Anti-diabetes mechanism of action by synacinn TM in adipocytes

Abstract

Type 2 diabetes mellitus is described as a defective action of insulin to properly regulate glucose transport within cells and clinically known as insulin resistance. Several factors such as elevated free fatty acid, glucocorticoids as well as abnormal levels of cytokines have been reported to cause insulin resistance. Potentially, phytochemical agents with insulin resistance reverting effect could serve as an alternative treatment for type 2 diabetes mellitus. Synacinn™ is a polyherbal supplement formulated from Andrographis paniculata, Curcuma xanthorrhiza, Cinnamomum zeylanicum, Eugenia polyantha and Orthosiphon stamineous. It is claimed as a hypoglycemic agent for diabetes mellitus treatment. Even though the anti-diabetes potential of each singular herbs has been well examined, scientific evidence has never been reported for polyherbal combination. In this study, the potential anti-diabetes mechanism of standardized Syancinn™ was investigated using two types of in vitro models; normal and insulin-resistant 3T3-L1 adipocytes. It was found that Synacinn™ improved the insulin-mediated glucose utilization in both models. For normal adipocytes, the increase of glucose utilization resulted in overexpression of glucose transporter 4, insulin receptor 1 and protein kinase B. Meanwhile in insulin resistant adipocytes, Synacinn™ increased the glucose transporter 4 expression without affecting the insulin receptor 1 and protein kinase B expression, indicating that Synacinn™ mechanism of action is dominant on the glucose transport rather than repairing the insulin signal transduction. This study also shows that Synacinn™ is a mild peroxisome proliferator-activated receptor gamma ligand and pro-adipogenic agent. During adipogenesis, Synacinn™ stimulated the peroxisome proliferator-activated receptor gamma nuclear transcriptional activity, as well as expression of (cytosine-cytosine-adenosine-adenosine-thymidine)-enhancer-binding protein alpha, adiponectin, glucose transporter 4 and protein kinase B. In terms of safety, standardized Syancinn™ was free from heavy metals and microbial contaminations and the concentrations used in the experiment do not affect the normal embryogenesis of zebrafish. Collectively, results suggest that Synacinn™ is a peroxisome proliferator-activated receptor gamma ligand agent which acted through two mechanisms: 1) restores the insulin-mediated glucose utilization by activating the glucose transporter 4 expression in insulin resistant adipocytes and 2) enhances the adipogenesis into insulin-sensitive adipocytes containing abundance of glucose transporter 4 resulted from activation of (cytosine-cytosine-adenosine-adenosine-thymidine)-enhancer-binding protein alpha and proliferator-activated receptor gamma.