The Binding of Silibinin, the Main Constituent of Silymarin, to Site I on Human Serum Albumin

Access this Article

Search this Article

Author(s)

    • Yamasaki Keishi
    • Faculty of Pharmaceutical Sciences, Sojo University|DDS Research Institute, Sojo University
    • Maruyama Toru
    • Graduate School of Pharmaceutical Sciences, Kumamoto University
    • Otagiri Masaki
    • Faculty of Pharmaceutical Sciences, Sojo University|DDS Research Institute, Sojo University
    • Sato Hiroki
    • Graduate School of Pharmaceutical Sciences, Kumamoto University
    • Anraku Makoto
    • Faculty of Pharmaceutical Sciences, Sojo University|DDS Research Institute, Sojo University
    • Seo Hakaru
    • Faculty of Pharmaceutical Sciences, Sojo University|DDS Research Institute, Sojo University

Abstract

<p>Silibinin is the main constituent of silymarin, an extract from the seeds of milk thistle (<i>Silybum marianum</i>). Because silibinin has many pharmacological activities, extending its clinical use in the treatment of a wider variety of diseases would be desirable. In this study, we report on the binding of silibinin to plasma proteins, an issue that has not previously been extensively studied. The findings indicated that silibinin mainly binds to human serum albumin (HSA). Mutual displacement experiments using ligands that primarily bind to sites I and II clearly revealed that silibinin binds tightly and selectively to site I (subsites Ia and/or Ic) of HSA, which is located in subdomain IIA. Thermodynamic analyses suggested that hydrogen bonding and van der Waals interactions are major contributors to silibinin–HSA interactions. Furthermore, the binding of silibinin to HSA was found to be decreased with increasing ionic strength and detergent concentration of the media, suggesting that electrostatic and hydrophobic interactions are involved in the binding. Trp214 and Arg218 were identified as being involved in the binding of silibinin to site I, based on binding experiments using chemically modified- and mutant-HSAs. In conclusion, the available evidence indicates that silibinin binds to the region close to Trp214 and Arg218 in site I of HSA with assistance by multiple forces and can displace site I drugs (<i>e.g.</i>, warfarin or iodipamide), but not site II drugs (<i>e.g.</i>, ibuprofen).</p>

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 40(3), 310-317, 2017

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130005398492
  • Text Lang
    ENG
  • ISSN
    0918-6158
  • Data Source
    J-STAGE 
Page Top