title: Salvianolic acid B inhibits the amyloid formation of human islet amyloid polypeptide and protects pancreatic beta-cells against cytotoxicity.
abstract: 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.
authors.affiliation: Department of Bio-pharmaceutics, Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Biao
authors.initials: B
authors.lastname: Cheng
authors.forename: Hao
authors.initials: H
authors.lastname: Gong
authors.forename: Xiaochao
authors.initials: X
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D001572:Benzofurans / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D058228:Islet Amyloid Polypeptide / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D027561:Salvia miltiorrhiza / Q000737:chemistry; D053630:Depsides
chemical_list: D000682:Amyloid; D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D058228:Islet Amyloid Polypeptide; C076944:salvianolic acid B; D053630:Depsides