The Protective Effect And Underlying Mechanisms Of Nepetaangustifolia On High Glucose-induced HUVEC Vein Endothelial Cells

The study used high glucose-induced human umbilical vein endothelial cells(HUVECs)to build inflammatory model,which was used to investigate the protective effect of Nepeta angustifolia C.Y.Wu(NA)and the underlying mechanisms.And the study evaluated the influence of NA on diabetic mice induced by alloxan.These studies were used to provide theoretical basis for prevention and treatment of vascular lesions related with diabetes mellitus.The research used ELISA kits and reactive oxygen species kit to measure the expression of cell adhesion molecules(CAMs)and ROS in high glucose-induced HUVECs,respectively.The intracellular protein expression of cell adhesion molecules and nuclear factor-?B(NF-?B)activation in HUVECs were analyzed by western blot.Our results suggested all of concentration-groups of NA(50,100,150,200?g/m L)can inhibit the produce of CAMs and ROS with a concentration-dependent manner.There were significant difference(P < 0.05)between concentration-groups of NA(100,150,200?g/m L)with model group.In addition,NA also could inhibit phosphorylation of I?B-? and decrease p65 quantity to entry nuclear and NF-?B-DNA binding activity.The research used western blot and immunofluorescence microscopy to study the expression of heme oxygenase-1(HO-1)and activation of nuclear factor erythroid 2-related factor 2(Nrf2)in HUVECs treated with NA.The resultsindicated that NA can promote the expression of HO-1 with a concentration and time-dependent manner in HUVECs.The levels reached a peak at 12 h.And NA also could active Nrf2 in cytoplasm and then promoted it entry to nuclear in a time-dependent manner.The expression of CAMs and ROS were significantly increased(P < 0.05)in HUVECs that were pretreated with tin protoporphyrin(Sn PP,HO-1 inhibitor)followed by treatment with NA.In diabetic mice,NA could significantly improve the symptoms of polydipsia,polyphagia,polyuria and reduced the concentrations of blood sugar,malondialdehyde(MDA),nitric oxide(NO),triglycerides(TG)and total cholesterol(TC)and renal index as compared with model group(P < 0.05).Accordingly,NA could significantly promote glucose tolerance and the activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in diabetic mice treated with NA.In a word,our results indicated that NA could inhibit the produce of CAMs and ROS and protect endothelia cell by decreasing inflammatory response and oxidative stress,which could improve the endothelial dysfunction.And NA exerted its anti-inflammatory and antioxidant effects via inhibiting the activation of NF-?B and activating the Nrf2 pathway-dependent expression of HO-1 in vitro.On the other hand,our experimental results in vivo suggested that NA could reduce blood sugar level,increase the glucose tolerance and antioxidant capacity and reduce the damage result from oxidative stress,which could help to prevent or treat with vascular lesions related with diabetes mellitus.