Alterations in Synaptic Connectivity and Synaptic Transmission in Alzheimer's Disease with High Physical Activity.

Background: Alzheimer's disease (AD) is a progressive neurodegeneration disease. Physical activity is one of the most promising modifiable lifestyles that can be effective in slowing down the progression of AD at an early stage. Objective: Explore the molecular processes impaired in AD that were conversely preserved and enhanced by physical activity. Methods: Integrated transcriptomic analyses were performed in datasets that contain AD patients and elders with different degrees of physical activity. The changes of the hub genes were validated through analyzing another two datasets. The expression of the hub genes was further detected in the hippocampus and cortexes of APP/PS1 transgenic mice with or without physical activity by Quantitative polymerase chain reaction (qPCR). Results: Cross-comparison highlighted 195 DEGs displaying opposed regulation patterns between AD and high physical activity (HPA). The common DEGs were predominantly involved in synaptic vesicle recycling and synaptic transmission, largely downregulated in AD patients but upregulated in the elders with HPA. Two key modules and four hub genes that were related to synaptic vesicle turnover were obtained from the PPI network. The expression of these hub genes (SYT1, SYT4, SH3GL2, and AP2M1) was significantly decreased in AD transgenic mice and was reversed by HPA training. Conclusions: HPA may reverse AD pathology by upregulating a range of synaptic vesicle transport related proteins which might improve the efficiency of synaptic vesicle turnover and facilitate inter-neuronal information transfer. The study provides novel insights into the mechanisms underlining the protective effects of HPA on AD.

Toxicity study of ethanol extract from Oroxylumindicum (L.) Vent in rats.

OBJECTIVE: To evaluate the safety of Oroxylumindicum(L.) Vent extract administered for 26 weeks in Wistar rats. METHODS: Oroxylumindicum (L.) Vent extract was administrated to male and female rats by gavage once daily at doses of 54, 225, and450 mg?kg-1?d-1. The rats were sacrificed after administration for13 weeks and 26 weeks. Part of the rats in each group were allowed to recover for 4 weeks after 26-week administration. Systematic examinations including haematology, urology, blood biochemistry and histomorphology were performed at the end of 13, 26 weeks of administration and 4 weeks of recovery. RESULTS: No treatment related adverse effect shappened on rats'general status, body weight, food consumption, urinary index and histomorphology examination. Although during the administration, in some rats of extract's groups, the value of Red blood cell count (RBC), white blood cell counts (WBC), hemoglobin (HGB), haematocrit (HCT) and K iron were decreased, and biochemistry index, such as glucose (GLU), triglyceride (TG), alanine transaminase (ALT) and blood urea nitrogen(BUN) were increased, the above parameters were within the normal ranges and all returned to baseline after the drug stopping for 4 weeks. CONCLUSION: The administration of Oroxylumindicum(L.) Vent extractat levers up to 450 mg/kg (equals to 75 times of clinical dose) is well toleratedfor both genders without significant toxicity within the administration duration in this study.

Potential chronic liver toxicity in rats orally administered an ethanol extract of Huangqin (Radix Scutellariae Baicalensis).

OBJECTIVE: To investigate on the cytotoxicity and penetration enhancement effect of essential oils (EOs) from warming the interior medicinals (WIM) from Traditional Chinese Medicine (TCM). METHODS: EOs were extracted from WIM of Bichengqie (Litseae Fructus), Dingxiang (Flos Syzygii Aromatici), Huajiao (Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang (Fructus Foeniculi) with warm nature, and Ganjiang (Rhizoma Zingiberis), Gaoliangjiang (Rhizoma Alpiniae Officinari), Rougui (Cortex Cinnamomi Cassiae), and Wuzhuyu (Fructus Evodiae Rutaecarpae) with hot nature, respectively. Their chemical compositions were analyzed by gas chromatography-mass spectrometry (GC-MS). The cytotoxicity of the extracted eight EOs on HaCaT cells was measured and compared. Moreover, analyses of cell cycle and cell apoptosis were performed to investigate the cytotoxic mechanism. The transdermal penetration enhancement effects of the extracted eight EOs on ibuprofen were further compared by the modified Franz diffusion cell method. RESULTS: The most abundant constituents in the extracted eight EOs were determined to be monoterpenes, especially oxygen-containing monoterpenes. The HaCaT cell cytotoxicity of EOs from WIM with hot nature were significantly (P = 0.020) higher than that with warm nature. Both ginger oil and zanthoxylum oil significantly induced G0/G1 phase arrestment in HaCaT cell cycle. For ginger oil from WIM with hot nature and zanthoxylum oil from WIM with warm nature, the main mechanisms of the cytotoxicity were found to be the induction of cellular necrosis and the cellular apoptosis, respectively. Furthermore, most of the tested EOs showed remarkable penetration enhancement activity on ibuprofen. However, no statistical significance (P = 0.18) was found between penetration enhancement activity of EOs from WIM with warm nature and EOs from WIM with hot nature. CONCLUSION: With the enhanced penetration activity, the extracted EOs from the WIM demonstrated their significant effect of the cytotoxicity on the skin cells.