Yong-Hong Fu

Anti-Biofilm and Antivirulence Activities of Metabolites from Plectosphaerella cucumerina against Pseudomonas aeruginosa

This study reported the efficacy of the metabolites of Plectosphaerella cucumerina, one phyllosphere fungus from Orychophragmus violaceus, against Pseudomonas aeruginosa quorum sensing (QS) and QS-regulated biofilms. The minimum inhibitory concentration (MIC) of the ethyl acetate (EtOAc) extract from P. cucumerina against P. aeruginosa PAO1 was 1.25 mg mL−1. At sub-MIC concentrations, P. cucumerina extract (0.25–1 mg mL−1) not only inhibited biofilm formation but also disrupted preformed biofilms of P. aeruginosa PAO1 without affecting its growth. Fluorescence and scanning electron microscope (SEM) showed architectural disruption of the biofilms when treated with P. cucumerina metabolites. Further investigation demonstrated that metabolites in P. cucumerina attenuated the QS-dependent virulence factors. LC-MS/MS spectra coupled with experimentally standard samples suggested that patulin and emodin might act as the principal components possessing anti-biofilm and antivirulence activities. This is the first report of (1) the isolation of P. cucumerina from the phyllosphere of O. violaceus and (2) anti-biofilm, antivirulence, and biofilm disruption activities of this fungus. Thus, this study provides fascinating new pathways for screening antipathogenic agents.

Metabolic profiling of goldfish (Carassius auratis) after long-term glyphosate-based herbicide exposure

Glyphosate is an efficient herbicide widely used worldwide. However, its toxicity to non-targeted organisms has not been fully elucidated. In this study, the toxicity of glyphosate-based herbicide was evaluated on goldfish (Carassius auratus) after long-term exposure. Tissues of brains, kidneys and livers were collected and submitted to NMR-based metabolomics analysis and histopathological inspection. Plasma was collected and the blood biochemical indexes of AST, ALT, BUN, CRE, LDH, SOD, GSH-Px, GR and MDA were measured. Long-term glyphosate exposure caused disorders of blood biochemical indexes and renal tissue injury in goldfish. Metabolomics analysis combined with correlation network analysis uncovered significant perturbations in oxidative stress, energy metabolism, amino acids metabolism and nucleosides metabolism in glyphosate dosed fish, which provide new clues to the toxicity of glyphosate. This integrated metabolomics approach showed its applicability in discovering the toxic mechanisms of pesticides, which provided new strategy for the assessment of the environmental risk of herbicides to non-target organisms.

Insight into biological system responses in goldfish (Carassius auratus) to multiple doses of avermectin exposure by integrated 1H NMR-based metabolomics

The toxic effects of AVM were investigated using a teleost experimental model, the juvenile goldfish (Carassius auratus). Goldfish were consecutively exposed to AVM for 7 days and then the tissues of brains, kidneys and livers and plasma were collected and subjected to a NMR based metabolomics study. AVM changed the metabolomic profiles of goldfish dose-dependently and significantly changed the levels of metabolites in dosed goldfish, such as the branch-chain amino acids (BCAAs), aromatic amino acids (AAAs), betaine, taurine, lactate, etc. These metabolite changes affect energy metabolism, amino acid metabolism, nucleic acids metabolism, osmotic equilibrium as well as redox equilibrium, and are related with the toxicity of AVM. 1H NMR-based metabolomics approach promises to be an advantageous tool for the systematic and holistic view of the response of aquatic organisms to pesticides and is thus suitable for the assessment of the environmental risk of pesticides and the understanding of the underlying mechanism.

1H NMR-Based Global Metabolic Studies of Pseudomonas aeruginosa upon Exposure of the Quorum Sensing Inhibitor Resveratrol

Quorum sensing (QS) is a process of bacterial communication that has been a novel target for drug discovery. Pyocyanin quantification assay confirmed that resveratrol was an effective quorum sensing inhibitor (QSI) against Pseudomonas aeruginosa PAO1. In this study, the global metabolite changes of P. aeruginosa PAO1 exposed to QSI resveratrol were investigated by 1H NMR spectroscopy. A total of 40 metabolites containing amino acids, organic acid, organic amine, and energy storage compounds were identified. The changed metabolic profile indicated that resveratrol influenced pathways including oxidative stress, protein synthesis, and energy metabolism. Oxidative stress could upregulate the expression of genes related to QS in P. aeruginosa. It suggested that resveratrol could inhibit the QS systems in P. aeruginosa PAO1 by relieving oxidative stress due to its antioxidant activity. On the other hand, resveratrol could attenuate the pathogenicity of P. aeruginosa PAO1 by disturbing the TCA cycle so that anaerobic respiration could suppress the virulence because anaerobiosis could induce the loss of cytotoxicity regulated by QS in P. aeruginosa. These findings deepened our comprehending of the metabolic responses of P. aeruginosa PAO1 to resveratrol and pinpointed the possible underlying mechanism of resveratrols inhibition effect on QS in P. aeruginosa PAO1.

(1)H NMR-based metabolomics study of liver damage induced by ginkgolic acid (15:1) in mice.

&NA; Ginkgolic acid (15:1) is a major toxic component in extracts obtained from Ginkgo biloba (EGb) that has allergic and genotoxic effects. This study is the first to explore the hepatotoxicity of ginkgolic acid (15:1) using a NMR (nuclear magnetic resonance)‐based metabolomics approach in combination with biochemistry assays. Mice were orally administered two doses of ginkgolic acid (15:1), and mouse livers and serum were then collected for NMR recordings and biochemical assays. The levels of activity of alanine aminotransferase (ALT) and glutamic aspartate transaminase (AST) observed in the ginkgolic acid (15:1)‐treated mice suggested that it had induced severe liver damage. An orthogonal signal correction partial least‐squares discriminant analysis (OSC‐PLSDA) performed to determine the metabolomic profile of mouse liver tissues indicated that many metabolic disturbances, especially oxidative stress and purine metabolism, were induced by ginkgolic acid (15:1). A correlation network analysis combined with information related to structural similarities further confirmed that purine metabolism was disturbed by ginkgolic acid (15:1). This mechanism might represent the link between the antitumour activity and the liver injury‐inducing effect of ginkgolic acid (15:1). A SUS (Shared and Unique Structure) plot suggested that a two‐dose treatment of ginkgolic acid (15:1) had generally the same effect on metabolic variations but that its effects were dose‐dependent, revealing some of the common features of ginkgolic acid (15:1) dosing. This integrated metabolomics approach helped us to characterise ginkgolic acid (15:1)‐induced liver damage in mice. Graphical abstract Figure. No caption available. HighlightsThe liver damage of GA (15:1) was studied by NMR‐based metabolomics approach for the first time.The serum biochemical parameters were altered by GA (15:1) treatment in a dose‐dependent manner.SUS plot showed common features of GA (15:1) dosing and dose‐dependent metabolic changes.GA (15:1) induced disturbance in purine metabolism contributed to its antitumor and toxic effects.

Isoniazid-induced hepatotoxicity and neurotoxicity in rats investigated by 1 H NMR based metabolomics approach

Isoniazid (INH) is a well-known therapeutic and preventive agent against tuberculosis. However, high rates of side effects with various symptoms concerning hepatotoxicity and neurotoxicity have been reported, hindering its wide and safe application in clinic. In this investigation, rats were intoxicated with INH by gavage at doses of 200 and 400 mg/kg for 7 consecutive days to develop a rat model of acute INH-induced toxicity, which was investigated by a 1H NMR-based metabolomics complemented with clinical assays, histopathological inspection and western blotting. INH decreased the weights of dosed rats and induced seizure and hepatic steatosis dose-dependently. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) of the NMR profiles of rat livers, brains and serum revealed that INH dose-dependently induced oxidative stress, disorders of excitatory and inhibitory amino acid neurotransmitters, and disturbances of energy metabolism and osmotic balance, which could help clarify the mechanisms of INH-induced hepatotoxicity and neurotoxicity. This integrated metabolomics approach showcased its ability to characterize the global metabolic status of organism, providing a powerful and feasible tool to probe drug induced toxicity or side effects.

Nuclear magnetic resonance-based metabolomics approach to evaluate preventive and therapeutic effects of Gastrodia elata Blume on chronic atrophic gastritis

HighlightsCAG rats model was established to investigate preventive and therapeutic effects of Gastrodia elata Blume on chronic atrophic gastritis.NMR‐based metabolomics were firstly used to provide a global view of the efficacy of Gastrodia elata Blume treatment.Gastrodia elata Blume could apparently ameliorate the damaged gastric glands and enhance gastric acid secretion.Gastrodia elata Blume could effectively treat CAG via regulating energy and purine metabolisms, and by anti‐oxidation and anti‐inflammation effects. Abstract Chronic atrophic gastritis (CAG) is one of the most common digestive system diseases worldwide which defined by WHO as initial step of cancer. Gastrodia elata Blume (GEB) is a traditional herbal with multiple pharmacological activities which was widely used in Asian countries. This study aims to explore the preventive and therapeutical effects of Gastrodia elata Blume on auto‐immune induced CAG in rats. Tissues of stomachs were collected and submitted to 1H NMR‐based metabolomics analysis and histopathological inspection. The biochemical indexes of MDA, SOD, GSH, NO and XOD were measured. Gastrodia elata Blume could apparently ameliorate the damaged gastric glands and the biochemical parameters, enhance gastric acid secretion, and significantly relieve the inflammation of the stomach. Orthogonal signal correction‐partial least squares‐discriminant analysis (OSC‐PLS‐DA) of NMR profiles and correlation network analysis revealed that Gastrodia elata Blume could effectively treat CAG via regulating energy and purine metabolisms, and by anti‐oxidation and anti‐inflammation effects.

Acute psychoactive and toxic effects of D. metel on mice explained by 1H NMR based metabolomics approach

Datura metel L. (D. metel) is one well-known folk medical herb with wide application and also the most abused plants all over the world, mainly for spiritual or religious purpose, over-dosing of which often produces poisonous effects. In this study, mice were orally administered with the extract of D. metel once a day at doses for 10 mg/kg and 40 mg/kg for consecutive 4 days, 1H NMR based metabolomics approach aided with histopathological inspection and biochemical assays were used for the first time to study the psychoactive and toxic effects of D. metel. Histopathological inspection revealed obvious hypertrophy of hepatocytes, karyolysis and karyorrhexis in livers as well as distinct nerve cell edema, chromatolysis and lower nuclear density in brains. The increased tissue level of methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD), decreased tissue level of glutathione (GSH) along with increased serum level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) suggested brain and liver injury induced by D. metel. Orthogonal signal correction–partial least squares–discriminant analysis (OSC–PLS–DA) of NMR profiles supplemented with correlation network analysis revealed significant altered metabolites and related pathway that contributed to oxidative stress, energy metabolism disturbances, neurotransmitter imbalance and amino acid metabolism disorders.