Dendrobium officinale polysaccharide attenuates cognitive impairment in circadian rhythm disruption mice model by modulating gut microbiota.

Dendrobium officinale polysaccharide (DOP) has received an increasing amount of attention as it could alleviate AD-related cognitive impairment via the regulation of microglial activation. However, the modulatory mechanism of DOP on circadian rhythm disruption (CRD) and related cognitive impairment needs further investigation. In our study, the circadian rhythm disruption mice showed a deficit in recognition and spatial memory. DOP treatment reshaped the perturbation of gut microbiota caused by CRD, including up-regulated the abundance of Akkermansia and Alistipes, down-regulated the abundance of Clostridia. In addition, DOP restored histopathological changes, reduced inflammatory cells infiltration and strengthened mucosal integrity. Mechanistically, DOP ameliorated intestinal barrier dysfunction by up-regulating tight junction protein expression, which in turn improved the invasion of lipopolysaccharide to blood and brain. The change of these contributes to inhibiting the NF-κB activation and neuroinflammation, and thus attenuating hippocampus neuronal damage and the deposition of Aß. Meanwhile, our results revealed that DOP could reverse the levels of metabolites derived related to cognitive function improvement, and these metabolites were closely associated with the key microbiota. Therefore, we speculated that DOP has the potential to provide neuroprotection against cognitive impairment by modulating the gut microbiota.

The Modulatory Effect of Cyclocarya paliurus Flavonoids on Intestinal Microbiota and Hypothalamus Clock Genes in a Circadian Rhythm Disorder Mouse Model.

Circadian rhythm disruption is detrimental and results in adverse health consequences. We used a multi-omics profiling approach to investigate the effects of Cyclocarya paliurus flavonoid (CPF)-enriched diets on gut microbiota, metabolites, and hypothalamus clock genes in mice with induced circadian rhythm disruption. It was observed that CPF supplementation altered the specific composition and function of gut microbiota and metabolites induced by circadian rhythm disruption. Analysis showed that the abundance of Akkermansia increased, while the abundance of Clostridiales and Ruminiclostridium displayed a significant downward trend after the CPF intervention. Correlation analysis also revealed that these gut microbes had certain correlations with the metabolites, suggesting that CPFs help the intestinal microbiota to repair the intestinal environment and modulate the release of some beneficial metabolites. Notably, single-cell RNA-seq revealed that CPF supplementation significantly regulated the expression of genes associated with circadian rhythm, myelination, and neurodegenerative diseases. Altogether, these findings highlight that CPFs may represent a promising dietary therapeutic strategy for treating circadian rhythm disruption.

RNA-seq analysis of green tea polyphenols modulation of differently expressed genes in Enterococcus faecalis under low pH.

Enterococcus faecasslis (E. faecalis) is a resident bacterium in the host. The increase in internal stress like low pH may affect the biological effects of E. faecalis. The prebiotic-like function of tea polyphenols can enhance the beneficial effects of its tolerance to environmental stress. In this study, RNA-sequence analysis was used to explore the protective effect of green tea polyphenols (GTP) on E. faecalis under low pH stress. A total of 28 genes were found to be responsive to GTP under low pH stress, including 16 up-regulated and 12 down-regulated. GTP intervention can partly relieve some undesired negative influences, such as the down-regulation of the base excision repair gene and amino acid transport and metabolism gene. The significantly changes were associated with selenocompound metabolism and aminoacyl-tRNA biosynthesis after the intervention of GTP. The present study provided new insights into the growth and continuous adaptation of E. faecalis under stress.

RNA-seq transcriptomic analysis of green tea polyphenols regulation of differently expressed genes in Saccharomyces cerevisiae under ethanol stress.

Saccharomyces cerevisiae has been widely used to produce alcoholic beverages and bio-fuels; however, its performance is remarkably compromised by the increased ethanol concentration during the fermentation process. In this study, RNA-sequence analysis was used to investigate the protective effect of green tea polyphenols (GTP) on S. cerevisiae cells from ethanol-induced damage. GO and KEGG analysis showed that to deal with the stress of ethanol, large amounts of genes related to cell wall, cell membrane, basic metabolism and redox regulation were significantly differentially expressed (P < 0.05), while these undesired changes could be partly relieved by administration of GTP, suggesting its potential to enhance the ethanol tolerance of S. cerevisiae. The present study provided a global view of the transcriptomic changes of S. cerevisiae in response to the accumulation of ethanol and the treatment of GTP, which might deepen our understanding about S. cerevisiae and the fermentation process, and thus benefit the development of the bioethanol production industry.

Transcriptomic and proteomic effects of (-)-epigallocatechin 3-O-(3-O-methyl) gallate (EGCG3"Me) treatment on ethanol-stressed Saccharomyces cerevisiae cells.

Saccharomyces cerevisiae (S. cerevisiae) is the main fermentation strain in brewing industry. However, the accumulation of ethanol during the fermentation inhibits the growth of S. cerevisiae. Polyphenols are important bioactive ingredients in oolong tea, and epigallocatechin-3-O-(3"-O-methyl)-gallate (EGCG3"Me) has exhibited ameliorate effect on alcohol intoxication. Therefore, in the current work, we used RNA-seq transcriptomics and iTRAQ proteomic analysis to study the effect of EGCG3"Me on ethanol-stressed S. cerevisiae. After EGCG3"Me intervention (0.8%, w/v), 178 up-regulated and 172 down-regulated genes were identified, meanwhile, 190 differentially expressed proteins (DEPs) were identified. In addition, KEGG pathways for metabolic pathways, biosynthesis of secondary metabolites and microbial metabolism were among the most DEPs after EGCG3"Me intervention. The integrated transcriptomic and proteomic analysis indicated EGCG3"Me may alleviate ethanol-induced damage on the cell wall and cell membrane of S. cerevisiae, and facilitate the redox balance and glycolysis. This study provides new insights into the mechanisms underlying the molecular response to ethanol in S. cerevisiae by the treatment of EGCG3"Me.

A metagenomic analysis of the modulatory effect of Cyclocarya paliurus flavonoids on the intestinal microbiome in a high-fat diet-induced obesity mouse model.

BACKGROUND: As a result of a low bioavailability, the majority of Cyclocarya paliurus flavonoids (CPF) remain in the large intestine where they accumulate to exert a modulatory effect on the intestinal micro-ecology. Therefore, the present study investigated the modulatory effect of CPF on intestinal microbiota. RESULTS: CPF dramatically ameliorated the obesity-induced gut dysbiosis. A significant decrease (P < 0.05) was observed in the ratio of Firmicutes/Bacteroidetes after CPF treatment for 8 weeks. Moreover, Kyoto Encyclopedia of Genes and Genomes pathways of biosynthesis of amino acids, the two-component system and ATP-binding cassette transporters enriched the most differentially expressed genes after CPF intervention. CONCLUSION: The results of the present study indicate that CPF might have prebiotic-like activity and could be used as a functional food component with potential therapeutic utility to prevent obesity-related metabolic disorders by manipulating the gut flora and affecting certain metabolic pathways, thus contributing to the improvement of human health. © 2019 Society of Chemical Industry.

Identifying hQC Inhibitors of Alzheimer's Disease by Effective Customized Pharmacophore-Based Virtual Screening, Molecular Dynamic Simulation, and Binding Free Energy Analysis.

Human glutaminyl cyclase (hQC) appeared as a promising new target with its inhibitors attracted much attention for the treatment of Alzheimer's disease (AD) in recent years. But so far, only a few compounds have been reported as hQC inhibitors. To find novel and potent hQC inhibitors, a high-specificity ZBG (zinc-binding groups)-based pharmacophore model comprising customized ZBG feature was first generated using HipHop algorithm in Discovery Studio software for screening out hQC inhibitors from the SPECS database. After purification by docking studies and drug-like ADMET properties filters, four potential hit compounds were retrieved. Subsequently, these hit compounds were subjected to 30-ns molecular dynamic (MD) simulations to explore their binding modes at the active side of hQC. MD simulations demonstrated that these hit compounds formed a chelating interaction with the zinc ion, which was consistent with the finding that the electrostatic interaction was the major driving force for binding to hQC confirmed with MMPBSA energy decomposition. Higher binding affinities of these compounds were also verified by the binding free energy calculations comparing with the references. Thus, these identified compounds might be potential hQC candidates and could be used for further investigation.

A transcriptome analysis of the ameliorate effect of Cyclocarya paliurus triterpenoids on ethanol stress in Saccharomyces cerevisiae.

Saccharomyces cerevisiae (S. cerevisiae) plays a critical role in ethanol fermentation. However, during the fermentation, yeast cells are exposed to the accumulation of ethanol, which significantly affect the cell growth and the target product yield. In the present work, we employed RNA-sequence (RNA-seq) to investigate the ameliorate effect of Cyclocarya paliurus (C. paliurus) triterpenoids on S. cerevisiae under the ethanol stress. After C. paliurus triterpenoids intervention (0.3% v/v), 84 differentially expressed genes (DEGs) were identified, including 39 up-regulated and 45 down-regulated genes. The addition of triterpenoids decreased the filamentous and invasive growth of cells, and benefit to the redox balance and glycolysis. This study offers a global view through transcriptome analysis to understand the molecular response to ethanol in Sc131 by the treatment of C. paliurus triterpenoids, which may be helpful to enhance ethanol tolerance of S. cerevisiae in the fermentation of Chinese fruit wine.

The evaluation of the quality of Feng Huang Oolong teas and their modulatory effect on intestinal microbiota of high-fat diet-induced obesity mice model.

The variations in the contents of tea catechins and free amino acids in relation to the quality of Fenghuang Oolong teas (FOT) were determined. It demonstrated that in FOT, which were grown at a high altitude, the contents of methylated estered tea catechins were relatively higher. By human flora-associated (HFA) mice model, the effect of FOT on high-fat diet-induced obesity was investigated by high-throughput sequencing. The shifts in relative abundance of the dominant taxa at the phylum, family and genus levels showed their dramatically effects. A large increase in Bacteroidetes with decrease of Firmicutes was observed after the administration of FOT for 8 weeks. Together, these results suggest that FOT are rich in tea catechins, especially O-methylated tea catechin derivatives, which may be affected by the unique growth environment, and FOT may have prebiotic-like activity and can be used as functional food components in manipulating intestinal microbiota.

A metagenomics approach to the intestinal microbiome structure and function in high fat diet-induced obesity mice fed with oolong tea polyphenols.

To investigate the modulatory effect of oolong tea polyphenols (OTP) on intestinal microbiota, OTP was prepared by column chromatography and its influence on the gut flora structure was analyzed by high-throughput sequencing with a human flora-associated high fat diet (HFD) induced obesity mouse model. We observed a robust increase in bacterial biodiversity and the abundance of genera known to be butyrate- and acetate-producing bacteria. A large increase in Bacteroidetes with a decrease in Firmicutes was observed after the administration of OTP for 4 weeks, and the corresponding decrease in the Firmicutes/Bacteroidetes ratio reflected the positive modulatory effect of OTP on the intestinal microbiota. In addition, KEGG pathways for the biosynthesis of amino acids, carbon metabolism, and the ribosome were among the most differentially expressed genes after OTP intervention. The current study revealed that OTP rich in tea catechins, especially O-methylated derivatives, may have prebiotic-like activity and can be used as a functional food component with potential therapeutic utility to prevent obesity-related metabolic disorders by manipulating the intestinal microbiota.

In vitro and vivo antioxidant activities of daylily flowers and the involvement of phenolic compounds.

Daylily (Hemerocallis fulva Linn.) flowers were hot air-dried and freeze-dried after harvest. Antioxidant properties of water and ethanol extracts prepared from these dried flowers were evaluated in terms of total antioxidant activity, reducing capacity, and metal chelating activity. Extracts from daylily flowers exhibited strong antioxidant activity. Ethanol was more efficiency to extract antioxidants than water, and freeze-drying preserved higher activities than air-drying. Rutin, (+)-catechin, and gallic acid were identified in the extracts by HPLC, and were highly related to the antioxidant activities. The antioxidant activity was further evaluated by feeding mice with ethanol extract from freeze-dried daylily flowers for 60 days. The results demonstrated that the extract at dosage of 40-225 mg/100 g significantly increased the activity of SOD (superoxide dismutase) and reduced the lipid peroxidation in both blood and liver of rat.