ABSTRACT
Diabetes is a lifelong non-communicable disease caused by continuous high blood sugar,which poses a great threat to people's health. Diabetic cognitive dysfunction is the neurological impairment caused by the disorder of glucose and lipid metabolism in diabetes mellitus,which is characterized by inattention,decreased learning and memory ability,and then developed into alzheimer's disease.The pathogenesis of diabetic cognitive dysfunction is not fully understood.there are no effective drugs for this disease, hypoglycemic drugs are mainly used in the clinical treatment of diabetic cognitive dysfunction,and most drugs are accompanied by serious adverse reactions while playing a therapeutic role,drug resistance and liver injury are easy to occur.In recent years,there have been a lot of research achievements on the prevention and treatment of cognitive dysfunction in diabetes mellitus with traditional Chinese medicine(TCM).Modern medicine believes that diabetes belongs to the category of consumptive thirst of TCM, and the diabetic cognitive dysfunction is consumptive thirst combined with dementia and forgetfulness.Qi and Yin deficiency runs through the whole process of consumptive thirst,the Qi injured,Then the Qi defficiency would cause blood circulation malfunction, long-time poor blood condition would cause blood stagnating in the brain and blocking the brain,which would lead to the brain disease.TCM can improve the diabetic cognitive dysfunction by lowering blood sugar,inhibiting neuron damage, deposition of Amyloid beta(Aβ)and abnormal phosphorylation of Tau protein.This article reviews the pathogenesis of diabetic cognitive dysfunction from glucolipid metabolic disorders,disruption of blood brain barrier,inflammation,oxidative stress and non enzymatic glycosylation,insulin resistance in diabetes etc.,and explores the prevention and treatment of diabetic cognitive dysfunction by Chinese medicine,to provide a reference for the research and development of drug prevention and treatment of diabetic cognitive dysfunction.
ABSTRACT
The disruption of blood-brain barrier(BBB) induced by oxidative stress is an important pathological reaction which results in secondary brain injury during the cerebral ischemia-reperfusion. This study was designed to investigate the protective effect and mechanism of p-hydroxybenzaldehyde (p-HBA) from Gastrodia elata on BBB. The BBB is mainly consisted of vascular endothelial cells and astrocytes, so brain microvascular endothelial cell line (bEnd.3) and astrocytes (Ast) in mice were used in this study to establish BBB model. H₂O₂-induced oxidative stress was employed to induct the BBB damage. The bEnd.3 cells or astrocytes were exposed to different concentrations of H₂O₂ (0.125, 0.25, 0.5, 0.75 mmol·L⁻¹) for 4 h, then exposed to 0.5 mmol·L⁻¹ H₂O₂ for different duration (1, 2, 4, 6 h) to detect the reasonable condition of oxidative injury. After intervention by different concentrations of p-HBA(12.5, 25, and 50 mg·L⁻¹), LDH leakage rate was detected for bEnd.3 and Ast cells; the expression levels of tight junction protein claudin-5 and occludin in bEnd.3 cells were determined by Western blot and immunofluorescence. Nrf2, HO-1 and NQO1 in normal bEnd.3 cells and astrocytes as well as H₂O₂-induced damaged in astrocytes were detected by western blot after treatment with p-HBA. The results showed that the optimal condition of H₂O₂ induced damage in bEnd.3 cells and astrocytes was set up as exposure the cells to 0.5 mmol·L⁻¹ H₂O₂ for 4 h. Different concentrations of p-HBA could decrease LDH leakage rate after bEnd.3 and Ast injury was induced by H₂O₂; increase the protein expression levels of claudin-5, occludin, Nrf2, HO-1 and NQO1; and increase the expression levels of Nrf2, HO-1 and NQO1 in normal and H₂O₂-induced damaged astrocytes. These findings indicate that the p-HBA has protective effect on the BBB, and the related mechanism seems to involve up-regulating tight junction protein of the bEnd.3 cells and enhancing endogenous antioxidant capacity by activating the Nrf2/ARE pathway in both of bEnd.3 cells and astrocytes.