Legalon (silibinin)

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, progesterone receptor; qRT-PCR, quantitative real-time polymerase chain reaction; RT, room temperature; Sili, silibinin; si-RNAs, small interfering RNAs; TNBC, triple-negative breast cancer; VP, verteporfin; YAP, Yes-associated protein.

P=N/A, N=110, Recruiting, Istituto Oncologico Veneto IRCCS | Not yet recruiting --> Recruiting

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.

P=N/A, N=104, Not yet recruiting, The First Hospital of Jilin University; The First Hospital of Jilin University

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.

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.

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.

Four silymarin derivatives (silibinin, isosilibinin, silicristin, silidianin), known for liver protection, were explored as potential multi-target anticancer agents using computational methods...This multi-scale computational study identifies silicristin and silidianin as promising multi-target anticancer candidates. Their stability, favorable electronic profiles, and low predicted toxicity support further in vitro and in vivo validation.

P=N/A, N=362, Completed, Mylan Inc. | Trial completion date: Jul 2023 --> Oct 2024 | Trial primary completion date: Jul 2023 --> Oct 2024 | Recruiting --> Completed

In conclusion, our in-silico findings could facilitate the discovery of potential therapeutic agents against breast cancer. Silibinin and Isotretinoin impede cancer cell development in vitro; nonetheless, this study demonstrated that they directly upregulate sFRP4 and induce apoptosis in breast cancer cells.

Molecular dynamics and trajectory analysis confirmed stable binding with SIRT1, with binding energies between -12 and -16 kcal/mol and stability within 0.2-1.1 nm. These findings suggest that these phytochemicals have potential for further in-vivo and clinical studies to validate their therapeutic effects.

This study indicates that STAT3 expression prevails in reactive astrocytes surrounding triple-negative BrM in comparison to HER2-positive and luminal BrM, and these findings mirror those observed in animal models. A high STAT3 expression correlates with higher risk of intracranial recurrence and shorter progression-free survival, particularly in patients with triple-negative BrM.