Select Your Own Counterparts: Self-Supervised Graph Contrastive Learning With Positive Sampling.

Contrastive learning (CL) has emerged as a powerful approach for self-supervised learning. However, it suffers from sampling bias, which hinders its performance. While the mainstream solutions, hard negative mining (HNM) and supervised CL (SCL), have been proposed to mitigate this critical issue, they do not effectively address graph CL (GCL). To address it, we propose graph positive sampling (GPS) and three contrastive objectives. The former is a novel learning paradigm designed to leverage the inherent properties of graphs for improved GCL models, which utilizes four complementary similarity measurements, including node centrality, topological distance, neighborhood overlapping, and semantic distance, to select positive counterparts for each node. Notably, GPS operates without relying on true labels and enables preprocessing applications. The latter aims to fuse positive samples and enhance representative selection in the semantic space. We release three node-level models with GPS and conduct extensive experiments on public datasets. The results demonstrate the superiority of GPS over state-of-the-art (SOTA) baselines and debiasing methods. In addition, the GPS has also been proven to be versatile, adaptive, and flexible.

Evaluation of drug interactions of Saposhnikoviae Radix and its major components with astragaloside IV and paeoniflorin using in vitro and in vivo experiments.

Saposhnikoviae Radix (SR) may enhance the pharmacodynamics of Huangqi Chifeng Tang (HQCFT) in the treatment of cerebral infarction according to our previous research, but the underlying mechanism is unknown. Herein, an in vivo pharmacokinetic assay in rats and in vitro MDCK-MDR1 cell assays were used to investigate the possible mechanism of SR, its main components, and its interactions with Astragali Radix (AR) and Paeoniae Radix (PR). An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS)-based analytical method for quantifying astragaloside IV (ASIV) and paeoniflorin (PAE) in microdialysis and transport samples was developed. The pharmacokinetic parameters of SR were determined using noncompartmental analyses CCK-8 assays were used to detect the cytotoxicity of ASIV, PAE, cimifugin (CIM), prim-o-glucosylcimifugin (POG) and their combinations. Moreover, drug transport was studied using MDCK-MDR1 cells. Western blotting was performed to measure the protein expression levels of P-GP and MRP1. Claudin-5, ZO-1, and F-actin expression was determined via immunohistochemical staining of MDCK-MDR1 cells. harmacokinetic studies revealed that, compared with those of Huangqi Chifeng Tang-Saposhnikoviae Radix (HQCFT-SR), the Tmax of ASIV increased by 11.11 %, and the MRT0-t and Tmax of PAE increased by 11.19 % and 20 %, respectively, in the HQCFT group. Transport studies revealed that when ASIV was coincubated with 28 µM CIM or POG, the apparent permeability coefficient (Papp) increased by 71.52 % and 50.33 %, respectively. Coincubation of PAE with 120 µM CIM or POG increased the Papp by 87.62 % and 60.95 %, respectively. Moreover, CIM and POG significantly downregulated P-gp and MRP1 (P < 0.05), inhibited the expression of Claudin-5, ZO-1, and F-actin (P < 0.05), and affected intercellular tight junctions (TJs). In conclusion, our study successfully established a selective, sensitive and reproducible UPLC‒MS/MS analytical method to detect drug‒drug interactions between SR, AR and PR in vivo and in vitro, which is beneficial for enhancing the therapeutic efficacies of AR and PR. Moreover, this study provides a theoretical basis for further research on the use of SR as a drug carrier.

Integrated network pharmacology and phosphoproteomic analyses of Baichanting in Parkinson's disease model mice.

The incidence rate of Parkinson's disease (PD) is increasing yearly. Neuronal apoptosis caused by abnormal protein phosphorylation is closely related to the pathogenesis of Parkinson's disease. At present, few PD-specific apoptosis pathways have been revealed. To investigate the effect of Baichanting (BCT) on apoptosis from the perspective of protein phosphorylation, α-syn transgenic mice were selected to observe the behavioral changes of the mice, and the apoptosis of substantia nigra cells were detected by the HE method and TUNEL method. Network pharmacology combined with phosphorylation proteomics was used to find relevant targets for BCT treatment of PD and was further verified by PRM and western blotting. BCT improved the morphology of neurons in the substantia nigra and reduced neuronal apoptosis. The main enriched pathways in the network pharmacology results were apoptosis, the p53 signaling pathway and autophagy. Western blot results showed that BCT significantly regulated the protein expression levels of BAX, Caspase-3, LC3B, P53 and mTOR and upregulated autophagy to alleviate apoptosis. Using phosphorylated proteomics and PRM validation, we found that Pak5, Grin2b, Scn1a, BcaN, L1cam and Braf are closely correlated with the targets of the web-based pharmacological screen and may be involved in p53/mTOR-mediated autophagy and apoptosis pathways. BCT can inhibit the activation of the p53/mTOR signaling pathway, thereby enhancing the autophagy function of cells, and reducing the apoptosis of neurons which is the main mechanism of its neuroprotective effect.

Integrating network pharmacology and renal metabonomics to reveal the protective mechanism of resveratrol on gouty nephropathy.

Resveratrol (Res) has been demonstrated to have beneficial effects on gouty nephropathy (GN). However, the mechanisms of Res on GN remain unclear. This study aimed to investigate the mechanisms of Res on GN. In this study, network pharmacology technology was used to predict the Res targets in the prevention and treatment of GN. Renal metabonomics was used to identify differential metabolites in kidney tissue of GN model rats. Finally, molecular docking technology was used to verify the binding ability of Res to key targets. Metabonomics analysis showed that 24 potentially important metabolites were involved in the prevention and treatment of GN with Res. After exposure to Res, metabolite levels normalized. The network pharmacology analysis showed that 24 key targets were involved in the prevention and treatment of GN disease. According to the metabolite-gene network diagram, we identified two core genes, PTGS1 and PTGS2, and found that both were involved in the arachidonic acid metabolism pathway. Molecular docking further verified the affinity of Res binding to PTGS1 and PTGS2. In conclusion, the mechanism of Res against GN may be the regulation of arachidonic acid metabolism through the regulation of PTGS 1 and PTGS 2.

[Mechanism of acteoside in prevention and treatment of gouty arthritis based on liver metabolomics].

This study aims to reveal the effect of acteoside on gouty arthritis(GA) in rats based on liver metabolomics. The ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to search for the potential biomarkers and metabolic pathways. SD rats were randomly assigned into blank, model, colchicine(0.3 mg·kg~(-1)), and high-, medium-, low-dose(200, 100, and 50 mg·kg~(-1), respectively) acteoside groups(n=7). The rats were administrated once a day for 7 continuous days. Monosodium urate(MSU) was used to induce GA model in rats during administration. The degree of joint swelling and pathological changes of synovial tissue in rats were observed, and the levels of interleukin(IL)-1ß, IL-18 and tumor necrosis factor(TNF)-α in the synovial tissue of rats were measured. UPLC-Q-TOF-MS was employed to collect rat liver data, and Progenesis QI and EZ info were used for data analysis. Human Metabolomics Database(HMDB) and Kyoto Encyclopedia of Genes and Genomes(KEGG) were employed to predict the potential biomarkers and metabolic pathways. The results showed that acteoside alleviated joint swelling, reduced synovial tissue damage, and lowered the levels of inflammatory cytokines in GA rats. A total of 19 common biomarkers were identified, 17 of which can be regulated by acteoside. Seven metabolic pathways were enriched, such as glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism, among which glycerophospholipid metabolism was strongly disturbed. The metabolomics analysis suggested that acteoside may down-regulate the expression of inflammatory cytokines and alleviate the symptoms of GA rats by regulating glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism. The findings provide a reference for future research and development of acteoside.

Integrating fecal metabolomics and intestinal microbiota to study the mechanism of cannabidiol in the treatment of idiopathic pulmonary fibrosis.

Introduction: Idiopathic pulmonary fibrosis is a chronic interstitial lung disease characterized by excessive deposition of extracellular matrix. Cannabidiol, a natural component extracted from plant cannabis, has been shown to have therapeutic effects on lung diseases, but its exact mechanism of action is unknown, hindering its therapeutic effectiveness. Methods: To establish a pulmonary fibrosis model, combined with UPLC-Q-TOF/MS metabolomics and 16S rDNA sequencing, to explore cannabidiol's mechanism in treating pulmonary fibrosis. The rats were randomly divided into the control group, pulmonary fibrosis model group, prednisone treatment group, and cannabidiol low, medium, and high dose groups. The expression levels of HYP, SOD, and MDA in lung tissue and the expression levels of TNF-α, IL-1ß, and IL-6 in serum were detected. Intestinal microbiota was detected using UPLC-QTOF/MS analysis of metabolomic properties and 16S rDNA sequencing. Results: Pathological studies and biochemical indexes showed that cannabidiol treatment could significantly alleviate IPF symptoms, significantly reduce the levels of TNF-α, IL-1ß, IL-6, MDA, and HYP, and increase the expression level of SOD (p < 0.05). CBD-H can regulate Lachnospiraceae_NK4A136_group, Pseudomonas, Clostridia_UCG-014, Collinsella, Prevotella, [Eubacterium]_coprostanoligenes_group, Fusobacterium, Ruminococcus, and Streptococcus, it can restore intestinal microbiota function and reverse fecal metabolism trend. It also plays the role of fibrosis through the metabolism of linoleic acid, glycerol, linolenic acid, and sphingolipid. Discussion: Cannabidiol reverses intestinal microbiota imbalance and attenuates pulmonary fibrosis in rats through anti-inflammatory, antioxidant, and anti-fibrotic effects. This study lays the foundation for future research on the pathological mechanisms of IPF and the development of new drug candidates.

HuangQi ChiFeng decoction maintains gut microbiota and bile acid homeostasis through FXR signaling to improve atherosclerosis.

Huangqi Chifeng Decoction (HQCFT), a traditional Chinese medicine preparation, has long been used to treat cardiovascular and cerebrovascular diseases. However, the mechanism of the beneficial effect of HQCFT on atherosclerosis remains to be explored. In this work, to investigate the effects of HQCFT on bile acid (BA) metabolism and the gut microbiome in atherosclerosis, ApoE-/- mice were fed a with high-fat diet for 16 weeks to establish the AS model. HQCFT(1.95 g kg-1 and 3.9 g kg-1 per day) was administered intragastrically for 8 weeks to investigate the regulatory effects of HQCFT on gut microbiota and bile acid metabolism and to inhibit the occurrence and development of AS induced by a high-fat diet. Histopathology, liver function and blood lipids were used to assess whether HQCFT can reduce plaque area, regulate lipid levels and alleviate liver steatosis in AS mice. In addition, 16S rDNA sequencing was used to screen the gut microbiota structure, and ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS) was used to determine the bile acid profile. The mRNA and protein expression levels of bile acid metabolism were detected by RT‒PCR and WB to find the potential correlation. Results: HQCFT can regulate gut microbiota disorders, which was achieved by increasing gut microbiota diversity and altering Proteobacteria, Desulfobacterota, Deferribacteres, Rodentibacter, Parasutterella, and Mucispirillum interference abundance to improve AS-induced gut microbiota. HQCFT can also adjust the content of bile acids (TCA, LCA, DCA, TDCA, TLCA, UDCA, etc.), regulate bile acid metabolism, relieve liver fat accumulation, and inhibit the process of AS. In addition, HQCFT can restore the abnormal metabolism of bile acid caused by AS by regulating the expression of farnesoid X receptor (FXR), liver X receptor α (LXRα), ABCA1, ABCG1 and CYP7A1. Conclusion: HQCFT may play a part in the prevention of atherosclerosis by inhibiting the FXR/LXRα axis, increasing the expression of CYP7A1 in the liver, and regulating the interaction between the gut microbiota and bile acid metabolism.

BioMed Research International Study Quality on the Role of Pyroptosis Bionic in Gouty Arthritis and Traditional Chinese Medicine Biomechanics Intervention.

Gouty arthritis (GA) cause great harm to patients. Cellular pyroptosis, a mode of programmed cell death associated with inflammatory response, is closely related to GA. Both cysteamine aspartate-1-dependent and non-dependent pathways are involved in the progression of GA. During GA development, high blood uric acid levels leads to excessive biologically-inspired NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation to drive caspase-1 activation for promoting the maturation of interleukin-1ß precursors, and caspase-1 activation disrupts the amino terminus in gasdermin D-N (GSDMD-N) and carboxy-terminal gasdermin-C structural domains, causing pores in the membrane and thus inducing the onset of scorch death. Therefore, modulating the onset of scorch death may become an important target for drug intervention in diseases. Chinese medicine is substantially biologically inspired and used synergistically to treat GA through multiple pathways and targets, which may regulate the relevant pathways through cellular pyroptosis quality. This study focuses on the interpretable regulatory mechanism of cellular pyroptosis bionic in GA and the role of Chinese medicine on GA, which provides a new scientific basis and strategy for targeting cellular pyroptosis bionic as the prevention and treatment quality of GA.

Integrative metabolomics and network pharmacology to study the preventative impact of dioscin treatment on hyperuricemia.

This work aims to combine network pharmacology and metabolomics to explore the mechanism of action of dioscin on hyperuricemia (HUA). The preventative impact of dioscin on HUA and its putative mechanism were examined using network pharmacological analysis and metabonomics. Network pharmacology study further pointed out the potential targets of dioscin after a review of the relevant biomarker pathways discovered by metabolomic analysis. Molecular docking was then used to examine how the active chemicals interacted with the target proteins. The therapeutic effect of dioscin on HUA was shown to be mediated by 13 potentially important metabolites as a result of metabonomic research. Most of these metabolites are regulated after dioscin therapy to help patients recover. Based on network pharmacology, we identified 10 central genes, which is partly in agreement with metabolomics data. Using metabolomics and network pharmacology, this study investigated the primary targets and mechanisms of dioscin in the treatment of HUA. It is advantageous that dioscin has been developed as an additional drug for the treatment of HUA.

Improvement of K-Means Algorithm and Its Application in Air Passenger Grouping.

The k-means is one of the most popular clustering analysis algorithm and widely used in various fields. Nevertheless, it continues to have some shortcomings, for example, extremely sensitive to the initial center points selection and the special points such as noise or outliers. Therefore, this paper proposed initial center points' selection optimization and phased assignment optimization to improve the k-means algorithm. The experimental results on 15 real-world and 10 synthetic datasets show that the improved k-means outperforms its main competitor k-means ++ and under the same setting conditions, namely, using the default parameters,its clustering performance is better than Affinity Propagation, Mean Shift, and DBSCAN. The proposed algorithm was applied to analyze the airline seat selection data to air passengers grouping. The clustering results, as well as absolute deviation rate analysis, realized customer grouping and found out suitable audience group for the recommendation of seat selection services.

Integrating Metabolomics and Network Pharmacology to Explore the Protective Effect of Ginsenoside Re against Radiotherapy Injury in Mice.

Ionizing radiation (IR) can cause radiation damage, mutagenesis, or carcinogenesis in the irradiated subject. It is manifested as metabolic disorders of the body and damage to the immune system, nervous system, and endocrine system, which can lead to physiological and pathological changes and endogenous metabolic disorders. Ginsenoside Re (G-Re), a single component of traditional Chinese medicine, has a certain ameliorating effect on radiation damage. However, its mechanism of action in the treatment of radiotherapy injury remains unclear. With this purpose, the hematopoietic function of mice damaged by X-ray radiation was studied, and the protective effect of G-Re on mice damaged by radiation was preliminarily evaluated. Network pharmacology and metabolomics analysis are used to further reveal the mechanism of G-Re to improve radiation damage through metabolomics research. Results of metabolomics analysis showed that 16 potential biomarkers were identified as participating in the therapeutic effect of G-Re on IR. Most of these metabolites are adjusted to recover after G-Re treatment. The pathways involved included glycerophospholipid metabolism, sphingolipid metabolism, and linoleic acid metabolism. According to network pharmacology analysis, we found 10 hub genes, which is partly consistent with the findings of metabolomics. Further comprehensive analysis focused on 4 key targets, including SRC, EGFR, AKT1, and MAPK8, and their related core metabolites and pathways. This study combines metabolomics and network pharmacology analysis to explore the key targets and mechanisms of G-Re in the treatment of IR, in order to provide new strategies for clinical treatment of radiotherapy injury.

Ginkgolide B inhibits NLRP3 inflammasome activation and promotes microglial M2 polarization in Aß1-42-induced microglia cells.

Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome-mediated chronic neuroinflammation plays a crucial role in the progression of Alzheimer's disease (AD), which is related to microglial activation. Using quantitative proteomic analysis, we identified 25 up-regulated and 83 down-regulated proteins in amyloid beta (Aß)1-42-induced BV2 cells. Among the differentiallyexpressedproteins involved in inflammation, the NLRP3 protein level increased dramatically. Ginkgolide B (GB) prevents Aß-induced neuroinflammation and neurotoxic effects in multiple neurodegenerative disorders. However, its role in NLRP3 inflammasome-mediated neuroinflammation in AD remain unknown. We found that GB treatment ameliorated Aß1-42-induced pathological damages and inhibited NLRP3 inflammasome activation. Furthermore, GB enhanced the expression of M2 microglial markers and suppressed the expression of M1 microglial markers. Our findings suggest that GB treatment prevents the pathological processes of AD and suppresses neuroinflammation by inhibiting NLRP3 inflammasome activation and promoting microglial M2 polarization.

FPSC-DTI: drug-target interaction prediction based on feature projection fuzzy classification and super cluster fusion.

Identifying drug-target interactions (DTIs) is an important part of drug discovery and development. However, identifying DTIs is a complex process that is time consuming, costly, long, and often inefficient, with a low success rate, especially with wet-experimental methods. Computational methods based on drug repositioning and network pharmacology can effectively overcome these defects. In this paper, we develop a new fusion method, called FPSC-DTI, that fuses feature projection fuzzy classification (FP) and super cluster classification (SC) to predict DTI. As the experimental result, the mean percentile ranking (MPR) that was yielded by FPSC-DTI achieved 0.043, 0.084, 0.072, and 0.146 on enzyme, ion channel (IC), G-protein-coupled receptor (GPCR), and nuclear receptor (NR) datasets, respectively. And the AUC values exceeded 0.969 over all four datasets. Compared with other methods, FPSC-DTI obtained better predictive performance and became more robust.

High-throughput serum metabolomics analysis of gouty arthritis rat treated by total saponins of Rhizoma Dioscoreae Makino by UPLC-Q/TOF-MS.

Rhizoma Dioscoreae Makino (RDM) is effective in treating gouty arthritis (GA) and hyperuricacidemia, especially in promoting uric acid excretion and reducing the inflammatory reaction. Bioactive constituents in RDM are mainly steroidal saponins such as dioscin, trillin, protodioscin and protogracillin. However, the mechanism of its anti-GA action is still unclear, owing to the complex pathological and physiological characteristics of GA, and integration of RDM with multiple components, multiple targets and multiple pathways. Herein, a GA rat model was induced with monosodium urate (MSU), and RDM reduced inflammation of rat synovium tissue. Through metabolomics analysis, 35 potential biomarkers with significant changes involved in the pathogenesis of GA induced by MSU were identified, and perturbations were restored after RDM treatment. The most correlated pathways involved in d-galactose, d-mannose, d-glucose, myoinositol, Phosphatidylcholine (PC) (16:0/16:0), LysoPC (15:0), phosphatidic acid (PA) [18:1(9Z)/18:1(11Z)] and glutathione induced by MSU were galactose metabolism, inositol phosphate metabolism, glycerophospholipid metabolism and glutathione metabolism, and the derivations of all those biomarkers could be regulated by RDM treatment. RDM has a therapeutic effect on GA by intervening in changes in endogenous metabolisms and the related metabolic pathways.

UPLC-MS-based serum metabolomics reveals protective effect of Ganoderma lucidum polysaccharide on ionizing radiation injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum Polysaccharide (GLP),traditional Chinese medicine (TCM) active ingredient, has a long history and has good curative effects on radiation injury. However, the mechanism of GLP treating radiation injury has not been clearly elucidated. THE AIM OF THE STUDY: This study was aimed to investigate the preventive effects of GLP on mice with radiation injury and to explore its mechanisms by serum metabolomics. MATERIALS AND METHODS: Thirty mice were randomly divided into three groups,and namely 10 per group. The normal control group and the radiation model with normal saline and GLP group with GLP treatment (96 mg·kg-1) for 14 days. 2 h after 7th day after the intragastric administration, the model group and GLP group were subjected to whole body irradiation by X-rays except the normal control group. The peripheral blood WBC, RBC, HGB, PLT indicators.UPLC-Q-TOF-MS technique was used to analyze the serum of normal group, model group and GLP group, and to explore its potential key biomarkers and corresponding related metabolic pathways. RESULTS: The number of peripheral blood leukocytes (WBC) in the radiation model group was lower than that in the GLP group and the number of platelets (PLT) in the GLP group was significantly higher than that in the model group.Combined with the methods of principal component analysis (PCA), projection to latent structure-discrimination analysis (PLS-DA), three group were clearly distinguished from each other and 18 metabolites were identified as the potential biomarkers in the GLP treated mice. The identified biomarkers indicated that there were perturbations of the taurine and hypotaurine metabolism and glycerophospholipid metabolism. CONCLUSION: GLP can play a role in radiation protection by improving the expression of related potential biomarkers and related metabolic pathways in serum of radiation-induced mice.

Anti-inflammatory Effect of Total Saponin Fraction from Dioscorea nipponica Makino on Gouty Arthritis and Its Influence on NALP3 Inflammasome.

OBJECTIVE: To investigate the mechanism of Chinese herbal medicine Dioscorea nipponica for the treatment of monosodium urate crystals-induced gouty arthritis (GA) in rats. METHODS: Sixty male Wistar rats were divided into 6 groups: normal, model, indomethacin and three total saponin (900, 300 and 100 mg/kg) groups. The liver, kidney and serum levels of lysosomal enzymes, antioxidant capacities, and inflammatory factors were measured. In addition, the mRNA and protein levels of the NALP3 inflammasome components in the mononuclear cells of rats' peripheral blood were analyzed using real-time polymerase chain reaction and Western blotting methods, respectively. RESULTS: Total saponins groups could reduce the activities of ß-galactosidase, ß-N acetyl glucosamine enzyme, ß-glucuronidase, acid phosphatase, and malonaldehyde as well as the contents of TNF-α, IL-1ß and IL-8 (all P<0.05). They could also increase the activities of glutathione peroxidase and total superoxide dismutase (both P<0.05). Further studies showed that total saponins groups of high, middle and low doses could all increase the mRNA and protein levels of caspase-1, adapter apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and NALP3 in the mononuclear cells of peripheral blood (all P<0.05). CONCLUSION: Dioscorea nipponica may treat GA by regulating lysosomal enzymes, antioxidant capacities and the NALP3 inflammasome.

An integrated metabolomics and 16S rRNA gene sequencing approach exploring the molecular pathways and potential targets behind the effects of Radix Scrophulariae.

To assess the impact of the caecal microbiota on faecal metabolic phenotypes in the presence of Radix Scrophulariae (Chinese name: Xuanshen), an integrated approach involving 16S rRNA gene sequencing combined with ultrahigh-performance liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOF-MS)-based faecal metabolomics was applied to Radix Scrophulariae-treated rats. Interestingly, Radix Scrophulariae led to significant gut microbiota changes at the phylum and genus levels in treated rats compared to control rats. Additionally, distinct changes in faecal metabolites, including linoleic acid (LA), guanosine, inosine, hypoxanthine, xanthine, 4-hydroxycinnamic acid, cholic acid, N-acetyl-d-glucosamine, l-urobilinogen and uridine, were observed in Radix Scrophulariae-treated rats. Of these, seven metabolites were up-regulated, and the remaining three metabolites were down-regulated. Moreover, there were substantial associations between altered levels of gut microbiota genera and discrepant levels of faecal metabolites, particularly for compounds involved in LA and purine metabolism. These results demonstrated that the gut microbiota is altered in association with faecal metabolism following treatment with Radix Scrophulariae. Our findings suggest that further application of this 16S rRNA gene sequencing and UHPLC/TOF-MS-based metabolomics approach will facilitate the assessment of the pharmacological action of Radix Scrophulariae and thus expand the scope of this herb.

[Liver metabonomics of acute gouty arthritis treated by Diosocorea nipponica].

To explore the prevention and protection effect of Diosocorea nipponica (DNM)) on acute gouty arthritis (AGA) rats based on liver metabonomics, and find potential biomarkers and related pathways. AGA model rats were induced by monosodium urate crystal suspension. UPLC-TOF-MS coupled with pattern recognition technique was employed to find out the potential biomarkers and related metabolic pathways. Eleven common potential biomarkers were identified. Among the potential intervention targets in normal rats given by DNM, 4 biomarkers were up-regulated, and the other 4 targets were down regulated. Among the potential intervention targets in AGA rats given by DNM, 5 metabolites were up-regulated by MSU and 5 metabolites were down regulated. The abnormal expression levels of adenosine monophosphate, 5-methyltetrahydrofolic acid, oxidized glutathione, hypoxanthine, docosahexaenoic acid, glutathione, uridine diphosphate glucose and inosine could be corrected by DNM extract. Three pathways were founded with greatest correlation, including purine metabolism, starch and sucrose metabolism and glutathione metabolism. Therefore, it could be inferred that D. nipponica has the effect for anti-acute gouty arthritis by intervening endogenous metabolites from the liver under physiological condition and acute gouty arthritis condition.

[Study on potential effect of Dioscorea nipponica in intervening peripheral system of rats based on metabonomic analysis].

To study the potential effect of Dioscorea nipponica(DN) in intervening peripheral system of rats based on metabolomic analysis. The identification of the potential intervention targets of DN in peripheral system may facilitate its safe application and therapeutic potential exploitation. Totally 20 male SD rats were randomly divided into the blank group and the DN-treated groups, with 10 rates in each group. The DN-treated group was orally administrated with DN extracts once a day for 5 days, with the dose of 80 mg x kg(-1) (equivalent to 15 g crude drug in human), and the blank group was given equal volume of saline once a day for 5 days. Heart, liver, spleen, lung, and kidney tissues and serum samples were collected from each rat 24 h later after the last administration. The ultra-performance liquid chromatography/quadrupole time-of-flight-mass spectrometry based metabolomics was used to investigate the effect of DN in intervening peripheral system of rats. After the treatment with DN, 5 modulated metabolites in heart tissue, 6 in liver tissue, 5 in spleen tissue, 3 in lung tissue, 5 in kidney tissue and 6 in serum sample were identified and considered as the potential intervention targets of DN. Effect of DN in regulating some endogenous metabolites was beneficial for protecting peripheral system, while that in other endogenous metabolites produced potential toxicity to peripheral system. The metabolomic analysis revealed the coexistence of protective and toxic effects of DN on peripheral system, which may be a practical guidance for its safe application and beneficial to the expansion of its application scope.

Total saponins from Discorea nipponica makino ameliorate urate excretion in hyperuricemic rats.

OBJECTIVE: The objective was to study the mechanism of reducing level of the uric acid by rhizoma dioscoreae nipponese. MATERIALS AND METHODS: A total of 40 rats were divided into four groups: A normal group, hyperuricemia group, benzbromarone group (9 mg/kg) and total saponins from rhizoma dioscoreae nipponese (TDN) group (40 mg/kg). Adenine (100 mg/kg) and ethambutol (250 mg/kg) were used to induce hyperuricemic rats. Immunohistochemical and Western blotting methods were used to detect the mRNA and proteins expressions of rat organic anion transporter1 (rOAT1), rat organic anion transporter3 (rOAT3) and rat urate transporter1 (rURAT1) in the kidneys of different groups. RESULTS: It was found that the reduced concentration of blood uric acid was due to the enhancement of renal uric acid excretion. It was realized by up-regulating proteins expressions of rOAT1 and rOAT3 and down-regulating of rURAT1. CONCLUSION: The findings suggested that there were uricosuric effects of TDN by regulating renal organic ion transporters in hyperuricemic animals. Altogether, TDN may be a good Chinese herb in treating hyperuricemia, even a potential drug for gouty arthritis.