ฤทธิ์ต้านเบาหวานของอนุพันธ์อินเตอร์รับตินที่สกัดจากเฟิร์นไซโคลซอรัส เทอร์มิแนนส์

Abstract

The fern Cyclosorus terminans has long been consumed as a vegetable in northern Thailand. It has been reported as the source of coumarin derivatives, interruptins A and B. In this study, they were found to exhibit in vitro antidiabetic property by enhancing the glucose consumption into hepatocytes and skeletal muscle cells through PPAR-Y pathway. Likewise, both interruptins A and B also increased glycogen accumulation in heptaocytes, while only interruptin B could encourage glycogen content in muscle cells. Interestingly, prepared interruptin-rich extract (IRE) demonstrated not only no cytotoxicity toward hepatocytes and skeletal muscle cells, but also activated glucose uptake into both cells. Furthermore, acute toxicity study Wistar rats revealed no mortality or signs of toxicity after a single oral of 2,000 mg/kg IRE administration and indicated the LDso as 2,000-5,000 mg/kg body weight. Moreover, interruptin B displayed potent anti-inflammation through NO radical scavenging and NO production inhibition in macrophage RAW264.7 cells with ICso of 67.68 and 0.81 JM followed by interruptin A with JCso of 90.07 and 12.18 |uM, respectively. These compounds also down-regulated iNOS and up-regulated PPAR-Y mRNA expression in a dose-dependent manner. Additionally, the appropriate HPLC method for analysis the corresponding interruptins content in C. terminans extract was successfully validated according to ICH requirement. To the best of our knowledge, this is the first study describing anti-diabetic activity in liver and muscle cells and anti-inflammatory activity in macrophage cells of isolated interruptins A and B. These actions may be due to an induction of PPAR-Y. These results are very promising to find that C. terminans extract with active interruptin derivatives might be a potential natural material for anti-diabetic application. Nevertheless, more research is still required to address questions surrounding in vivo anti-diabetes.