Phytoestrogens refer to a class of compounds in plants that can bind to and activate estrogen receptors in mammalian organisms,exerting varying degrees of protective and improvement effects on the body.Modern pharmacological studies have found that phytoestrogens have therapeutic effects on the cardiovascular system,nervous system,endocrine system,immune system,and so on.It is worth noting that the binding of phytoestrogens to estrogen receptors in the brain can produce central neuroprotective effects and improve learning and cognitive impairment in Alzheimer's pectients through multiple targeted pathways.This paper describes the research progress and related mechanisms of phytoestrogen-like monomers,Chinese herbal medicine,and compound formulations in Alzheimer's disease.The aim is to provide new drug design ideas and solutions for the effective treatment of senile dementia with traditional Chinese medicine.

Objective:To investigate the effect and mechanism of Ganoderma lucidum triterpenoids (GLTs) on improving scopolamine-induced learning and memory impairment and anxious- and depressive-like behavior mice based on brain-derived neurotrophic factor(BDNF)-tyrosine kinase receptor type B(TrkB)-cAMP response element binding protein(CREB) pathway.Methods:Fifty SPF-grade female KM mice aged 3 months were randomly divided into control group, model group, GLTs low-dose group (0.35 g/kg), GLTs medium-dose group (0.70 g/kg) and GLTs high-dose group (1.40 g/kg), with 10 mice in each group. The mice in GLTs low-dose, GLTs medium-dose and GLTs high-dose group were given corresponding GLTs by gavage once a day according grouping for 34 days, while mice in control group and model group were given the same volume of 0.9% NaCl by gavage once a day for 34 days. From 22nd day to 34th day of the experiment, except the mice in the control group, mice in the other groups all received intraperitoneal injections of scopolamine (3 mg/kg, once a day) to establish the learning and memory impairment model. The learning and memory ability of mice were assessed by Morris water maze and Y maze tests. The anxious- and depressive- like behavior of mice were assessed by elevated plus maze and forced swimming test. The morphology of neurons in hippocampus and cortex were observed by hematoxylin-eosin (HE) staining.The expression levels of postsynaptic density-95(PSD-95) and synaptophysin(SYN), and proteins related to the BDNF-TrkB-CREB pathway in the hippocampal region were detected by Western blot and ELISA.GraphPad Prism 9.0 software was used for statistical analysis. Repetitive measurement ANOVA was used for the multiple group comparison of Morris water maze data.One-way ANOVA was used for the multiple group comparison of the other data, and Tukey multiple test was used for further pairwise comparison.Results:(1) The interaction between the time and group on the escape latencies showed no significant among the 5 groups of mice ( F=0.77, P=0.58). However, the main effects of group and time on escape latency were both significant among the 5 groups of mice ( F=5.27, 41.94, both P<0.05). From day 3 to day 5, the escape latencies of the medium-dose and high-dose GLTs groups were lower than that of the model group (both P<0.05). There was a statistically significant difference in the time spent in the target quadrant among the 5 groups in Morris water maze test( F=12.78, P<0.05), with the medium-dose and high-dose GLTs groups spending more time in the target quadrant than the model group (both P<0.05). Y maze test results showed that there was a statistically significant difference in the percentage of spontaneous alternation among the 5 groups ( F=13.46, P<0.05). The percentage of spontaneous alternations in GLTs medium-dose group ((54.47±2.28) %) and high-dose group ((55.39±3.34) %) was significantly higher than that in model group((41.65±4.22)%) (both P<0.05). (2) The results of the elevated plus maze and forced swimming test indicated that there were statistically significant differences in the time spent in the open arms and the immobility time among the 5 groups of mice( F=25.67, 4.40, both P<0.05). The high-dose GLTs group spent more time in the open arms than the model group ( P<0.05) and had a shorter immobility time than the model group ( P<0.05). (3) The HE staining results showed that there were significant differences in the number of cell necrosis in hippocampal CA3 and cortex in 5 groups ( F=12.70, 19.55, both P<0.05). The high-dose GLTs group had a lower number of necrotic cells in both the CA3 region and the cortical region compared with the model group (both P<0.05). (4) The Western blot results indicated that there were statistically significant differences in the protein expression levels of PSD-95, SYN, BDNF, p-CREB and the ratio of p-CREB/CREB in the hippocampal region of the brains of the 5 groups of mice ( F=5.62, 4.15, 5.89, 5.62, 5.19, all P<0.05). The ELISA results showed that there were statistically significant differences in the protein expression levels of p-TrkB and the ratio of p-TrkB/TrkB in the hippocampal region of the brains of the 5 groups of mice ( F=6.36, 10.95, both P<0.05). The high-dose GLTs group had higher protein expression levels of SYN, PSD-95, BDNF, p-CREB, and a higher ratio of p-CREB/CREB compared to the model group (all P<0.05). Additionally, the high-dose GLTs group had higher expression levels of p-TrkB and a higher ratio of p-TrkB/TrkB ((5.03±1.30) pg/mL, 0.56±0.10) compared to the model group ((0.88±0.26) pg/mL, 0.11 ±0.03) (both P<0.05). Conclusion:GLTs can improve the learning and memory ability and anxious- and depressive-like behavior in scopolamine model mice, and the mechanism may be related to the up-regulation of BDNF-TrkB-CREB pathway related protein expression and the enhancement of synaptic plasticity.

Objective:To investigate the effect and mechanism of Ganoderma lucidum triterpenoids (GLTs) on improving scopolamine-induced learning and memory impairment and anxious- and depressive-like behavior mice based on brain-derived neurotrophic factor(BDNF)-tyrosine kinase receptor type B(TrkB)-cAMP response element binding protein(CREB) pathway.Methods:Fifty SPF-grade female KM mice aged 3 months were randomly divided into control group, model group, GLTs low-dose group (0.35 g/kg), GLTs medium-dose group (0.70 g/kg) and GLTs high-dose group (1.40 g/kg), with 10 mice in each group. The mice in GLTs low-dose, GLTs medium-dose and GLTs high-dose group were given corresponding GLTs by gavage once a day according grouping for 34 days, while mice in control group and model group were given the same volume of 0.9% NaCl by gavage once a day for 34 days. From 22nd day to 34th day of the experiment, except the mice in the control group, mice in the other groups all received intraperitoneal injections of scopolamine (3 mg/kg, once a day) to establish the learning and memory impairment model. The learning and memory ability of mice were assessed by Morris water maze and Y maze tests. The anxious- and depressive- like behavior of mice were assessed by elevated plus maze and forced swimming test. The morphology of neurons in hippocampus and cortex were observed by hematoxylin-eosin (HE) staining.The expression levels of postsynaptic density-95(PSD-95) and synaptophysin(SYN), and proteins related to the BDNF-TrkB-CREB pathway in the hippocampal region were detected by Western blot and ELISA.GraphPad Prism 9.0 software was used for statistical analysis. Repetitive measurement ANOVA was used for the multiple group comparison of Morris water maze data.One-way ANOVA was used for the multiple group comparison of the other data, and Tukey multiple test was used for further pairwise comparison.Results:(1) The interaction between the time and group on the escape latencies showed no significant among the 5 groups of mice ( F=0.77, P=0.58). However, the main effects of group and time on escape latency were both significant among the 5 groups of mice ( F=5.27, 41.94, both P<0.05). From day 3 to day 5, the escape latencies of the medium-dose and high-dose GLTs groups were lower than that of the model group (both P<0.05). There was a statistically significant difference in the time spent in the target quadrant among the 5 groups in Morris water maze test( F=12.78, P<0.05), with the medium-dose and high-dose GLTs groups spending more time in the target quadrant than the model group (both P<0.05). Y maze test results showed that there was a statistically significant difference in the percentage of spontaneous alternation among the 5 groups ( F=13.46, P<0.05). The percentage of spontaneous alternations in GLTs medium-dose group ((54.47±2.28) %) and high-dose group ((55.39±3.34) %) was significantly higher than that in model group((41.65±4.22)%) (both P<0.05). (2) The results of the elevated plus maze and forced swimming test indicated that there were statistically significant differences in the time spent in the open arms and the immobility time among the 5 groups of mice( F=25.67, 4.40, both P<0.05). The high-dose GLTs group spent more time in the open arms than the model group ( P<0.05) and had a shorter immobility time than the model group ( P<0.05). (3) The HE staining results showed that there were significant differences in the number of cell necrosis in hippocampal CA3 and cortex in 5 groups ( F=12.70, 19.55, both P<0.05). The high-dose GLTs group had a lower number of necrotic cells in both the CA3 region and the cortical region compared with the model group (both P<0.05). (4) The Western blot results indicated that there were statistically significant differences in the protein expression levels of PSD-95, SYN, BDNF, p-CREB and the ratio of p-CREB/CREB in the hippocampal region of the brains of the 5 groups of mice ( F=5.62, 4.15, 5.89, 5.62, 5.19, all P<0.05). The ELISA results showed that there were statistically significant differences in the protein expression levels of p-TrkB and the ratio of p-TrkB/TrkB in the hippocampal region of the brains of the 5 groups of mice ( F=6.36, 10.95, both P<0.05). The high-dose GLTs group had higher protein expression levels of SYN, PSD-95, BDNF, p-CREB, and a higher ratio of p-CREB/CREB compared to the model group (all P<0.05). Additionally, the high-dose GLTs group had higher expression levels of p-TrkB and a higher ratio of p-TrkB/TrkB ((5.03±1.30) pg/mL, 0.56±0.10) compared to the model group ((0.88±0.26) pg/mL, 0.11 ±0.03) (both P<0.05). Conclusion:GLTs can improve the learning and memory ability and anxious- and depressive-like behavior in scopolamine model mice, and the mechanism may be related to the up-regulation of BDNF-TrkB-CREB pathway related protein expression and the enhancement of synaptic plasticity.

Objective:To investigate the change and clinical significance of serum alkaline phosphatase (ALP) level in patients with acute spontaneous intracerebral hemorrhage(AICH).Methods:81 patients with AICH admitted to the Neurosurgery Department of Tianjin Third Central Hospital from January 2019 to October 2020 were retrospectively analyzed. 81 patients with non cerebral hemorrhage who came from the health examination center or complained of dizziness and had no hepatobiliary and skeletal diseases were selected as the control group. The clinical data of all the patients were recorded, including gender, age, Glasgow Coma Scale (GCS) score, hemorrhage location, liver function indexes, the history of hypertension, diabetes, heart disease, smoking, drinking, and so on. The differences in clinical data between the two groups were compared. Pearson correlation was used to analyze the correlation between liver function indexes and GCS score. The independent risk factors for AICH were screened by binary logistic regression, and the receiver operating characteristic (ROC) curve was used to evaluate the value of serum ALP in predicting intracerebral hemorrhage.Results:Serum ALP level in AICH group was significantly higher than that in the control group [85.0(70.0, 103.0) U/L vs 65.0(54.5, 71.5)U/L, Z=6.740, P<0.001]. Pearson correlation analysis showed that serum ALP had a negative correlation with GCS score ( r=0.255, P=0.022). Binary logistic regression analysis showed that hypertension ( OR=20.440, 95% CI 8.572-48.737) and ALP ( OR=1.077, 95% CI 1.049-1.105) were risk factors for intracerebral hemorrhage. Serum ALP level was an independent risk factor ( OR=1.069, 95% CI 1.038-1.101) for AICH after adjusting for confounding variables including age, AST, history of hypertension. ROC curve showed that the area under the curve (AUC) of serum ALP in predicting intracerebral hemorrhage was 0.807 (95% CI 0.740-0.873, P<0.001), with sensitivity of 67.9% and specificity of 81.5%. Conclusions:Serum ALP level may be related to the occurrence and severity of AICH. Therefore, serum ALP level can be used as a reference index to evaluate the occurrence, severity of patients with AICH.