Silibinin inhibits the toxic aggregation of human islet amyloid polypeptide

Biochem Biophys Res Commun. 2012 Mar 16;419(3):495-9. doi: 10.1016/j.bbrc.2012.02.042. Epub 2012 Feb 14.

Abstract

In type 2 diabetes mellitus (T2DM), misfolded human islet amyloid polypeptide (hIAPP) forms amyloid deposits in pancreatic islets. These amyloid deposits contribute to the dysfunction of β-cells and the loss of β-cell mass in T2DM patients. Inhibition of hIAPP fibrillization has been regarded as a potential therapeutic approach for T2DM. Silibinin, a major active flavonoid extracted from herb milk thistle (Silybum marianum), has been used for centuries to treat diabetes in Asia and Europe with unclear mechanisms. In this study, we tested whether silibinin has any effect on the amyloidogenicity of hIAPP. Our results provide first evidence that silibinin inhibits hIAPP fibrillization via suppressing the toxic oligomerization of hIAPP and enhances the viability of pancreatic β-cells, therefore silibinin may serve as a potential therapeutic agent for T2DM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antioxidants / pharmacology*
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Islet Amyloid Polypeptide / antagonists & inhibitors*
  • Islet Amyloid Polypeptide / chemistry
  • Islet Amyloid Polypeptide / metabolism
  • Molecular Sequence Data
  • Protein Conformation / drug effects
  • Silybin
  • Silymarin / pharmacology*

Substances

  • Antioxidants
  • Hypoglycemic Agents
  • Islet Amyloid Polypeptide
  • Silymarin
  • Silybin