ABSTRACT
Objective To explore the regulatory effeet of Qifu Yin ( QFY) on JAK2/STAT3 pathway in rats with type 2 diabetic cognitive impairment.Methods A small dose of STZ combined with high-fat and high- sugar feed was used to build the model.After success, they were divided into model group, QFY low-dose, high-dose group, and metformin group.After four weeks of intervention, fasting blood glucose ( FBG ) was measured; Morris water maze was used to detect spatial learning and memory ability in rats; Nissl staining and immunofluorescence staining were respectively used to detect the degree of brain injury and the expression of lba-1 , a marker of microglia .EL1SA was used to detect the expression of TNF-cx, IL6, ILK) and BDNF.Western blot was employed to detect the expression of JAK2/STAT3 pathway.Results Compared with the control group, the model group showed significant increase in blood glucose, decreased spatial learning and memory capacity, severely damaged hipp-ocampal neurons, increased activated microglia, significantly higher levels of TNF-cx, 1L6, p-JAK2/JAK2 and p-STAT3/STAT3, and signif icantly lower levels of ILK) and BDNF.Compared with the model group, QFY group effectively reduced FBG, inhibited the con-tinuous rise of FBG, improved learning and memory a- bility, improved hippocampal neuronal damage, reduced activated microglia, reduced TNF-cx, 1L6, p- JAK2/JAK2 and p-STAT3/STAT3 levels, and increased ILK) and BDNF levels.Conclusion QFY has been shown to improve type 2 diabetic cognitive impairment , and the mechanism may be related to the inhibition of blood glucose rise and regulation of the JAK2/STAT3 pathway, thereby inhibiting microglia activation.
ABSTRACT
Objective: To study the mechanism that TSG can reduce plasma glucose level by inhibiting sodium-dependent glucose cotransporters 2 (SGLT2) and α-glucosidase in vitro and in vivo. Methods: Molecular docking method was used to study the binding affinities of TSG and diabetes related targets. The structures of targets were taken from Protein Data Bank or references. 1-NBDG and PNPG were used as the substrates for the inhibition assays of TSG against SGLT2 and α-glucosidase respectively in vitro. The antihyperglycemic activity of TSG was operated by oral glucose tolerance test (OGTT) and urinary glucose excretion (UGE) test in rats. Results: TSG was identified as the inhibitors of SGLT2 with the docking score of -9.35 less than -9.79 of dapagliflozin as the positive control and α-glucosidase with the docking score of -5.44 compared to -5.58 of acarbose as the positive control. TSG showed the inhibitory rate of 21.6% at the dose of 10 μmol/L against SGLT2 and 32.5% at the dose of 100 μmol/L in vitro test. Compared with model group, the group of 120 mg/kg dose had significant difference (P < 0.05) but the overall effect was not as strong as dapagliflozin in OGTT and UGE test. The result of rat in vivo test showed that glucose inhibition rate of TSG (120 mg/kg) was (9.3 ± 1.0)%, urinary glucose content was (435.5 ± 84.0) mg/kg, which showed certain hypoglycemic effect. Conclusion: TSG exhibited antiglycemic activity through inhibiting SGLT2 and α-glucosidase, which was considered to be a new lead compound of dual target inhibitors.