In Silico Insights into Micro-Mechanism Understanding of Extracts of Taxus Chinensis Fruits Against Alzheimer's Disease.

BACKGROUND: The taxus chinensis fruit (TCF) shows promises in treatment of aging-related diseases such as Alzheimer's disease (AD). However, its related constituents and targets against AD have not been deciphered. OBJECTIVE: This study was to uncover constituents and targets of TCF extracts against AD. METHODS: An integrated approach including ultrasound extractions and constituent identification of TCF by UPLC-QE-MS/MS, target identification of constituents and AD by R data-mining from Pubchem, Drugbank and GEO databases, network construction, molecular docking and the ROC curve analysis was carried out. RESULTS: We identified 250 compounds in TCF extracts, and obtained 3,231 known constituent targets and 5,326 differential expression genes of AD, and 988 intersection genes. Through the network construction and KEGG pathway analysis, 19 chemicals, 31 targets, and 11 biological pathways were obtained as core compounds, targets and pathways of TCF extracts against AD. Among these constituents, luteolin, oleic acid, gallic acid, baicalein, naringenin, lovastatin and rutin had obvious anti-AD effect. Molecular docking results further confirmed above results. The ROC AUC values of about 87% of these core targets of TCF extracts was greater than 0.5 in the two GEO chips of AD, especially 10 targets with ROC AUC values greater than 0.7, such as BCL2, CASP7, NFKBIA, HMOX1, CDK2, LDLR, RELA, and CCL2, which mainly referred to neuron apoptosis, response to oxidative stress and inflammation, fibroblast proliferation, etc.Conclusions:The TCF extracts have diverse active compounds that can act on the diagnostic genes of AD, which deserve further in-depth study.

Effect of kaempferol on hedgehog signaling pathway in rats with --chronic atrophic gastritis - Based on network pharmacological screening and experimental verification.

OBJECTIVE: The effect of active ingredients of Chaishaoliujun Decoction (CD) on chronic atrophic gastritis (CAG) was screened by network pharmacological method and verified by preliminary experiment. METHODS: Firstly, the active ingredients and drug targets of CD were retrieved in TCMSP database; CAG-related targets from PharmGkb, OMIM, GeneCards and DrugBank databases were collected as well. Secondly, the drug targets and disease targets were mapped to obtain the intersection targets. PPI network and active ingredient-common target network were constructed for the intersection targets obtained and KEGG enrichment analysis was also carried out. Finally, the core active ingredient (kaempferol), effective targets (IL-1ß、IL-6) and hedgehog signaling pathway were verified by animal experiments. RESULTS: There were 137 active ingredients, 243 potential target so and 48 intersection targets with CAG in CD. 147 KEGG enrichment pathways were obtained, mainly involving JAK/STAT signaling pathway, PI3K/Akt signaling pathway, hedgehog signaling pathway, etc. The results of animal experiments showed: The content of IL-1ß and IL-6 in model group was significantly increased compared with the normal group, while the mRNA and protein expressions of Shh, Ptch1 and Gli1 were also significantly decreased (P < 0.05); compared with model group, the content of IL-1ß and IL-6 in the vitacoenzyme group, the CD group and the kaempferol group were significantly decreased, while the mRNA and protein expressions of Shh, Ptch1 and Gli1 were significantly increased (P < 0.05). CONCLUSION: Kaempferol, the active ingredient of CD, could reduce the levels of IL-6 and IL-1ß by regulating hedgehog signaling pathway so as to play a role in the treatment of CAG. Hence this paper could provide the methodological basis and theoretical basis for further revealing the pharmacological mechanism of CD.

Exploration in the Mechanism of Action of Licorice by Network Pharmacology.

Licorice is a popular sweetener and a thirst quencher in many food products particularly in Europe and the Middle East and also one of the oldest and most frequently used herbs in traditional Chinese medicine. As a wide application of food additive, it is necessary to clarify bioactive chemical ingredients and the mechanism of action of licorice. In this study, a network pharmacology approach that integrated drug-likeness evaluation, structural similarity analysis, target identification, network analysis, and KEGG pathway analysis was established to elucidate the potential molecular mechanism of licorice. First, we collected and evaluated structural information of 282 compounds in licorice and found 181 compounds that met oral drug rules. Then, structural similarity analysis with known ligands of targets in the ChEMBL database (similarity threshold = 0.8) was applied to the initial target identification, which found 63 compounds in licorice had 86 multi-targets. Further, molecular docking was performed to study their binding modes and interactions, which screened out 49 targets. Finally, 17 enriched KEGG pathways (p < 0.01) of licorice were obtained, exhibiting a variety of biological activities. Overall, this study provided a feasible and accurate approach to explore the safe and effective application of licorice as a food additive and herb medicine.

Identfication of Potent LXRß-Selective Agonists without LXRα Activation by In Silico Approaches.

Activating Liver X receptors (LXRs) represents a promising therapeutic option for dyslipidemia. However, activating LXRα may cause undesired lipogenic effects. Discovery of highly LXRß-selective agonists without LXRα activation were indispensable for dyslipidemia. In this study, in silico approaches were applied to develop highly potent LXRß-selective agonists based on a series of newly reported 3-(4-(2-propylphenoxy)butyl)imidazolidine-2,4-dione-based LXRα/ß dual agonists. Initially, Kohonen and stepwise multiple linear regression SW-MLR were performed to construct models for LXRß agonists and LXRα agonists based on the structural characteristics of LXRα/ß dual agonists, respectively. The obtained LXRß agonist model gave a good predictive ability (R²train = 0.837, R²test = 0.843, Q²LOO = 0.715), and the LXRα agonist model produced even better predictive ability (R²train = 0.968, R²test = 0.914, Q²LOO = 0.895). Also, the two QSAR models were independent and can well distinguish LXRß and LXRα activity. Then, compounds in the ZINC database met the lower limit of structural similarity of 0.7, compared to the 3-(4-(2-propylphenoxy)butyl)imidazolidine-2,4-dione scaffold subjected to our QSAR models, which resulted in the discovery of ZINC55084484 with an LXRß prediction value of pEC50 equal to 7.343 and LXRα prediction value of pEC50 equal to -1.901. Consequently, nine newly designed compounds were proposed as highly LXRß-selective agonists based on ZINC55084484 and molecular docking, of which LXRß prediction values almost exceeded 8 and LXRα prediction values were below 0.

Discovery of molecular mechanism of a clinical herbal formula upregulating serum HDL-c levels in treatment of metabolic syndrome by in vivo and computational studies.

Decreased HDL cholesterol (HDL-c) is considered as an independent risk factor of cardiovascular disease in metabolic syndrome (Mets). Wendan decoction (WDD), a famous clinical traditional Chinese medicine formula in Mets in China, which can obviously up-regulate serum HDL-c levels in Mets. However, till now, the molecular mechanism of up-regulation still remained unclear. In this study, an integrated approach that combined serum ABCA1 in vivo assay, QSAR modeling and molecular docking was developed to explore the molecular mechanism and chemical substance basis of WDD upregulating HDL-c levels. Compared with Mets model group, serum ABCA1 and HDL-c levels intervened by two different doses of WDD for two weeks were significantly up-regulated. Then, kohonen and LDA were applied to develop QSAR models for ABCA1 up-regulators based flavonoids. The derived QSAR model produced the overall accuracy of 100%, a very powerful tool for screening ABCA1 up-regulators. The QSAR model prediction revealed 67 flavonoids in WDD were ABCA1 up-regulators. Finally, they were subjected to the molecular docking to understand their roles in up-regulating ABCA1 expression, which led to discovery of 23 ABCA1 up-regulators targeting LXR beta. Overall, QSAR modeling and docking studies well accounted for the observed in vivo activities of ABCA1 affected by WDD.

Systematic Understanding of Mechanisms of a Chinese Herbal Formula in Treatment of Metabolic Syndrome by an Integrated Pharmacology Approach.

Metabolic syndrome (MS) is becoming a worldwide health problem. Wendan decoction (WDD)-a famous traditional Chinese medicine formula-has been extensively employed to relieve syndromes related to MS in clinical practice in China. However, its pharmacological mechanisms still remain vague. In this study, a comprehensive approach that integrated chemomics, principal component analysis, molecular docking simulation, and network analysis was established to elucidate the multi-component and multi-target mechanism of action of WDD in treatment of MS. The compounds in WDD were found to possess chemical diversity, complexity and drug-likeness compared to MS drugs. Six nuclear receptors were obtained to have strong binding affinity with 217 compounds of five herbs in WDD. The importance roles of targets and herbs were also identified due to network parameters. Five compounds from Radix Glycyrrhizae Preparata can hit all six targets, which can assist in screening new MS drugs. The pathway network analysis demonstrated that the main pharmacological effects of WDD might lie in maintaining lipid and glucose metabolisms and anticancer activities as well as immunomodulatory and hepatoprotective effects. This study provided a comprehensive system approach for understanding the multi-component, multi-target and multi-pathway mechanisms of WDD during the treatment of MS.

Change in refractive index of muscle tissue during laser-induced interstitial thermotherapy.

This paper presents a long-period fiber-grating (LPG) based Michelson interferometric refractometry to monitor the change in refractive index of porcine muscle during laser-induced interstitial thermotherapy (LITT). As the wavelength of RI interferometer alters with the change in refractive index around the probe, the LPG based refractometry is combined with LITT system to measure the change in refractive index of porcine muscle when irradiated by laser. The experimental results show the denaturation of tissue alters the refractive index significantly and the LPG sensor can be applied to monitor the tissue state during the LITT.

[Four properties law of nature data of Chinese materia medica in "Chinese herbal medicine (CHM)"].

OBJECTIVE: In order to provide theoretical clues and data support for the use of Chinese medicine clinical drug, experimental study of Chinese materia medica and development of new resources of Chinese materia medica, the four properties as the core, the relationships of property, flavor, channel tropism and toxicity in nature data of Chinese materia medica were analyzed. METHOD: The spearman rank correlation method was employed to analyze 8 356 Chinese drugs with characteristic of four properties from " Chinese Herbal Medicine" based on data level coding. RESULT: It was discovered that four properties showed significant positive correlations with tastes of "pungent and sweet" , channels of "spleen" , "stomach" , "kidney" and "toxicity" , but also showed significant negative correlations with tastes of "bitter" and "light" and six channels such as "large intestine" , "heart", "bladder" , "gallbladder" , "small intestine" and "lung" (in descending order of correlation ) (P <0. 01). CONCLUSION: It was indicated that the more hot the Chinese medicine nature, the more possible it contained "toxicity" , tastes of "pungent" and "sweet" , and the more possible it was belong to channels of "spleen" , "stomach" and "kidney". As well, the more cold the Chinese medicine nature, the more possible it contained tastes of "bitter" and "light", and the more possible it was belong to six channels such as "large intestine", etc.

[Mining rules on determination of four properties based on traditional Chinese medicine functional combination].

OBJECTIVE: It laid the foundation of the large sample data mining for a comprehensive summary concerning four properties theory of traditional Chinese medicine (TCM), and also provided theory clues on determination of four properties for the new resource development of TCM and the clinical use of Chinese medicine. METHOD: Four properties data of 8 980 Chinese medicines from "Chinese herbal medicine (CHM)" and associated function index data were chose as data sets. Then, the IBM SPSS Clementine 14.1 data mining platform and Apriori model were adopted to mining classification-association rules, setting the minimum support threshold of rule antecedent and the minimum confidence threshold as 0.5% and 60%. RESULT: 11 classification-association rules involved in warm, cold and mild natures were found. CONCLUSION: It was discovered that the TCM with functions of "dispelling wind-cold, warming the middle, stopping pain and expelling wind-removing dampness, tonifying kidney yang, unblocking meridians and expelling wind-removing dampness, dispelling cold to stop pain, strengthening sinews-bones and expelling wind-removing dampness" was likely warm-natured, with functions of "tonifying the lung" was likely mild-natured, and with functions of " clearing heat and drying dampness, clearing heat and purging fire, eliminating restlessness" was likely cold-natured.

[Potential role of arbuscular mycorrhiza in bioremediation of uranium contaminated environments].

With the increasing demand for new energy, nuclear industry has been developing very fast, and uranium (U) pollution becomes a serious environmental problem especially in the mining area. The discharge of U products and wastes can contaminate soil and water, and finally threaten human health. On the other side, as an environment-friendly biotechnology, the importance of mycorrhizal technology in remediation of polluted environments has received much attention in recent years. Following a brief introduction of the environmental impacts of U contamination, this review summarized the effects of arbuscular mycorrhiza (AM) on U uptake and accumulation by plants based on recent research progresses, suggested possible application of AM fungi in remediation of U contaminated environment, and finally discussed about the perspectives in relevant research area.

Plant growth and soil microbial community structure of legumes and grasses grown in monoculture or mixture.

A greenhouse pot experiment was conducted to investigate the influence of soil moisture content on plant growth and the rhizosphere microbial community structure of four plant species (white clover, alfalfa, sudan grass, tall fescue), grown individually or in a mixture. The soil moisture content was adjusted to 55% or 80% water holding capacity (WHC). The results indicated that the total plant biomass of one pot was lower at 55% WHC. At a given soil moisture, the total plant biomass of white clover and tall fescue in the mixture was lower than that in a monoculture, indicating their poor competitiveness. For leguminous plants, the decrease in soil moisture reduced the total microbial biomass, bacterial biomass, fungal biomass, and fungal/bacterial ratio in soil as assessed by the phospholipid fatty acid analysis, whereas, lower soil moisture increased those parameters in the tall fescue. The microbial biomass in the soil with legumes was higher than that in the soil with grasses and the two plant groups differed in soil microbial community composition. At high soil moisture content, microbial communities of the plant mixture were similar to those of the legume monoculture, and the existence of legumes in the mixture enhanced the bacterial and fungal biomass in the soil compared to the grasses grown in the monoculture, indicating that legumes played a dominant role in the soil microbial community changes in the plant mixture.