Norathyriol is a metabolite of mangiferin. Mangiferin has been reported to inhibit α-glucosidase. To the best of our knowledge, no study has been conducted to determine or compare those two compounds on inhibiting α-glucosidase in vitro and in vivo by far. In this study, we determined the inhibitory activity of norathyriol and mangiferin on α-glucosidase in vitro and evaluated their antidiabetic effect in diabetic mice. The results showed that norathyriol inhibited α-glucosidase in a noncompetitive manner with an IC50 value of 3.12 μM, which is more potent than mangiferin (IC50 = 358.54 μM) and positive drug acarbose (IC50 = 479.2 μM) in the zymological experiment. Both of norathyriol and mangiferin caused significant (p < 0.05) reduction in fasting blood glucose and the blood glucose levels at two hours after carbohydrate loading and it was interesting that mangiferin and norathyriol can make the decline of the blood glucose earlier than other groups ever including normal group in the starch tolerance test. However, norathyriol and mangiferin did not significantly influence carbohydrate absorption in the glucose tolerance test. Therefore, the antidiabetic effects of norathyriol and mangiferin might be associated with α-glucosidase, and norathyriol was more potent than mangiferin.

Diabetes and cognitive dysfunction are highly prevalent disorders, while the underlying mechanism is still elusive. The effects of Gastrodin on central nervous system have been emphasized recently. In this study, we aim to explore the potential mechanism leading to cognitive dysfunction in diabetes and the therapeutic effect of Gastrodin. Diabetes was induced by a single injection of streptozotocin. RNA sequencing technique was used to identify the potential factors involved. Western blot and immunofluorescence were applied to detect the protein expression. Our results have shown that spatial learning was impaired and hippocampal pyramidal neurons were damaged in diabetic rats, which could be ameliorated by Gastrodin intervention. Transcriptional analysis identified differential expression genes, which were confirmed by qPCR and western blot. Furthermore, p21 activated kinase 2 (PAK2) was selected and its inhibitor could promote the survival of primary hippocampal neurons. It suggested that PAK2 pathway may be involved in cognitive dysfunction in diabetes and a therapeutic target for Gastrodin intervention.