Effects of Qi-Fu-Yin on aging of APP/PS1 transgenic mice by regulating the intestinal microbiome.

Introduction: Alzheimer's disease is the most common form of dementia and closely related to aging. Qi-Fu-Yin is widely used to treat dementia, but its anti-aging effects is unknown. Methods: We used 11-month-old APP/PS1 transgenic mice for behavioral tests to observe the changes in cognitive function and age-related symptoms after Qi-Fu-Yin treatment. Fecal samples were collected for 16sRNA sequencing and metagenomic sequencing. Differences among the groups of intestinal microbiota and the associations with aging and intestinal microbiota were analyzed based on the results. Results: Here we found that Qi-Fu-Yin improved the ability of motor coordination, raised survival rate and prolonged the survival days under cold stress stimulation in aged APP/ PS1 transgenic mice. Our data from 16sRNA and metagenomic sequencing showed that at the Family level, the intestinal microbiota was significantly different among wild-type mice, APP/PS1 transgenic mice and the Qi-Fu-Yin group by PCA analysis. Importantly, Qi-Fu-Yin improved the functional diversity of the major KEGG pathways, carbohydrate-active enzymes, and major virulence factors in the intestinal flora of APP/PS1 transgenic mice. Among them, the functions of eight carbohydrate-active enzymes (GT2_Glycos_transf_2, GT4, GT41, GH2, CE1, CE10, CE3, and GH24) and the functions of top three virulence factors (defensive virulence factors, offensive virulence factors and nonspecific virulence factors) were significantly and positively correlated with the level of grasping ability. We further indicated that the Qi-Fu-Yin significantly reduced the plasma levels of IL-6. Conclusion: Our results indicated that the effects of Qi-Fu-Yin anti-aging of APP/PS1 transgenic mice might be through the regulation of intestinal flora diversity, species richness and the function of major active enzymes.

A network pharmacology-based study on key pharmacological pathways and targets of Qi Fu Yin acting on Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a central nervous system (CNS) disease characterized by progressive cognitive dysfunction and memory loss. Qi Fu Yin is mainly used to treat dementia, particularly AD, in the clinic, but its comprehensive mechanisms are not known. OBJECTIVE: In this research, we aimed to investigate the mechanisms of Qi Fu Yin in AD by network pharmacology and molecular docking. METHODS: First, the chemical constituents in Qi Fu Yin were obtained from five databases and classified according to their structure. Targets of chemical constituents and AD-related targets were also collected from the databases. Then, overlapping genes between Qi Fu Yin and AD were identified by intersection analysis. MetaCore was used to gather enrichment information. Combination synergy analysis was performed by Cytoscape. After ligand-receptor docking, the binding affinity was verified by ADP-Glo™ kinase assay and fluorescence resonance energy transfer (FRET) assay. RESULTS: We found 12 classes with 977 components in Qi Fu Yin. A total of 511 compounds and 577 potential target proteins in Qi Fu Yin were found to be related to AD. The pathways of Qi Fu Yin in AD included oxidative stress and immune response. There was the best binding affinity between 11 pairs of genes and compounds. Furthermore, CDK5 was inhibited by nepetin with an IC50 of 3.172 µM and kaempferol with an IC50 of 2.659 µM. Ceanothic acid and 18 beta-glycyrrhetinic acid inhibited GSK3ß, and the IC50 values were 8.732 µM and 8.06 µM, respectively. CONCLUSION: Qi Fu Yin might alleviate Tau hyperphosphorylation by nepetin, kaempferol, ceanothic acid and 18 beta-glycyrrhetinic acid.

Study on active ingredient and mechanism in preventing vascular dementia of Tianzhusan coming from Tujia medicine.

To make clear of the absorbed components of Tianzhusan (TZS) and its possible mechanism in preventing vascular dementia (VD), the rats' models of VD were prepared by a permanent ligation of the bilateral common carotid arteries. After 60 days, rats were administrated with TZS for 0.1 g x kg(-1), and the volume is 0.02 mL x g(-1). After 3 days, the medicated serum was prepared and detected by UPLC, and then we predicted the possible chemical structure of the absorbed components of TZS. According to the absorbed components, the potential targets of TZS were found by ligand profiling of Discovery Studio 3.5. All of these target genes were submitted to DAVID onine for gene set enrichment analysis (GSEA). The 5 absorbed components of TZS have been predicted, and four of them have been identified as parishin B, parishin C, parishin, pennogenin-3-O-alpha-L-rhamnopyranosy-(1-->2)-beta-D-glucoside. Through reverse finding targets, we got 861 pharmacophore models and 9 pathways from KEGG, BIOCARTA after document verification. These results showed that the efficacy mechanism of TZS on VD perhaps were be related with these absorbed components and pathways. If the traditional herbs could be proved effective by efficacy tests, the serum pharmacochemistry, computer-aided drug design, system biology and other technologies can be used in the next experiments, which will be beneficial to fast discovery of material basis and mechanisms of traditional medicine coming form ethnic minorities.

[Study on intersection and regulation mechanism of "efficacy-toxicity network" of aconite in combination environment of Sini decoction].

OBJECTIVE: To explore the intersection and regulation mechanism of "efficacy-toxicity network" of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata's action gene in the combination environment of Sini decoction with the network pharmacological method. METHOD: The gene interaction network of Aconiti Lateralis Radix Praeparata, Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma were mined and established with Cytoscape software and Agilent literature search plug-in. The "efficiency-toxicity network" intersection of Aconiti Lateralis Radix Praeparata was formed according to its effects in anti-heart failure, neurotoxicity and cardiotoxicity. The target genes were clustered with Clusterviz plug-in. And the possible pathways of the "efficacy-tox- icity network" intersection of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata were forecasted in DAVID database. RESULT: There were five genes related to neurotoxicity, cardiotoxicity and anti-heart failure function of Aconiti Lateralis Radix Praeparata, namely AKT1, BAX, HCC, IL6 and IL8, which formed 47 nodes genes in the "efficiency-toxicity network" intersection of Aconiti Lateralis Radix Praeparata. There were 29 and 27 coincident genes in the "efficiency-toxicity network" of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata. There were 23 and 17 possible regulatory pathways. CONCLUSION: In the combination environment of Sini decoction, Glycyrrhizae Radix et Rhizoma and Zingiberis Rhizoma may regulate the efficiency-toxicity network of Aconiti Lateralis Radix Praeparata by influencing immune-inflammatory signaling pathway, apoptosis-autophagy signaling pathway, nerve cell and myocardial ischemia and hypoxia protection signaling pathways.