ABSTRACT
Lycium barbarum polysaccharide (LBP) have a certain curative effect on hypoglycemic and neuroprotective effects, but the specific mechanism is unclear and needs to be further explored. This study aimed to clarify the mechanisms of LBP in the treatment of ICV-STZ mice model of AD from the perspectives of insulin resistance, IRS1/PI3K/AKT signaling pathway, and synaptic protein expression. We used male C57BL/6J mice injected with STZ (3 mg/kg) in the lateral ventricle as an AD model. After treatment with LBP, the learning and memory abilities of ICV-STZ mice were enhanced, and the pathological changes in brain tissue were alleviated. LBP can regulate the expression of proteins related to the IRS1/PI3K/AKT signaling pathway and thereby reducing Aß deposition and tau protein phosphorylation in the brain of ICV-STZ mice. In addition, LBP also can up-regulate the expression of synaptic proteins. The results indicated that LBP played a neuroprotective role by regulating the IRS1/PI3K/AKT pathway, inhibiting tau protein hyperphosphorylation and improving the expression levels of synapse-related proteins.
Subject(s)
Alzheimer Disease , Drugs, Chinese Herbal , Insulin Receptor Substrate Proteins , Mice, Inbred C57BL , Neuronal Plasticity , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , tau Proteins , Animals , Male , Mice , Alzheimer Disease/chemically induced , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Brain/drug effects , Brain/metabolism , Brain/pathology , Cognition/drug effects , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , Insulin Receptor Substrate Proteins/metabolism , Insulin Resistance , Neuronal Plasticity/drug effects , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Streptozocin , Synapses/drug effects , tau Proteins/metabolismABSTRACT
Phenylethanoid Glycosides of Cistanche (PhGs) have a certain curative effect on AD animal model, Echinacea (ECH) and verbascoside (ACT), as the quality control standard of Cistanche deserticola Y. C. Ma and the main representative compounds of PhGs have been proved to have neuroprotective effects, but the specific mechanism needs to be further explored. This study explored the mechanisms of PhGs, ECH, and ACT in the treatment of Alzheimer's disease (AD) from the perspectives of glial cell activation, TLR4/NF-κB signaling pathway, and synaptic protein expression. We used APP/PS1 mice as AD models. After treatment with PhGs, ECH, and ACT, the learning and memory abilities of APP/PS1 mice were enhanced, and the pathological changes in brain tissue were alleviated. The expression of pro-inflammatory M1 microglia markers (CD11b, iNOS, and IL-1ß) was decreased; the expression of M2 microglia markers (Arg-1 and TGF-ß1) was increased, which promoted the transformation of microglia from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. In addition, PhGs, ECH, and ACT could down-regulate the expression of proteins related to the TLR4/NF-κB signaling pathway and up-regulate the expression of synaptic proteins. The results indicated that PhGs, ECH, and ACT played a neuroprotective role by regulating the activation of glial cells and inhibiting the TLR4/NF-κB inflammatory pathway, and improving the expression levels of synapse-related proteins.
Subject(s)
Alzheimer Disease , Cistanche , Mice , Animals , NF-kappa B/metabolism , Cistanche/metabolism , Toll-Like Receptor 4 , Glycosides/pharmacology , Glycosides/therapeutic use , Glycosides/metabolism , Signal Transduction/physiology , Memory Disorders/drug therapy , Memory Disorders/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Microglia/metabolismABSTRACT
Backgroud: Hydroxysafflor yellow A (HSYA) has a certain improvement effect on Alzheimer's disease (AD) rats, but its specific mechanism is still unclear. The purpose of this study was to observe the regulatory effect of HSYA on learning and memory ability of AD rats induced by Aß1-42.Materials and methods: Morris water maze test was used to evaluate the effect of HSYA on the learning and memory ability of AD model rats. To explore the effective targets and potential molecular mechanisms of HSYA in AD treatment based on quantitative proteomics.Results: Through the Morris water maze experiment, we found that after HSYA treatment, the learning ability of rats in the model group has been significantly improved. Quantitative proteomics results showed that among the 11 common differential proteins between the "model/sham operation" comparison group and the "HSYA treatment/model" comparison group, the cholesterol synthesis rate-limiting enzyme mevalonate decarboxylase (Mvd) Western Blot results are consistent with the results of quantitative proteomics analysis. We found that HSYA can inhibit the expression of BACE protein in hippocampus of AD rats and decrease the level of Aß1-42. Besides, HSYA could also reduce cholesterol levels in serum and hippocampus.Conclusion: In summary, HSYA can effectively improve learning and memory disorders in AD rats, and exert neuroprotective effects by effectively controlling serum and brain cholesterol to down-regulate the expression of BACE and thus reduce the content of Aß1-42.
