RhoA/Rock2/Limk1/cofilin1 pathway is involved in attenuation of neuronal dendritic spine loss by paeonol in the frontal cortex of D-galactose and aluminum­induced Alzheimer's disease­like rat model.

Alzheimer's disease (AD) has become the most prevalent neurodegenerative disorder. Given the pathogenesis of AD is unclear, there is currently no drug approved to halt or delay the progression of AD. Therefore, it is pressing to explore new targets and drugs for AD. In China, polyphenolic Chinese herbal medicine has been used for thousands of years in clinical application, and no toxic effects have been reported. In the present study, using D­galactose and aluminum­induced rat model, the effects of paeonol on AD were validated via the Morris water maze test, open field test, and elevated plus maze test. Neuronal morphology in frontal cortex was assessed using ImageJ's Sholl plugin and RESCONSTRUCT software. RhoA/Rock2/Limk1/cofilin1 signaling pathway­related molecules were determined by Western blotting. Cofilin1 and p­cofilin1 were analyzed by immunofluorescence. Results showed that pre­treatment with paeonol attenuated D­galactose and aluminum­induced behavioral dysfunction and AD­like pathological alterations in the frontal cortex. Accompanied by these changes were the alterations in the dendrite and dendritic spine densities, especially the mushroom­type and filopodia­type spines in the apical dendrites, as well as actin filaments. In addition, the activity and intracellular distribution of cofilin1 and the molecules RhoA/Rock2/Limk1 that regulate the signaling pathway for cofilin1 phosphorylation have also changed. Our data suggests that paeonol may be through reducing Aß levels to alleviate the loss of fibrillar actin and dendrites and dendritic spines via the Rho/Rock2/Limk1/cofilin1 signaling pathway in the frontal cortex, and ultimately improving AD­like behavior.

Novel derivative of Paeonol, Paeononlsilatie sodium, alleviates behavioral damage and hippocampal dendritic injury in Alzheimer's disease concurrent with cofilin1/phosphorylated-cofilin1 and RAC1/CDC42 alterations in rats.

Alzheimer's disease (AD) is a typical hippocampal amnesia and the most common senile dementia. Many studies suggest that cognitive impairments are more closely correlated with synaptic loss than the burden of amyloid deposits in AD progression. To date, there is no effective treatment for this disease. Paeonol has been widely employed in traditional Chinese medicine. This compound improves learning behavior in an animal model; however, the mechanism remains unclear. In this study, Paeononlsilatie sodium (Pa), a derivative of Paeonol, attenuated D-galactose (D-gal) and AlCl3-induced behavioral damages in rats based on evaluations of the open field test (OFT), elevated plus maze test (EPMT), and Morris water maze test (MWMT). Pa increased the dendritic complexity and the density of dendritic spines. Correlation analysis indicated that morphological changes in neuronal dendrites are closely correlated with behavioral changes. Pa treatment reduced the production of Aß, affected the phosphorylation and redistribution of cofilin1 and inhibited rod-like formation in hippocampal neurons. The induction of D-gal and AlCl3 promoted the expression of RAC1/CDC42 expression; however, the tendency of gene expression was inhibited by pretreatment with Pa. Taken together, our results suggest that Pa may represent a novel therapeutic agent for the improvement of cognitive and emotional behaviors and dendritic morphology in an AD animal model.

Bacterial community dynamics and functional variation during the long-term decomposition of cyanobacterial blooms in-vitro.

Cyanobacterial blooms drastically influence carbon and nutrient cycling in eutrophic freshwater lakes. To understand the mineralization process of cyanobacteria-derived particulate organic matter (CyanPOM), the aerobic degradation of cyanobacterial blooms dominated by Microcystis sp. was investigated over a 95-day microcosm experiment. Approximately 91%, 95% and 83% of the initial particulate organic carbon (POC), particulate organic nitrogen (PON), and particulate organic phosphorus (POP) were decomposed, respectively. The POC:PON ratio gradually increased from 5.9 to 13.5, whereas the POC:POP ratio gradually decreased from 230.3 to 120. These results indicated that the coupling of POC, PON, and POP changed during the decomposition of CyanPOM. Moreover, approximately 29%, 51% and 46% of POC, PON, and POP were mineralized to dissolved organic carbon, NO3-, and PO43-, respectively. Rhodospirillales (10.9%), Burkholderiales (16.5%), and Verrucomicrobiales (14.3%) dominated during the rapid phase (days 0-21), whereas Sphingomonadales (12.8%), Rhizobiales (11.8%), and Xanthomonadales (36.5%) dominated during the slow phase (days 21-50) of CyanPOM decomposition. Nitrospira (16.6%-32.9%) dominated and NO3- increased during the refractory phase (days 50-95), thus suggesting the occurrence of nitrification. Redundancy analysis revealed that bacterial communities during rapid decomposition were distinct from those during the slow and refractory periods. POC:POP, NH4+, and NO3- were the major driving factors for the patterns of bacterial communities. Furthermore, increase in nitrogen metabolism, methane metabolism, amino acid related enzymes and pyruvate metabolism characterized the functional variation of bacterial communities during degradation. Therefore, CyanPOM is an important nutrient source, and its decomposition level shapes bacterial communities.

Inhibition of the growth of cyanobacteria during the recruitment stage in Lake Taihu.

Microcystis is the dominant algal bloom genus in Lake Taihu. Thus, controlling the recruitment and growth of Microcystis is the most crucial aspect of solving the problem of algal blooms. Different concentrations (0.025, 0.05, and 0.1 g L(-1)) of tea extract were used to treat barrels of lake water at the recruitment stage of cyanobacteria. There was an inhibitory effect on algal growth in all treatment groups. The inhibitory effect on cyanobacteria was stronger than on other algae. The metabolic activity of cells in the treatment groups was significantly enhanced compared to the control, as an adaptation to the stress caused by tea polyphenols. The photosynthetic activity diminished in the treatment groups and was barely detected in the 0.05 and 0.1 g L(-1) treatments. The levels of reactive oxygen species increased substantially in treated cells with the algal cells experiencing oxidative damage. The effect of tea on zooplankton was also studied. The number of Bosmina fatalis individuals did not change significantly in the 0.025 and 0.05 g L(-1) treatments. These results suggested that the application of tea extracts, during the recruitment stage of blue-green algae, suppressed the recruitment and growth of cyanobacteria, thus offering the potential to prevent cyanobacterial blooms.

Inhibition of Camellia sinensis (L.) O. Kuntze on Microcystis aeruginosa and isolation of the inhibition factors.

Low concentration of tea (Camellia sinensis (L.) O. Kuntze) was shown to inhibit the growth of the toxic cyanobacterium Microcystis aeruginosa. The inhibition efficiency was 40% at 0.1 g dry tea/L and 90% at 0.2 g/L after a 12-day culture. All varieties of tea used in the test could inhibit Microcystis growth, in which the inhibitory effect of green tea was greater than that of black tea. Antialgal allelochemicals were isolated from tea by solvent extraction, gel-chromatography and high performance liquid chromatography. Two algal-inhibition compounds were identified by liquid chromatography/mass spectrometry as epigallocatechin-3-gallate, epicatechin-3-gallate respectively. These are the main polyphenols in tea that have inhibitory effects on the growth of cyanobacteria. The combined effect of these polyphenols makes tea a promising source of algicide to inhibit the growth of algal blooms.

Formulation, antileukemia mechanism, pharmacokinetics, and biodistribution of a novel liposomal emodin.

Emodin is a multifunctional Chinese traditional medicine with poor water solubility. D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a pegylated vitamin E derivate. In this study, a novel liposomal-emodin-conjugating TPGS was formulated and compared with methoxypolyethyleneglycol 2000-derivatized distearoyl-phosphatidylethanolamine (mPEG2000-DSPE) liposomal emodin. TPGS improved the encapsulation efficiency and stability of emodin egg phosphatidylcholine/cholesterol liposomes. A high encapsulation efficiency of 95.2% ± 3.0%, particle size of 121.1 ± 44.9 nm, spherical ultrastructure, and sustained in vitro release of TPGS liposomal emodin were observed; these were similar to mPEG2000-DSPE liposomes. Only the zeta potential of -13.1 ± 2.7 mV was significantly different to that for mPEG2000-DSPE liposomes. Compared to mPEG2000-DSPE liposomes, TPGS liposomes improved the cytotoxicity of emodin on leukemia cells by regulating the protein levels of myeloid cell leukemia 1 (Mcl-1), B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein, which was further enhanced by transferrin. TPGS liposomes prolonged the circulation time of emodin in the blood, with the area under the concentration-time curve (AUC) 1.7 times larger than for free emodin and 0.91 times larger than for mPEG2000-DSPE liposomes. In addition, TPGS liposomes showed higher AUC for emodin in the lung and kidney than for mPEG2000-DSPE liposomes, and both liposomes elevated the amount of emodin in the heart. Overall, TPGS is a pegylated agent that could potentially be used to compose a stable liposomal emodin with enhanced therapeutics.