.10.009","article-title":"Genomic and metabolomic insights into the selection and differentiation of bioactive compounds in citrus","volume":"17","author":"Liang","year":"2024","journal-title":"Mol Plant"},{"key":"10.1016\/j.phymed.2026.157858_bib0042","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2022.115656","article-title":"Carthamus tinctorius L.: A natural neuroprotective source for anti-Alzheimer's disease drugs","volume":"298","author":"Liang","year":"2022","journal-title":"J Ethnopharmacol"},{"issue":"3","key":"10.1016\/j.phymed.2026.157858_bib0043","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1080\/00498254.2025.2507139","article-title":"HSYA from safflower mitigates oxidative stress, inflammation, and apoptosis in liver ischemia-reperfusion injury","volume":"55","author":"Liao","year":"2025","journal-title":"Xenobiotica"},{"issue":"6","key":"10.1016\/j.phymed.2026.157858_bib0044","doi-asserted-by":"crossref","first-page":"9887","DOI":"10.1002\/jcb.28271","article-title":"Delphinidin inhibits epidermal growth factor-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma cells","volume":"120","author":"Lim","year":"2019","journal-title":"J Cell Biochem"},{"issue":"9","key":"10.1016\/j.phymed.2026.157858_bib0045","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.3109\/13880209.2013.877491","article-title":"Hydroxysafflor yellow A suppresses liver fibrosis induced by carbon tetrachloride with high-fat diet by regulating PPAR-\u03b3\/p38 MAPK signaling","volume":"52","author":"Liu","year":"2014","journal-title":"Pharm Biol"},{"issue":"1-3","key":"10.1016\/j.phymed.2026.157858_bib0046","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.tox.2004.06.007","article-title":"The subchronic toxicity of hydroxysafflor yellow A of 90 days repeatedly intraperitoneal injections in rats","volume":"203","author":"Liu","year":"2004","journal-title":"Toxicology"},{"key":"10.1016\/j.phymed.2026.157858_bib0047","first-page":"4099","article-title":"Enhanced absorption of hydroxysafflor yellow A using a self-double-emulsifying drug delivery system: in vitro and in vivo studies","volume":"7","author":"Lv","year":"2012","journal-title":"Int J Nanomedicine"},{"key":"10.1016\/j.phymed.2026.157858_bib0048","first-page":"2709","article-title":"Mechanism of enhanced oral absorption of hydrophilic drug incorporated in hydrophobic nanoparticles","volume":"8","author":"Lv","year":"2013","journal-title":"Int J Nanomedicine"},{"issue":"3","key":"10.1016\/j.phymed.2026.157858_bib0049","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1208\/s12249-014-0255-z","article-title":"A novel oral preparation of hydroxysafflor yellow A base on a chitosan complex: a strategy to enhance the oral bioavailability","volume":"16","author":"Ma","year":"2015","journal-title":"AAPS PharmSciTech"},{"issue":"10","key":"10.1016\/j.phymed.2026.157858_bib0050","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1248\/bpb.b17-00281","article-title":"The Role of E-Cadherin\/\u03b2-Catenin in Hydroxysafflor Yellow A Inhibiting Adhesion, Invasion, Migration and Lung Metastasis of Hepatoma Cells","volume":"40","author":"Ma","year":"2017","journal-title":"Biol Pharm Bull"},{"issue":"3","key":"10.1016\/j.phymed.2026.157858_bib0051","first-page":"3503","article-title":"Hydroxyl safflower yellow A regulates the tumor immune microenvironment to produce an anticancer effect in a mouse model of hepatocellular carcinoma","volume":"17","author":"Ma","year":"2019","journal-title":"Oncol Lett"},{"key":"10.1016\/j.phymed.2026.157858_bib0052","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.109210","article-title":"1,2,3-Triazole-modified sorafenib derivatives induce DNA damage, apoptosis, and PI3K\/AKT pathway suppression in hepatocellular carcinoma: Design, synthesis, and evaluation","volume":"167","author":"Mao","year":"2025","journal-title":"Bioorg Chem"},{"issue":"1","key":"10.1016\/j.phymed.2026.157858_bib0053","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/hep.31288","article-title":"Epidemiology of Hepatocellular Carcinoma","volume":"73","author":"McGlynn","year":"2021","journal-title":"Hepatology"},{"issue":"7","key":"10.1016\/j.phymed.2026.157858_bib0054","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.devcel.2021.02.010","article-title":"Autophagy and organelle homeostasis in cancer","volume":"56","author":"Miller","year":"2021","journal-title":"Dev Cell"},{"key":"10.1016\/j.phymed.2026.157858_bib0055","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2020.173214","article-title":"Hepatoprotective effects of hydroxysafflor yellow A in D-galactose-treated aging mice","volume":"881","author":"Min","year":"2020","journal-title":"Eur J Pharmacol"},{"issue":"11","key":"10.1016\/j.phymed.2026.157858_bib0056","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/s41580-024-00757-5","article-title":"Mechanisms of autophagy-lysosome dysfunction in neurodegenerative diseases","volume":"25","author":"Nixon","year":"2024","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.phymed.2026.157858_bib0057","doi-asserted-by":"crossref","DOI":"10.1016\/j.jpba.2023.115801","article-title":"Potential roles of HSYA in attenuating sepsis-induced liver injury through multi-omics analysis","volume":"238","author":"Pan","year":"2024","journal-title":"J Pharm Biomed Anal"},{"issue":"11","key":"10.1016\/j.phymed.2026.157858_bib0058","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1055\/s-0030-1250111","article-title":"Targeting inflammatory pathways by flavonoids for prevention and treatment of cancer","volume":"76","author":"Prasad","year":"2010","journal-title":"Planta Med"},{"key":"10.1016\/j.phymed.2026.157858_bib0059","doi-asserted-by":"crossref","DOI":"10.1016\/j.mam.2021.100973","article-title":"Autophagy in liver diseases: A review","volume":"82","author":"Qian","year":"2021","journal-title":"Mol Aspects Med"},{"issue":"12","key":"10.1016\/j.phymed.2026.157858_bib0060","article-title":"Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the","volume":"9","author":"Ramos-Tovar","year":"2020","journal-title":"Liver. Antioxidants (Basel)"},{"key":"10.1016\/j.phymed.2026.157858_bib0061","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2025.1637053","article-title":"Pharmacological actions and applications of safflower flavonoids","volume":"12","author":"Ren","year":"2025","journal-title":"Front Nutr"},{"issue":"4","key":"10.1016\/j.phymed.2026.157858_bib0062","doi-asserted-by":"crossref","DOI":"10.3390\/cells9040875","article-title":"Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives","volume":"9","author":"Roehlen","year":"2020","journal-title":"Cells"},{"issue":"1","key":"10.1016\/j.phymed.2026.157858_bib0063","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41423-020-00572-w","article-title":"Immunobiology and immunotherapy of HCC: spotlight on innate and innate-like immune cells","volume":"18","author":"Ruf","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"10.1016\/j.phymed.2026.157858_bib0064","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2021.114590","article-title":"Safflower (Carthamus tinctorius L.) oil could improve abdominal obesity, blood pressure, and insulin resistance in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled clinical trial","volume":"282","author":"Ruyvaran","year":"2022","journal-title":"J Ethnopharmacol"},{"issue":"1","key":"10.1016\/j.phymed.2026.157858_bib0065","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3350\/cmh.2023.0125","article-title":"Recent advances in the management of hepatocellular carcinoma","volume":"30","author":"Sankar","year":"2024","journal-title":"Clin Mol Hepatol"},{"issue":"8","key":"10.1016\/j.phymed.2026.157858_bib0066","doi-asserted-by":"crossref","first-page":"348","DOI":"10.4103\/2221-1691.383689","article-title":"Hydroxysafflor yellow A protects against thioacetamide-induced liver fibrosis in rats via suppressing proinflammatory\/fibrogenic mediators and promoting hepatic stellate cell senescence and apoptosis","volume":"13","author":"Seif el-Din","year":"2023","journal-title":"Asian Pacific Journal of Tropical Biomedicine"},{"key":"10.1016\/j.phymed.2026.157858_bib0067","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.874408","article-title":"New Drugs for Hepatic Fibrosis","volume":"13","author":"Shan","year":"2022","journal-title":"Front Pharmacol"},{"issue":"23","key":"10.1016\/j.phymed.2026.157858_bib0068","doi-asserted-by":"crossref","first-page":"9427","DOI":"10.1021\/jf071933i","article-title":"Anthocyanins induce the activation of phase II enzymes through the antioxidant response element pathway against oxidative stress-induced apoptosis","volume":"55","author":"Shih","year":"2007","journal-title":"J Agric Food Chem"},{"key":"10.1016\/j.phymed.2026.157858_bib0069","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.114653","article-title":"Oroxylin A activates ferritinophagy to induce hepatic stellate cell senescence against hepatic fibrosis by regulating cGAS-STING pathway","volume":"162","author":"Sun","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.phymed.2026.157858_bib0070","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.carres.2017.05.009","article-title":"Oxidation of 3,5-di-C-(per-O-acetylglucopyranosyl)phloroacetophenone in the synthesis of hydroxysafflor yellow A","volume":"448","author":"Suzuki","year":"2017","journal-title":"Carbohydr Res"},{"key":"10.1016\/j.phymed.2026.157858_bib0071","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2021.730176","article-title":"Liver Fibrosis: Therapeutic Targets and Advances in Drug Therapy","volume":"9","author":"Tan","year":"2021","journal-title":"Front Cell Dev Biol"},{"issue":"7","key":"10.1016\/j.phymed.2026.157858_bib0072","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.phymed.2013.02.001","article-title":"Activation of PPAR\u03b3 is required for hydroxysafflor yellow A of Carthamus tinctorius to attenuate hepatic fibrosis induced by oxidative stress","volume":"20","author":"Wang","year":"2013","journal-title":"Phytomedicine"},{"issue":"1-2","key":"10.1016\/j.phymed.2026.157858_bib0073","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ijpharm.2008.03.006","article-title":"Enhancing effect of Labrafac Lipophile WL 1349 on oral bioavailability of hydroxysafflor yellow A in rats","volume":"358","author":"Wang","year":"2008","journal-title":"Int J Pharm"},{"key":"10.1016\/j.phymed.2026.157858_bib102","doi-asserted-by":"crossref","first-page":"153579","DOI":"10.1016\/j.phymed.2021.153579","article-title":"Hydroxysafflor yellows alleviate thrombosis and acetaminophen-induced toxicity in vivo by enhancing blood circulation and poison excretion","volume":"87","author":"Wang","year":"2021","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2026.157858_bib0074","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155814","article-title":"Hydroxysafflor yellow A ameliorates alcohol-induced liver injury through PI3K\/Akt and STAT3\/NF-\u03baB signaling pathways","volume":"132","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2026.157858_bib0075","article-title":"Hydroxysafflor yellow A: a natural pigment with potential anticancer therapeutic effect","volume":"15","author":"Wang","year":"2024","journal-title":"Front Pharmacol"},{"issue":"1","key":"10.1016\/j.phymed.2026.157858_bib0076","doi-asserted-by":"crossref","first-page":"4489","DOI":"10.1038\/s41467-025-59774-3","article-title":"Elucidation of the biosynthetic pathway of hydroxysafflor yellow A","volume":"16","author":"Wang","year":"2025","journal-title":"Nat Commun"},{"key":"10.1016\/j.phymed.2026.157858_bib0077","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2021.111227","article-title":"Hydroxysafflor yellow A promotes apoptosis via blocking autophagic flux in liver cancer","volume":"136","author":"Wu","year":"2021","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.phymed.2026.157858_bib0078","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2022.113462","article-title":"Comprehensive review of two groups of flavonoids in Carthamus tinctorius L","volume":"153","author":"Xian","year":"2022","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.phymed.2026.157858_bib0079","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2021.153694","article-title":"Hydroxysafflor yellow A, a natural compound from Carthamus tinctorius L with good effect of alleviating atherosclerosis","volume":"91","author":"Xue","year":"2021","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2026.157858_bib0080","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155830","article-title":"Hydroxysafflor yellow A exerts anti-fibrotic and anti-angiogenic effects through miR-29a-3p\/PDGFRB axis in liver fibrosis","volume":"132","author":"Xue","year":"2024","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2026.157858_bib0081","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ejphar.2015.02.015","article-title":"Hydroxysafflor yellow A inhibits angiogenesis of hepatocellular carcinoma via blocking ERK\/MAPK and NF-\u03baB signaling pathway in H22 tumor-bearing mice","volume":"754","author":"Yang","year":"2015","journal-title":"Eur J Pharmacol"},{"issue":"42","key":"10.1016\/j.phymed.2026.157858_bib0082","doi-asserted-by":"crossref","first-page":"26923","DOI":"10.1021\/acs.jafc.5c10765","article-title":"The Chemo-Enzymatic Synthesis of 8,9-Dihydrohydroxysafflor Yellow A and Its Neuroprotective Effects against Cerebral Ischemia-Reperfusion Injury","volume":"73","author":"Yang","year":"2025","journal-title":"J Agric Food Chem"},{"issue":"7","key":"10.1016\/j.phymed.2026.157858_bib0083","first-page":"1973","article-title":"The application of nanoparticles in cancer immunotherapy: Targeting tumor microenvironment","volume":"6","author":"Yang","year":"2021","journal-title":"Bioact Mater"},{"issue":"1","key":"10.1016\/j.phymed.2026.157858_bib0084","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.phymed.2026.157858_bib0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155956","article-title":"Elucidating hydroxysafflor yellow A's multi-target mechanisms against alcoholic liver disease through integrative pharmacology","volume":"134","author":"Yu","year":"2024","journal-title":"Phytomedicine"},{"issue":"14","key":"10.1016\/j.phymed.2026.157858_bib0086","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25147573","article-title":"Effects of Hydroxysafflor Yellow A (HSYA) on UVA-Induced Damage in HaCaT Keratinocytes","volume":"25","author":"Yu","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"16","key":"10.1016\/j.phymed.2026.157858_bib0087","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23168846","article-title":"Chemokines in Primary Liver Cancer","volume":"23","author":"Zajkowska","year":"2022","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.phymed.2026.157858_bib0088","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.biopha.2018.09.086","article-title":"Hydroxysafflor yellow A suppresses angiogenesis of hepatocellular carcinoma through inhibition of p38 MAPK phosphorylation","volume":"109","author":"Zhang","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.phymed.2026.157858_bib0089","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/4560012","article-title":"Pharmacological Actions, Molecular Mechanisms, Pharmacokinetic Progressions, and Clinical Applications of Hydroxysafflor Yellow A in Antidiabetic Research","volume":"2021","author":"Zhang","year":"2021","journal-title":"J Immunol Res"},{"issue":"2-3","key":"10.1016\/j.phymed.2026.157858_bib0090","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.ejphar.2011.04.015","article-title":"Hydroxysafflor yellow A protects against chronic carbon tetrachloride-induced liver fibrosis","volume":"660","author":"Zhang","year":"2011","journal-title":"Eur J Pharmacol"},{"issue":"1-2","key":"10.1016\/j.phymed.2026.157858_bib0091","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ijpharm.2017.10.040","article-title":"Solid lipid nanoparticles as carriers for oral delivery of hydroxysafflor yellow A","volume":"535","author":"Zhao","year":"2018","journal-title":"Int J Pharm"},{"key":"10.1016\/j.phymed.2026.157858_bib0092","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2020.579332","article-title":"Hydroxysafflor Yellow A: A Systematical Review on Botanical Resources, Physicochemical Properties, Drug Delivery System, Pharmacokinetics, and Pharmacological Effects","volume":"11","author":"Zhao","year":"2020","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.phymed.2026.157858_bib0093","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2019.118642","article-title":"Improvement strategies for the oral bioavailability of poorly water-soluble flavonoids: An overview","volume":"570","author":"Zhao","year":"2019","journal-title":"Int J Pharm"},{"issue":"4","key":"10.1016\/j.phymed.2026.157858_bib0094","article-title":"A specialized flavone biosynthetic pathway has evolved in the medicinal plant","volume":"2","author":"Zhao","year":"2016","journal-title":"Scutellaria baicalensis. Sci Adv"},{"issue":"4","key":"10.1016\/j.phymed.2026.157858_bib0095","doi-asserted-by":"crossref","first-page":"e1773","DOI":"10.1002\/wrna.1773","article-title":"microRNAs-based diagnostic and therapeutic applications in liver fibrosis","volume":"14","author":"Zhao","year":"2023","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"10.1016\/j.phymed.2026.157858_bib0096","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2024.117109","article-title":"Protective effect of hydroxysafflor yellow a on thioacetamide-induced liver injury and osteopenia in zebrafish","volume":"492","author":"Zhao","year":"2024","journal-title":"Toxicol Appl Pharmacol"},{"issue":"14","key":"10.1016\/j.phymed.2026.157858_bib0097","doi-asserted-by":"crossref","DOI":"10.3390\/polym17141900","article-title":"Combating Traumatic Brain Injury: A Dual-Mechanism Hydrogel Delivering Salvianolic Acid A and Hydroxysafflor Yellow A to Block TLR4\/NF-\u03baB and Boost Angiogenesis","volume":"17","author":"Zhou","year":"2025","journal-title":"Polymers (Basel)"},{"key":"10.1016\/j.phymed.2026.157858_bib0098","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.biopha.2018.05.057","article-title":"Anti-tumor properties of anthocyanins from Lonicera caerulea 'Beilei' fruit on human hepatocellular carcinoma: In vitro and in vivo study","volume":"104","author":"Zhou","year":"2018","journal-title":"Biomed Pharmacother"},{"issue":"5","key":"10.1016\/j.phymed.2026.157858_bib0099","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1055\/s-2003-39714","article-title":"Neuroprotective effects of hydroxysafflor yellow A: in vivo and in vitro studies","volume":"69","author":"Zhu","year":"2003","journal-title":"Planta Med"}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S094471132600098X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S094471132600098X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T03:50:41Z","timestamp":1774929041000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S094471132600098X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":102,"alternative-id":["S094471132600098X"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2026.157858","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hydroxy Safflower Yellow A: A Natural Compound from Carthamus tinctorius L. with Potent Activity Against Liver Fibrosis and Cancer","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2026.157858","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"157858"}}