Tanshinone IIA Ameliorates Spatial Learning and Memory Deficits by Inhibiting the Activity of ERK and GSK-3ß.

BACKGROUND: Alzheimer disease (AD) is the most common type of dementia which is becoming a primary problem in the present society, but it lacks effective treatment methods and means of AD. Tanshinone IIA (Tan IIA) has been reported to have neuroprotective effects to restrain the Aß25-35-mediated apoptosis. However, few studies try to understand how Aß1-42 affects hyperphosphorylation of tau and how Tan IIA regulates this process at the molecular level. METHODS: Fifty male Sprague-Dawley rats were randomly divided into 5 groups and infused through the lateral ventricle with Aß1-42 except the control group. Then the rats were treated with Tan IIA through intragastric administration for 4 weeks. After the ability of learning and memory being measured, histomorphological examination and Western blot were used to detect the possible mechanism in the AD-associated model rats. RESULTS: We observed that Aß1-42 infusion could induce spatial learning and memory deficits in rats. Simultaneously, Aß1-42 also could reduce the neuron in cornu ammonis 1 and dentate gyrus of hippocampus, as well as increase the levels of cleaved caspase 3, hyperphosphorylated tau at the sites Ser396, Ser404, and Thr205 with enhancing staining of black granules in brain. We also found that Aß1-42 could increase the activity of extracellular signal-regulated protein kinase (ERK) and glycogen synthase kinase-3ß (GSK-3ß). Meanwhile, these phenomena could be ameliorated when Tan IIA was used. CONCLUSION: We concluded that Tan IIA might have neuroprotective effect and improving learning and memory ability to be a viable candidate in AD therapy with mechanisms involving the ERK and GSK-3ß signal pathway.

Suanzaoren Tang Exerts Neuroprotective Effect by Inhibiting Hippocampal Neuroinflammation in APP/PS1 Double Transgenic Mice / 中国实验方剂学杂志

Objective:To observe the effect of Suanzaoren Tang on hippocampal neuroinflammation in APP/PS1 mice and to explore its possible mechanism of neuroprotection. Method:The mice were randomly divided into blank group, model group, donepezil group(0.92 mg·kg-1), Suanzaoren Tang low and high-dose groups(12.96,25.92 g·kg-1). After 30 days of continuous administration in each group, pathological changes of dentate gyrus (DG) in hippocampus of mice in each group were observed by Nissl staining.The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum of each group were detected by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of TNF-α and IL-1β in hippocampus of each group. The expression levels of glial fibrillary acidic protein (GFAP) and ionic calcium binding protein 1 (IBA1) in hippocampus of each group were detected by immunohistochemical staining (ICH) and Western blot. Result:Compared with blank group, the granule cells in DG region were unevenly arranged in model group, with obvious cell loss, and the nissl bodies in some neurons disappeared or condensed, serum TNF-α and IL-1β content significantly increased (Pα and IL-1β mRNA expression quantity significantly increased (PPα and IL-1β in the serum were decreased(PPα and IL-1β mRNA in the hippocampus were decreased(PPPPConclusion:Suanzaoren Tang can improve neuronal loss in APP/PS1 double transgenic mice, and its mechanism may be related to the regulation of hippocampal neuroinflammation in mice.

Network pharmacology deciphering multiple mechanisms of volatiles of Wendan granule for treatment of senile dementia / 中国药理学与毒理学杂志

OBJECTIVE To explore the mechanisms of the volatiles of Wendan granule for the treatment of senile dementia,network pharmacology method integrating absorption,distribution,metab-olism, and excretion (ADME) screening, target fishing, network constructing, pathway analyzing, and correlated diseases prediction was applied. METHODS Twelve small molecular compounds of WDG were selected as the objects from 74 volatiles with the relative abundances above 2%,and their ADME parameters were collected from Traditional Chinese Medicine Systems Pharmacology platform (TCMSP), and then the corresponding targets, genes, pathways and diseases were predicted according to the data provided by TCMSP,DrugBank,Uniport and the Database for Annotation,Visualization and Integrated Discovery(DAVID).The related pathways and correlation analysis were explored by the Kyoto Encyclo-pedia and Genomes (KEGG) database. Finally, the networks of compound-target, target-pathway and pathway-disease of WDG were constructed by Cytoscape software. RESULTS Twelve compounds interacted with 49 targets, of which top three targets were Gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), Prostaglandin G/H synthase 2 (PGHS-2) and Sodium-dependent noradrenaline transporter.Interestingly,these targets were highly associated with depression,insomnia and Alzheimer′s disease that mainly corresponded to mental and emotional illnesses. CONCLUSION The integrated network pharmacology method provides precise probe to illuminate the molecular mechanisms of volatiles of WDG for relieving senile dementia related syndromes,which will also facilitate the application of traditional Chinese medicine in modern medicine,as well as follow-up studies such as upgrading the quality stan-dard of clinical medicine and novel drug development.

Body mass index correlates with the level of serum prostate-specific antigen in men in Fangcheng area of Guangxi / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the influence of body mass index (BMI) on the serum prostate-specific antigen (PSA) level in males in the Fangcheng area of Guangxi.</p><p><b>METHODS</b>We reviewed the health examination data of males collected from September 2009 to December 2011, including their height, weight, BMI, and serum PSA level. The subjects were categorized as underweight (BMI <18.5 kg/m2), normal (BMI 18.5-22.9 kg/m2), overweight (BMI 23.0-27.4 kg/m2), and obese (BMI > or = 27.5 kg/m2), and divided into four age groups: 20-29, 30-39, 40-49, and > or = 50 years old. The PSA levels were stratified by the BMI category for statistical analysis.</p><p><b>RESULTS</b>A total of 2,397 men were included in this study, with a mean age of (37.4 +/- 11.0) yr, BMI of (23.3 +/- 3.4) kg/m2, and PSA level of (0.98 +/- 0.93) microg/L. There were significant differences in the age-associated PSA levels in the groups with BMI < 23 (0.81 microg/L) and > or = 23 kg/m2 (0.78 microg/L) (P < 0.05), as well as in those with BMI < 27.5 (0.81 microg/L) and > or = 27. 5 kg/m2 (0.70 microg/L) (P < 0.05). In the 30-39 and 40-49 age groups, the PSA levels were significantly decreased with the increase of BMI (P < 0.05).</p><p><b>CONCLUSION</b>Increased BMI is associated with decreased PSA in men <50 years old in the Fangcheng area of Guangxi, which should be taken into consideration while determining whether to carry out prostate biopsy as part of early prostate cancer detection in young men with marginal PSA levels.</p>