4.3 Article

Salvianolic acid B inhibits the amyloid formation of human islet amyloid polypeptideand protects pancreatic beta-cells against cytotoxicity

Journal

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
Volume 81, Issue 4, Pages 613-621

Publisher

WILEY
DOI: 10.1002/prot.24216

Keywords

amyloid; salvianolic acid B; islet amyloidogenic polypeptide; membrane disruption; type 2 diabetes

Funding

  1. National Basic Research Program of China [2009BC918304, 2012CB524901]
  2. Natural Science Foundation of China [30970607, 31271370, 81100687, 81172971, 81222043]
  3. Program for New Century Excellent Talents in University [NECT10-0623, NECT11-0170]
  4. Huazhong University of Science and Technology Analytical and Testing Center

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The misfolding of human islet amyloid polypeptide (hIAPP) is regarded as one of the causative factors of type 2 diabetes mellitus (T2DM). Salvia miltiorrhiza (Danshen), one of the most commonly used of traditional Chinese medicines, is often used in Compound Recipes for treating diabetes, however with unclear mechanisms. Since salvianolic acid B (SalB) is the most abundant bioactive ingredient of salvia miltiorrhiza water-extract. In this study, we tested whether SalB has any effect on the amyloidogenicity of hIAPP. Our results clearly suggest that SalB can significantly inhibit the formation of hIAPP amyloid and disaggregate hIAPP fibrils. Furthermore, photo-crosslinking based oligomerization studies suggest SalB significantly suppresses the toxic oligomerization of hIAPP monomers. Cytotoxicity protection effects on pancreatic INS-1 cells by SalB were also observed using MTT-based assays, potentially due to the inhibition on the membrane disruption effects and attenuated mitochondria impairment induced by hIAPP. These results provide evidence that SalB may further be studied on the possible pharmacological treatment for T2DM. Proteins 2013. (c) 2012 Wiley Periodicals, Inc.

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