To investigate the effects of gensenoside Rg1 on expressions of phosphorylated tau protein (P-tau), protein phosphatase 2A (PP2A) and tau protein in Alzheimer's disease-like tau phosphorylation rat brain slices, and to explore the mechanisms of gensenoside Rg1 in inhibiting tau phosphorylation.

To investigate the effects of Naoerkang (NEK), a compound traditional Chinese herbal medicine, on the expressions of beta-amyloid peptide 1-42 (Abeta(1-42)) and neprilysin (NEP) in hippocampal tissues in a rat model of Alzheimer's disease (AD).

OBJECTIVETo investigate the effect of ginsenoside Rg1 on the expressions of phosphory protein Tau (P-Tau), N-methyl-D-aspartate receptor subunit 1 (NR1) and N-methyl-D-aspartate receptor subunit 2B(NR2B) in rat brain slice model of Alzheimer's disease.

METHODBrains of 5-week-old Wistar rats were cut into slices which were 400 microm thick. These brain slices were randomly divided into normal control group, untreated group, low-dose ginsenoside Rg1 group, medium-dose ginsenoside Rg1 group and high-dose ginsenoside Rg1 group, with 10 slices in each group. All brain slices were cultured with artificial cerebrospinal fluid (ACSF) that was aerated via polyethylene tubing attached to a source of 95% O2, 5% CO2 at (32.0 +/- 0.5) degrees C. And brain slices in the ginsenoside R1 groups were administrated with the ginsenoside Rg1 (60, 120 and 240 micromol x L(-1) respectively) in ACSF for 2 h firstly. Then okadaic acid (OA) was administrated into ACSF of untreated group and ginsenoside Rg1 groups separately for 3 h to induce Tau phosphorylation to prepare AD models. The concentration of OA in each group was 1 micromol x L(-1). And there was no any intervention for the brain slices in the normal control group. The expressions of P-Tau, NR1 and NR2B in brain slices in each group were determined by immunohistochemical method, and the results were analyzed by image acquisition and analysis system.

RESULTCompared with the normal control group, the expression of P-Tau was significantly increased (P < 0.05 or P < 0.01) and the expressions of NR1 and NR2B were decreased (P < 0.01) in untreated group. Compared with the untreated group, the expression of P-Tau was significantly decreased (P < 0.01 or P < 0.05) and the expressions of NR1 and NR2B were increased (P < 0.01 or P < 0.05) in ginsenoside Rg1 groups, especially in high-dose ginsenoside Rg1 group.

CONCLUSIONGinsenoside Rg1 can play the role of anti-dementia by inhibiting the expression of P-Tau so as to slow the formation of neurofibrillary tangles and increasing the expression of NR1 and NR2B so as to improve learning and memory abilities in rat brain slice model of Alzheimer's disease.

Alzheimer Disease ; metabolism ; pathology ; Animals ; Brain ; drug effects ; metabolism ; pathology ; Disease Models, Animal ; Gene Expression Regulation ; drug effects ; Ginsenosides ; pharmacology ; Hippocampus ; drug effects ; metabolism ; pathology ; In Vitro Techniques ; Male ; Phosphoproteins ; metabolism ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate ; metabolism ; tau Proteins ; metabolism

OBJECTIVETo observe the effect of ginsenoside Rg1 on the expressions of phosphory protein Tau (P-Tau) and caspase-3 in brain slices from AD model rats.

METHODThe brains of 5-week-old Wista rats were cut into slices which were 400 microm thick. These brain slices were divided into five groups: normal contral group, untreated group, low-dose, medium-dose and high-dose ginsenoside Rg1 groups (60, 120, 240 micromol x L(-1)). And there were 10 slices in each group. These brain slices were cultured with artificial cerebrospinal fluid. After the brain slices in ginsenoside Rg1 groups were administration with ginsenoside Rg1 for 2 h preventively, brain slices in untreated group and ginsenoside Rg1 groups were administrated with okadaic acid (OA) for 3 h to induce hyperphosphorylation of Tau protein to prepare AD models. And the effects of ginsenoside Rg1 on the expressions of P-Tau and caspase-3 in brain slices from AD model rats in each group were observed with immunohistochemistry and image analysis technology.

RESULTThe levels of the expressions of P-Tau and caspase-3 in the untreated group were significantly higher than those in the normal control group (P < 0.01). Compared with untreated group, the levels of the expressions of P-Tau and caspase-3 in ginsenoside Rg1 groups were significantly low (P < 0.01 or P < 0.05).

CONCLUSIONGinsenoside Rg1 could inhibit the expression of P-Tau to slow the formation of neurofibrillary tangles and could inhibit the expression of caspase-3 to inhibit neuronal apoptosis to protect the nerve cells, so as to play the role of anti-dementia.

Alzheimer Disease ; drug therapy ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Caspase 3 ; metabolism ; Disease Models, Animal ; Ginsenosides ; therapeutic use ; Immunohistochemistry ; Male ; Rats ; Rats, Wistar ; tau Proteins ; metabolism

Objective:To explore the effects and molecular mechanisms of ginsenoside Rg1 on the expression of neuronal autophagosome-related proteins in a rat model of Alzheimer's disease(AD).Methods:Six-week-old SD rats were decapitated to prepare hippocampal brain slices.The slices were randomly divided into the blank control group, the model group, the low-concentration, medium-concentration and high-concentration Rg1 groups, with 10 in each group.In the model group, Aβ 1-42(final concentration: 5 μmol/L)was added into an artificial cerebrospinal fluid(CSF)for 2 h treatment.The low-concentration, medium-concentration and high-concentration Rg1 groups were treated with Aβ 1-42(final concentration: 5 μmol/L)for 2 h, and then treated with Rg1(final concentrations: 60 μmol/L, 120 μmol/L, 240 μmol/L, respectively)for 3 h. The blank control group was not given any intervention drugs.At the end of intervention, histological changes of hippocampal brain slices in each group were examined via hematoxylin-eosin(HE)staining.Autophagosomes in hippocampal brain slices of each group were detected using transmission electron microscopy.The expression levels of autophagy-related proteins(P62, LC3-Ⅱ/LC3-Ⅰ), Aβ 1-42and shank protein in hippocampal brain slices of each group were detected with Western blot. Results:The results of HE staining showed that the arrangement of hippocampal neurons were disordered in the model group, with death and depletion of neurons.The arrangement and depletion of hippocampal neurons in each Rg1 group were less severe compared with the model group, with most significant improvement seen in the high-concentration Rg1 group.The results of transmission electron microscopy showed that the number of autophagosomes in brain slices in the model group was significantly higher than that in the blank control group, while each Rg1 group had fewer autophagosomes than the model group.The results of Western blot showed that, compared with the blank control group, levels of Shank1, P62 and LC3-Ⅰ proteins in brain slices were decreased(all P<0.05), while levels of Aβ 1-42and LC3-Ⅱ protein were significantly increased(all P<0.05)in the model group.Compared with the model group, levels of Shank1, P62 and LC3-Ⅰ proteins in brain slices were increased(all P<0.05), while levels of Aβ 1-42and LC3-Ⅱ protein were decreased( P<0.05)in each Rg1 group.These changes were the most significant in the high-concentration Rg1 group. Conclusions:Ginsenoside Rg1 may inhibit autophagy by up-regulating the expression of Shank1, P62 and LC3-Ⅰ proteins in hippocampal brain slices of rats in the AD model, thus playing protective roles in brain neurons.

Objective:To investigate the association of apolipoprotein E(ApoE)gene polymorphism with lipid metabolism and common chronic cardiovascular and cerebrovascular diseases in the elderly.Methods:A total of 4 322 elderly outpatients and inpatients from our hospital were enrolled in this retrospective analysis.The distribution of ApoE subtypes in the elderly was analyzed.Then 600 cases(321 cases with atherosclerosis and 279 healthy controls)were included to analyze blood lipid-related biochemical indexes.ApoE genotypes were determined by DNA microarray analysis.Results:ApoE E3 was the most common subtype, making up 67.1%(2 898/4 322)in this study population.The distribution of ApoE subtypes in the elderly with chronic cardiovascular and cerebrovascular diseases was basically the same as that in the elderly population.However, in patients with neurodegenerative diseases, the rate of ApoE E4 carriers was 26.4%(152/576), which was higher than that of ApoE E2 carriers(12.2%, 70/576)( P<0.01). Triglyceride(TG)levels in those with atherosclerosis carrying ApoEε2 and ε4 alleles were higher than those in healthy controls carrying ApoEε2 and ε4 alleles ApoEε2 alleles: (1.85±2.09)mmol/L vs.(2.00±1.44)mmol/L, ApoEε4 alleles: (1.53±1.31)mmol/L vs.(1.84±1.32)mmol/L, P<0.05.TG( OR=4.360, 95% CI: 2.150-8.844), high density lipoprotein cholesterol( OR=0.486, 95% CI: 0.307-0.770), low density lipoprotein cholesterol( OR=2.321, 95% CI: 1.020-5.281)and ApoE alleles( OR=0.335, 95% CI: 0.210-0.533)were risk factors for atherosclerosis( P<0.01). Conclusions:ApoE polymorphism is associated with lipid metabolism in elderly patients.Genetic background may be among the factors affecting lipid metabolism.ApoE ε4 allele carriers have an increased risk of dyslipidemia, cardiovascular and neurodegenerative diseases.