RESUMEN
Cognitive impairment refers to the abnormality of the hippocampus， cortex and other parts of the brain， which is manifested by the decline of cognitive abilities such as learning， memory and attention. With the increase in people's work pressure and bad living habits， the incidence of cognitive impairment is getting higher and higher， which seriously affects people's normal life. However， there are adverse reactions such as gastrointestinal reactions and extrapyramidal reactions in Western drug treatment for cognitive impairment. Therefore， the development of a drug with relatively minimal adverse reactions is of great significance. Traditional Chinese medicine （TCM） has the characteristics of "multi-component， multi-pathway and multi-target"， and the incidence of adverse reactions is relatively low. Studies have shown that the pathogenesis of cognitive impairment is closely related to oxidative stress， inflammation， apoptosis， autophagy and other processes of neurons in the cerebral cortex and hippocampus. Phosphatidylinositol 3-kinase （PI3K）-protein kinase B （Akt） signal pathway plays an important role in the transmission of intracellular and intracellular signals， and in the regulation of cellular inflammation， apoptosis， autophagy， etc. TCM monomers， TCM extracts， and TCM compounds exert anti-inflammatory， antioxidant， anti-apoptotic and autophagy regulation effects by regulating the PI3K/Akt signaling pathway to improve cognitive impairment. This review first summarized the composition and regulatory process of the PI3K/Akt signaling pathway， and then discussed the research progress on the improvement of cognitive impairment through the improvement of oxidative stress， inflammation， apoptosis and autophagy of neurons. Finally， the recent research status of the regulation of this signaling pathway by TCM extracts， TCM monomers and TCM compounds to improve cognitive impairment was summarized. This study provides a theoretical basis for the future study of new TCM related to cognitive impairment.
RESUMEN
Objective:To study the effect of Qiwei Baizhusan (QWBZS) on liver insulin phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） signal pathway of diabetic mice induced by high-fat diet and streptozotocin (STZ). Method:The methods of network pharmacology and animal experiments were used to study the hypoglycemic effect of QWBZS. Active chemical components of the drug and disease targets selected through public databases were used to construct the protein-protein interaction network (PPIN), and gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomics(KEGG) enrichment analysis was performed to identify relevant signal pathways in vivo. In the pharmacological experiment, the diabetic mice model was established through intraperitoneal injection with 80 mg·kg-1·d-1 STZ high-glucose, high-fat diet. The mice were divided into normal group (normal saline), model group (normal saline) and QWBZS group (18.7 g·kg-1·d-1). After 28 days, the hypoglycemic effect of the drug and its effect on serum total cholesterol (T-CHO), fasting insulin (FINS) and serum tumor necrosis factor-α (TNF-α) were determined. Western blot and Real-time fluorescence quantitative PCR (Real-time PCR) were used to detect protein and mRNA expressions of insulin receptor (IR), insulin receptor substrate-1 (IRS-1)，phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) in liver tissues． Result:A total of 36 active components in this drug were identified by network pharmacology. KEGG analysis suggested that QWBZS might play a role in reducing blood glucose by regulating PI3K Akt signal pathway. Compared with the model group, the levels of blood glucose, serum T-Cho and TNF-α of the intervention group were significantly lower (P<0.01), while the FINS of the intervention group was significantly higher (P<0.01). Protein and mRNA expressions of IR，IRS-1，PI3K and Akt in liver tissues of mice in QWBZS treatment group increased markedly (P<0.05，P<0.01). Conclusion:QWBZS could regulate the levels of blood glucose, TNF-α, T-CHO, and FINS in the serum of diabetic mice induced by high-fat diet and STZ. It can improve PI3K/Akt signal pathway of diabetic mice by regulating protein and mRNA expressions of IR，IRS-1，PI3K and Akt/PKB.