Legalon (silibinin)

SBN is a plant-derived molecular glue that intercepts PD-L1 glycomaturation co-translationally in the ER. When combined with canonical PD-L1 dimerizers, SBN collapses adaptive PD-L1 expression and renders cancer cells exquisitely susceptible to the cytolytic insults of T cells. Due to its favorable safety profile and oral bioavailability, SBN is a promising "glycotherapeutic" phytochemical for T-cell-based immunotherapy, particularly in IFN-rich tumors with reactive PD-L1 expression programs.

SF@LA-NPs developed in this study significantly enhanced the delivery efficiency and antitumor activity of silibinin in glioblastoma cells. Moreover, a dual-mechanism mode of action was elucidated, involving ROS-induced mitochondrial apoptosis and compensatory protective autophagy. These findings provide a promising nano-platform and a theoretical basis for combination therapies targeting apoptosis-autophagy crosstalk in glioblastoma.

Silibinin and sodium oxamate, as HIF-1α and LDHA blockers, respectively, were used to treat K-562 and HL-60 cells...In contrast, PD-L1 expression remained unchanged after treatment. Our findings suggest that blocking signaling pathways involved in metabolic reprogramming of cancer cells could be a promising approach for modulating the expression of certain immune checkpoint ligands, warranting further investigation.

Structure-based screening identified silibinin and estradiol benzoate as LRP1-specific agonists that activate the WTAP-LRP1 pathway to promote cartilage repair in vivo. Collectively, our findings establish m6A-dependent metabolic reprogramming as a pivotal epigenetic mechanism of cartilage regeneration with therapeutic potential for promoting chondrogenesis.

In summary, this study demonstrates that SM-mediated targeting of UCP2 enhances hepatic mitochondrial function and suppresses excessive mitophagy, thereby ameliorating TBil in TAA-induced HE. These findings suggest that SM may represent a promising therapeutic strategy for TAA-induced HE.

Ultimately, silibinin has emerged as a multifunctional natural compound with significant therapeutic benefits. However, further mechanistic investigations and well-designed clinical trials are required to validate its efficacy and optimize dosage.

Silibinin potentiates paclitaxel cytotoxicity by suppressing H19 transcription, offering a potential strategy to overcome paclitaxel resistance. The combination promotes apoptosis via caspase activation, highlighting a novel synergistic therapeutic approach in breast cancer treatment.

Screening of a compound library using this probe identified four natural products, namely Ginkgetin, Silibinin, Ledebouriellol, and Antcin C (R), as potent UGT1A8 inhibitors. Collectively, these findings position UPro1A8 as a robust molecular tool for advancing UGT1A8 functional studies.

These findings may facilitate the development of traditional medicinebased therapeutic strategies and provide insights for potential lead optimization in breast cancer drug discovery.

K-562 and HL-60 cells were treated with silibinin, an HIF-1α inhibitor, and sodium oxamate, a LDH-A inhibitor...Interestingly, the expression of MCT1, but not MCT4, was downregulated in K-562 cells after treatment. Our findings show that HIF-1α and LDH-A inhibitors not only serve as cytotoxic drugs but also regulate the expression of lactate transporter and interfere with the metabolism-related mechanisms in AML cells.

These findings highlight the value of combining competing endogenous RNA regulatory networks with nanomaterial based targeted delivery systems for GC therapy. The CLip@Sil platform offers a promising direction for the future development of precise and biomimetic nanotherapeutics in oncology.

The cytotoxic mechanism of action was characterized by a decreased cell viability, morphological alterations, elevation of intracellular ROS, decreased mitochondrial potential, mitochondrial and nuclear dysmorphologies, activation of caspases 9 and 3/7 and apoptosis occurrence, and decreased long-term colony formation. These findings show that SIL could represent a potential alternative therapy for HPV-negative OPSCC by triggering mitochondrial apoptosis and exerting a decline in the colonogenicity of Detroit 562 cancer cells.