Legalon (silibinin) / Viatris - LARVOL DELTA

Phenylalanine-Coated PLGA Nanoparticles for Targeted Delivery of Silibinin in Hepatocellular Carcinoma. (PubMed, Mol Pharm) - "This enhanced effect is attributed to their higher internalization via LAT transporters, which are overexpressed in HCC cells. These results suggest that LAT-targeted nanoparticles represent a promising technological approach to enhance the antitumor efficacy of antineoplastic agents in hepatocellular carcinoma."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Silibinin enhances daunorubicin chemosensitivity in Acute Myeloid Leukemia by suppressing PDIA3-mediated autophagy (ASH 2025) - "We measured autophagy flux using chloroquine (HCQ) and ATG5 siRNA. Silibinin,identified as an inhibitor of PDIA3, has been shown to restore autophagy and enhance chemosensitivityin both in vitro and in vivo models. This research highlights PDIA3 as a promising therapeutic target andpositions silibinin as a potentially effective chemosensitizer for the treatment of AML."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • ATG5 • CASP3 • GLI2 • PDIA3 • TINCR

Effect of oral silymarin in patients with acute hepatotoxic mushroom poisoning: an analysis of poison center data. (PubMed, Clin Toxicol (Phila)) - "Intravenous silibinin may reduce mortality in patients with hepatotoxic mushroom poisoning, but it is unavailable in some countries...We were unable to demonstrate a reduction in mortality, acute liver failure, or hospital length of stay associated with oral silymarin use. However, it appeared to decrease the incidence of acute kidney injury."

Journal • Acute Kidney Injury • Hepatology • Liver Failure • Nephrology • Renal Disease

Silibinin inhibits F-actin assembly leading to G2/M cell cycle arrest in human breast cancer cells - is targeted therapy on the horizon? (PubMed, Biochem Pharmacol) - "Our results reveal the F-actin assembly is inhibited by silibinin, and this results in G2/M cell cycle arrest in human breast cancer cells, providing new ideas for anti-cancer therapies including TNBCs. Abbreviations: ABPs, actin binding proteins; ARP2, actin-related protein2; Capza1, capping actin protein of muscle Z-line subunit alpha 1; CDC2, Cell Division Cycle protein 2/CDK1, Cyclin-Dependent Kinase 1; CDKi, cyclin-dependent kinase inhibitors; CDKs, cyclin-dependent kinases; CETSA, cellular thermal shift assay; CFL1, cofilin 1; Cyto D, Cytochalasin D; DARTS, drug affinity responsive target stability; DIAPH3, diaphanous related formin 3; DMEM, Dulbecco's Modified Eagle medium; ER, estrogen receptor; F-actin, filamentous actin; FBS, fetal bovine serum; G-actin, globular actin; GSN, gelsolin; HER2, human epidermal growth factor receptor 2; LAMP1, lysosomal associated membrane protein 1; NLS, nuclear localization signal; PDB, protein data bank; PFN1, profilin 1; PR,..."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ACTR2 • CDK1 • DIAPH3 • ER • GSN • HER-2 • LAMP1 • PGR

Ex vivo evaluation of the antimicrobial properties, physical and mechanical characteristics, and cytotoxicity of orthodontic cement containing silibinin against Streptococcus mutans biofilm. (PubMed, Int Orthod) - "RMGIC containing 5% silibinin effectively reduced S. mutans biofilm around orthodontic brackets without adversely affecting its physical-mechanical properties and showed no toxicity to HGF cells."

Journal • Preclinical

The Role of Natural Products in Liver Cancer: Focus on Angiogenesis, Inflammation, Oxidative Stress, and Apoptosis. (PubMed, Mol Nutr Food Res) - "Compounds such as silymarin, silibinin, resveratrol, curcumin, quercetin, genistein, naringenin, cucurbitacin, lycopene, crocin, aronia, Nigella sativa, epigallocatechin-3-gallate, and ginger (Zingiber officinale) demonstrate promise in HCC treatment, primarily through mechanisms involving the suppression of inflammation, regulation of oxidative stress, and promotion of apoptosis. This study searched PubMed, Scopus, Web of Science, Google Scholar, and ClinicalTrials.gov databases to evaluate the molecular mechanisms by which natural compounds are associated with HCC. The literature search was performed using the keywords "hepatocellular carcinoma," "angiogenesis," "inflammation," "oxidative stress," "natural products," and "apoptosis." By evaluating the findings cumulatively, the aim was to reveal the up-to-date scientific evidence for using natural compounds as potential therapeutic agents in treating HCC."

Journal • Review • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Immunology • Liver Cancer • Liver Cirrhosis • Obesity • Oncology • Solid Tumor • Transplantation

STRONG: Silibinin in Association With Concomitant Chemoradiotherapy and Maintenance Temozolomide in STAT3 Positive IDH Wild-type, Newly Diagnosed Glioblastoma Patients (clinicaltrials.gov) - P=N/A | N=110 | Recruiting | Sponsor: Istituto Oncologico Veneto IRCCS | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Role of Bisphenol A in the Development and Progression of Colorectal Cancer: Possible Sex-Specific Effects of Endogenous and Exogenous Estrogens. (PubMed, Biomedicines) - "The natural flavonolignan compound silibinin (SIL), acting as an estrogen agonist, may play a protective role in CRC in one or both sexes...To this end, we combined ex vivo, in vitro, and in vivo approaches to deepen our understanding of the molecular mechanisms involved. The data provided by this study will contribute to understanding the role of estrogens and their receptors in the onset and progression of CRC and the potential protective role of SIL in both sexes."

Journal • Colorectal Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor

Unveiling the therapeutic potential of silibinin in head and neck squamous cell carcinoma via network pharmacology. (PubMed, Sci Rep) - "Our data suggested that silibinin may inhibit HNSCC progression through modulation of the interleukin-17 signaling pathway. Molecular docking confirmed strong binding affinity between silibinin and key targets, supporting its potential as an HNSCC therapeutic agent."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IL17A

Silibinin mitigates AKI-to-CKD transition via MAPK and PI3K/AKT signaling pathways in Ischemia-Reperfusion injury. (PubMed, Sci Rep) - "Collectively, our findings demonstrated silibinin as a multi-target therapeutic candidate that impedes AKI-CKD transition via coordinated regulation of PI3K/AKT and MAPK pathways. These findings position silibinin as a promising agent for clinical intervention, potentially improving long-term renal outcomes in AKI patients at risk of progressing to CKD."

IO biomarker • Journal • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • Reperfusion Injury • BCL2 • CASP3 • TGFB1

New association of milk thistle and artichoke extracts enhances egg quality in caged-laying hens. (PubMed, Front Vet Sci) - "Given the antioxidant potential of silibinin and chlorogenic acid, their combined intermittent administration supports and maintains the egg quality in caged-laying hens exposed to metabolic stress and after the peak of production. However, further studies could be of interest to verify whether similar changes in egg-quality indices are observed with other phytoextract administration protocols, such as continuous administration, and at different administered doses."

Journal • Metabolic Disorders

Hepatoprotective effects of silibinin and chlorogenic acid standardised extract to alleviate the fatty liver syndrome and improve blood indices in caged-laying hens after the peak of production. (PubMed, Vet Anim Sci) - "At T5, in treated hens, the duodenum (proximal tract) showed unexpectedly higher pH, compared to the control hens (P < 0.05). This study showed that the combined phytoextracts administration is useful in improving the liver health of caged-laying hens affected by liver disorders, reducing liver steatosis, associated with an upgrade of main blood indices."

Journal • Hematological Disorders • Hepatology

Flavonoid-modulated JAK-STAT signaling mitigates malignant transformation and drug resistance in breast tumors: A clinically relevant 3PM-guided innovation. (PubMed, J Adv Res) - "Notably, natural compounds, including but not restricted to apigenin, quercetin, naringenin, morin, luteolin, butein, xanthohumol, silibinin, baicalein, nobiletin, rosmanol, orientin, eriocitrin, breviscapine, 8-hydroxydaidzein, icariside I, cardamonin, epigallocatechin-3-gallate, fisetin, brutieridin, melitidin, isoliquiritigenin, and sophoraflavanone G, have been recognized as potent JAK-STAT modulators in BC models...The paper follows principles of Predictive, Preventive, and Personalized Medicine (3PM), promoting the paradigm shift from reactive to proactive medicine. Contextually, it underscores the importance of multidisciplinary research to elucidate flavonoid-specific mechanisms, identify predictive biomarker panels, and develop advanced delivery systems, integrates patient phenotyping, multi-level diagnostics, and AI-driven data interpretation to enable cost-effective primary and secondary prevention, and therapeutic algorithms tailored to personalised patient..."

Journal • Review • Breast Cancer • Oncology • Solid Tumor

Evaluation of efficacy and safety of temozolomide and silibinin on the patients with glioblastoma (ChiCTR) - P=N/A | N=104 | Not yet recruiting | Sponsor: The First Hospital of Jilin University; The First Hospital of Jilin University

New trial • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Unexpected Harvest: Clinical Insights from Three Cases of Amanita Toxicity (ACG 2025) - "Patient B was a 32-year-old man with active alcohol and methamphetamine use...He received NAC, octreotide, activated charcoal, penicillin G, and underwent placement of percutaneous cholecystostomy tube on HD 1...Biliary drainage via cholecystostomy is a potential novel method for amatoxin removal from the enterohepatic circuit and should be reserved for situations in which silibinin is unavailable or clinical progression is rapid. Although there is potential for complications, particularly in coagulopathic patients, it should be considered against the risk for progressive ALF requiring liver transplant.Figure: Laboratory values for Patients A, B, and C."

Clinical • CNS Disorders • Hepatology • Inflammation • Liver Failure • Renal Disease

Acute Liver Failure Following Wild Mushroom Ingestion: A Case of Suspected Amanita Toxicity Managed With Silibinin and N-Acetylcysteine (ACG 2025) - "This case adds to the evidence supporting Silibinin as a therapeutic in early management of amatoxin-related hepatotoxicity.Figure: Wild mushroom species which appear similar: (a) An edible Volvariella volvacea (paddy straw mushroom); (b) A deadly poisonous Amanita phalloides (death cap). (All photo taken by Tibuhwa DD in the field)."

Clinical • Hepatology • Immunology • Liver Failure

Therapeutic Potential of Quercetin, Silibinin, and Crocetin in a High-Fat Diet-Induced Mouse Model of MASLD: The Role of CD36 and PLIN3. (PubMed, Life (Basel)) - "Quercetin, silibinin, and crocetin mitigate MASLD progression by reducing steatohepatitis. These effects are associated with distinct modulations of CD36 and PLIN3 protein expression, suggesting that these pathways are promising therapeutic targets in MASLD management. Natural compounds offer a multi-targeted hepatoprotective approach warranting further clinical investigation."

Journal • Preclinical • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • CD36 • SCARB1

Mao Jian Black Tea Ethanol Extract Alleviates Alcoholic Liver Injury in Mice via Regulation of the PI3K/Akt/NF-κB Signaling Pathway. (PubMed, Foods) - "The animal model was established using the NIAAA method, and C57BL/6 mice were divided into the following groups: negative control group (NC), model control group (MG), silibinin positive control group (SL, 54 mg/kg), and MJBT_EE high- and low-dose groups (40 mg/mL, 20 mg/mL)...The mechanism of action of MJBT_EE_H primarily involved activation of the PI3K/Akt pathway and suppression of excessive p-NF-κB activation. These findings indicate that Maojian black tea ethanol extract exerts significant protective effects against alcohol-induced liver injury, potentially through improving lipid metabolism, reducing oxidative stress and inflammatory responses, and modulating the PI3K/Akt/NF-κB signaling pathway."

Journal • Preclinical • Hepatology • Inflammation • Liver Failure • Metabolic Disorders • IL1B • IL6 • TNFA

Hepatoprotective Effect of Silymarin Herb in Prevention of Liver Dysfunction Using Pig as Animal Model. (PubMed, Nutrients) - "In parallel, emerging computational approaches, including machine-learning-assisted chemotype fingerprinting, automated histology scoring, and Bayesian exposure modeling, are being explored as supportive tools to enhance reproducibility and translational relevance; however, these frameworks remain exploratory and require empirical validation, particularly in modeling enterohepatic recirculation. Collectively, current porcine evidence supports silymarin as a context-dependent yet credible hepatoprotective agent, highlighting priorities for future research to better define its therapeutic potential in clinical nutrition and veterinary practice."

Journal • Preclinical • Review • Cardiovascular • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Metabolic Disorders • Reperfusion Injury

Animal models of lean metabolic dysfunction-associated steatotic liver disease (MASLD): bridging pathogenesis and novel Drug discovery. (PubMed, Expert Opin Drug Discov) - "These platforms have been used to test candidate therapies, including GLP-1 analogues (exendin-4, liraglutide), kinsenoside, silibinin, and bile-acid modulators, and to interrogate gut - liver axis disruption that supports microbiota-targeted strategies. Animal models have advanced our understanding of their unique drivers, including bile acid dysregulation, leptin signaling, and oxidative stress. These insights may guide the development of targeted therapies tailored to lean patients and improve clinical outcomes through individualized approaches."

Journal • Preclinical • Review • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor • LEP

Natural SilibininLinoleate: A Protective Antioxidant in Edible Vegetable Oils. (PubMed, Foods) - "This study evaluated the potential of silibinin linoleate (SL), a natural derivative of silibinin, as an antioxidant to improve the thermal stability of sunflower oil (SF)...However, this effect was specific to the highest tested concentration and does not indicate superiority across all concentrations. These findings suggest that SL has potential as a natural antioxidant for improving oil stability, but further studies are needed to validate SL as a practical and scalable alternative to synthetic antioxidants in the food industry."

Journal

LIVER INJURY FROM THE DEATH CAP MUSHROOM: THE PHILADELPHIA EXPERIENCE AND ROLE FOR SILIBININ (AASLD 2025) - "9 patients received activated charcoal, 8 patients received n-acetylcysteine, 1 patient received Penicillin G and 2 patients received penicillin-derivatives. Despite exceptionally high peak liver chemistries and synthetic dysfunction, all patients who received silibinin exhibited biochemical improvement and none ultimately required liver transplantation. This case series highlights that patients with Amanita phalloides ingestion have significant risk of liver injury and should be ideally treated at a transplant center. Additionally, silibinin may be an effective treatment for toxicity compared to supportive therapy alone, though further studies are needed."

Hepatology • Liver Failure

Anti-inflammatory and Antioxidant Effects of Silibinin on Valproate-Induced Pancreatitis in Male Wistar Rats. (PubMed, Endocr Metab Immune Disord Drug Targets) - "Silibinin shows promise as an adjunct therapy to reduce VPA-associated pancreatic damage. Further clinical studies are warranted."

Journal • Preclinical • Inflammation • Pancreatitis • IL6 • TNFA

Silybum marianum seeds mitigate pro-inflammatory functions of human neutrophils and alleviate ulcerative colitis in rats. (PubMed, Inflammopharmacology) - "For the UC, rats were given oral (p.o.) doses of AESS and sulfasalazine (SSZ) for one week before colitis induction, then histological structure and inflammatory and oxidative markers were examined. Findings showed that AESS exhibited antioxidant capacities due to its flavonoids and mainly their flavonolignans, such as silychristin, silydianin, and silibinin A and silibinin B. Myeloperoxidase and HRP activities demonstrated that AESS decreased total oxygen radicals, H₂O₂ and hypochlorous acid (HOCl), and modulated neutrophil degranulation. AESS (100 and 1000 mg/kg, p.o.) prevents the rise of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β and preserves the microstructure of the colon and its redox status during the UC. Flavonolignans of AESS possess anti-inflammatory and antioxidant potentials, making it a safe candidate to prevent inflammation."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Stress Ulcer • Ulcerative Colitis • MPO • TNFA

Niosome-loaded silibinin and methotrexate for synergistic breast cancer combination chemotherapy: in silico and in vitro study. (PubMed, Cancer Cell Int) - "The designed nano-niosome, NiO@MTXSiL, is safe, stable, and has an optimal size and surface charge. It offers high drug loading capacity for co-delivering hydrophobic and hydrophilic chemotherapeutics with different anti-cancer mechanisms, improving anti-tumor response and overcoming MDR. It shows higher cytotoxicity against MDA-MB-231 breast cancer cells compared to free drugs, making it a promising candidate to combat MTX resistance in breast cancer."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • CCND1 • CDK4 • CDK6 • CDKN1A • RB1 • TP53