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

Year 2023, , 1299 - 1309, 29.12.2023

Sümeyra Gültekin

https://doi.org/10.17826/cumj.1366590

Abstract

Amaç: Bu çalışmada, silymarinin hepatosellüler karsinom (HCC) için bir ilaç olma potansiyeli in situ olarak değerlendirilmiştir.
Gereç ve Yöntem: Çalışmada SwissADME, silymarinin farmakokinetik ve ilaç benzeri özelliklerini değerlendirmek için kullanılmıştır. Moleküler docking, silymarinin WNT/β-katenin yolağı ile ilişkili olan ve HCC'de bu yolakla ilişkilendirilen moleküler bileşiklerle etkileşimini modellemek için gerçekleştirilmiştir. Hedef proteinler (AFP, PIK3CA, β-katenin, PTEN, AAT, AXIN1, GSTM1, GSK3B, PI3K3CA, GSTT1, CCND1, albumin, p53, MET, CTNNB1 ve APC) SwissTargetPrediction veritabanından elde edilmiştir. Protein-protein etkileşimleri STRING ve Cytoscape veritabanlarından alınmıştır. PASS platformu, potansiyel biyoaktivite özelliklerini tahmin etmek için kullanılmıştır.
Bulgular: Silymarin en iyi bağlanmayı -11,7 Kcal/mol değeriyle APC proteiniyle göstermiştir. Araştırılan proteinler arasında AXIN1 en az bağlanmayı gösterse de, -7,4 Kcal/mol değeri iyi bir bağlanma afinitesi olarak kabul edilebilir.
Sonuç: Bu çalışmada silymarinin WNT/β-katenin yolağının aşırı aktivasyonunu inhibe etme ve hepatoprotektif özelliklerinin ötesinde HCC için potansiyel bir ilaç adayı olma potansiyeli tanımlanmıştır. Bununla birlikte, silymarinin etkinliğini ve güvenliğini doğrulamak için WNT/β-katenin yolağını hedef alan daha fazla preklinik ve klinik araştırmaya ihtiyaç vardır.

Keywords

İlaç yeniden kullanımı, moleküler docking, silymarin, WNT/β-katenin yolağı

Exploring the drug repurposing potential of silymarin beyond hepatotoxicity treatment through WNT/β-catenin signaling pathway

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.

Keywords

Drug repurposing, molecular docking, silymarin, WNT/β-catenin pathway

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