Silymarin'in WNT/β-katenin yolağı aracılığıyla hepatotoksisite ötesinde terapötik yeniden kullanım potansiyelinin keşfi

Abstract

Purpose: In this study, the potential of silymarin as a drug for hepatocellular carcinoma (HCC) was evaluated in situ. Materials and Methods: The SwissADME tool was utilized to assess the pharmacokinetic and drug-like properties of silymarin. Molecular docking was performed to model the interaction of silymarin with molecular compounds known to play a role in the WNT/β-catenin pathway and associated with this pathway in HCC. Target proteins (AFP, PIK3CA, β-catenin, PTEN, AAT, AXIN1, GSTM1, GSK3B, PI3K3CA, GSTT1, CCND1, albumin, p53, MET, CTNNB1, and APC) were obtained from the SwissTargetPrediction database. Protein-protein interactions were obtained from the STRING and Cytoscape databases. The PASS platform was used to predict potential bioactivity properties. Results: The study data revealed that silymarin exhibited the highest binding affinity to the APC protein, with a value of -11.7 Kcal/mol. Although AXIN1 showed the least binding among the studied proteins, with a value of -7.4 Kcal/mol, this can still be considered a good binding affinity. Conclusion: This study demonstrated the potential of silymarin to inhibit the overactivation of the WNT/β-catenin pathway and identified silymarin as a potential drug candidate for HCC, beyond its hepatoprotective properties. However, further preclinical and clinical studies targeting the WNT/β-catenin pathway are required to confirm the effectiveness and safety of silymarin.