Salvianolic acid B inhibits the amyloid formation of human islet amyloid polypeptideand 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.

Biological activities of salvianolic acid B fromSalvia miltiorrhizaon type 2 diabetes induced by high-fat diet and streptozotocin

“…However, which compound from this extract is responsible for the antidiabetic effects is still unclear. In addition, a recent in vitro study (Cheng et al, 2013) has shown that SalB possessed the capacity to inhibit the formation of human islet armyloid polypeptide (hIAPP) amyloid and disaggregate hIAPP fibrils, and protected hIAPP-induced cytotoxicity on pancreatic INS-1 cells, which suggested a potential use of SalB for the treatment of diabetes. A systematic study, therefore, was required to verify the antidiabetic effects of SalB and to reveal its possible mechanism.…”

Brazilin inhibits fibrillogenesis of human islet amyloid polypeptide, disassembles mature fibrils, and alleviates cytotoxicity

“…The resulting solutions were incubated under constant shaking at 25 C. For the disaggregation experiments, hIAPP monomers were rst incubated as described above for 24 h, which is sufficiently long for hIAPP to grow into mature brils. 45 Subsequently, equal volumes of brazilin solutions with different concentrations were added into the bril solutions. The resulting disaggregation solutions were incubated at 25 C under constant shaking.…”

Bioassay-guided Isolation of the Antidiabetic Active Principle from Salvia miltiorrhiza and its Stimulatory Effects on Glucose Uptake Using 3T3-L1 Adipocytes

“…Our studies show that purified SAB from S. miltiorrhiza improves glucose tolerance supporting to the evidence that S. miltiorrhiza can be exploited further for its anti-diabetic properties. Based on our data and the existing literature, we acknowledge that multiple pathways for SAB action might be involved for its overall antihyperglycemic activity in vivo and there is evidence that SAB may reduce diabetes through its protective effect on pancreatic beta-cells [10].…”

“…Among phenolic acids, salvianolic acid B is a major component of S. miltiorrhiza and extensive pharmacological studies have been reported for this compound. Salvianolic acid B inhibited the amyloid formation of human islet amyloid polypeptide and protects pancreatic beta cells against cytotoxicity [10]. Many authors have studied the effect of salvianolic acid B on different organ systems in animals as well as in humans.…”