The binding of silibinin, the main constituent of silymarin, to site i on human serum albumin

Keishi Yamasaki, Hiroki Sato, Saori Minagoshi, Karin Kyubun, Makoto Anraku, Shigeyuki Miyamura, Hiroshi Watanabe, Kazuaki Taguchi, Hakaru Seo, Toru Maruyama, Masaki Otagiri

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Silibinin is the main constituent of silymarin, an extract from the seeds of milk thistle (Silybum marianum). 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 (e.g., warfarin or iodipamide), but not site II drugs (e.g., ibuprofen).

Original languageEnglish
Pages (from-to)310-317
Number of pages8
JournalBiological and Pharmaceutical Bulletin
Issue number3
Publication statusPublished - 2017
Externally publishedYes


  • Binding site
  • Human serum albumin (HSA)
  • Silibinin
  • Silymarin
  • Site I

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science


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