{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T09:01:49Z","timestamp":1779958909172,"version":"3.53.1"},"reference-count":129,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dihydrosanguinarine (DHSA) is a naturally occurring benzo[c]phenanthridine alkaloid primarily isolated from plants of the Papaveraceae family. DHSA exhibits broad pharmacological activities, including antitumor, anti-inflammatory, hypoglycemic, neuroprotective, analgesic, anxiolytic, antiarrhythmic, and antimicrobial effects. Mechanistically, DHSA regulates multiple signaling pathways and molecular targets, including TMEM16A, p53, Ras\/Raf\/MEK\/ERK, PI3K\/AKT, NF-\u03baB, PPAR\u03b3, GABAA receptors, and voltage-gated sodium channels. Compared with its biosynthetic precursor sanguinarine (SA), DHSA exhibits a comparatively favorable safety profile while retaining considerable biological activity. Pharmacokinetic studies further suggest that DHSA possesses acceptable membrane permeability, gastrointestinal absorption potential, enterohepatic circulation characteristics, and sustained systemic exposure. In addition, structure\u2013activity relationship (SAR) and electrostatic surface potential (ESP) analyses indicate that the chemically accessible C6 position may provide opportunities for rational structural optimization. Nevertheless, the clinical translation of DHSA still faces several challenges. Therefore, this review systematically summarizes the physicochemical properties, pharmacological activities, molecular mechanisms, SAR characteristics, ESP distribution, toxicity, pharmacokinetic behavior, and clinical prospects of DHSA, aiming to provide a theoretical basis for its future drug development and translational application.<\/jats:p>","DOI":"10.3390\/ijms27114852","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T08:00:36Z","timestamp":1779955236000},"page":"4852","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dihydrosanguinarine: A Review of Its Pharmacology, Structure\u2013Activity Relationship, Toxicity, Pharmacokinetics, and Clinical Prospects"],"prefix":"10.3390","volume":"27","author":[{"given":"Xiaoqi","family":"Yin","sequence":"first","affiliation":[{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyi","family":"Cao","sequence":"additional","affiliation":[{"name":"New Cornerstone Science Laboratory, Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuxuan","family":"Fang","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ce","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Basic Medicine Sciences, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"Research Center for Infectious Diseases, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong","family":"Cheng","sequence":"additional","affiliation":[{"name":"New Cornerstone Science Laboratory, Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9293-1923","authenticated-orcid":false,"given":"Long","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"Research Center for Infectious Diseases, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"School of Public Health, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E239","DOI":"10.1007\/BF02854894","article-title":"Drug discovery from natural sources","volume":"8","author":"Chin","year":"2006","journal-title":"AAPS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/cpr.12143","article-title":"Plant natural products: From traditional compounds to new emerging drugs in cancer therapy","volume":"47","author":"Ouyang","year":"2014","journal-title":"Cell Prolif."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s11658-019-0164-y","article-title":"Progress in research on paclitaxel and tumor immunotherapy","volume":"24","author":"Zhu","year":"2019","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10210","DOI":"10.1002\/anie.201601967","article-title":"Artemisinin-A Gift from Traditional Chinese Medicine to the World (Nobel Lecture)","volume":"55","author":"Tu","year":"2016","journal-title":"Angew. Chem. (Int. Ed. Engl.)"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113857","DOI":"10.1016\/j.ejmech.2021.113857","article-title":"Screening S protein\u2014ACE2 blockers from natural products: Strategies and advances in the discovery of potential inhibitors of COVID-19","volume":"226","author":"Ma","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/162265a0","article-title":"Isolation from argemone oil of dihydrosanguinarine and sanguinarine; toxicity of sanguinarine","volume":"162","author":"Sarkar","year":"1948","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Y\u00e1\u00f1ez-Barrientos, E., Barragan-Galvez, J.C., Hidalgo-Figueroa, S., Reyes-Luna, A., Gonzalez-Rivera, M.L., Cruz Cruz, D., Isiordia-Espinoza, M.A., Deveze-\u00c1lvarez, M.A., Villegas G\u00f3mez, C., and Alonso-Castro, A.J. (2023). Neuropharmacological Effects of the Dichloromethane Extract from the Stems of Argemone ochroleuca Sweet (Papaveraceae) and Its Active Compound Dihydrosanguinarine. Pharmaceuticals, 16.","DOI":"10.3390\/ph16081175"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.1038\/ncomms4283","article-title":"Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae","volume":"5","author":"Fossati","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11314","DOI":"10.1039\/C4CC05209A","article-title":"New methods for the synthesis of naphthyl amines; application to the synthesis of dihydrosanguinarine, sanguinarine, oxysanguinarine and (\u00b1)-maclekarpines B and C","volume":"50","author":"Tatton","year":"2014","journal-title":"Chem. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"108779","DOI":"10.1016\/j.intimp.2022.108779","article-title":"Dihydrosanguinarine based RNA-seq approach couple with network pharmacology attenuates LPS-induced inflammation through TNF\/IL-17\/PI3K\/AKT pathways in mice liver","volume":"109","author":"Xiang","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.jep.2009.07.029","article-title":"Antifungal activity of the benzo[c]phenanthridine alkaloids from Chelidonium majus Linn against resistant clinical yeast isolates","volume":"125","author":"Meng","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"115492","DOI":"10.1016\/j.jep.2022.115492","article-title":"Antinociceptive and gastroprotective activities of Bocconia arborea S. Watson and its bioactive metabolite dihydrosanguinarine in murine models","volume":"296","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","first-page":"1593","article-title":"Alkaloids from Papaver coreanum","volume":"6","author":"Lee","year":"2011","journal-title":"Nat. Prod. Commun."},{"key":"ref_14","first-page":"2413","article-title":"Spectrum-effect relationship and mechanism of anti-inflammatory effects of different extracts of Corydalis yanhusuo","volume":"50","author":"Ma","year":"2019","journal-title":"Chin. Tradit. Herb. Drugs"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"152895","DOI":"10.1016\/j.phymed.2019.152895","article-title":"Dihydrosanguinarine suppresses pancreatic cancer cells via regulation of mut-p53\/WT-p53 and the Ras\/Raf\/Mek\/Erk pathway","volume":"59","author":"Wu","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6916","DOI":"10.1021\/acsomega.7b01134","article-title":"Dihydrosanguinarine Enhances Glucose Uptake in Mouse 3T3-L1 Cells","volume":"2","author":"Chow","year":"2017","journal-title":"ACS Omega"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1080\/14786419.2010.487187","article-title":"Inhibitory activity of dihydrosanguinarine and dihydrochelerythrine against phytopathogenic fungi","volume":"25","author":"Feng","year":"2011","journal-title":"Nat. Prod. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jchromb.2005.10.030","article-title":"A liquid chromatographic-mass spectrometric evidence of dihydrosanguinarine as a first metabolite of sanguinarine transformation in rat","volume":"830","author":"Klejdus","year":"2006","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/jvp.12835","article-title":"Sanguinarine metabolism and pharmacokinetics study in vitro and in vivo","volume":"43","author":"Wu","year":"2020","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1007\/s00424-020-02434-w","article-title":"Benzophenanthridine alkaloids suppress lung adenocarcinoma by blocking TMEM16A Ca2+-activated Cl\u2212 channels","volume":"472","author":"Zhang","year":"2020","journal-title":"Pflug. Arch."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jep.2016.09.013","article-title":"Corydalis bungeana Turcz. attenuates LPS-induced inflammatory responses via the suppression of NF-\u03baB signaling pathway in vitro and in vivo","volume":"194","author":"Zhai","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.ijbiomac.2022.07.024","article-title":"Prediction and verification of potential lead analgesic and antiarrhythmic components in Corydalis yanhusuo W. T. Wang based on voltage-gated sodium channel proteins","volume":"216","author":"Sun","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wei, X., Li, X., Hu, S., Cheng, J., and Cai, R. (2023). Regulation of Ferroptosis in Lung Adenocarcinoma. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202309.0765.v1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"122034","DOI":"10.1016\/j.lfs.2023.122034","article-title":"TMEM16A ion channel: A novel target for cancer treatment","volume":"331","author":"Li","year":"2023","journal-title":"Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102050","DOI":"10.1016\/j.ceca.2019.06.004","article-title":"The multifaceted role of TMEM16A in cancer","volume":"82","author":"Jan","year":"2019","journal-title":"Cell Calcium"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1053\/j.gastro.2023.02.012","article-title":"Pancreatic Cancer: Changing Epidemiology and New Approaches to Risk Assessment, Early Detection, and Prevention","volume":"164","author":"Stoffel","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41575-021-00457-x","article-title":"Pancreatic cancer epidemiology: Understanding the role of lifestyle and inherited risk factors","volume":"18","author":"Klein","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/sj.bjc.6603886","article-title":"p53 and its isoforms in cancer","volume":"97","author":"Bourdon","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0092-8674(00)81871-1","article-title":"p53, the cellular gatekeeper for growth and division","volume":"88","author":"Levine","year":"1997","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.molimm.2024.03.006","article-title":"CXCL1-CXCR2 axis mediates inflammatory response after sciatic nerve injury by regulating macrophage infiltration","volume":"169","author":"Jiang","year":"2024","journal-title":"Mol. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"157095","DOI":"10.1016\/j.phymed.2025.157095","article-title":"Sophora Flos extract ameliorates inflammatory bowel disease via inhibiting the PI3K\/AKT\/mTOR signaling pathway activation and modulating M1\/M2 polarization in macrophages","volume":"146","author":"Li","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"112942","DOI":"10.1016\/j.intimp.2024.112942","article-title":"Anti-inflammatory effects of MerTK by inducing M2 macrophage polarization via PI3K\/Akt\/GSK-3\u03b2 pathway in gout","volume":"142","author":"Chen","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41401-020-0411-9","article-title":"Baicalin prevents LPS-induced activation of TLR4\/NF-\u03baB p65 pathway and inflammation in mice via inhibiting the expression of CD14","volume":"42","author":"Fu","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e70024","DOI":"10.1111\/cbdd.70024","article-title":"Mollugin Derivatives as Anti-Inflammatory Agents: Design, Synthesis, and NF-\u03baB Inhibition","volume":"104","author":"Gao","year":"2024","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/cbdd.14020","article-title":"A new insight into the treatment of diabetes by means of pan PPAR agonists","volume":"100","author":"Chandra","year":"2022","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.1038\/s41467-020-18565-8","article-title":"CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis","volume":"11","author":"Hao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hernandez-Quiles, M., Broekema, M.F., and Kalkhoven, E. (2021). PPARgamma in Metabolism, Immunity, and Cancer: Unified and Diverse Mechanisms of Action. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.624112"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s11658-024-00559-9","article-title":"Effects of mifepristone on adipocyte differentiation in mouse 3T3-L1 cells","volume":"29","author":"Hashimoto","year":"2024","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"216179","DOI":"10.1016\/j.canlet.2023.216179","article-title":"Glucose transporter 4: Insulin response mastermind, glycolysis catalyst and treatment direction for cancer progression","volume":"563","author":"Chang","year":"2023","journal-title":"Cancer Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.beem.2007.09.004","article-title":"PPAR agonists: Multimodal drugs for the treatment of type-2 diabetes","volume":"21","author":"Gross","year":"2007","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1054-3589(06)54001-3","article-title":"The role of GABA in the mediation and perception of pain","volume":"54","author":"Enna","year":"2006","journal-title":"Adv. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"108675","DOI":"10.1016\/j.neuropharm.2021.108675","article-title":"Delta-containing GABA(A) receptors in pain management: Promising targets for novel analgesics","volume":"195","author":"Luo","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"115800","DOI":"10.1016\/j.biopha.2023.115800","article-title":"Current status of GABA receptor subtypes in analgesia","volume":"168","author":"Qian","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/add.15636","article-title":"Opioid use disorder and the brain: A clinical perspective","volume":"117","author":"Herlinger","year":"2022","journal-title":"Addiction"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.14309\/ajg.0000000000002887","article-title":"Opioids and the Gastrointestinal Tract: The Role of Peripherally Active \u00b5-Opioid Receptor Antagonists in Modulating Intestinal Permeability","volume":"119","author":"Lacy","year":"2024","journal-title":"Am. J. Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Barbieri, R., Nizzari, M., Zanardi, I., Pusch, M., and Gavazzo, P. (2023). Voltage-Gated Sodium Channel Dysfunctions in Neurological Disorders. Life, 13.","DOI":"10.3390\/life13051191"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1039\/D2MD00081D","article-title":"Inhibition of Na(V)1.7: The possibility of ideal analgesics","volume":"13","author":"Kitano","year":"2022","journal-title":"RSC Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.sbi.2019.03.023","article-title":"A structural perspective on GABA(A) receptor pharmacology","volume":"54","author":"Scott","year":"2019","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12426","DOI":"10.1080\/07391102.2023.2167116","article-title":"GABA(A) and serotonergic receptors participation in anxiolytic effect of chalcones in adult zebrafish","volume":"41","author":"Mendes","year":"2023","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_50","first-page":"335","article-title":"Arrhythmia-Induced Cardiomyopathy","volume":"115","author":"Sossalla","year":"2018","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s00246-012-0303-y","article-title":"Cardiac sodium channel Nav1.5 mutations and cardiac arrhythmia","volume":"33","author":"Song","year":"2012","journal-title":"Pediatr. Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0140-6736(24)02081-6","article-title":"Multidrug-resistant Gram-negative bacterial infections","volume":"405","author":"Macesic","year":"2025","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"102553","DOI":"10.1016\/j.psj.2023.102553","article-title":"Common viral and bacterial avian respiratory infections: An updated review","volume":"102","author":"Yehia","year":"2023","journal-title":"Poult. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"100187","DOI":"10.1016\/j.modpat.2023.100187","article-title":"What Is New in Fungal Infections?","volume":"36","author":"Parsons","year":"2023","journal-title":"Mod. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Zieli\u0144ska, S., W\u00f3jciak-Kosior, M., Dzi\u0105gwa-Becker, M., Gle\u0144sk, M., Sowa, I., Fija\u0142kowski, K., Rura\u0144ska-Smutnicka, D., Matkowski, A., and Junka, A. (2019). The Activity of Isoquinoline Alkaloids and Extracts from Chelidonium majus against Pathogenic Bacteria and Candida sp.. Toxins, 11.","DOI":"10.3390\/toxins11070406"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.bmc.2011.11.052","article-title":"Bacterial biofilm formation inhibitory activity revealed for plant derived natural compounds","volume":"20","author":"Artini","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0378-8741(98)00182-2","article-title":"Two antimicrobial alkaloids from Bocconia arborea","volume":"66","author":"Navarro","year":"1999","journal-title":"J. Ethnopharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1080\/14786419.2018.1512991","article-title":"Benzophenanthridine alkaloids from the roots of Thalictrum microgynum Lecoy.ex Oliv","volume":"33","author":"Jiang","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Sulaiman, M., Jannat, K., Nissapatorn, V., Rahmatullah, M., Paul, A.K., de Lourdes Pereira, M., Rajagopal, M., Suleiman, M., Butler, M.S., and Break, M.K.B. (2022). Antibacterial and Antifungal Alkaloids from Asian Angiosperms: Distribution, Mechanisms of Action, Structure-Activity, and Clinical Potentials. Antibiotics, 11.","DOI":"10.3390\/antibiotics11091146"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1158\/1541-7786.MCR-07-2019","article-title":"DUSP1 is controlled by p53 during the cellular response to oxidative stress","volume":"6","author":"Liu","year":"2008","journal-title":"Mol. Cancer Res. MCR"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Akhter, N., Wilson, A., Arefanian, H., Thomas, R., Kochumon, S., Al-Rashed, F., Abu-Farha, M., Al-Madhoun, A., Al-Mulla, F., and Ahmad, R. (2023). Endoplasmic Reticulum Stress Promotes the Expression of TNF-\u03b1 in THP-1 Cells by Mechanisms Involving ROS\/CHOP\/HIF-1\u03b1 and MAPK\/NF-\u03baB Pathways. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015186"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"914","DOI":"10.3724\/abbs.2023109","article-title":"The crisscross between p53 and metabolism in cancer","volume":"55","author":"Mao","year":"2023","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"110311","DOI":"10.1016\/j.intimp.2023.110311","article-title":"Tirzepatide attenuates lipopolysaccharide-induced left ventricular remodeling and dysfunction by inhibiting the TLR4\/NF-kB\/NLRP3 pathway","volume":"120","author":"Liu","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"158090","DOI":"10.1016\/j.phymed.2026.158090","article-title":"Multitarget mechanisms and clinical integration of traditional Chinese medicine in breast cancer","volume":"155","author":"Wang","year":"2026","journal-title":"Phytomedicine"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Poznyak, A., Grechko, A.V., Poggio, P., Myasoedova, V.A., Alfieri, V., and Orekhov, A.N. (2020). The Diabetes Mellitus-Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051835"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41568-025-00798-8","article-title":"The fibroinflammatory response in cancer","volume":"25","author":"Xiao","year":"2025","journal-title":"Nat. Rev. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e14913","DOI":"10.1111\/cns.14913","article-title":"Hyperglycemia-induced Sirt3 downregulation increases microglial aerobic glycolysis and inflammation in diabetic neuropathic pain pathogenesis","volume":"30","author":"Li","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.vascn.2017.02.020","article-title":"Potential functional and pathological side effects related to off-target pharmacological activity","volume":"87","author":"Lynch","year":"2017","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.2174\/0118715206374787250227064528","article-title":"Redefining Anthraquinone-based Anticancer Drug Design through Subtle Chemical Modifications","volume":"25","author":"Mishra","year":"2025","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s13346-024-01648-0","article-title":"A comprehensive review on doxorubicin: Mechanisms, toxicity, clinical trials, combination therapies and nanoformulations in breast cancer","volume":"15","author":"Bisht","year":"2025","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1093\/neuonc\/noaa172","article-title":"Actinomycin D: A new opening for an old drug","volume":"22","author":"Finocchiaro","year":"2020","journal-title":"Neuro-Oncology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"378","DOI":"10.2165\/00003495-198326050-00002","article-title":"Acyclovir. A review of its pharmacodynamic properties and therapeutic efficacy","volume":"26","author":"Richards","year":"1983","journal-title":"Drugs"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1177\/1203475415574970","article-title":"The Rise and Fall of Oral Ketoconazole","volume":"19","author":"Gupta","year":"2015","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Kluska, M., and Wo\u017aniak, K. (2021). Natural Polyphenols as Modulators of Etoposide Anti-Cancer Activity. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126602"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e004006","DOI":"10.1136\/jitc-2021-004006","article-title":"Hyperbaric oxygen facilitates teniposide-induced cGAS-STING activation to enhance the antitumor efficacy of PD-1 antibody in HCC","volume":"10","author":"Li","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/s12032-023-02129-z","article-title":"6-Methoxydihydrosanguinarine exhibits cytotoxicity and sensitizes TRAIL-induced apoptosis of hepatocellular carcinoma cells through ROS-mediated upregulation of DR5","volume":"40","author":"Wang","year":"2023","journal-title":"Med. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/ptr.7601","article-title":"6-Methoxydihydrosanguinarine induces apoptosis and autophagy in breast cancer MCF-7 cells by accumulating ROS to suppress the PI3K\/AKT\/mTOR signaling pathway","volume":"37","author":"Zhang","year":"2023","journal-title":"Phytother. Res. PTR"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Han, L., Gao, C., Jin, X., Li, Y., Chen, L., Li, D., Deng, Q., and Bian, X. (2025). Bioactive natural alkaloid 6-Methoxydihydrosanguinarine exerts anti-tumor effects in hepatocellular carcinoma cells via ferroptosis. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1500461"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5307","DOI":"10.1007\/s12013-025-01850-y","article-title":"6-Methoxydihydrosanguinarine Suppresses the Proliferation of Non-small Cell Lung Cancer Cells through Elevation of ROS and Activation of IRE1\/JNK Signaling","volume":"83","author":"Qi","year":"2025","journal-title":"Cell Biochem. Biophys."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"178544","DOI":"10.1016\/j.ejphar.2026.178544","article-title":"6-Methoxydihydrosanguinarine synergizes with cisplatin to enhance lung cancer cell death via ROS-mediated autophagy, ER stress, and JNK activation","volume":"1014","author":"Fu","year":"2026","journal-title":"Eur. J. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Liu, X., Ren, Y., Qin, S., and Yang, Z. (2024). Exploring the mechanism of 6-Methoxydihydrosanguinarine in the treatment of lung adenocarcinoma based on network pharmacology, molecular docking and experimental investigation. BMC Complement. Med. Ther., 24.","DOI":"10.1186\/s12906-024-04497-z"},{"key":"ref_82","first-page":"328","article-title":"The Mechanism of Ethoxydihydrosanguinarine Targeting EGFR to Inhibit Malignant Progression and Induce Apoptosis of Colorectal Cancer","volume":"53","author":"Tan","year":"2024","journal-title":"Acta Med. Univ. Sci. Technol. Huazhong"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.fct.2013.04.051","article-title":"6-Acetonyl-5,6-dihydrosanguinarine (ADS) from Chelidonium majus L. triggers proinflammatory cytokine production via ROS-JNK\/ERK-NF\u03baB signaling pathway","volume":"58","author":"Kim","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/bs.pmbts.2024.03.013","article-title":"Current progress in high-throughput screening for drug repurposing","volume":"205","author":"Khambhati","year":"2024","journal-title":"Progress Mol. Biol. Transl. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1080\/15376510903313825","article-title":"Phenotype of hepatic xenobiotic metabolizing enzymes and CYP450 isoforms of sanguinarine treated rats: Effect of P450 inducers on its toxicity","volume":"19","author":"Eruvaram","year":"2009","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Laines-Hidalgo, J.I., Mu\u00f1oz-S\u00e1nchez, J.A., Loza-M\u00fcller, L., and V\u00e1zquez-Flota, F. (2022). An Update of the Sanguinarine and Benzophenanthridine Alkaloids\u2019 Biosynthesis and Their Applications. Molecules, 27.","DOI":"10.3390\/molecules27041378"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.2174\/1871520621666210126091512","article-title":"Sanguinarine: A Double-Edged Sword of Anticancer and Carcinogenesis and Its Future Application Prospect","volume":"21","author":"Lou","year":"2021","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Singh, N., and Sharma, B. (2018). Toxicological Effects of Berberine and Sanguinarine. Front. Mol. Biosci., 5.","DOI":"10.3389\/fmolb.2018.00021"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"105911","DOI":"10.1016\/j.yrtph.2025.105911","article-title":"Insights into sanguinarine toxicity in Rats: Integrating toxicokinetics, oxidative stress, and gut microbial alterations","volume":"162","author":"Xu","year":"2025","journal-title":"Regul. Toxicol. Pharmacol. RTP"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"109228","DOI":"10.1016\/j.cbpc.2021.109228","article-title":"Cardiotoxicity of sanguinarine via regulating apoptosis and MAPK pathways in zebrafish and HL1 cardiomyocytes","volume":"252","author":"Wang","year":"2022","journal-title":"Comp. Biochem. Physiol. Toxicol. Pharmacol. CBP"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.toxlet.2021.07.001","article-title":"Developmental toxicity caused by sanguinarine in zebrafish embryos via regulating oxidative stress, apoptosis and wnt pathways","volume":"350","author":"Yang","year":"2021","journal-title":"Toxicol. Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.toxlet.2011.06.018","article-title":"Embryonic toxicity of sanguinarine through apoptotic processes in mouse blastocysts","volume":"205","author":"Chan","year":"2011","journal-title":"Toxicol. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"108898","DOI":"10.1016\/j.fsi.2023.108898","article-title":"Sanguinarine exposure induces immunotoxicity and abnormal locomotor behavior in zebrafish","volume":"139","author":"Li","year":"2023","journal-title":"Fish Shellfish Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"105259","DOI":"10.1016\/j.pestbp.2022.105259","article-title":"Neurotoxicity of sanguinarine via inhibiting mitophagy and activating apoptosis in zebrafish and PC12 cells","volume":"188","author":"Yang","year":"2022","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.3109\/13880209.2014.891139","article-title":"Cytotoxic activity of the alkaloids from Broussonetia papyrifera fruits","volume":"52","author":"Pang","year":"2014","journal-title":"Pharm. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.tiv.2009.01.016","article-title":"Cytotoxic activity of sanguinarine and dihydrosanguinarine in human promyelocytic leukemia HL-60 cells","volume":"23","author":"Vrba","year":"2009","journal-title":"Toxicol. Vitr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1016\/j.fct.2008.04.013","article-title":"The toxicity and pharmacokinetics of dihydrosanguinarine in rat: A pilot study","volume":"46","author":"Vrublova","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.toxlet.2019.04.031","article-title":"Characterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes","volume":"311","author":"Gao","year":"2019","journal-title":"Toxicol. Lett."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.phytochem.2017.10.010","article-title":"Sanguinarine is reduced by NADH through a covalent adduct","volume":"145","author":"Sandor","year":"2018","journal-title":"Phytochemistry"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.toxlet.2013.11.028","article-title":"NQO1 involves in the imine bond reduction of sanguinarine and recombinant adeno-associated virus mediated NQO1 overexpression decreases sanguinarine-induced cytotoxicity in rat BRL cells","volume":"225","author":"Zhang","year":"2014","journal-title":"Toxicol. Lett."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jpba.2009.09.014","article-title":"Metabolism of sanguinarine in human and in rat: Characterization of oxidative metabolites produced by human CYP1A1 and CYP1A2 and rat liver microsomes using liquid chromatography-tandem mass spectrometry","volume":"52","author":"Deroussent","year":"2010","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1177\/019262339101900312","article-title":"Incidence and pathology of spontaneous renal pelvis transitional cell carcinomas in rats","volume":"19","author":"Chandra","year":"1991","journal-title":"Toxicol. Pathol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/S1734-1140(13)71498-1","article-title":"Reductive metabolism of the sanguinarine iminium bond by rat liver preparations","volume":"65","author":"Wu","year":"2013","journal-title":"Pharmacol. Rep. PR"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00216-009-2903-9","article-title":"Fluorescence of sanguinarine: Fundamental characteristics and analysis of interconversion between various forms","volume":"395","author":"Kubala","year":"2009","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Van Niekerk, A., Laubscher, R., and Laflamme, L. (2009). Demographic and circumstantial accounts of burn mortality in Cape Town, South Africa, 2001\u20132004: An observational register based study. BMC Public Health, 9.","DOI":"10.1186\/1471-2458-9-374"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/bcp.14404","article-title":"Warfarin and food, herbal or dietary supplement interactions: A systematic review","volume":"87","author":"Tan","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1111\/bcp.14833","article-title":"Drug-drug interactions with warfarin: A systematic review and meta-analysis","volume":"87","author":"Wang","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_108","unstructured":"Pratt, V.M., Scott, S.A., Pirmohamed, M., Esquivel, B., Kattman, B.L., and Malheiro, A.J. (2012). Omeprazole Therapy and CYP2C19 Genotype, Medical Genetics Summaries."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e18636","DOI":"10.7717\/peerj.18636","article-title":"CYP3A4 and CYP3A5: The crucial roles in clinical drug metabolism and the significant implications of genetic polymorphisms","volume":"12","author":"Zhang","year":"2024","journal-title":"PeerJ"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s40104-025-01220-x","article-title":"Dihydrosanguinarine enhances tryptophan metabolism and intestinal immune function via AhR pathway activation in broilers","volume":"16","author":"Su","year":"2025","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jchromb.2015.01.001","article-title":"Simultaneous quantitative determination of sanguinarine, chelerythrine, dihydrosanguinarine and dihydrochelerythrine in chicken by HPLC-MS\/MS method and its applications to drug residue and pharmacokinetic study","volume":"985","author":"Xie","year":"2015","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/jvp.12729","article-title":"Pharmacokinetics of sanguinarine, chelerythrine, and their metabolites in broiler chickens following oral and intravenous administration","volume":"42","author":"Hu","year":"2019","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1182\/hematology.2024000556","article-title":"Are TP53 mutations all alike?","volume":"2024","author":"Wong","year":"2024","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s11060-022-04214-1","article-title":"Deep DNA sequencing of MGMT, TP53 and AGT in Mexican astrocytoma patients identifies an excess of genetic variants in women and a predictive biomarker","volume":"161","year":"2023","journal-title":"J. Neuro-Oncol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"153025","DOI":"10.1016\/j.prp.2020.153025","article-title":"Diagnostic accuracy of p53 immunohistochemistry as surrogate of TP53 sequencing in endometrial cancer","volume":"216","author":"Raffone","year":"2020","journal-title":"Pathol. Res. Pract."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/s41418-022-00988-z","article-title":"Cell cycle regulation: P53-p21-RB signaling","volume":"29","author":"Engeland","year":"2022","journal-title":"Cell Death Differ."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1093\/molehr\/4.12.1099","article-title":"The relationship between BcI2, Bax and p53: Consequences for cell cycle progression and cell death","volume":"4","author":"Basu","year":"1998","journal-title":"Mol. Hum. Reprod."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s12020-023-03362-2","article-title":"Metabolic adverse events of multitarget kinase inhibitors: A systematic review","volume":"81","author":"Acitelli","year":"2023","journal-title":"Endocrine"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1186\/s12964-024-01711-w","article-title":"Mechanisms, combination therapy, and biomarkers in cancer immunotherapy resistance","volume":"22","author":"Yang","year":"2024","journal-title":"Cell Commun. Signal. CCS"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"4309","DOI":"10.1080\/21655979.2022.2031412","article-title":"Active pharmaceutical ingredient (API) chemicals: A critical review of current biotechnological approaches","volume":"13","author":"Kumar","year":"2022","journal-title":"Bioengineered"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Park, G., Kim, M.K., Go, S.H., Choi, M., and Jang, Y.P. (2022). Analytical Quality by Design (AQbD) Approach to the Development of Analytical Procedures for Medicinal Plants. Plants, 11.","DOI":"10.3390\/plants11212960"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Almaghrabi, M. (2025). Multitarget-Directed Ligands for Alzheimer\u2019s Disease: Recent Novel MTDLs and Mechanistic Insights. Pharmaceuticals, 18.","DOI":"10.3390\/ph18111685"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"eaaw8412","DOI":"10.1126\/scitranslmed.aaw8412","article-title":"Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials","volume":"11","author":"Lin","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"107100","DOI":"10.1016\/j.phrs.2024.107100","article-title":"Novel nano-drug delivery system for natural products and their application","volume":"201","author":"Huang","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"357","DOI":"10.4155\/tde-2023-0020","article-title":"Nano-drug delivery system: A promising approach against breast cancer","volume":"14","author":"Malik","year":"2023","journal-title":"Ther. Deliv."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.fitote.2010.05.001","article-title":"Applications of novel drug delivery system for herbal formulations","volume":"81","author":"Ajazuddin","year":"2010","journal-title":"Fitoterapia"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"052002","DOI":"10.1088\/2057-1976\/acedb2","article-title":"Nano-based drug delivery system for therapeutics: A comprehensive review","volume":"9","author":"Prakash","year":"2023","journal-title":"Biomed. Phys. Eng. Express"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12951-018-0392-8","article-title":"Nano based drug delivery systems: Recent developments and future prospects","volume":"16","author":"Patra","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.tcb.2024.06.003","article-title":"Deciphering the significance of p53 mutant proteins","volume":"35","author":"Butera","year":"2025","journal-title":"Trends Cell Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4852\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T08:03:28Z","timestamp":1779955408000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4852"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":129,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114852"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114852","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]}}}