{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:13:13Z","timestamp":1779297193363,"version":"3.51.4"},"reference-count":136,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"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>Prostate cancer (PCa) is the second most frequently diagnosed solid malignancy in men and a major cause of cancer-related mortality worldwide. While localized disease is associated with excellent long-term survival, advanced and castration-resistant PCa continues to represent a major therapeutic challenge. Current management ranges from active surveillance for indolent tumors to multimodal systemic approaches for metastatic disease. In this context, natural compounds are attracting increasing interest as adjunctive or novel therapeutic agents. Among these, silymarin, a Silybum marianum-derived flavonolignan complex, has shown promising antineoplastic activity in preclinical PCa models. In vitro, silymarin compounds consistently inhibit PCa cell proliferation by inducing G1 and G2\/M cell cycle arrest, upregulating cyclin-dependent kinase inhibitors, and activating caspase-dependent apoptotic pathways. They also modulate key oncogenic signaling pathways involved in cell survival, proliferation, invasion, and metastasis. In vivo xenograft and transgenic models further show reduced tumor growth, angiogenesis, and metastatic spread with limited systemic toxicity. Emerging clinical evidence, including systematic reviews and meta-analyses, suggests translational potential; however, robust randomized trials are needed to define optimal formulations, dosing strategies, and therapeutic efficacy in PCa patients. This review provides a comprehensive overview of the molecular mechanisms, preclinical efficacy, and emerging clinical evidence supporting silymarin as a candidate for future PCa research.<\/jats:p>","DOI":"10.3390\/ijms27104605","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:39:34Z","timestamp":1779295174000},"page":"4605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Silybum marianum-Derived Compounds in Prostate Cancer: Mechanisms of Action and Translational Potential"],"prefix":"10.3390","volume":"27","author":[{"given":"Federica","family":"Randisi","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Life Sciences (DBSV), University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2726-6655","authenticated-orcid":false,"given":"Giulia","family":"Modoni","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Sciences (DBSV), University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1657-1665","authenticated-orcid":false,"given":"Mattia","family":"Riva","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Sciences (DBSV), University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7209-9191","authenticated-orcid":false,"given":"Gianpaolo","family":"Perletti","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Sciences (DBSV), University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Odorico","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Sciences (DBSV), University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9363-1201","authenticated-orcid":false,"given":"Emanuela","family":"Marras","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Sciences (DBSV), University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5683-0885","authenticated-orcid":false,"given":"Marzia Bruna","family":"Gariboldi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Sciences (DBSV), University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1001\/jama.2025.0228","article-title":"Prostate Cancer","volume":"333","author":"Raychaudhuri","year":"2025","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-020-00243-0","article-title":"Prostate Cancer","volume":"7","author":"Rebello","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_3","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA. Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wasim, S., Lee, S.Y., and Kim, J. (2022). Complexities of Prostate Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214257"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3322\/caac.21871","article-title":"Cancer Statistics, 2025. CA","volume":"75","author":"Siegel","year":"2025","journal-title":"Cancer J. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.eururo.2012.02.054","article-title":"International Variation in Prostate Cancer Incidence and Mortality Rates","volume":"61","author":"Center","year":"2012","journal-title":"Eur. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.eururo.2016.05.043","article-title":"Global Incidence and Mortality for Prostate Cancer: Analysis of Temporal Patterns and Trends in 36 Countries","volume":"70","author":"Wong","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/S0140-6736(21)00950-8","article-title":"Prostate Cancer","volume":"398","author":"Sandhu","year":"2021","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"291","DOI":"10.4103\/aja.aja_128_18","article-title":"Neuroendocrine Cells of Prostate Cancer: Biologic Functions and Molecular Mechanisms","volume":"21","author":"Huang","year":"2019","journal-title":"Asian J. Androl."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.cell.2015.10.025","article-title":"The Molecular Taxonomy of Primary Prostate Cancer","volume":"163","author":"Abeshouse","year":"2015","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1172\/JCI132031","article-title":"Genomics of Lethal Prostate Cancer at Diagnosis and Castration Resistance","volume":"130","author":"Mateo","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.cell.2015.05.001","article-title":"Integrative Clinical Genomics of Advanced Prostate Cancer","volume":"161","author":"Robinson","year":"2015","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1038\/s41416-021-01675-5","article-title":"BRCA1 and BRCA2 Pathogenic Variants and Prostate Cancer Risk: Systematic Review and Meta-Analysis","volume":"126","author":"Nyberg","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_14","first-page":"S3","article-title":"Risk Factors for Prostate Cancer","volume":"4","author":"Gann","year":"2002","journal-title":"Rev. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/CLEP.S16747","article-title":"Risk Factors for the Onset of Prostatic Cancer: Age, Location, and Behavioral Correlates","volume":"4","author":"Leitzmann","year":"2012","journal-title":"Clin. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.eururo.2020.09.042","article-title":"EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer\u20142020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent","volume":"79","author":"Mottet","year":"2021","journal-title":"Eur. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/his.13767","article-title":"Grading of Prostate Cancer: A Work in Progress","volume":"74","author":"Kweldam","year":"2019","journal-title":"Histopathology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1097\/01.ju.0000113300.74132.8b","article-title":"Watchful Waiting and Factors Predictive of Secondary Treatment of Localized Prostate Cancer","volume":"171","author":"Wu","year":"2004","journal-title":"J. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1056\/NEJMoa040720","article-title":"Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer","volume":"351","author":"Tannock","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.eururo.2020.01.012","article-title":"Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019","volume":"77","author":"Gillessen","year":"2020","journal-title":"Eur. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1200\/OP-24-00591","article-title":"When You Get to the Fork in the Road, Take It: The Challenges in Managing Patients With Advanced Prostate Cancer","volume":"21","author":"Viscuse","year":"2025","journal-title":"JCO Oncol. Pract."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1001\/jamaoncol.2024.1549","article-title":"Cardiovascular Events and Androgen Receptor Signaling Inhibitors in Advanced Prostate Cancer","volume":"10","author":"Taktak","year":"2024","journal-title":"JAMA Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.eururo.2017.10.036","article-title":"Genomic Markers in Prostate Cancer Decision Making","volume":"73","author":"Cucchiara","year":"2018","journal-title":"Eur. Urol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e2423186","DOI":"10.1001\/jamanetworkopen.2024.23186","article-title":"Trends and Disparities in Next-Generation Sequencing in Metastatic Prostate and Urothelial Cancers","volume":"7","author":"Jo","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Salehi, B., Fokou, P.V.T., Yamthe, L.R.T., Tali, B.T., Adetunji, C.O., Rahavian, A., Mudau, F.N., Martorell, M., Setzer, W.N., and Rodrigues, C.F. (2019). Phytochemicals in Prostate Cancer: From Bioactive Molecules to Upcoming Therapeutic Agents. Nutrients, 11.","DOI":"10.3390\/nu11071483"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.semcancer.2016.06.003","article-title":"Bioactive Natural Products for Chemoprevention and Treatment of Castration-Resistant Prostate Cancer","volume":"40\u201341","author":"Kallifatidis","year":"2016","journal-title":"Semin. Cancer Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1111\/cas.13318","article-title":"Heat Shock Protein 70 Inhibitors Suppress Androgen Receptor Expression in LNCaP95 Prostate Cancer Cells","volume":"108","author":"Kita","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"54683","DOI":"10.18632\/oncotarget.18003","article-title":"Resveratrol Enhances Polyubiquitination-Mediated ARV7 Degradation in Prostate Cancer Cells","volume":"8","author":"Wilson","year":"2017","journal-title":"Oncotarget"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Fontana, F., Raimondi, M., Marzagalli, M., Di Domizio, A., and Limonta, P. (2020). Natural Compounds in Prostate Cancer Prevention and Treatment: Mechanisms of Action and Molecular Targets. Cells, 9.","DOI":"10.3390\/cells9020460"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1016\/j.cellsig.2013.01.014","article-title":"Crosstalk from Survival to Necrotic Death Coexists in DU-145 Cells by Curcumin Treatment","volume":"25","author":"Kang","year":"2013","journal-title":"Cell. Signal."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhang, C., Sheng, J., Li, G., Zhao, L., Wang, Y., Yang, W., Yao, X., Sun, L., Zhang, Z., and Cui, R. (2020). Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01461"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e12576","DOI":"10.1111\/cpr.12576","article-title":"\u0394-Tocotrienol Induces Apoptosis, Involving Endoplasmic Reticulum Stress and Autophagy, and Paraptosis in Prostate Cancer Cells","volume":"52","author":"Fontana","year":"2019","journal-title":"Cell Prolif."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1080\/17512433.2016.1208563","article-title":"Silibinin: A Potential Old Drug for Cancer Therapy","volume":"9","author":"Zhu","year":"2016","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Jaffar, H.M., Al-Asmari, F., Khan, F.A., Rahim, M.A., and Zongo, E. (2024). Silymarin: Unveiling Its Pharmacological Spectrum and Therapeutic Potential in Liver Diseases\u2014A Comprehensive Narrative Review. Food Sci. Nutr., 12.","DOI":"10.1002\/fsn3.4010"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"836","DOI":"10.15414\/jmbfs.2020.9.4.836-843","article-title":"Milk Thistle (Silybum Marianum): A Valuable Medicinal Plant with Several Therapeutic Purposes","volume":"9","year":"2020","journal-title":"J. Microbiol. Biotechnol. Food Sci."},{"key":"ref_36","first-page":"4457","article-title":"Anticancer Potential of Silymarin: From Bench to Bed Side","volume":"26","author":"Agarwal","year":"2006","journal-title":"Anticancer Res."},{"key":"ref_37","first-page":"35","article-title":"Silibinin Inhibits Fibronectin Induced Motility, Invasiveness and Survival in Human Prostate Carcinoma PC3 Cells via Targeting Integrin Signaling","volume":"768","author":"Deep","year":"2014","journal-title":"Mutat. Res.-Fundam. Mol. Mech. Mutagen."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/mc.22537","article-title":"Silibinin Inhibits Hypoxia-induced HIF-1\u03b1-mediated Signaling, Angiogenesis and Lipogenesis in Prostate Cancer Cells: In Vitro Evidence and in Vivo Functional Imaging and Metabolomics","volume":"56","author":"Deep","year":"2017","journal-title":"Mol. Carcinog."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"10017","DOI":"10.18632\/oncotarget.2488","article-title":"Silibinin Inhibits Aberrant Lipid Metabolism, Proliferation and Emergence of Androgen-Independence in Prostate Cancer Cells via Primarily Targeting the Sterol Response Element Binding Protein 1","volume":"5","author":"Nambiar","year":"2014","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/2515690X211068826","article-title":"Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions","volume":"27","author":"Koltai","year":"2022","journal-title":"J. Evid.-Based Integr. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1021\/np400955q","article-title":"Flavonolignans from Aspergillus iizukae, a Fungal Endophyte of Milk Thistle (Silybum marianum)","volume":"77","author":"Raja","year":"2014","journal-title":"J. Nat. Prod."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00432-007-0197-x","article-title":"Effects of Silymarin on the Spontaneous Proliferation and Cell Cycle of Human Peripheral Blood Leukemia T Cells","volume":"133","author":"Gharagozloo","year":"2007","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Boira, C., Chapuis, E., Scandolera, A., and Reynaud, R. (2024). Silymarin Alleviates Oxidative Stress and Inflammation Induced by UV and Air Pollution in Human Epidermis and Activates \u03b2-Endorphin Release through Cannabinoid Receptor Type 2. Cosmetics, 11.","DOI":"10.3390\/cosmetics11010030"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Sayyad, M., Sutar, A.D., Shivhare, K., Shukla, R., and Flora, S.J.S. (2025). Silymarin as a Phytopharmaceutical Agent: Advances in Mechanistic Insights, Formulation Strategies, and Pre-Clinical Applications. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1711653"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3390\/antiox4010204","article-title":"Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives","volume":"4","author":"Surai","year":"2015","journal-title":"Antioxidants"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.intimp.2017.06.030","article-title":"Silymarin Impacts on Immune System as an Immunomodulator: One Key for Many Locks","volume":"50","author":"Esmaeil","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3985207","DOI":"10.1155\/ijcp\/3985207","article-title":"The Impact of Silymarin on Inflammation and Oxidative Stress: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"2025","author":"Vajdi","year":"2025","journal-title":"Int. J. Clin. Pract."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bijak, M. (2017). Silybin, a Major Bioactive Component of Milk Thistle (Silybum marianum L. Gaernt.)\u2014Chemistry, Bioavailability, and Metabolism. Molecules, 22.","DOI":"10.3390\/molecules22111942"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1039\/D2NP00013J","article-title":"Silybin and Its Congeners: From Traditional Medicine to Molecular Effects","volume":"39","year":"2022","journal-title":"Nat. Prod. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Duan, W., Ou, Z., Huang, Y., Zhang, Y., Zhang, L., Zhao, Y., He, R., Zhang, Y., Ge, Y., and Lou, H. (2023). Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries. Antioxidants, 12.","DOI":"10.3390\/antiox12122119"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.jtcme.2017.07.002","article-title":"Herbal Remedies for Liver Fibrosis: A Review on the Mode of Action of Fifty Herbs","volume":"8","author":"Latief","year":"2018","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/ptr.5768","article-title":"Effects of Silymarin on Diabetes Mellitus Complications: A Review","volume":"31","author":"Stolf","year":"2017","journal-title":"Phyther. Res."},{"key":"ref_53","first-page":"3","article-title":"Silymarin and Diabetic Nephropathy","volume":"1","author":"Nasri","year":"2012","journal-title":"J. Ren. Inj. Prev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.endinu.2017.12.004","article-title":"Silymarin Prevents Diabetes-Induced Hyperpermeability in Human Retinal Endothelial Cells","volume":"65","author":"Turch","year":"2018","journal-title":"Endocrinol. Diabetes Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ctim.2018.08.010","article-title":"The Effects of Silymarin Supplementation on Metabolic Status and Oxidative Stress in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Clinical Trials","volume":"41","author":"Hadi","year":"2018","journal-title":"Complement. Ther. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.phymed.2018.03.050","article-title":"Lower Glycemic Indices and Lipid Profile among Type 2 Diabetes Mellitus Patients Who Received Novel Dose of Silybum marianum (L.) Gaertn. (Silymarin) Extract Supplement: A Triple-Blinded Randomized Controlled Clinical Trial","volume":"44","author":"Gargari","year":"2018","journal-title":"Phytomedicine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1055\/a-1528-2721","article-title":"Recapitulation of Evidence of Phytochemical, Pharmacokinetic and Biomedical Application of Silybin","volume":"71","author":"Islam","year":"2021","journal-title":"Drug Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Wadhwa, K., Pahwa, R., Kumar, M., Kumar, S., Sharma, P.C., Singh, G., Verma, R., Mittal, V., Singh, I., and Kaushik, D. (2022). Mechanistic Insights into the Pharmacological Significance of Silymarin. Molecules, 27.","DOI":"10.3390\/molecules27165327"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"153320","DOI":"10.1016\/j.phymed.2020.153320","article-title":"Silymarin and Neurodegenerative Diseases: Therapeutic Potential and Basic Molecular Mechanisms","volume":"79","author":"Haddadi","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1111\/cns.12175","article-title":"Neuroprotective Potential of Silymarin against CNS Disorders: Insight into the Pathways and Molecular Mechanisms of Action","volume":"19","author":"Borah","year":"2013","journal-title":"CNS Neurosci. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1046\/j.1460-9568.2002.02290.x","article-title":"Silymarin Protects Dopaminergic Neurons against Lipopolysaccharide-Induced Neurotoxicity by Inhibiting Microglia Activation","volume":"16","author":"Wang","year":"2002","journal-title":"Eur. J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1271\/bbb.100524","article-title":"Silymarin Attenuated the Amyloid \u03b2 Plaque Burden and Improved Behavioral Abnormalities in an Alzheimer\u2019s Disease Mouse Model","volume":"74","author":"Urata","year":"2010","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/2008-2231-22-24","article-title":"Silymarin Effect on Amyloid-\u03b2 Plaque Accumulation and Gene Expression of APP in an Alzheimer\u2019s Disease Rat Model","volume":"22","author":"Yaghmaei","year":"2014","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/s10753-019-00980-9","article-title":"Silymarin Restores Regulatory T Cells (Tregs) Function in Multiple Sclerosis (MS) Patients In Vitro","volume":"42","author":"Shariati","year":"2019","journal-title":"Inflammation"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Zhang, C., Sui, Y., Liu, S., and Yang, M. (2023). Anti-Viral Activity of Bioactive Molecules of Silymarin against COVID-19 via In Silico Studies. Pharmaceuticals, 16.","DOI":"10.3390\/ph16101479"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jns.2011.07.035","article-title":"Silymarin Protects Neurons from Oxidative Stress Associated Damages in Focal Cerebral Ischemia: A Behavioral, Biochemical and Immunohistological Study in Wistar Rats","volume":"309","author":"Raza","year":"2011","journal-title":"J. Neurol. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1600-079X.2010.00819.x","article-title":"Melatonin or Silymarin Reduces Maneb- and Paraquat-Induced Parkinsons Disease Phenotype in the Mouse","volume":"50","author":"Singhal","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1111\/j.1476-5381.2009.00295.x","article-title":"Silibinin Prevents Amyloid b Peptide-Induced Memory Impairment and Oxidative Stress in Mice","volume":"157","author":"Lu","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.bbr.2009.10.024","article-title":"Silibinin Attenuates Cognitive Deficits and Decreases of Dopamine and Serotonin Induced by Repeated Methamphetamine Treatment","volume":"207","author":"Lu","year":"2010","journal-title":"Behav. Brain Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ijbiomac.2014.01.023","article-title":"Polyphenol Compounds Belonging to Flavonoids Inhibit Activity of Coagulation Factor X","volume":"65","author":"Bijak","year":"2014","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.ijbiomac.2016.12.002","article-title":"Flavonolignans Inhibit ADP Induced Blood Platelets Activation and Aggregation in Whole Blood","volume":"95","author":"Bijak","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1007\/s00044-013-0829-4","article-title":"Thrombin Inhibitory Activity of Some Polyphenolic Compounds","volume":"23","author":"Bijak","year":"2014","journal-title":"Med. Chem. Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Ray, P.P., Islam, M.A., Islam, M.S., Han, A., Geng, P., Aziz, M.A., and Mamun, A. (2024). Al A Comprehensive Evaluation of the Therapeutic Potential of Silibinin: A Ray of Hope in Cancer Treatment. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1349745"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.canlet.2008.03.053","article-title":"Multitargeted Therapy of Cancer by Silymarin","volume":"269","author":"Ramasamy","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1002\/ptr.6470","article-title":"Silymarin Antiproliferative and Apoptotic Effects: Insights into Its Clinical Impact in Various Types of Cancer","volume":"33","author":"Hosseinabadi","year":"2019","journal-title":"Phyther. Res."},{"key":"ref_76","first-page":"1904","article-title":"Silymarin Induces Inhibition of Growth and Apoptosis through Modulation of the MAPK Signaling Pathway in AGS Human Gastric Cancer Cells","volume":"42","author":"Kim","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.bbadis.2009.12.009","article-title":"Pathological Roles of MAPK Signaling Pathways in Human Diseases","volume":"1802","author":"Kim","year":"2010","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41392-023-01705-z","article-title":"Targeting the RAS\/RAF\/MAPK Pathway for Cancer Therapy: From Mechanism to Clinical Studies","volume":"8","author":"Bahar","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1007\/s00405-013-2444-x","article-title":"Silibinin Induced the Apoptosis of Hep-2 Cells via Oxidative Stress and down-Regulating Survivin Expression","volume":"270","author":"Yang","year":"2013","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1002\/mc.22208","article-title":"Silymarin Inhibits Melanoma Cell Growth Both in Vitro and in Vivo by Targeting Cell Cycle Regulators, Angiogenic Biomarkers and Induction of Apoptosis","volume":"54","author":"Vaid","year":"2015","journal-title":"Mol. Carcinog."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Won, D.H., Kim, L.H., Jang, B., Yang, I.H., Kwon, H.J., Jin, B., Oh, S.H., Kang, J.H., Hong, S.D., and Shin, J.A. (2018). In Vitro and in Vivo Anti-Cancer Activity of Silymarin on Oral Cancer. Tumor Biol., 40.","DOI":"10.1177\/1010428318776170"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1007\/s10495-011-0631-z","article-title":"Silibinin Triggers Apoptotic Signaling Pathways and Autophagic Survival Response in Human Colon Adenocarcinoma Cells and Their Derived Metastatic Cells","volume":"16","author":"Kauntz","year":"2011","journal-title":"Apoptosis"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41392-024-02080-z","article-title":"Cyclin-Dependent Protein Kinases and Cell Cycle Regulation in Biology and Disease","volume":"10","author":"Pellarin","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ejphar.2014.09.019","article-title":"Silymarin Induces Cell Cycle Arrest and Apoptosis in Ovarian Cancer Cells","volume":"743","author":"Fan","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1093\/carcin\/bgh180","article-title":"Silibinin Causes Cell Cycle Arrest and Apoptosis in Human Bladder Transitional Cell Carcinoma Cells by Regulating CDKI-CDK-Cyclin Cascade, and Caspase 3 and PARP Cleavages","volume":"25","author":"Tyagi","year":"2004","journal-title":"Carcinogenesis"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1038\/sj.onc.1209146","article-title":"Silymarin and Silibinin Cause G1 and G2-M Cell Cycle Arrest via Distinct Circuitries in Human Prostate Cancer PC3 Cells: A Comparison of Flavanone Silibinin with Flavanolignan Mixture Silymarin","volume":"25","author":"Deep","year":"2006","journal-title":"Oncogene"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s12672-025-01800-3","article-title":"Silymarin: A Promising Modulator of Apoptosis and Survival Signaling in Cancer","volume":"16","author":"Sharma","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"112409","DOI":"10.1016\/j.biopha.2021.112409","article-title":"Silybum Marianum Total Extract, Silymarin and Silibinin Abate Hepatocarcinogenesis and Hepatocellular Carcinoma Growth via Modulation of the HGF\/c-Met, Wnt\/\u03b2-Catenin, and PI3K\/Akt\/MTOR Signaling Pathways","volume":"145","author":"Yassin","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.ejphar.2015.08.057","article-title":"Silibinin-Induced Glioma Cell Apoptosis by PI3K-Mediated but Akt-Independent Downregulation of FoxM1 Expression","volume":"765","author":"Zhang","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"119197","DOI":"10.1016\/j.lfs.2021.119197","article-title":"Silymarin Nanoliposomes Attenuate Renal Injury on Diabetic Nephropathy Rats via Co-Suppressing TGF-\u03b2\/Smad and JAK2\/STAT3\/SOCS1 Pathway","volume":"271","author":"Chen","year":"2021","journal-title":"Life Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.fct.2018.04.028","article-title":"Silibinin Is a Direct Inhibitor of STAT3","volume":"116","author":"Verdura","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.molmed.2015.04.001","article-title":"EGFR and NF-\u039aB: Partners in Cancer","volume":"21","author":"Shostak","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e70643","DOI":"10.1002\/cam4.70643","article-title":"The Effects of Silibinin Combined With EGFR-TKIs in the Treatment of NSCLC","volume":"14","author":"Wang","year":"2025","journal-title":"Cancer Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.4161\/epi.22070","article-title":"Epigenetic Modifications and P21-Cyclin B1 Nexus in Anticancer Effect of Histone Deacetylase Inhibitors in Combination with Silibinin on Non-Small Cell Lung Cancer Cells","volume":"7","author":"Mateen","year":"2012","journal-title":"Epigenetics"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Eckschlager, T., Plch, J., Stiborova, M., and Hrabeta, J. (2017). Histone Deacetylase Inhibitors as Anticancer Drugs. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071414"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1038\/aps.2009.94","article-title":"Silibinin Inhibits Prostate Cancer Invasion, Motility and Migration by Suppressing Vimentin and MMP-2 Expression","volume":"30","author":"Wu","year":"2009","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.cellbi.2008.03.019","article-title":"Evaluation of Silibinin on the Viability, Migration and Adhesion of the Human Prostate Adenocarcinoma (PC-3) Cell Line","volume":"32","author":"Mokhtari","year":"2008","journal-title":"Cell Biol. Int."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/cam4.186","article-title":"Silibinin Inhibits Accumulation of Myeloid-Derived Suppressor Cells and Tumor Growth of Murine Breast Cancer","volume":"3","author":"Forghani","year":"2014","journal-title":"Cancer Med."},{"key":"ref_99","first-page":"166","article-title":"Silibinin Improved the Function of T Cells in Peripheral Blood Mononuclear Cells (PBMCs) Co-Cultured with U-87 MG Cell Line","volume":"14","author":"Abadi","year":"2024","journal-title":"Avicenna J. Phytomedicine"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"51","DOI":"10.34172\/bi.2022.23698","article-title":"Silibinin Induces Immunogenic Cell Death in Cancer Cells and Enhances the Induced Immunogenicity by Chemotherapy","volume":"13","author":"Jafari","year":"2023","journal-title":"BioImpacts"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1080\/13880209.2016.1270972","article-title":"Silibinin Sensitizes Chemo-Resistant Breast Cancer Cells to Chemotherapy","volume":"55","author":"Molavi","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.canlet.2013.07.017","article-title":"Silibinin Reverses Drug Resistance in Human Small-Cell Lung Carcinoma Cells","volume":"339","author":"Sadava","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Verdura, S., Encinar, J.A., Teixidor, E., Segura-Carretero, A., Micol, V., Cuy\u00e0s, E., Bosch-Barrera, J., and Menendez, J.A. (2022). Silibinin Overcomes EMT-Driven Lung Cancer Resistance to New-Generation ALK Inhibitors. Cancers, 14.","DOI":"10.3390\/cancers14246101"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Delmas, D., Xiao, J., Vejux, A., and Aires, V. (2020). Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity. Molecules, 25.","DOI":"10.3390\/molecules25092009"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/ptr.6231","article-title":"Topical Silymarin Administration for Prevention of Acute Radiodermatitis in Breast Cancer Patients: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial","volume":"33","author":"Karbasforooshan","year":"2019","journal-title":"Phyther. Res."},{"key":"ref_106","first-page":"OC11","article-title":"Effect of Silymarin in the Prevention of Cisplatin Nephrotoxicity, a Clinical Trial Study","volume":"9","author":"Momeni","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1002\/ptr.5857","article-title":"Topical Silymarin Administration for Prevention of Capecitabine-Induced Hand\u2013Foot Syndrome: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial","volume":"31","author":"Elyasi","year":"2017","journal-title":"Phyther. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1208\/s12248-013-9486-2","article-title":"Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer","volume":"15","author":"Ting","year":"2013","journal-title":"AAPS J."},{"key":"ref_109","first-page":"1920","article-title":"A Flavonoid Antioxidant, Silymarin, Inhibits Activation of ErbB1 Signaling and Induces Cyclin-Dependent Kinase Inhibitors, G1 Arrest, and Anticarcinogenic Effects in Human Prostate Carcinoma DU145 Cells1","volume":"58","author":"Zi","year":"1998","journal-title":"Cancer Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"7490","DOI":"10.1073\/pnas.96.13.7490","article-title":"Silibinin Decreases Prostate-Specific Antigen with Cell Growth Inhibition via G1 Arrest, Leading to Differentiation of Prostate Carcinoma Cells: Implications for Prostate Cancer Intervention","volume":"96","author":"Zi","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.bbrc.2015.10.143","article-title":"Autophagy Inhibition Enhances Silibinin-Induced Apoptosis by Regulating Reactive Oxygen Species Production in Human Prostate Cancer PC-3 Cells","volume":"468","author":"Kim","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s10555-010-9237-0","article-title":"Antimetastatic Efficacy of Silibinin: Molecular Mechanisms and Therapeutic Potential against Cancer","volume":"29","author":"Deep","year":"2010","journal-title":"Cancer Metastasis Rev."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1158\/1940-6207.CAPR-10-0370","article-title":"Role of E-Cadherin in Antimigratory and Antiinvasive Efficacy of Silibinin in Prostate Cancer Cells","volume":"4","author":"Deep","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1016\/j.cellsig.2012.07.009","article-title":"Silibinin Inhibits Wnt\/\u03b2-Catenin Signaling by Suppressing Wnt Co-Receptor LRP6 Expression in Human Prostate and Breast Cancer Cells","volume":"24","author":"Lu","year":"2012","journal-title":"Cell. Signal."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"6822","DOI":"10.1158\/0008-5472.CAN-08-1332","article-title":"Stage-Specific Inhibitory Effects and Associated Mechanisms of Silibinin on Tumor Progression and Metastasis in Transgenic Adenocarcinoma of the Mouse Prostate Model","volume":"68","author":"Raina","year":"2008","journal-title":"Cancer Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"7773","DOI":"10.1158\/1078-0432.CCR-08-1309","article-title":"Silibinin Inhibits Established Prostate Tumor Growth, Progression, Invasion, and Metastasis and Suppresses Tumor Angiogenesis and Epithelial-Mesenchymal Transition in Transgenic Adenocarcinoma of the Mouse Prostate Model Mice","volume":"14","author":"Singh","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1093\/carcin\/bgm218","article-title":"Silibinin Suppresses in Vivo Growth of Human Prostate Carcinoma PC-3 Tumor Xenograft","volume":"28","author":"Singh","year":"2007","journal-title":"Carcinogenesis"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1002\/ijc.23879","article-title":"Isosilibinin Inhibits Advanced Human Prostate Cancer Growth in Athymic Nude Mice: Comparison with Silymarin and Silibinin","volume":"123","author":"Deep","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1158\/1078-0432.CCR-08-1846","article-title":"Silibinin Suppresses Growth of Human Prostate Carcinoma PC-3 Orthotopic Xenograft via Activation of Extracellular Signal-Regulated Kinase 1\/2 and Inhibition of Signal Transducers and Activators of Transcription Signaling","volume":"15","author":"Singh","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3138\/canlivj-2023-0021","article-title":"Effects of Silymarin Use on Liver Enzymes and Metabolic Factors in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis","volume":"7","author":"Malik","year":"2024","journal-title":"Can. Liver J."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2572","DOI":"10.1002\/ptr.8173","article-title":"Effects of Silymarin Supplementation on Liver and Kidney Functions: A Systematic Review and Dose\u2013Response Meta-Analysis","volume":"38","author":"Mohammadi","year":"2024","journal-title":"Phyther. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e15774","DOI":"10.1111\/dth.15774","article-title":"Pharmacological Prevention Strategy for Capecitabine-Induced Hand-Foot Syndrome: A Network Meta-Analysis of Randomized Control Trials","volume":"35","author":"Kao","year":"2022","journal-title":"Dermatol. Ther."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/cncr.24723","article-title":"A Randomized, Controlled, Double-Blind, Pilot Study of Milk Thistle for the Treatment of Hepatotoxicity in Childhood Acute Lymphoblastic Leukemia (ALL)","volume":"116","author":"Ladas","year":"2010","journal-title":"Cancer"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1177\/10781552241268778","article-title":"Evaluation of Oral Silymarin Formulation Efficacy in Prevention of Doxorubicin Induced Hepatotoxicity in Patients with Non-Metastatic Breast Cancer","volume":"31","author":"Karimi","year":"2025","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s10637-006-9019-2","article-title":"A Phase I and Pharmacokinetic Study of Silybin-Phytosome in Prostate Cancer Patients","volume":"25","author":"Flaig","year":"2007","journal-title":"Investig. New Drugs"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1002\/pros.21118","article-title":"A Study of High-Dose Oral Silybin-Phytosome Followed by Prostatectomy in Patients with Localized Prostate Cancer","volume":"70","author":"Flaig","year":"2010","journal-title":"Prostate"},{"key":"ref_127","first-page":"3063","article-title":"Dietary Feeding of Silibinin Inhibits Advance Human Prostate Carcinoma Growth in Athymic Nude Mice and Increases Plasma Insulin-like Growth Factor-Binding Protein-3 Levels","volume":"62","author":"Singh","year":"2002","journal-title":"Cancer Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.eururo.2005.08.005","article-title":"Randomized, Double-Blind, Placebo-Controlled Crossover Study in Men with Prostate Cancer and Rising PSA: Effectiveness of a Dietary Supplement","volume":"48","author":"Roobol","year":"2005","journal-title":"Eur. Urol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"239","DOI":"10.5507\/bp.2010.036","article-title":"The Safety and Efficacy of a Silymarin and Selenium Combination in Men after Radical Prostatectomy\u2014A Six Month Placebo-Controlled Double-Blind Clinical Trial","volume":"154","author":"Vidlar","year":"2010","journal-title":"Biomed. Pap."},{"key":"ref_130","first-page":"727","article-title":"Evaluation of Efficacy of Cholecalciferol and Silymarin in Improving Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia: A Double-Blind, Randomized, Controlled Trial","volume":"91","author":"Valipour","year":"2024","journal-title":"Urol. J."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.phymed.2013.07.018","article-title":"Use of Selenium-Silymarin Mix Reduces Lower Urinary Tract Symptoms and Prostate Specific Antigen in Men","volume":"21","author":"Vostalova","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"155598","DOI":"10.1016\/j.phymed.2024.155598","article-title":"Effects of Natural Extract Interventions in Prostate Cancer: A Systematic Review and Network Meta-Analysis","volume":"129","author":"Huang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Anestopoulos, I., Sfakianos, A.P., Franco, R., Chlichlia, K., Panayiotidis, M.I., Kroll, D.J., and Pappa, A. (2017). A Novel Role of Silibinin as a Putative Epigenetic Modulator in Human Prostate Carcinoma. Molecules, 22.","DOI":"10.3390\/molecules22010062"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Mu\u00f1oz, A.M., Victoria-Montesinos, D., Ballester, P., Cerd\u00e1, B., and Zafrilla, P. (2024). A Descriptive Review of the Antioxidant Effects and Mechanisms of Action of Berberine and Silymarin. Molecules, 29.","DOI":"10.3390\/molecules29194576"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Di Costanzo, A., and Angelico, R. (2019). Formulation Strategies for Enhancing the Bioavailability of Silymarin: The State of the Art. Molecules, 24.","DOI":"10.3390\/molecules24112155"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4605\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:39:54Z","timestamp":1779295194000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":136,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104605"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104605","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]}}}