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Sample records for supply bioactive metabolites

  1. Bioactive secondary metabolites from marine microbes for drug discovery.

    PubMed

    Nikapitiya, Chamilani

    2012-01-01

    The isolation and extraction of novel bioactive secondary metabolites from marine microorganisms have a biomedical potential for future drug discovery as the oceans cover 70% of the planet's surface and life on earth originates from sea. Wide range of novel bioactive secondary metabolites exhibiting pharmacodynamic properties has been isolated from marine microorganisms and many to be discovered. The compounds isolated from marine organisms (macro and micro) are important in their natural form and also as templates for synthetic modifications for the treatments for variety of deadly to minor diseases. Many technical issues are yet to overcome before wide-scale bioprospecting of marine microorganisms becomes a reality. This chapter focuses on some novel secondary metabolites having antitumor, antivirus, enzyme inhibitor, and other bioactive properties identified and isolated from marine microorganisms including bacteria, actinomycetes, fungi, and cyanobacteria, which could serve as potentials for drug discovery after their clinical trials.

  2. Prediction of Estrogenic Bioactivity of Environmental Chemical Metabolites.

    PubMed

    Pinto, Caroline L; Mansouri, Kamel; Judson, Richard; Browne, Patience

    2016-09-19

    The US Environmental Protection Agency's (EPA) Endocrine Disruptor Screening Program (EDSP) is using in vitro data generated from ToxCast/Tox21 high-throughput screening assays to assess the endocrine activity of environmental chemicals. Considering that in vitro assays may have limited metabolic capacity, inactive chemicals that are biotransformed into metabolites with endocrine bioactivity may be missed for further screening and testing. Therefore, there is a value in developing novel approaches to account for metabolism and endocrine activity of both parent chemicals and their associated metabolites. We used commercially available software to predict metabolites of 50 parent compounds, out of which 38 chemicals are known to have estrogenic metabolites, and 12 compounds and their metabolites are negative for estrogenic activity. Three ER QSAR models were used to determine potential estrogen bioactivity of the parent compounds and predicted metabolites, the outputs of the models were averaged, and the chemicals were then ranked based on the total estrogenicity of the parent chemical and metabolites. The metabolite prediction software correctly identified known estrogenic metabolites for 26 out of 27 parent chemicals with associated metabolite data, and 39 out of 46 estrogenic metabolites were predicted as potential biotransformation products derived from the parent chemical. The QSAR models estimated stronger estrogenic activity for the majority of the known estrogenic metabolites compared to their parent chemicals. Finally, the three models identified a similar set of parent compounds as top ranked chemicals based on the estrogenicity of putative metabolites. This proposed in silico approach is an inexpensive and rapid strategy for the detection of chemicals with estrogenic metabolites and may reduce potential false negative results from in vitro assays.

  3. Secondary Metabolites from Higher Fungi: Discovery, Bioactivity, and Bioproduction

    NASA Astrophysics Data System (ADS)

    Zhong, Jian-Jiang; Xiao, Jian-Hui

    Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin.

  4. Induced sclerotium formation exposes new bioactive metabolites from Aspergillus sclerotiicarbonarius.

    PubMed

    Petersen, Lene M; Frisvad, Jens C; Knudsen, Peter B; Rohlfs, Marko; Gotfredsen, Charlotte H; Larsen, Thomas O

    2015-10-01

    Sclerotia are known to be fungal survival structures, and induction of sclerotia may prompt production of otherwise undiscovered metabolites. Aspergillus sclerotiicarbonarius (IBT 28362) was investigated under sclerotium producing conditions, which revealed a highly altered metabolic profile. Four new compounds were isolated from cultivation under sclerotium formation conditions and their structures elucidated using different analytical techniques (HRMS, UV, 1D and 2D NMR). This included sclerolizine, an alkylated and oxidized pyrrolizine, the new emindole analog emindole SC and two new carbonarins; carbonarins I and J. We have identified the three latter as true sclerotial metabolites. All metabolites were tested for antifungal and antiinsectan activity, and sclerolizine and carbonarin I displayed antifungal activity against Candida albicans, while all four showed antiinsectan activity. These results demonstrate induction of sclerotia as an alternative way of triggering otherwise silent biosynthetic pathways in filamentous fungi for the discovery of novel bioactive secondary metabolites.

  5. Unbiased Evaluation of Bioactive Secondary Metabolites in Complex Matrices

    PubMed Central

    Inui, Taichi; Wang, Yuehong; Pro, Samuel M.; Franzblau, Scott G.; Pauli, Guido F.

    2012-01-01

    The majority of bioactive principles in a complex matrix such as natural products and botanical medicines are secondary rather than primary metabolites. In addition to being chemically diverse, the bioactivity of an ethnobotanical can comprise from one to several bioactive compounds, present in a complex mixture. Conventional discovery efforts utilize bioassay-guided fractionation (BGF) to isolate individual active compounds. When applied to complex natural products, BGF is often challenged by an apparent loss of activity during fractionation, resulting in weakly active isolated compounds. Metabolomic analysis can potentially complement existing the BGF paradigm by capturing the chemical complexity of the metabolites. The proposed biochemometric approach establishes a link between the chemistry of a secondary metabolome and a deserved health impact, using a high-throughput, high-resolution capable biological endpoint. The proof of principle is demonstrated for the anti-tuberculosis (TB) activity of the Alaskan ethnobotanical, Oplopanax horridus. Biochemometric analysis identified the 100 most active constituents from thousands of metabolites in the active extract by means of 2D orthogonal chromatography using countercurrent and GC-MS methods. Previously isolated O. horridus phytoconstituents were used as reference markers of known structure and bio(in)activity. Positive correlations allowed distinction of anti-TB actives from inactive compounds. A total of 29 bioactives from 3 main structural classes were assigned based on MS data. Biochemometric analysis is a new tool for the standardization of herbal medicines and ethnobotanicals, as well as for drug discovery from nature. The method can assign multiple active compounds in complex mixtures without their prior isolation or structure elucidation, while still providing an interface to structural information. PMID:22766306

  6. Proteomics analysis of UV-irradiated Lonicera japonica Thunb. with bioactive metabolites enhancement.

    PubMed

    Zhang, Lin; Li, Ximin; Zheng, Wen; Fu, Zhirong; Li, Wenting; Ma, Luyu; Li, Ke; Sun, Lianli; Tian, Jingkui

    2013-12-01

    A previous study showed that the contents of caffeoylquinic acids and iridoids, the major bioactive components in the postharvest Lonicera japonica Thunb., were induced by enhanced ultraviolet (UV)-A or UV-B irradiation. To clarify the UV-responsive key enzymes in the bioactive metabolites biosynthetic pathway and the related plant defense mechanism in L. japonica, 2DE in combination with MALDI-TOF/TOF MS was employed. Seventy-five out of 196 differential proteins were positively identified. Based on the functions, these proteins were grouped into nine categories, covering a wide range of molecular processes including the secondary metabolites (caffeoylquinic acids and iridoids) biosynthetic-related proteins, photosynthesis, carbohydrate and energy metabolism, stress, DNA, transport-related proteins, lipid metabolism, amino acid metabolism, cell wall. Of note is the increasing expression of 1-deoxy-d-xylulose 5-phosphate reductoisomerase and 5-enol-pyruvylshikimate-phosphate synthase, which was crucial to supply more precursor for the secondary metabolites including caffeoylquinic acids and iridoids. Thus, this study provides both the clues at the protein level for the increase of the two bioactive components upon UV irradiation and the profile of UV-responsive proteins in L. japonica.

  7. Major bioactive metabolites from marine fungi: A Review

    PubMed Central

    Hasan, Saba; Ansari, Mohammad Israil; Ahmad, Anis; Mishra, Maitreyi

    2015-01-01

    Biologists and chemists of the world have been attracted towards marine natural products for the last five decades. Approximately 16,000 marine natural products have been isolated from marine organisms which have been reported in approximately 6,800 publications, proving marine microorganisms to be a invaluable source for the production of novel antibiotic, anti tumor, and anti inflammatory agents. The marine fungi particularly those associated with marine alga, sponge, invertebrates, and sediments appear to be a rich source for secondary metabolites, possessing Antibiotic, antiviral, antifungal and antiyeast activities. Besides, a few growth stimulant properties which may be useful in studies on wound healing, carcinogenic properties, and in the study of cancers are reported. Recent investigations on marine filamentous fungi looking for biologically active secondary metabolites indicate the tremendous potential of them as a source of new medicines. The present study reviews about some important bioactive metabolites reported from marine fungal strains which are anti bacterial, anti tumour and anti inflammatory in action. It highlights the chemistry and biological activity of the major bioactive alkaloids, polyketides, terpenoids, isoprenoid and non-isoprenoid compounds, quinones, isolated from marine fungi. PMID:26124556

  8. Bioactive Secondary Metabolites Produced by the Fungal Endophytes of Conifers

    PubMed Central

    Stierle, Donald B.

    2016-01-01

    This is a review of bioactive secondary metabolites isolated from conifer-associated endophytic fungi from 1990–2014. This includes compounds with antimicrobial, anti-inflammatory, anti-proliferative or cytotoxic activity towards human cancer cell lines, and activity against plant pathogens or plant insect pests. Compounds that were originally reported without associated activity were included if other studies ascribed activity to these compounds. Compounds were not included if they were exclusively phytotoxic or if they were isolated from active extracts but were not determined to be the active component of that extract. PMID:26669101

  9. Bioactive Secondary Metabolites Produced by the Fungal Endophytes of Conifers.

    PubMed

    Stierle, Andrea A; Stierle, Donald B

    2015-10-01

    This is a review of bioactive secondary metabolites isolated from conifer-associated endophytic fungi from 1990-2014. This includes compounds with antimicrobial, anti-inflammatory, anti-proliferative and cytotoxic activity towards human cancer cell lines, and activity against either plant pathogens or plant insect pests. Compounds that were originally reported without associated activity were included if other studies ascribed activity to these compounds. Compounds were not included if they were exclusively phytotoxic or if they were isolated from active extracts but were not determined to be the active component of that extract.

  10. Production of bioactive secondary metabolites by marine vibrionaceae.

    PubMed

    Mansson, Maria; Gram, Lone; Larsen, Thomas O

    2011-01-01

    Bacteria belonging to the Vibrionaceae family are widespread in the marine environment. Today, 128 species of vibrios are known. Several of them are infamous for their pathogenicity or symbiotic relationships. Despite their ability to interact with eukaryotes, the vibrios are greatly underexplored for their ability to produce bioactive secondary metabolites and studies have been limited to only a few species. Most of the compounds isolated from vibrios so far are non-ribosomal peptides or hybrids thereof, with examples of N-containing compounds produced independent of nonribosomal peptide synthetases (NRPS). Though covering a limited chemical space, vibrios produce compounds with attractive biological activities, including antibacterial, anticancer, and antivirulence activities. This review highlights some of the most interesting structures from this group of bacteria. Many compounds found in vibrios have also been isolated from other distantly related bacteria. This cosmopolitan occurrence of metabolites indicates a high incidence of horizontal gene transfer, which raises interesting questions concerning the ecological function of some of these molecules. This account underlines the pending potential for exploring new bacterial sources of bioactive compounds and the challenges related to their investigation.

  11. CHIMALI 2014: Bioactive Metabolites and Contaminants in Fruits and Vegetables.

    PubMed

    Mulinacci, Nadia; Innocenti, Marzia

    2015-07-01

    The X Italian Congress of Food Chemistry (CHIMALI 2014) was organized in Florence, Italy, in July 2014 with 9 plenary lectures including 2 held by international guests, 51 oral communications, and 116 posters. These contributions were presented in five sessions: food authentication and traceability; botanicals and nutraceutical products; bioactive metabolites in foods: effects of extraction and processing; health foods: chemical composition, technological aspects, and biological properties; and treatment and valorization of food byproducts. The day dedicated to botanicals continued with a round table discussion titled "Botanicals, nutraceuticals and health claims: future perspectives and contribution of the scientific community", during which the role of European Food Safety and Authority (EFSA) was discussed and some experiences of well-known producers of botanical extracts were illustrated, together with the contributions of some experts on this theme.

  12. Marine actinomycetes: an ongoing source of novel bioactive metabolites.

    PubMed

    Subramani, Ramesh; Aalbersberg, William

    2012-12-20

    Actinomycetes are virtually unlimited sources of novel compounds with many therapeutic applications and hold a prominent position due to their diversity and proven ability to produce novel bioactive compounds. There are more than 22,000 known microbial secondary metabolites, 70% of which are produced by actinomycetes, 20% from fungi, 7% from Bacillus spp. and 1-2% by other bacteria. Among the actinomycetes, streptomycetes group are considered economically important because out of the approximately more than 10,000 known antibiotics, 50-55% are produced by this genus. The ecological role of actinomycetes in the marine ecosystem is largely neglected and various assumptions meant there was little incentive to isolate marine strains for search and discovery of new drugs. The search for and discovery of rare and new actinomycetes is of significant interest to drug discovery due to a growing need for the development of new and potent therapeutic agents. Modern molecular technologies are adding strength to the target-directed search for detection and isolation of bioactive actinomycetes, and continued development of improved cultivation methods and molecular technologies for accessing the marine environment promises to provide access to this significant new source of chemical diversity with novel/rare actinomycetes including new species of previously reported actinomycetes.

  13. Bioactive metabolites from an endophytic Cryptosporiopsis sp. inhabiting Clidemia hirta.

    PubMed

    Zilla, Mahesh K; Qadri, Masroor; Pathania, Anup S; Strobel, Gary A; Nalli, Yedukondalu; Kumar, Sunil; Guru, Santosh K; Bhushan, Shashi; Singh, Sanjay K; Vishwakarma, Ram A; Riyaz-Ul-Hassan, Syed; Ali, Asif

    2013-11-01

    An endophytic Cryptosporiopsis sp. was isolated from Clidemia hirta and analyzed for its secondary metabolites that lead to the isolation of three bioactive molecules. The compounds were purified from the culture broth of the fungus and their structures were determined by spectroscopic methods as (R)-5-hydroxy-2-methylchroman-4-one (1), 1-(2,6-dihydroxyphenyl)pentan-1-one (2) and (Z)-1-(2-(2-butyryl-3-hydroxyphenoxy)-6-hydroxyphenyl)-3-hydroxybut-2-en-1-one (3). Compound 1 exhibited significant cytotoxic activity against the human leukemia cell line, HL-60 with an IC50 of 4 μg/ml. This compound induced G2 arrest of the HL-60 cell cycle significantly. In addition, out of these compounds, 2 and 3 were active against several bacterial pathogens. Compound 2 was active against Bacillus cereus, Escherichia coli and Staphylococcus aureus with IC50 values varying from 18 to 30 μg/ml, and compound 3 displayed activity against Pseudomonas fluorescens with an IC50 value of 6 μg/ml. Compounds 2 and 3 are novel whereas compound 1 was reported earlier but the stereochemistry of its C-2 methyl is established for the first time.

  14. Advancement into the Arctic region for bioactive sponge secondary metabolites.

    PubMed

    Abbas, Samuel; Kelly, Michelle; Bowling, John; Sims, James; Waters, Amanda; Hamann, Mark

    2011-01-01

    Porifera have long been a reservoir for the discovery of bioactive compounds and drug discovery. Most research in the area has focused on sponges from tropical and temperate waters, but more recently the focus has shifted to the less accessible colder waters of the Antarctic and, to a lesser extent, the Arctic. The Antarctic region in particular has been a more popular location for natural products discovery and has provided promising candidates for drug development. This article reviews groups of bioactive compounds that have been isolated and reported from the southern reaches of the Arctic Circle, surveys the known sponge diversity present in the Arctic waters, and details a recent sponge collection by our group in the Aleutian Islands, Alaska. The collection has yielded previously undescribed sponge species along with primary activity against opportunistic infectious diseases, malaria, and HCV. The discovery of new sponge species and bioactive crude extracts gives optimism for the isolation of new bioactive compounds from a relatively unexplored source.

  15. [Coculture of actinomycetes with Bacillus subtilis and its effect on the bioactive secondary metabolites].

    PubMed

    Huang, Bing; Liu, Ning; Huang, Ying; Chen, Jinchun

    2009-06-01

    To explore the effect of coculturing actinomycetes with Bacillus subtilis on the production of bioactive secondary metabolites, we studied the difference between fermentation products of monocultures and the corresponding cocultures of 22 actinomycetes by antimicrobial assay and HPLC-PDA analysis. We selected Streptomyces strain FXJ2.014 with high bioactivity for further analysis and found additional metabolites in fermentation extracts of cocultures of strains FXJ2.014, FXJ1.296 and AS 4.1252 respectively with B. subtilis. Quinomycin A was the main bioactive metabolite produced by the monoculture of strain FXJ2.014, while a new quinomycin-like component named FXJ2.014-HB was produced when strain FXJ2.014 was cocultured with B. subtilis. Further tests of antimicrobial and antitumor activities indicated that FXJ2.014-HB and Quinomycin A had significant differences in terms of bioactivity. Moreover, the inhibitory activity of FXJ2.014-HB to a variety of tumor cell lines was weaker than the highly toxic Quinomycin A, indicating its potential to be an antibiotic with low cell toxicity. In conclusion, coculture can be used as a promising approach to discover bioactive secondary metabolites from actinomycetes.

  16. Advancement into the Arctic Region for Bioactive Sponge Secondary Metabolites

    PubMed Central

    Abbas, Samuel; Kelly, Michelle; Bowling, John; Sims, James; Waters, Amanda; Hamann, Mark

    2011-01-01

    Porifera have long been a reservoir for the discovery of bioactive compounds and drug discovery. Most research in the area has focused on sponges from tropical and temperate waters, but more recently the focus has shifted to the less accessible colder waters of the Antarctic and, to a lesser extent, the Arctic. The Antarctic region in particular has been a more popular location for natural products discovery and has provided promising candidates for drug development. This article reviews groups of bioactive compounds that have been isolated and reported from the southern reaches of the Arctic Circle, surveys the known sponge diversity present in the Arctic waters, and details a recent sponge collection by our group in the Aleutian Islands, Alaska. The collection has yielded previously undescribed sponge species along with primary activity against opportunistic infectious diseases, malaria, and HCV. The discovery of new sponge species and bioactive crude extracts gives optimism for the isolation of new bioactive compounds from a relatively unexplored source. PMID:22163194

  17. Bioactive Metabolites from Pathogenic and Endophytic Fungi of Forest Trees.

    PubMed

    Masi, Marco; Maddau, Lucia; Linaldeddu, Benedetto Teodoro; Scanu, Bruno; Evidente, Antonio; Cimmino, Alessio

    2017-03-14

    Fungi play an important role in terrestrial ecosystems interacting positively or negatively with plants. These interactions are complex and the outcomes are different depending on the fungal lifestyles, saprotrophic, mutualistic or pathogenic. Furthermore, fungi are well known for producing secondary metabolites, originating from different biosynthetic pathways, which possess biological properties of considerable biotechnological interest. Among the terrestrial ecosystems, temperate forests represent an enormous reservoir of fungal diversity. This review will highlight the goldmine of secondary metabolites produced by pathogenic and endophytic fungi of forest trees with focus on their biological activities.

  18. [Bioactive secondary metabolites produced by plants of the genus Physalis].

    PubMed

    Agata, Karolina; Kusiak, Joanna; Stępień, Bartłomiej; Bergier, Katarzyna; Kuźniak, Elżbieta

    2010-12-30

    Plants from the genus Physalis L. (family Solanaceae), native to warm and subtropical regions of Central and South America, are particularly rich in secondary metabolites, e.g.: withanolides, physalins, calystegines, tropane and nortropane alkaloids. Due to the high biological activities of these compounds, in the tropics Physalis plants have been used for centuries as medicinal herbs in the treatment of urinary and skin diseases, gonorrhea, ulcers, sores and as a vermicidal drug. This review describes the main categories of secondary metabolites, their distribution, chemistry, biosynthesis as well as biological activities. Particular attention is given to their potent anticancer activities.

  19. A Brief Review of Bioactive Metabolites Derived from Deep-Sea Fungi

    PubMed Central

    Wang, Yan-Ting; Xue, Ya-Rong; Liu, Chang-Hong

    2015-01-01

    Deep-sea fungi, the fungi that inhabit the sea and the sediment at depths of over 1000 m below the surface, have become an important source of industrial, agricultural, and nutraceutical compounds based on their diversities in both structure and function. Since the first study of deep-sea fungi in the Atlantic Ocean at a depth of 4450 m was conducted approximately 50 years ago, hundreds of isolates of deep-sea fungi have been reported based on culture-dependent methods. To date more than 180 bioactive secondary metabolites derived from deep-sea fungi have been documented in the literature. These include compounds with anticancer, antimicrobial, antifungal, antiprotozoal, and antiviral activities. In this review, we summarize the structures and bioactivities of these metabolites to provide help for novel drug development. PMID:26213949

  20. A Brief Review of Bioactive Metabolites Derived from Deep-Sea Fungi.

    PubMed

    Wang, Yan-Ting; Xue, Ya-Rong; Liu, Chang-Hong

    2015-07-23

    Deep-sea fungi, the fungi that inhabit the sea and the sediment at depths of over 1000 m below the surface, have become an important source of industrial, agricultural, and nutraceutical compounds based on their diversities in both structure and function. Since the first study of deep-sea fungi in the Atlantic Ocean at a depth of 4450 m was conducted approximately 50 years ago, hundreds of isolates of deep-sea fungi have been reported based on culture-dependent methods. To date more than 180 bioactive secondary metabolites derived from deep-sea fungi have been documented in the literature. These include compounds with anticancer, antimicrobial, antifungal, antiprotozoal, and antiviral activities. In this review, we summarize the structures and bioactivities of these metabolites to provide help for novel drug development.

  1. Bioactive Secondary Metabolites Produced by the Oak Pathogen Diplodia corticola.

    PubMed

    Masi, Marco; Maddau, Lucia; Linaldeddu, Benedetto Teodoro; Cimmino, Alessio; D'Amico, Wanda; Scanu, Bruno; Evidente, Marco; Tuzi, Angela; Evidente, Antonio

    2016-01-13

    Three new lactones and a new fatty acid ester, named sapinofuranones C and D, diplopyrone B, and diplobifuranylone C, respectively, were isolated from Diplodia corticola, together with sphaeropsidins A and C, diplopyrone, diplobifuranylones A and B, diplofuranone A, and the (S,S)-enantiomer of sapinofuranone B. Sapinofuranones C and D, diplopyrone B, and diplobifuranylone C were characterized as (5S)-5-((1,S-1,6-dihydroxyhexa-2,4-dienyl)-dihydrofuran-2-one, 4,5-dihydroxy-deca-6,8-dienoic acid methyl ester, (5S)-5-hydroxy-6-(penta-1,3-dienyl)-5,6-dihydro-pyran-2-one, and 5'-((1R)-1-hydroxyethyl)-2',5'-dihydro-2H-[2,2']bifuranyl-5-one by spectroscopic and chemical methods, respectively. The relative configuration of sapinofuranone C was assigned by X-ray diffraction analysis, whereas its absolute configuration was determined by applying the advanced Mosher's method to its 11-O-p-bromobenzoyl derivative. The same method was used to assign the absolute configuration to C-5 of diplopyrone B and to that of the hydroxyethyl of the side chain of diplobifuranylone C, respectively. The metabolites isolated were tested at 1 mg/mL on leaves of cork oak, grapevine cv. 'Cannonau', and tomato using the leaf puncture assay. They were also tested on tomato cuttings at 0.2, 0.1, and 0.05 mg/mL. Each compound was tested for zootoxic activity on Artemia salina L. larvae. The efficacy of sapinofuranone C and diplopyrone B on three plant pathogens, namely, Athelia rolfsii, Fusarium avenaceum, and Phytophthora nicotianae was also evaluated. In all phytotoxic assays only diplopyrone B was found to be active. It also showed strong inhibition on the vegetative growth of A. rolfsii and P. nicotianae. All metabolites were inactive in the assay performed for the zootoxic activity (A. salina) even at the highest concentration used (200 μg/mL). Diplopyrone B showed a promising antioomycete activity for the control of Phytophthora spp. also taking into account the absence of zootoxic activity.

  2. Facilitated uptake of a bioactive metabolite of maritime pine bark extract (pycnogenol) into human erythrocytes.

    PubMed

    Kurlbaum, Max; Mülek, Melanie; Högger, Petra

    2013-01-01

    Many plant secondary metabolites exhibit some degree of biological activity in humans. It is a common observation that individual plant-derived compounds in vivo are present in the nanomolar concentration range at which they usually fail to display measurable activity in vitro. While it is debatable that compounds detected in plasma are not the key effectors of bioactivity, an alternative hypothesis may take into consideration that measurable concentrations also reside in compartments other than plasma. We analysed the binding of constituents and the metabolite δ-(3,4-dihydroxy-phenyl)-γ-valerolactone (M1), that had been previously detected in plasma samples of human consumers of pine bark extract Pycnogenol, to human erythrocytes. We found that caffeic acid, taxifolin, and ferulic acid passively bind to red blood cells, but only the bioactive metabolite M1 revealed pronounced accumulation. The partitioning of M1 into erythrocytes was significantly diminished at higher concentrations of M1 and in the presence of glucose, suggesting a facilitated transport of M1 via GLUT-1 transporter. This concept was further supported by structural similarities between the natural substrate α-D-glucose and the S-isomer of M1. After cellular uptake, M1 underwent further metabolism by conjugation with glutathione. We present strong indication for a transporter-mediated accumulation of a flavonoid metabolite in human erythrocytes and subsequent formation of a novel glutathione adduct. The physiologic role of the adduct remains to be elucidated.

  3. Role of toxic and bioactive secondary metabolites in colonization and bloom formation by filamentous cyanobacteria Planktothrix.

    PubMed

    Kurmayer, Rainer; Deng, Li; Entfellner, Elisabeth

    2016-04-01

    Bloom-forming cyanobacteria Planktothrix agardhii and P. rubescens are regularly involved in the occurrence of cyanotoxin in lakes and reservoirs. Besides microcystins (MCs), which inhibit eukaryotic protein phosphatase 1 and 2A, several families of bioactive peptides are produced, thereby resulting in impressive secondary metabolite structural diversity. This review will focus on the current knowledge of the phylogeny, morphology, and ecophysiological adaptations of Planktothrix as well as the toxins and bioactive peptides produced. The relatively well studied ecophysiological adaptations (buoyancy, shade tolerance, nutrient storage capacity) can partly explain the invasiveness of this group of cyanobacteria that bloom within short periods (weeks to months). The more recent elucidation of the genetic basis of toxin and bioactive peptide synthesis paved the way for investigating its regulation both in the laboratory using cell cultures as well as under field conditions. The high frequency of several toxin and bioactive peptide synthesis genes observed within P. agardhii and P. rubescens, but not for other Planktothrix species (e.g. P. pseudagardhii), suggests a potential functional linkage between bioactive peptide production and the colonization potential and possible dominance in habitats. It is hypothesized that, through toxin and bioactive peptide production, Planktothrix act as a niche constructor at the ecosystem scale, possibly resulting in an even higher ability to monopolize resources, positive feedback loops, and resilience under stable environmental conditions. Thus, refocusing harmful algal bloom management by integrating ecological and phylogenetic factors acting on toxin and bioactive peptide synthesis gene distribution and concentrations could increase the predictability of the risks originating from Planktothrix blooms.

  4. Discovery of Bioactive Metabolites in Biofuel Microalgae That Offer Protection against Predatory Bacteria

    PubMed Central

    Bagwell, Christopher E.; Abernathy, Amanda; Barnwell, Remy; Milliken, Charles E.; Noble, Peter A.; Dale, Taraka; Beauchesne, Kevin R.; Moeller, Peter D. R.

    2016-01-01

    Microalgae could become an important resource for addressing increasing global demand for food, energy, and commodities while helping to reduce atmospheric greenhouse gasses. Even though Chlorophytes are generally regarded safe for human consumption, there is still much we do not understand about the metabolic and biochemical potential of microscopic algae. The aim of this study was to evaluate biofuel candidate strains of Chlorella and Scenedesmus for the potential to produce bioactive metabolites when grown under nutrient depletion regimes intended to stimulate production of triacylglycerides. Strain specific combinations of macro- and micro-nutrient restricted growth media did stimulate neutral lipid accumulation by microalgal cultures. However, cultures that were restricted for iron consistently and reliably tested positive for cytotoxicity by in vivo bioassays. The addition of iron back to these cultures resulted in the disappearance of the bioactive components by LC/MS fingerprinting and loss of cytotoxicity by in vivo bioassay. Incomplete NMR characterization of the most abundant cytotoxic fractions suggested that small molecular weight peptides and glycosides could be responsible for Chlorella cytotoxicity. Experiments were conducted to determine if the bioactive metabolites induced by Fe-limitation in Chlorella sp. cultures would elicit protection against Vampirovibrio chlorellavorus, an obligate predator of Chlorella. Introduction of V. chlorellavorus resulted in a 72% decrease in algal biomass in the experimental controls after 7 days. Conversely, only slight losses of algal biomass were measured for the iron limited Chlorella cultures (0–9%). This study demonstrates a causal linkage between iron bioavailability and bioactive metabolite production in strains of Chlorella and Scenedesmus. Further study of this phenomenon could contribute to the development of new strategies to extend algal production cycles in open, outdoor systems while ensuring the

  5. Discovery of Bioactive Metabolites in Biofuel Microalgae That Offer Protection against Predatory Bacteria.

    PubMed

    Bagwell, Christopher E; Abernathy, Amanda; Barnwell, Remy; Milliken, Charles E; Noble, Peter A; Dale, Taraka; Beauchesne, Kevin R; Moeller, Peter D R

    2016-01-01

    Microalgae could become an important resource for addressing increasing global demand for food, energy, and commodities while helping to reduce atmospheric greenhouse gasses. Even though Chlorophytes are generally regarded safe for human consumption, there is still much we do not understand about the metabolic and biochemical potential of microscopic algae. The aim of this study was to evaluate biofuel candidate strains of Chlorella and Scenedesmus for the potential to produce bioactive metabolites when grown under nutrient depletion regimes intended to stimulate production of triacylglycerides. Strain specific combinations of macro- and micro-nutrient restricted growth media did stimulate neutral lipid accumulation by microalgal cultures. However, cultures that were restricted for iron consistently and reliably tested positive for cytotoxicity by in vivo bioassays. The addition of iron back to these cultures resulted in the disappearance of the bioactive components by LC/MS fingerprinting and loss of cytotoxicity by in vivo bioassay. Incomplete NMR characterization of the most abundant cytotoxic fractions suggested that small molecular weight peptides and glycosides could be responsible for Chlorella cytotoxicity. Experiments were conducted to determine if the bioactive metabolites induced by Fe-limitation in Chlorella sp. cultures would elicit protection against Vampirovibrio chlorellavorus, an obligate predator of Chlorella. Introduction of V. chlorellavorus resulted in a 72% decrease in algal biomass in the experimental controls after 7 days. Conversely, only slight losses of algal biomass were measured for the iron limited Chlorella cultures (0-9%). This study demonstrates a causal linkage between iron bioavailability and bioactive metabolite production in strains of Chlorella and Scenedesmus. Further study of this phenomenon could contribute to the development of new strategies to extend algal production cycles in open, outdoor systems while ensuring the

  6. Advancement of green process through microwave-assisted extraction of bioactive metabolites from Arthrospira Platensis and bioactivity evaluation.

    PubMed

    Esquivel-Hernández, Diego A; Rodríguez-Rodríguez, José; Rostro-Alanis, Magdalena; Cuéllar-Bermúdez, Sara P; Mancera-Andrade, Elena I; Núñez-Echevarría, Jade E; García-Pérez, J Saúl; Chandra, Rashmi; Parra-Saldívar, Roberto

    2017-01-01

    Bioactivity and functional properties of cyanobacterial extract mostly depends on process of extraction, temperature and solvent used (polar or non-polar). To evaluate these parameters a design of experiment (DOE; using a 2(k) design) was performed with Arthrospira platensis. Extraction process was optimized through microwave-assisted extraction considering solvent ratio, temperature and time of extraction with polar (PS) and non-polar (NPS). Maximum extract yield obtained was 4.32±0.25% and 5.26±0.11% (w/w) respectively for PS and NPS. Maximum content of bioactive metabolites in PS extracts were thiamine (846.57±14.12μg/g), riboflavin (101.09±1.63μg/g), C-phycocyanin (2.28±0.10μg/g) and A-phycocyanin (4.11±0.03μg/g), while for NPS extracts were α-tocopherol (37.86±0.78μg/g), β-carotene (123.64±1.45μg/g) and 19.44±0.21mg/g of fatty acids. A. platensis PS extracts showed high antimicrobial activity and PS extracts had antioxidant activity of 0.79±0.12μmolTE/g for FRAP assay, while for NPS extracts 1.03±0.08μmol α-TE/g for FRAP assay.

  7. Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites.

    PubMed Central

    Spencer, Jeremy P E; Kuhnle, Gunter G C; Williams, Robert J; Rice-Evans, Catherine

    2003-01-01

    Understanding the cellular effects of flavonoid metabolites is important for predicting which dietary flavonoids might be most beneficial in vivo. Here we investigate the bioactivity in dermal fibroblasts of the major reported in vivo metabolites of quercetin, i.e. 3'-O-methyl quercetin, 4'-O-methyl quercetin and quercetin 7-O-beta-D-glucuronide, relative to that of quercetin, in terms of their further metabolism and their resulting cytotoxic and/or cytoprotective effects in the absence and presence of oxidative stress. Uptake experiments indicate that exposure to quercetin led to the generation of two novel cellular metabolites, one characterized as a 2'-glutathionyl quercetin conjugate and another product with similar spectral characteristics but 1 mass unit lower, putatively a quinone/quinone methide. A similar product was identified in cells exposed to 3'-O-methyl quercetin, but not in the lysates of those exposed to its 4'-O-methyl counterpart, suggesting that its formation is related to oxidative metabolism. There was no uptake or metabolism of quercetin 7-O-beta-D-glucuronide by fibroblasts. Formation of oxidative metabolites may explain the observed concentration-dependent toxicity of quercetin and 3'-O-methyl quercetin, whereas the formation of a 2'-glutathionyl quercetin conjugate is interpreted as a detoxification step. Both O -methylated metabolites conferred less protection than quercetin against peroxide-induced damage, and quercetin glucuronide was ineffective. The ability to modulate cellular toxicity paralleled the ability of the compounds to decrease the level of peroxide-induced caspase-3 activation. Our data suggest that the actions of quercetin and its metabolites in vivo are mediated by intracellular metabolites. PMID:12578560

  8. Rare actinomycetes Nocardia caishijiensis and Pseudonocardia carboxydivorans as endophytes, their bioactivity and metabolites evaluation.

    PubMed

    Tanvir, Rabia; Sajid, Imran; Hasnain, Shahida; Kulik, Andreas; Grond, Stephanie

    2016-04-01

    Two strains identified as Nocardia caishijiensis (SORS 64b) and Pseudonocardia carboxydivorans (AGLS 2) were isolated as endophytes from Sonchus oleraceus and Ageratum conyzoides respectively. The analysis of their extracts revealed them to be strongly bioactive. The N. caishijiensis extract gave an LC50 of 570 μg/ml(-1) in the brine shrimp cytotoxicity assay and an EC50 of 0.552 μg/ml(-1) in the DPPH antioxidant assay. Antimicrobial activity was observed against Methicillin resistant Staphlococcus aureus (MRSA) and Escherichia coli ATCC 25922 (14 mm), Klebsiella pneumoniae ATCC 706003 (13 mm), S. aureus ATCC 25923 (11 mm) and Candida tropicalis (20 mm). For the extract of P. carboxydivorans the EC50 was 0.670 μg/ml(-1) and it was observed to be more bioactive against Bacillus subtilis DSM 10 ATCC 6051 (21 mm), C. tropicalis (20 mm), S. aureus ATCC 25923 (17 mm), MRSA (17 mm), E. coli K12 (W1130) (16 mm) and Chlorella vulgaris (10 mm). The genotoxicity testing revealed a 20 mm zone of inhibition against the polA mutant strain E. coli K-12 AB 3027 suggesting damage to the DNA and polA genes. The TLC and bioautography screening revealed a diversity of active bands of medium polar and nonpolar compounds. Metabolite analysis by HPLC-DAD via UV/vis spectral screening suggested the possibility of stenothricin and bagremycin A in the mycelium extract of N. caishijiensis respectively. In the broth and mycelium extract of P. carboxydivorans borrelidin was suggested along with α-pyrone. The HPLC-MS revealed bioactive long chained amide derivatives such as 7-Octadecenamide, 9, 12 octadecandienamide. This study reports the rare actinomycetes N. caishijiensis and P. carboxydivorans as endophytes and evaluates their bioactive metabolites.

  9. Low water activity induces the production of bioactive metabolites in halophilic and halotolerant fungi.

    PubMed

    Sepcic, Kristina; Zalar, Polona; Gunde-Cimerman, Nina

    2010-12-27

    The aim of the present study was to investigate indigenous fungal communities isolated from extreme environments (hypersaline waters of solar salterns and subglacial ice), for the production of metabolic compounds with selected biological activities: hemolysis, antibacterial, and acetylcholinesterase inhibition. In their natural habitats, the selected fungi are exposed to environmental extremes, and therefore the production of bioactive metabolites was tested under both standard growth conditions for mesophilic microorganisms, and at high NaCl and sugar concentrations and low growth temperatures. The results indicate that selected halotolerant and halophilic species synthesize specific bioactive metabolites under conditions that represent stress for non-adapted species. Furthermore, adaptation at the level of the chemical nature of the solute lowering the water activity of the medium was observed. Increased salt concentrations resulted in higher hemolytic activity, particularly within species dominating the salterns. The appearance of antibacterial potential under stress conditions was seen in the similar pattern of fungal species as for hemolysis. The active extracts exclusively affected the growth of the Gram-positive bacterium tested, Bacillus subtilis. None of the extracts tested showed inhibition of acetylcholinesterase activity.

  10. Bioactive and Structural Metabolites of Pseudomonas and Burkholderia Species Causal Agents of Cultivated Mushrooms Diseases1

    PubMed Central

    Andolfi, Anna; Cimmino, Alessio; Cantore, Pietro Lo; Iacobellis, Nicola Sante; Evidente, Antonio

    2008-01-01

    Pseudomonas tolaasii, P. reactans and Burkholderia gladioli pv. agaricicola, are responsible of diseases on some species of cultivated mushrooms. The main bioactive metabolites produced by both Pseudomonas strains are the lipodepsipeptides (LDPs) tolaasin I and II and the so called White Line Inducing Principle (WLIP), respectively, LDPs which have been extensively studied for their role in the disease process and for their biological properties. In particular, their antimicrobial activity and the alteration of biological and model membranes (red blood cell and liposomes) was established. In the case of tolaasin I interaction with membranes was also related to the tridimensional structure in solution as determined by NMR combined with molecular dynamic calculation techniques. Recently, five news minor tolaasins, tolaasins A–E, were isolated from the culture filtrates of P. tolaasii and their chemical structure was determined by extensive use of NMR and MS spectroscopy. Furthermore, their antimicrobial activity was evaluated on target micro-organisms (fungi—including the cultivated mushrooms Agaricus bisporus, Lentinus edodes, and Pleurotus spp.—chromista, yeast and bacteria). The Gram positive bacteria resulted the most sensible and a significant structure-activity relationships was apparent. The isolation and structure determination of bioactive metabolites produced by B. gladioli pv. agaricicola are still in progress but preliminary results indicate their peptide nature. Furthermore, the exopolysaccharide (EPS) from the culture filtrates of B. gladioli pv. agaricicola, as well as the O-chain and lipid A, from the lipopolysaccharide (LPS) of the three bacteria, were isolated and the structures determined. PMID:19787100

  11. Low Water Activity Induces the Production of Bioactive Metabolites in Halophilic and Halotolerant Fungi

    PubMed Central

    Sepcic, Kristina; Zalar, Polona; Gunde-Cimerman, Nina

    2011-01-01

    The aim of the present study was to investigate indigenous fungal communities isolated from extreme environments (hypersaline waters of solar salterns and subglacial ice), for the production of metabolic compounds with selected biological activities: hemolysis, antibacterial, and acetylcholinesterase inhibition. In their natural habitats, the selected fungi are exposed to environmental extremes, and therefore the production of bioactive metabolites was tested under both standard growth conditions for mesophilic microorganisms, and at high NaCl and sugar concentrations and low growth temperatures. The results indicate that selected halotolerant and halophilic species synthesize specific bioactive metabolites under conditions that represent stress for non-adapted species. Furthermore, adaptation at the level of the chemical nature of the solute lowering the water activity of the medium was observed. Increased salt concentrations resulted in higher hemolytic activity, particularly within species dominating the salterns. The appearance of antibacterial potential under stress conditions was seen in the similar pattern of fungal species as for hemolysis. The active extracts exclusively affected the growth of the Gram-positive bacterium tested, Bacillus subtilis. None of the extracts tested showed inhibition of acetylcholinesterase activity. PMID:21339946

  12. Bioactive and structural metabolites of pseudomonas and burkholderia species causal agents of cultivated mushrooms diseases.

    PubMed

    Andolfi, Anna; Cimmino, Alessio; Cantore, Pietro Lo; Iacobellis, Nicola Sante; Evidente, Antonio

    2008-05-09

    Pseudomonas tolaasii, P. reactans and Burkholderia gladioli pv. agaricicola, are responsible of diseases on some species of cultivated mushrooms. The main bioactive metabolites produced by both Pseudomonas strains are the lipodepsipeptides (LDPs) tolaasin I and II and the so called White Line Inducing Principle (WLIP), respectively, LDPs which have been extensively studied for their role in the disease process and for their biological properties. In particular, their antimicrobial activity and the alteration of biological and model membranes (red blood cell and liposomes) was established. In the case of tolaasin I interaction with membranes was also related to the tridimensional structure in solution as determined by NMR combined with molecular dynamic calculation techniques. Recently, five news minor tolaasins, tolaasins A-E, were isolated from the culture filtrates of P. tolaasii and their chemical structure was determined by extensive use of NMR and MS spectroscopy. Furthermore, their antimicrobial activity was evaluated on target micro-organisms (fungi-including the cultivated mushrooms Agaricus bisporus, Lentinus edodes, and Pleurotus spp.-chromista, yeast and bacteria). The Gram positive bacteria resulted the most sensible and a significant structure-activity relationships was apparent. The isolation and structure determination of bioactive metabolites produced by B. gladioli pv. agaricicola are still in progress but preliminary results indicate their peptide nature. Furthermore, the exopolysaccharide (EPS) from the culture filtrates of B. gladioli pv. agaricicola, as well as the O-chain and lipid A, from the lipopolysaccharide (LPS) of the three bacteria, were isolated and the structures determined.

  13. Submerged cultivation of medicinal mushrooms for production of valuable bioactive metabolites.

    PubMed

    Zhong, Jian-Jiang; Tang, Ya-Jie

    2004-01-01

    Mushrooms are abundant sources of a wide range of useful natural products. Nowadays, commercial mushroom products are from mushrooms collected from field cultivation, which is a time-consuming and labor-intensive process. Submerged cultivation of mushrooms has significant industrial potential, but its success on a commercial scale depends on cost compared with existing technology. Increasing product yields and development of novel production systems that address the problems associated with this new technology will certainly facilitate expansion. This article outlines the major valuable metabolites produced by mushroom cultivation and advances in submerged culture of mushrooms, taking Ganoderma lucidum, a popular folk and an oriental medicine used to treat many diseases, as a typical example. Our latest data on mushroom cultivation for efficient production of bioactive ganoderic acids and Ganoderma polysaccharides in bioreactors are presented.

  14. Search for hydrophilic marine fungal metabolites: a rational approach for their production and extraction in a bioactivity screening context.

    PubMed

    Le Ker, Carine; Petit, Karina-Ethel; Biard, Jean-François; Fleurence, Joël

    2011-01-10

    In the search for bioactive natural products, our lab screens hydrophobic extracts from marine fungal strains. While hydrophilic active substances were recently identified from marine macro-organisms, there was a lack of reported metabolites in the marine fungi area. As such, we decided to develop a general procedure for screening of hydrophobic metabolites. The aim of this study was to compare different processes of fermentation and extraction, using six representative marine fungal strains, in order to define the optimized method for production. The parameters studied were (a) which polar solvent to select, (b) which fermentation method to choose between solid and liquid cultures, (c) which raw material, the mycelium or its medium, to extract and (d) which extraction process to apply. The biochemical analysis and biological evaluations of obtained extracts led to the conclusion that the culture of marine fungi by agar surface fermentation followed by the separate extraction of the mycelium and its medium by a cryo-crushing and an enzymatic digestion with agarase, respectively, was the best procedure when screening for hydrophilic bioactive metabolites. During this development, several bioactivities were detected, confirming the potential of hydrophilic crude extracts in the search for bioactive natural products.

  15. Fusarial wilt control and growth promotion of pigeon pea through bioactive metabolites produced by two plant growth promoting rhizobacteria.

    PubMed

    Dutta, S; Morang, P; Nishanth Kumar, S; Dileep Kumar, B S

    2014-03-01

    The bioactive metabolites produced by two plant growth promoting rhizobacteria strains, a Pseudomonas aeruginosa strain RRLJ 04 and a Bacillus cereus strain BS 03, which showed growth promotion and disease control in pigeon pea against Fusarium udum, were isolated and screened for their efficacy to control fusarial wilt of pigeon pea under gnotobiotic and nursery condition. Bioactive metabolites viz., BM 1 and BM 2 from RRLJ 04 and BM 3 from BS 03 also showed in vitro antibiosis against F. udum. Seeds treated with 50 μl seed⁻¹ of BM 1, 30 μl seed⁻¹ of BM 2 and 70 μl seed⁻¹ of BM 3 and grown in pathogen infested soil showed suppression of wilt disease besides growth enhancement. Per cent disease control was 90 % with BM 2 application as compared to 87 and 83 %, respectively in BM 1 and BM 3 after 90 days of growth. BM 2 treated plants were more resistant to the pathogen as compared to the other fractions tested. Mycelial dry weight was found to be reduced on treatment with the bioactive metabolites. Formation of chlamydospore-like structures was observed in the pathogen mycelium treated with BM 3. The analytical studies confirmed that two of these metabolites are phenazine derivatives.

  16. Metabolite Profiling and Comparison of Bioactivity in Antrodia cinnamomea and Antrodia salmonea Fruiting Bodies.

    PubMed

    Chen, Chieh-Yin; Chien, Shih-Chang; Tsao, Nai-Wen; Lai, Chiem-Sing; Wang, Ya-Yun; Hsiao, Wen-Wei; Chu, Fang-Hua; Kuo, Yueh-Hsiung; Wang, Sheng-Yang

    2016-02-01

    Antrodia cinnamomea is a precious edible mushroom endemic to Taiwan that has been claimed to have significant health promotion activities. Antrodia salmonea is a new species of the genus Antrodia. In this study, we compared the metabolites and bioactivity of A. cinnamomea and A. salmonea fruiting bodies. The volatiles of A. cinnamomea and A. salmonea were characterized and 3,4,5-trimethoxybenzaldehyde was found to be the most abundant compound in A. cinnamomea; the other abundant compounds were δ-guaiene, isolongifolene, 1-octen-3-ol, 4-terpinenol, α-guaiene, and p-cymene. In A. salmonea, the main volatiles were α-cedrene, 1-octen-3-ol, D-limonene, cadinadiene, germacrene D, isolongifolene, and α-muurolene. Furthermore, five ergostane-type triterpenoids and two lanostane-type triterpenoids were selected as index compounds characterizing A. cinnamomea and A. salmonea extracts. The content of each compound varied between the two species. (R,S)-antcin B was the most abundant compound in A. cinnamomea fruiting bodies (75.18 ± 0.11 µg/mg). However, (R,S)-antcin C (184.85 ± 0.96 µg/mg) was the major triterpenoid in the A. salmonea fruiting body. Furthermore, two compounds, antcin M and methyl antcinate K, were only present in the A. salmonea fingerprint; therefore, antcin M and methyl antcinate K may be important for distinguishing between A. cinnamomea and A. salmonea fruiting bodies. Finally, examination of anti-inflammation activity and cytotoxicity showed that A. salmonea had more anti-inflammatory activity than A. cinnamomea; however, A. salmonea was more cytotoxic than A. cinnamomea. In conclusion, the composition and bioactivity of the fruiting bodies of A. cinnamomea and A. salmonea varies. Therefore, it is recommended that further toxicological evaluation and investigation of the biological activity of A. salmonea is carried out to ensure its safe and efficacious use as an alternative to A. cinnamomea.

  17. Metabolism of chicoric acid by rat liver microsomes and bioactivity comparisons of chicoric acid and its metabolites.

    PubMed

    Liu, Qian; Wang, Yutang; Xiao, ChunXia; Wu, Wanqiang; Liu, Xuebo

    2015-06-01

    Chicoric acid has recently become a hot research topic due to its potent bioactivities. However, there are few studies relevant to this acid's pharmacokinetic characteristics and the pharmacological activities of its metabolites. To compare the abilities of chicoric acid and its metabolites in scavenging free radicals and their effects on the viability of 3T3-L1 preadipocytes, an in vitro study of the metabolism of chicoric acid in rat liver microsomes was performed using liquid tandem mass spectrometry (HPLC-MS/MS). The results indicated that caffeic acid and caftaric acid were the hepatic phase I metabolites of chicoric acid. These three compounds had strong capacities for scavenging free radicals and had been demonstrated to increase intracellular ROS levels in 3T3-L1 preadipocytes, thereby reducing cell vitality. Finally, the pharmacological activities of chicoric acid were significantly stronger than those of its metabolites within a certain concentration range.

  18. Isolation, characterization and biological evaluation of bioactive metabolites from Nocardia levis MK-VL_113.

    PubMed

    Kavitha, Alapati; Prabhakar, Peddikotla; Narasimhulu, Manchala; Vijayalakshmi, Muvva; Venkateswarlu, Yenamandra; Rao, Karanam Venkateswara; Raju, Venkata Balaraju Subba

    2010-03-31

    An Actinomycete isolate found to be prominent in the laterite soils of Acharya Nagarjuna University (ANU) Campus, Guntur was identified as Nocardia levis MK-VL_113 by 16S rRNA analysis. Cultural, morphological and physiological characteristics of the strain were recorded. Screening of secondary metabolites obtained from 4-day old culture broth of the strain led to the isolation of two fractions active against a wide variety of Gram-positive, Gram-negative bacteria and fungi. The structure of the first active fraction was elucidated using FT-IR, EI-MS, (1)H NMR and (13)C NMR spectra and identified as 1-phenylbut-3-ene-2-ol which is first time reported as a natural product. The compound exhibited good antimicrobial potential against the opportunistic and pathogenic bacteria and fungi. The antifungal activity of the strain and its metabolite were further confirmed with in vitro and in vivo studies. Evidence for the antagonism of the strain against Fusarium oxysporum, causing wilt disease in sorghum was demonstrated by the formation of inhibition zone in in vitro plate assay and reduction in the incidence of wilt of sorghum plants by using a green house trial. Analysis of the rhizosphere soil extracts by high performance liquid chromatography also demonstrated the production of the compound by the strain under in vivo conditions. As compared to the commercial fungicide mancozeb, the bioactive compound, 1-phenylbut-3-ene-2-ol was highly effective in controlling wilt of sorghum. Besides, the partially purified second fraction (PPF) subjected to gas chromatography-mass spectrometry revealed the presence of phenylethyl alcohol, dibutyl phthalate and 1,2-benzenedicarboxylic acid, 3-nitro.

  19. Efficient production of bioactive metabolites from Antrodia camphorata ATCC 200183 by asexual reproduction-based repeated batch fermentation.

    PubMed

    Li, Hua-Xiang; Lu, Zhen-Ming; Geng, Yan; Gong, Jin-Song; Zhang, Xiao-Juan; Shi, Jin-Song; Xu, Zheng-Hong; Ma, Yan-He

    2015-10-01

    Large-scale submerged fermentation (SmF) of Antrodia camphorata (A. camphorata) usually encounters challenges including tedious preparation of mycelial inoculum, long fermentation period (10-14 d), and poor repeatability. Here we developed an asexual reproduction-based repeated batch fermentation (RBF) process for bioactive metabolites production by A. camphorata ATCC 200183. Compared with traditional batch fermentation, production time was shortened to 58 d from 80 d (overall time for eight cycles) using the RBF process established in this study, and accordingly, the productivities of bioactive metabolites (including antrodins) were improved by 40-60%. Kinetic parameters (α is 2.1-18.7 times as β) indicated that the cell growth was the major contribution for bioactive metabolites production. The RBF shows excellent batch-repeatability (Pearson correlation coefficient of 0.998±0.001), together with advantages of energy-efficient, low cost, and labor-saving, RBF process can be implemented to SmF by other filamentous fungi.

  20. Bioactivation of dibrominated biphenyls by cytochrome P450 activity to metabolites with estrogenic activity and estrogen sulfotransferase inhibition capacity.

    PubMed

    van Lipzig, Marola M H; Commandeur, Jan N; de Kanter, Frans J J; Damsten, Micaela C; Vermeulen, Nico P E; Maat, Evelina; Groot, Ed J; Brouwer, Abraham; Kester, Monique H A; Visser, Theo J; Meerman, John H N

    2005-11-01

    Exposure of humans and wildlife to xenobiotics, such as halogenated biphenyls, that interfere with the endogenous estrogen balance may lead to endocrine disruption. Such compounds may either mimic or block estradiol's action by agonistic or antagonistic action, respectively. They may also affect endogenous estradiol concentrations by induction or inhibition of enzymes that metabolize estradiol. In the present study, we demonstrate that estrogenic metabolites of two brominated biphenyls, 2,2'-dibromobiphenyl (2,2'-DBB) and 4,4'-dibromobiphenyl (4,4'-DBB), are formed by rat liver microsomal cytochrome P450 (CYP) activity. Bioactivation of 2,2'-DBB and 4,4'-DBB yielded various mono- and dihydroxylated bromobiphenyl metabolites, which were collected by preparative HPLC and analyzed by LC/MS. Several of the metabolites bound to the estrogen receptor (ER) activated the ER and inhibited human estrogen sulfotransferase (hEST). Seven monohydroxylated metabolites were positively identified using synthetic monohydroxylated reference compounds. These synthetic monohydroxylated bromobiphenyls also bound to and activated the ER and inhibited hEST. The highest ER affinity was observed for 4-OH-2,2'-DBB, with an EC50 of 6.6 nM. The highest ER activation was observed for 4-OH-3,4'-DBB (EC50 of 74 nM) while 4-OH-4'-MBB and 4-OH-2,2'-DBB induced a supramaximal (as compared to estradiol) ER activation. The strongest hEST inhibition was found with 4-OH-3,4'-DBB (EC50 = 40 nM). In conclusion, we show that two dibrominated biphenyls are bioactivated by CYP activity into very potent estrogenic metabolites and inhibitors of hEST. These findings are of vital importance for accurate risk assessment of exposure to environmental contaminants, such as halogenated biphenyls. Neglecting bioactivation through biotransformation will lead to underestimation of health risks of this class of xenobiotics.

  1. Metabolism of 20(S)-Ginsenoside Rg₂ by Rat Liver Microsomes: Bioactivation to SIRT1-Activating Metabolites.

    PubMed

    Ma, Li-Yuan; Zhou, Qi-Le; Yang, Xin-Bao; Wang, Hong-Ping; Yang, Xiu-Wei

    2016-06-10

    20(S)-Ginsenoside Rg₂ (1) has recently become a hot research topic due to its potent bioactivities and abundance in natural sources such as the roots, rhizomes and stems-leaves of Panax ginseng. However, due to the lack of studies on systematic metabolic profiles, the prospects for new drug development of 1 are still difficult to predict, which has become a huge obstacle for its safe clinical use. To solve this problem, investigation of the metabolic profiles of 1 in rat liver microsomes was first carried out. To identify metabolites, a strategy of combined analyses based on prepared metabolites by column chromatography and ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was performed. As a result, four metabolites M1-M4, including a rare new compound named ginsenotransmetin A (M1), were isolated and the structures were confirmed by spectroscopic analyses. A series of metabolites of 1, MA-MG, were also tentatively identified by UPLC-Q-TOF/MS in rat liver microsomal incubate of 1. Partial metabolic pathways were proposed. Among them, 1 and its metabolites M1, M3 and M4 were discovered for the first time to be activators of SIRT1. The SIRT1 activating effects of the metabolite M1 was comparable to those of 1, while the most interesting SIRT1 activatory effects of M3 and M4 were higher than that of 1 and comparable with that of resveratrol, a positive SIRT1 activator. These results indicate that microsome-dependent metabolism may represent a bioactivation pathway for 1. This study is the first to report the metabolic profiles of 1 in vitro, and the results provide an experimental foundation to better understand the in vivo metabolic fate of 1.

  2. FLAG tagging by CuAAC and nanogram-scale purification of the target protein for a bioactive metabolite involved in circadian rhythmic leaf movement in Leguminosae.

    PubMed

    Manabe, Yoshiyuki; Mukai, Makoto; Ito, Satoko; Kato, Nobuki; Ueda, Minoru

    2010-01-21

    We report a stepwise FLAG-tagging strategy for the purification of target proteins for bioactive metabolites. This method realizes the microscale purification and identification of target protein from as few as 1 x 10(5) differentiated cells. Using this method, we isolated and identified MetE as a cytosolic target protein of potassium isolespedezate, a metabolite controlling plant nyctinasty.

  3. Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites.

    PubMed

    Monagas, Maria; Urpi-Sarda, Mireia; Sánchez-Patán, Fernando; Llorach, Rafael; Garrido, Ignacio; Gómez-Cordovés, Carmen; Andres-Lacueva, Cristina; Bartolomé, Begoña

    2010-12-01

    Flavan-3-ols, occurring in monomeric, as well as in oligomeric and polymeric forms (also known as condensed tannins or proanthocyanidins), are among the most abundant and bioactive dietary polyphenols, but their in vivo health effects in humans may be limited because of their recognition as xenobiotics. Bioavailability of flavan-3-ols is largely influenced by their degree of polymerization; while monomers are readily absorbed in the small intestine, oligomers and polymers need to be biotransformed by the colonic microbiota before absorption. Therefore, phenolic metabolites, rather than the original high molecular weight compounds found in foods, may be responsible for the health effects derived from flavan-3-ol consumption. Flavan-3-ol phenolic metabolites differ in structure, amount and excretion site. Phase II or tissular metabolites derived from the small intestine and hepatic metabolism are presented as conjugated derivatives (glucuronic acid or sulfate esters, methyl ether, or their combined forms) of monomeric flavan-3-ols and are preferentially eliminated in the bile, whereas microbial metabolites are rather simple conjugated lactones and phenolic acids that are largely excreted in urine. Although the colon is seen as an important organ for the metabolism of flavan-3-ols, the microbial catabolic pathways of these compounds are still under consideration, partly due to the lack of identification of bacteria with such capacity. Studies performed with synthesized or isolated phase II conjugated metabolites have revealed that they could have an effect beyond their antioxidant properties, by interacting with signalling pathways implicated in important processes involved in the development of diseases, among other bioactivities. However, the biological properties of microbe-derived metabolites in their actual conjugated forms remain largely unknown. Currently, there is an increasing interest in their effects on intestinal infections, inflammatory intestinal

  4. A preliminary study of the algicidal mechanism of bioactive metabolites of Brevibacillus laterosporus on Oscillatoria in prawn ponds.

    PubMed

    Jia, Wen; Huang, Xianghu; Li, Changling

    2014-01-01

    The algae, Oscillatoria, is commonly found in prawn ponds and can lead to reduced productivity. We examined metabolites of the bacteria Brevibacillus laterosporus for algicidal qualities. To determine the possible algicidal mechanisms of these bioactive metabolites, different amounts of sterile filtrate of bacterial suspensions were added to cultures containing Oscillatoria. The dry weight, the concentrations of chlorophyll-a (chl-a), phycobiliprotein (PC, phycocyanin; APC, allophycocyanin; PE, phycoerythrin), and MDA (malondialdehyde) and the activities of SOD (superoxide dismutase), POD (peroxidase), and CAT (catalase) of algae were measured during the algicidal application. The results showed that lower concentrations of the sterile filtrate (addition ≤ 4 mL) accelerated the growth rate of Oscillatoria, but significant inhibition and lysis were observed with higher concentrations (addition ≥ 8 mL). In two trials (the additions were 8 mL and 10 mL, respectively), the algal dry weights were reduced by 26.02% and 45.30%, and the chl-a concentrations were decreased by 46.88% and 63.73%, respectively, after seven days. During the algicidal treatment, the concentrations of PC, APC, PE, and MDA and the activities of SOD, POD, and CAT were significantly increased in the early cultivation and declined quickly at later stages. Finally, the algae-lysing mechanism of the bioactive metabolites of the bacteria Brevibacillus laterosporus on Oscillatoria had been proposed.

  5. A Preliminary Study of the Algicidal Mechanism of Bioactive Metabolites of Brevibacillus laterosporus on Oscillatoria in Prawn Ponds

    PubMed Central

    Jia, Wen; Huang, Xianghu; Li, Changling

    2014-01-01

    The algae, Oscillatoria, is commonly found in prawn ponds and can lead to reduced productivity. We examined metabolites of the bacteria Brevibacillus laterosporus for algicidal qualities. To determine the possible algicidal mechanisms of these bioactive metabolites, different amounts of sterile filtrate of bacterial suspensions were added to cultures containing Oscillatoria. The dry weight, the concentrations of chlorophyll-a (chl-a), phycobiliprotein (PC, phycocyanin; APC, allophycocyanin; PE, phycoerythrin), and MDA (malondialdehyde) and the activities of SOD (superoxide dismutase), POD (peroxidase), and CAT (catalase) of algae were measured during the algicidal application. The results showed that lower concentrations of the sterile filtrate (addition ≤ 4 mL) accelerated the growth rate of Oscillatoria, but significant inhibition and lysis were observed with higher concentrations (addition ≥ 8 mL). In two trials (the additions were 8 mL and 10 mL, respectively), the algal dry weights were reduced by 26.02% and 45.30%, and the chl-a concentrations were decreased by 46.88% and 63.73%, respectively, after seven days. During the algicidal treatment, the concentrations of PC, APC, PE, and MDA and the activities of SOD, POD, and CAT were significantly increased in the early cultivation and declined quickly at later stages. Finally, the algae-lysing mechanism of the bioactive metabolites of the bacteria Brevibacillus laterosporus on Oscillatoria had been proposed. PMID:24744687

  6. A Review of Cyanobacterial Odorous and Bioactive Metabolites: Impacts and Management Alternatives in Aquaculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An increased demand has pushed extensive aquaculture towards intensively operated production systems, commonly resulting in eutrophic conditions and cyanobacterial blooms. This review summarizes cyanobacterial secondary metabolites that can cause undesirable tastes and odors (odorous metabolites) o...

  7. Optimization of cell disruption methods for efficient recovery of bioactive metabolites via NMR of three freshwater microalgae (chlorophyta).

    PubMed

    Ma, Nyuk Ling; Teh, Kit Yinn; Lam, Su Shiung; Kaben, Anne Marie; Cha, Thye San

    2015-08-01

    This study demonstrates the use of NMR techniques coupled with chemometric analysis as a high throughput data mining method to identify and examine the efficiency of different disruption techniques tested on microalgae (Chlorella variabilis, Scenedesmus regularis and Ankistrodesmus gracilis). The yield and chemical diversity from the disruptions together with the effects of pre-oven and pre-freeze drying prior to disruption techniques were discussed. HCl extraction showed the highest recovery of oil compounds from the disrupted microalgae (up to 90%). In contrast, NMR analysis showed the highest intensity of bioactive metabolites obtained for homogenized extracts pre-treated with freeze-drying, indicating that homogenizing is a more favorable approach to recover bioactive substances from the disrupted microalgae. The results show the potential of NMR as a useful metabolic fingerprinting tool for assessing compound diversity in complex microalgae extracts.

  8. Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the “Supply Problem”

    PubMed Central

    Gomes, Nelson G. M.; Dasari, Ramesh; Chandra, Sunena; Kiss, Robert; Kornienko, Alexander

    2016-01-01

    Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and clinical development. Thus, the lack of a sustainable large-scale supply has been an important challenge facing chemists and biologists involved in marine-based drug discovery. In the current review we describe the main strategies aimed to overcome the supply problem. These include: marine invertebrate aquaculture, invertebrate and symbiont cell culture, culture-independent strategies, total chemical synthesis, semi-synthesis, and a number of hybrid strategies. We provide examples illustrating the application of these strategies for the supply of marine invertebrate-derived anticancer agents. Finally, we encourage the scientific community to develop scalable methods to obtain selected metabolites, which in the authors’ opinion should be pursued due to their most promising anticancer activities. PMID:27213412

  9. Validation of determination of plasma metabolites derived from thyme bioactive compounds by improved liquid chromatography coupled to tandem mass spectrometry.

    PubMed

    Rubió, Laura; Serra, Aida; Macià, Alba; Borràs, Xenia; Romero, Maria-Paz; Motilva, Maria-José

    2012-09-15

    In the present study, a selective and sensitive method, based on microelution solid-phase extraction (μSPE) plate and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) was validated and applied to determine the plasma metabolites of the bioactive compounds of thyme. For validation process, standards of the more representative components of the phenolic and monoterpene fractions of thyme were spiked in plasma samples and then the quality parameters of the method were studied. Extraction recoveries (%R) of the studied compounds were higher than 75%, and the matrix effect (%ME) was lower than 18%. The LODs ranged from 1 to 65 μg/L, except for the thymol sulfate metabolite, which was 240 μg/L. This method was then applied for the analysis of rat plasma obtained at different times, from 0 to 6h, after an acute intake of thyme extract (5 g/kg body weight). Different thyme metabolites were identified and were mainly derived from rosmarinic acid (coumaric acid sulfate, caffeic acid sulfate, ferulic acid sulfate, hydroxyphenylpropionic acid sulfate, dihydroxyphenylpropionic acid sulfate and hydroxybenzoic acid) and thymol (thymol sulfate and thymol glucuronide). The most abundant thyme metabolites generated were hydroxyphenylpropionic acid sulfate and thymol sulfate, their respective concentrations in plasma being 446 and 8464 μM 1h after the intake of the thyme extract.

  10. Chemometrics-enhanced high performance liquid chromatography-ultraviolet detection of bioactive metabolites from phytochemically unknown plants.

    PubMed

    Alvarez-Zapata, Radamés; Sánchez-Medina, Alberto; Chan-Bacab, Manuel; García-Sosa, Karlina; Escalante-Erosa, Fabiola; García-Rodríguez, Rosa Virginia; Peña-Rodríguez, Luis Manuel

    2015-11-27

    This work describes the use of Colubrina greggii as a model to investigate the use of chemometric analysis combined with data from a leishmanicidal bioassay, using Principal Component Analysis (PCA) and Orthogonal Projections to Latent Structures (O-PLS), to detect biologically active natural products in crude extracts from plants having little or no phytochemical information. A first analysis of the HPLC-UV profiles of the extract and its semi-purified fractions using both Principal Component Analysis (PCA) and Orthogonal Partial Least Squares (O-PLS) indicated that the components at tR 48.2, 48.7, 51.8min correlated with the variation in bioactivity. However, a further O-PLS analysis of the HPLC-UV profiles of fractions obtained through a final semi-preparative HPLC purification showed two components at tR 48.7 and 49.5min which correlated with the variation of the bioactivity in a high performance predictive model, with high determination coefficient, high correlation coefficient values (R(2) and Q(2)=0.99) and a low root mean square error (RMSE=0.018). This study demonstrates that the association of chemometric analysis with bioassay results can be an excellent strategy for the detection and isolation of bioactive metabolites from phytochemically unknown plant crude extracts.

  11. Bioactive compounds or metabolites from black raspberries modulate T lymphocyte proliferation, myeloid cell differentiation and Jak/STAT signaling

    PubMed Central

    Mace, Thomas A.; King, Samantha A.; Ameen, Zeenath; Elnaggar, Omar; Young, Gregory; Riedl, Kenneth M.; Schwartz, Steven J.; Clinton, Steven K.; Knobloch, Thomas J.; Weghorst, Christopher M.; Lesinski, Gregory B.

    2014-01-01

    Bioactive phyotochemicals from natural products, such as black raspberries (BRB; Rubus occidentalis) have direct anti-cancer properties on malignant cells in culture and in xenograft models. BRB components inhibit cancer progression in more complex rodent carcinogenesis models. Although mechanistic targets for BRB phytochemicals in cancer cells are beginning to emerge, the potential role in modulating host immune processes impacting cancer have not been systematically examined. We hypothesized that BRB contain compounds capable of eliciting potent immunomodulatory properties that impact cellular mediators relevant to chronic inflammation and tumor progression. We studied both an ethanol extract from black raspberries (BRB-E) containing a diverse mixture of phytochemicals and two abundant phytochemical metabolites of BRB produced upon ingestion (Cyanidin-3-Rutinoside, C3R; Quercitin-3-Rutinoside, Q3R). BRB-E inhibited proliferation and viability of CD3/CD28 activated human CD4+ and CD8+ T lymphocytes. BRB-E also limited in vitro expansion of myeloid-derived suppressor cells (MDSC) and their suppressive capacity. Pre-treatment of immune cells with BRB-E attenuated IL-6-mediated phosphorylation of signal transducer and activator of transcription-3 (STAT3) and IL-2 induced STAT5 phosphorylation. In contrast, pre-treatment of immune cells with the C3R and Q3R metabolites inhibited MDSC expansion, IL-6-mediated STAT3 signaling, but not IL-2 induced STAT5 phosphorylation and were less potent inhibitors of T cell viability. Together these data indicate that BRB extracts and their physiologically-relevant metabolites contain phytochemicals that affect immune processes relevant to carcinogenesis and immunotherapy. Furthermore, specific BRB components and their metabolites may be a source of lead compounds for drug development that exhibit targeted immunological outcomes or inhibition of specific STAT-regulated signaling pathways. PMID:24893859

  12. Bioactive compounds or metabolites from black raspberries modulate T lymphocyte proliferation, myeloid cell differentiation and Jak/STAT signaling.

    PubMed

    Mace, Thomas A; King, Samantha A; Ameen, Zeenath; Elnaggar, Omar; Young, Gregory; Riedl, Kenneth M; Schwartz, Steven J; Clinton, Steven K; Knobloch, Thomas J; Weghorst, Christopher M; Lesinski, Gregory B

    2014-09-01

    Bioactive phytochemicals from natural products, such as black raspberries (BRB; Rubus occidentalis), have direct anticancer properties on malignant cells in culture and in xenograft models. BRB components inhibit cancer progression in more complex rodent carcinogenesis models. Although mechanistic targets for BRB phytochemicals in cancer cells are beginning to emerge, the potential role in modulating host immune processes impacting cancer have not been systematically examined. We hypothesized that BRB contain compounds capable of eliciting potent immunomodulatory properties that impact cellular mediators relevant to chronic inflammation and tumor progression. We studied both an ethanol extract from black raspberries (BRB-E) containing a diverse mixture of phytochemicals and two abundant phytochemical metabolites of BRB produced upon ingestion (Cyanidin-3-Rutinoside, C3R; Quercitin-3-Rutinoside, Q3R). BRB-E inhibited proliferation, and viability of CD3/CD28 activated human CD4(+) and CD8(+) T lymphocytes. BRB-E also limited in vitro expansion of myeloid-derived suppressor cells (MDSC) and their suppressive capacity. Pre-treatment of immune cells with BRB-E attenuated IL-6-mediated phosphorylation of signal transducer and activator of transcription-3 (STAT3) and IL-2-induced STAT5 phosphorylation. In contrast, pre-treatment of immune cells with the C3R and Q3R metabolites inhibited MDSC expansion, IL-6-mediated STAT3 signaling, but not IL-2-induced STAT5 phosphorylation and were less potent inhibitors of T cell viability. Together these data indicate that BRB extracts and their physiologically relevant metabolites contain phytochemicals that affect immune processes relevant to carcinogenesis and immunotherapy. Furthermore, specific BRB components and their metabolites may be a source of lead compounds for drug development that exhibits targeted immunological outcomes or inhibition of specific STAT-regulated signaling pathways.

  13. Correlation between species-specific metabolite profiles and bioactivities of blueberries (Vaccinium spp.).

    PubMed

    Lee, Sarah; Jung, Eun Sung; Do, Seon-Gil; Jung, Ga-Young; Song, Gwanpil; Song, Jung-Min; Lee, Choong Hwan

    2014-03-05

    Metabolite profiling of three blueberry species (Vaccinium bracteatum Thunb., V. oldhamii Miquel., and V. corymbosum L.) was performed using gas chromatography-time-of-flight-mass spectrometry (GC-TOF-MS) and ultraperformance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) combined multivariate analysis. Partial least-squares discriminant analysis clearly showed metabolic differences among species. GC-TOF-MS analysis revealed significant differences in amino acids, organic acids, fatty acids, sugars, and phenolic acids among the three blueberry species. UPLC-Q-TOF-MS analysis indicated that anthocyanins were the major metabolites distinguishing V. bracteatum from V. oldhamii. The contents of anthocyanins such as glycosides of cyanidin were high in V. bracteatum, while glycosides of delphinidin, petunidin, and malvidin were high in V. oldhamii. Antioxidant activities assessed using ABTS and DPPH assays showed the greatest activity in V. oldhamii and revealed the highest correlation with total phenolic, total flavonoid, and total anthocyanin contents and their metabolites.

  14. Pesticides and their metabolites in selected surface-water public supplies in New York State, 1999

    USGS Publications Warehouse

    Phillips, Patrick J.; Eckhardt, D.A.; Smith, M.A.; Rosenmann, Larry

    2000-01-01

    Sixteen different pesticides or their metabolites (degradations products) where detected in water samples collected in 1999 from three networks of lakes and reservoirs in upstate New York that are sources of public water supply. The networks sampled included the New York City network (10 reservoirs); the Finger Lakes-Great Lakes network (three Finger Lakes and two Great Lakes that supply large and small cities) and the western New York reservoir network (three reservoirs that supply small cities or towns). The concentrations of the compounds detected in the samples generally were low. Only a few of the compounds detected had a concentration exceeding 1 mg/L (microgram per liter), and no compounds detected in the New York City reservoirs network had concentrations exceeding 0.05 mg/L. None of the compounds detected exceeded any Federal or State water-quality standard. Compounds that were most frequently detected, and whose concentrations were highest, were the three herbicides atrazine, metolachlor, and simazine, and two herbicide metabolites (the atrazine metabolite deethylatrazine, and the metolachlor metabolite metolachlor ESA). Most of these compounds, or their parent compounds, are used on corn or other row crops. Median total pesticide and metabolite concentration for each network ranged from less than 0.02 mg/L for the New York City reservoirs network to more than 2 mg/L for the western New York reservoir network; the median for the Finger Lakes.Great Lakes network was about 0.1 mg/L. These differences reflect the amount of agricultural land use within each of the three networks, although other factors can affect pesticide and metabolite concentrations. The watersheds of the New York City reservoirs have the lowest percentage of agricultural land, and those of the western New York reservoirs have the highest. The highest herbicide or herbicide-metabolite concentrations among the New York City reservoirs were in the Cannonsville reservoir, whose watershed has

  15. Bioactive natural products from fungicolous Hawaiian isolates: secondary metabolites from a Phialemoniopsis sp.

    PubMed Central

    Kaur, Amninder; Rogers, Kristina D.; Swenson, Dale E.; Dowd, Patrick F.; Wicklow, Donald T.; Gloer, James B.

    2014-01-01

    Chemical investigations of two fungal isolates initially identified as members of the genus Phialemonium are described. Both isolates were obtained as colonists of other fungi collected on the island of Hawaii and were later assigned as P. curvatum. However, P. curvatum has recently been reclassified as a member of a new genus (Phialemoniopsis) and renamed as Phialemoniopsis curvata. Studies of solid–substrate fermentation cultures of one of these isolates afforded an oxirapentyn analogue and destruxin A4 as major components, while analysis of the second strain led to the isolation of several simple aromatic metabolites and a compound of mixed biogenetic origin called gabusectin that had previously been reported only in a patent. Structures were assigned mainly by detailed nuclear magnetic resonance and mass spectrometry analysis, and those of two of the major components were confirmed by X-ray crystallography. This report constitutes the first description of secondary metabolites from a member of the genus Phialemoniopsis. PMID:25379336

  16. Characterization and Optimization of Biosynthesis of Bioactive Secondary Metabolites Produced by Streptomyces sp. 8812.

    PubMed

    Rajnisz, Aleksandra; Guśpiel, Adam; Postek, Magdalena; Ziemska, Joanna; Laskowska, Anna; Rabczenko, Daniel; Solecka, Jolanta

    2016-01-01

    The nutritional requirements and environmental conditions for a submerged culture of Streptomyces sp. 8812 were determined. Batch and fed-batch Streptomyces sp. 8812 fermentations were conducted to obtain high activity of secondary metabolites. In the study several factors were examined for their influence on the biosynthesis of the active metabolites-7-hydroxy-6-oxo-2,3,4,6-tetrahydroisoquinoline-3-carboxy acid (C10H9NO4) and N-acetyl-3,4-dihydroxy-L-phenylalanine (C11H13NO5): changes in medium composition, pH of production medium, various growth phases of seed culture, amino acid supplementation and addition of anion exchange resin to the submerged culture. Biological activities of secondary metabolites were examined with the use of DD-carboxypeptidase 64-575 and horseradish peroxidase. Streptomyces sp. 8812 mycelium was evaluated under fluorescent microscopy and respiratory activity of the strain was analyzed. Moreover, the enzymatic profiles of the strain with the use of Api ZYM test were analyzed and genetic analysis made. Phylogenetic analysis of Streptomyces sp. 8812 revealed that its closest relative is Streptomyces capoamus JCM 4734 (98%), whereas sequence analysis for 16S rRNA gene using NCBI BLAST algorithm showed 100% homology between these two strains. Biosynthetic processes, mycelium growth and enzyme inhibitory activities of these two strains were also compared.

  17. Bioactivation of Trimethoprim to Protein-Reactive Metabolites in Human Liver Microsomes.

    PubMed

    Goldman, Jennifer L; Koen, Yakov M; Rogers, Steven A; Li, Kelin; Leeder, James S; Hanzlik, Robert P

    2016-10-01

    The formation of drug-protein adducts via metabolic activation and covalent binding may stimulate an immune response or may result in direct cell toxicity. Protein covalent binding is a potentially pivotal step in the development of idiosyncratic adverse drug reactions (IADRs). Trimethoprim (TMP)-sulfamethoxazole (SMX) is a combination antibiotic that commonly causes IADRs. Recent data suggest that the contribution of the TMP component of TMP-SMX to IADRs may be underappreciated. We previously demonstrated that TMP is bioactivated to chemically reactive intermediates that can be trapped in vitro by N-acetyl cysteine (NAC), and we have detected TMP-NAC adducts (i.e., mercapturic acids) in the urine of patients taking TMP-SMX. However, the occurrence and extent of TMP covalent binding to proteins was unknown. To determine the ability of TMP to form protein adducts, we incubated [(14)C]TMP with human liver microsomes in the presence and absence of NADPH. We observed protein covalent binding that was NADPH dependent and increased with incubation time and concentration of both protein and TMP. The estimated covalent binding was 0.8 nmol Eq TMP/mg protein, which is comparable to the level of covalent binding for several other drugs that have been associated with covalent binding-induced toxicity and/or IADRs. NAC and selective inhibitors of CYP2B6 and CYP3A4 significantly reduced TMP covalent binding. These results demonstrate for the first time that TMP bioactivation can lead directly to protein adduct formation, suggesting that TMP has been overlooked as a potential contributor of TMP-SMX IADRs.

  18. Bioactive metabolites produced by Chaetomium globosum, an endophytic fungus isolated from Ginkgo biloba.

    PubMed

    Qin, Jian-Chun; Zhang, Ya-Mei; Gao, Jin-Ming; Bai, Ming-Sheng; Yang, Sheng-Xiang; Laatsch, Hartmut; Zhang, An-Ling

    2009-03-15

    A novel cytotoxic chlorinated azaphilone derivative named chaetomugilin D (1), together with three known metabolites, chaetomugilin A (2), chaetoglobosins A (3) and C (4), has been isolated by a bioassay-guided fractionation from the EtOAc extract of the cultures of Chaetomium globosum, an endophytic fungus found in the leaves of Ginkgo biloba. Structure of 1 was established by analyses of spectroscopic methods, including 2D-NMR experiments (COSY, NOESY, HMQC, and HMBC). Compounds 1-4 displayed significant growth inhibitory activity against the brine shrimp (Artemia salina) and Mucor miehei.

  19. Filamentous fungi from extreme environments as a promising source of novel bioactive secondary metabolites

    PubMed Central

    Chávez, Renato; Fierro, Francisco; García-Rico, Ramón O.; Vaca, Inmaculada

    2015-01-01

    Natural product search is undergoing resurgence upon the discovery of a huge previously unknown potential for secondary metabolite (SM) production hidden in microbial genomes. This is also the case for filamentous fungi, since their genomes contain a high number of “orphan” SM gene clusters. Recent estimates indicate that only 5% of existing fungal species have been described, thus the potential for the discovery of novel metabolites in fungi is huge. In this context, fungi thriving in harsh environments are of particular interest since they are outstanding producers of unusual chemical structures. At present, there are around 16 genomes from extreme environment-isolated fungi in databases. In a preliminary analysis of three of these genomes we found that several of the predicted SM gene clusters are probably involved in the biosynthesis of compounds not yet described. Genome mining strategies allow the exploitation of the information in genome sequences for the discovery of new natural compounds. The synergy between genome mining strategies and the expected abundance of SMs in fungi from extreme environments is a promising path to discover new natural compounds as a source of medically useful drugs. PMID:26441853

  20. In vitro metabolism studies of nomifensine monooxygenation pathways: metabolite identification, reaction phenotyping, and bioactivation mechanism.

    PubMed

    Yu, Jian; Brown, Dean G; Burdette, Doug

    2010-10-01

    Multiple GSH adducts of the oxidative products of nomifensine (M1-M9) in human hepatocytes and liver microsomes have been identified recently. The current study reports three new types of monooxygenated metabolites of nomifensine identified in human liver microsomes: C-linked hydroxylated metabolites with modifications at the A ring (H1 and H4), an N-hydroxylamine (H6), and nomifensine N-oxides (H7 and H8). GSH conjugate formation in incubates containing cDNA-expressed P450s and GSH suggests that nomifensine GSH-sulfinamides (M1 and M2) are formed through the reaction between GSH and the oxidative product of H6. C-linked GSH conjugates M3, M4, M5, and M6 are probably formed via nomifensine benzoquinone imine intermediates via H4 and/or nomifensine epoxides. C-linked GSH conjugates M7, M8, and M9 are probably formed through similar mechanisms via H1. Nomifensine N-oxides do not form reactive metabolites that react with GSH. In vitro metabolism studies using a panel of cDNA-expressed human P450 and flavin monooxygenase (FMO) isoforms (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, FMO1, FMO3, and FMO5) indicated that CYP3A4, CYP2C19, and CYP2B6 generate the largest quantities of H1, H4, and H6, respectively. H7 and H8 are formed almost exclusively by FMOs. The contribution of the individual P450s involved in the formation of H1, H4, and H6 in human liver microsomes was confirmed by the inhibition of product formation by monoclonal anti-cytochrome 450 antibodies. These results showed that CYP3A4 and CYP2B6 contributed primarily to the formation of H1 and H6, respectively. CYP2C19 and CYP1A2 seemed to contribute significantly to the formation of H4.

  1. Metabolites of ginger component [6]-shogaol remain bioactive in cancer cells and have low toxicity in normal cells: chemical synthesis and biological evaluation.

    PubMed

    Zhu, Yingdong; Warin, Renaud F; Soroka, Dominique N; Chen, Huadong; Sang, Shengmin

    2013-01-01

    Our previous study found that [6]-shogaol, a major bioactive component in ginger, is extensively metabolized in cancer cells and in mice. It is unclear whether these metabolites retain bioactivity. The aim of the current study is to synthesize the major metabolites of [6]-shogaol and evaluate their inhibition of growth and induction of apoptosis in human cancer cells. Twelve metabolites of [6]-shogaol (M1, M2, and M4-M13) were successfully synthesized using simple and easily accessible chemical methods. Growth inhibition assays showed that most metabolites of [6]-shogaol had measurable activities against human cancer cells HCT-116 and H-1299. In particular, metabolite M2 greatly retained the biological activities of [6]-shogaol, with an IC(50) of 24.43 µM in HCT-116 human colon cancer cells and an IC(50) of 25.82 µM in H-1299 human lung cancer cells. Also exhibiting a relatively high potency was thiol-conjugate M13, with IC(50) values of 45.47 and 47.77 µM toward HCT-116 and H-1299 cells, respectively. The toxicity evaluation of the synthetic metabolites (M1, M2, and M4-M13) against human normal fibroblast colon cells CCD-18Co and human normal lung cells IMR-90 demonstrated a detoxifying metabolic biotransformation of [6]-shogaol. The most active metabolite M2 had almost no toxicity to CCD-18Co and IMR-90 normal cells with IC(50)s of 99.18 and 98.30 µM, respectively. TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) assay indicated that apoptosis was triggered by metabolites M2, M13, and its two diastereomers M13-1 and M13-2. There was no significant difference between the apoptotic effect of [6]-shogaol and the effect of M2 and M13 after 6 hour treatment.

  2. [Bioactivity of endophytic actinomycetes from medicinal plants and secondary metabolites from strain D62].

    PubMed

    Liu, Ning; Zhang, Hui; Zheng, Wen; Huang, Ying; Wang, Hai-Bin

    2007-10-01

    It is believed that genetic recombination of the endophytes with the hosts that occurred in evolutionary time could result in some endophytes producing certain phytochemical originally characteristic of the host. Based on this widely accepted hypothesis, there have been increasing research efforts focused on screening for novel natural products from endophytes. In this study, antimicrobial and antitumor activities of 165 actinomycetes isolated from medicinal plants collected from Xishuangbanna were tested by agar diffusion method and WST-8 assay respectively. The results showed that over 42% of the isolates exhibited antagonism against pathogenic strains, and 54.5% displayed excellent inhibition against mouse melanoma cell line B16 or/and human alveolar epithelial cell line A549. These results are superior to those of soil actinomycetes, indicating tremendous potential of endophytic of actinomycetes for exploration. Six compounds that had both antimicrobial and antitumor activities were separated and purified from isolate Streptomyces sp. D62 by resin adsorption, silica-gel column and sephadex chromatography, etc. On the basis of spectral analyses, they were identified as antimycin A4a (1), antimycin A7a (2), antimycin A2a (3), antimycin A1a (4), 10-hydroxy-10-methyl-dodec-2-en-1,4-olide (5) and 6-(2-(4-aminophenyl)-2-oxoethyl)-3,5-dimethyl-tetrahydropyran-2-one(6), with the last one defined as a novel compound. Based on all these results, it is convinced that endophytic actinomycetes are a promising resource for bioactive natural product discovery.

  3. Bioactive Secondary Metabolites from the Red Sea Marine Verongid Sponge Suberea Species

    PubMed Central

    Shaala, Lamiaa A.; Youssef, Diaa T. A.; Badr, Jihan M.; Sulaiman, Mansour; Khedr, Alaa

    2015-01-01

    In a continuation of our efforts to identify bioactive compounds from Red Sea Verongid sponges, the organic extract of the sponge Suberea species afforded seven compounds including two new dibrominated alkaloids, subereamollines C and D (1 and 2), together with the known compounds aerothionin (3), homoaerothionin (4), aeroplysinin-1 (5), aeroplysinin-2 (6) and a revised subereaphenol C (7) as ethyl 2-(2,4-dibromo-3,6-dihydroxyphenyl)acetate. The structures of the isolated compounds were assigned by different spectral data including optical rotations, 1D (1H and 13C) and 2D (COSY, multiplicity-edited HSQC, and HMBC) NMR and high-resolution mass spectroscopy. Aerothionin (3) and subereaphenol C (7) displayed potent cytotoxic activity against HeLa cell line with IC50 values of 29 and 13.3 µM, respectively. In addition, aeroplysinin-2 (6) showed potent antimigratory activity against the human breast cancer cell line MDA-MB-231 with IC50 of 18 µM. Subereamollines C and D are new congeners of the previously reported compounds subereamollines A and B with methyl ester functionalities on the side chain. These findings provide further insight into the biosynthetic capabilities of members of the genus Suberea and the chemical diversity as well as the biological activity of these compounds. PMID:25812033

  4. In vitro adrenal bioactivation and effects on steroid metabolism of DDT, PCBs and their metabolites in the gray seal (Halichoerus grypus)

    SciTech Connect

    Lund, B.O. . Dept. of Pharmacology and Toxicology)

    1994-06-01

    The irreversible binding of the DDT metabolites o,p[prime]-DDD [2-(2-chlorophenyl)-2(4-chlorophenyl)-1,1-dichloroethane] and MeSO[sub 2]-DDE [3-methylsulfonyl-2,2-bis(4-chlorophenyl)-1,1-dichloroethene], as well as their potential to inhibit mitochondrial steroid 11[beta]-hydroxylation in the gray seal adrenal gland, was studied. The adrenal bioactivated both o,p[prime]-DDD and MeSO[sub 2[minus

  5. Multiplexed site-specific genome engineering for overproducing bioactive secondary metabolites in actinomycetes.

    PubMed

    Li, Lei; Zheng, Guosong; Chen, Jun; Ge, Mei; Jiang, Weihong; Lu, Yinhua

    2017-03-01

    Actinomycetes produce a large variety of pharmaceutically active compounds, yet production titers often require to be improved for discovery, development and large-scale manufacturing. Here, we describe a new technique, multiplexed site-specific genome engineering (MSGE) via the 'one integrase-multiple attB sites' concept, for the stable integration of secondary metabolite biosynthetic gene clusters (BGCs). Using MSGE, we achieved five-copy chromosomal integration of the pristinamycin II (PII) BGC in Streptomyces pristinaespiralis, resulting in the highest reported PII titers in flask and batch fermentations (2.2 and 2g/L, respectively). Furthermore, MSGE was successfully extended to develop a panel of powerful Streptomyces coelicolor heterologous hosts, in which up to four copies of the BGCs for chloramphenicol or anti-tumour compound YM-216391 were efficiently integrated in a single step, leading to significantly elevated productivity (2-23 times). Our multiplexed approach holds great potential for robust genome engineering of industrial actinomycetes and novel drug discovery by genome mining.

  6. Bioactive Metabolites from Mangrove Endophytic Fungus Aspergillus sp. 16-5B

    PubMed Central

    Liu, Yayue; Chen, Senhua; Liu, Zhaoming; Lu, Yongjun; Xia, Guoping; Liu, Hongju; He, Lei; She, Zhigang

    2015-01-01

    Chemical investigation of the endophytic fungus Aspergillus sp. 16-5B cultured on Czapek’s medium led to the isolation of four new metabolites, aspergifuranone (1), isocoumarin derivatives (±) 2 and (±) 3, and (R)-3-demethylpurpurester A (4), together with the known purpurester B (5) and pestaphthalides A (6). Their structures were determined by analysis of 1D and 2D NMR spectroscopic data. The absolute configuration of Compound 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra, and that of Compound 4 was revealed by comparing its optical rotation data and CD with those of the literature. The structure of Compound 6 was further confirmed by single-crystal X-ray diffraction experiment using CuKα radiation. All isolated compounds were evaluated for their α-glucosidase inhibitory activities, and Compound 1 showed significant inhibitory activity with IC50 value of 9.05 ± 0.60 μM. Kinetic analysis showed that Compound 1 was a noncompetitive inhibitor of α-glucosidase. Compounds 2 and 6 exhibited moderate inhibitory activities. PMID:25996099

  7. Aquaculture of three phyla of marine invertebrates to yield bioactive metabolites: process developments and economics.

    PubMed

    Mendola, Dominick

    2003-07-01

    Large-scale, renewable supplies of chemical constituents derived from marine invertebrates have limited development of potential new natural product drugs. This paper describes the development of two in-sea aquaculture systems designed and engineered for production of large quantities of biomass for two species of marine invertebrates desired for their natural product chemical constituents. The two invertebrates and their products were: (1) the cosmopolitan, arborescent bryozoan Bugula neritina (Phylum Bryozoa) for its anticancer chemical constituent bryostatin 1; and (2) Ecteinascidia turbinate (Phylum Tunicata) the source of anticancer ecteinascidin 743. For the third invertebrate Phylum Porifera, and its representative sponge Acanthella cavernosa (desired for its anti-parasitic and anti-infective kalihinols) in-sea systems were not developed in favor of controlled environment tank aquaculture systems. For the bryozoan and tunicate, projected economics for commercial-scale in-sea production proved cost effective. This was in contrast to the controlled environment sponge culture tank system, which did not prove to be economical due to inherent slow growth and low natural product yields of the sponge in culture. A non-destructive method for "milking" natural product chemicals from sponges was tested and is described.

  8. Pesticides and their metabolites in three small public water-supply reservoir systems, western New York, 1998-99

    USGS Publications Warehouse

    Phillips, Patrick J.; Eckhardt, David A.; Rosenmann, Larry

    2000-01-01

    Twenty five pesticides or pesticide metabolites were detected in samples collected from May, 1998 through January, 1999 in three small public- supply reservoirs in western New York.Samples were collected at tributaries and reservoir outlets for comparison with samples from the water-supply intakes. No samples from public-water-supply intakes exceeded any Federal or State water-quality standards, although some samples from tributaries did exceed a few standards. The maximum concentrations of the most frequently detected pesticides in water-supply intake samples were between 10 and 50 percent of the lowest applicable water quality standard. Pesticides that exceeded water-quality standards at the tributary sites were the herbicides atrazine, alachlor, and cyanazine, and the insecticide p,p?-DDE. Land use in the watersheds that surround these reservoirs is largely agricultural; thus, the results do not necessarily represent conditions in other water-supply reservoirs in New York State. The most frequently detected pesticides or pesticide metabolites were the corn herbicides atrazine and metolachlor, and two metabolites of metolachlor -metolachlor ethanesulfonic acid (ESA)and metolachlor oxanilic acid (OA). More than half of the samples from the three water-supply intake sites contained at least one of these compounds at concentrations greater than 0.2 ?g/L (micrograms per liter); the concentrations ranged from 0.01 to nearly 10 ?g/L. Many samples contained metabolites of other commonly used herbicides at concentrations greater than those of their parent compounds. Only two insecticides or insecticide metabolites were detected (carbofuran and p,p?-DDE and concentrations of these compounds were less than 0.1 ?g/L. The total concentration of pesticides and metabolites at the three water-supply intake sites are correlated with land use. The highest concentrations were in the watershed with the greatest percentage of row-crop land use,and the lowest concentrations were in

  9. A fast method using a new hydrophilic-lipophilic balanced sorbent in combination with ultra-high performance liquid chromatography for quantification of significant bioactive metabolites in wines.

    PubMed

    Silva, Catarina L; Pereira, Jorge; Wouter, Van G; Giró, Carme; Câmara, José S

    2011-10-30

    This manuscript describes the development and validation of an ultra-fast, efficient, and high throughput analytical method based on ultra-high performance liquid chromatography (UHPLC) equipped with a photodiode array (PDA) detection system, for the simultaneous analysis of fifteen bioactive metabolites: gallic acid, protocatechuic acid, (-)-catechin, gentisic acid, (-)-epicatechin, syringic acid, p-coumaric acid, ferulic acid, m-coumaric acid, rutin, trans-resveratrol, myricetin, quercetin, cinnamic acid and kaempferol, in wines. A 50-mm column packed with 1.7-μm particles operating at elevated pressure (UHPLC strategy) was selected to attain ultra-fast analysis and highly efficient separations. In order to reduce the complexity of wine extract and improve the recovery efficiency, a reverse-phase solid-phase extraction (SPE) procedure using as sorbent a new macroporous copolymer made from a balanced ratio of two monomers, the lipophilic divinylbenzene and the hydrophilic N-vinylpyrrolidone (Oasis™ HLB), was performed prior to UHPLC-PDA analysis. The calibration curves of bioactive metabolites showed good linearity within the established range. Limits of detection (LOD) and quantification (LOQ) ranged from 0.006 μg mL(-1) to 0.58 μg mL(-1), and from 0.019 μg mL(-1) to 1.94 μg mL(-1), for gallic and gentisic acids, respectively. The average recoveries ± SD for the three levels of concentration tested (n=9) in red and white wines were, respectively, 89 ± 3% and 90 ± 2%. The repeatability expressed as relative standard deviation (RSD) was below 10% for all the metabolites assayed. The validated method was then applied to red and white wines from different geographical origins (Azores, Canary and Madeira Islands). The most abundant component in the analysed red wines was (-)-epicatechin followed by (-)-catechin and rutin, whereas in white wines syringic and p-coumaric acids were found the major phenolic metabolites. The method was completely validated

  10. Bioactive endophytic fungi isolated from Caesalpinia echinata Lam. (Brazilwood) and identification of beauvericin as a trypanocidal metabolite from Fusarium sp.

    PubMed Central

    Campos, Fernanda Fraga; Sales, Policarpo A; Romanha, Alvaro José; Araújo, Márcio SS; Siqueira, Ezequias P; Resende, Jarbas M; Alves, Tânia MA; Martins-Filho, Olindo A; dos Santos, Vera Lúcia; Rosa, Carlos A; Zani, Carlos L; Cota, Betania Barros

    2015-01-01

    Aiming to identify new sources of bioactive secondary metabolites, we isolated 82 endophytic fungi from stems and barks of the native Brazilian tree Caesalpinia echinata Lam. (Fabaceae). We tested their ethyl acetate extracts in several in vitro assays. The organic extracts from three isolates showed antibacterial activity against Staphylococcus aureus and Escherichia coli [minimal inhibitory concentration (MIC) 32-64 μg/mL]. One isolate inhibited the growth of Salmonella typhimurium (MIC 64 μg/mL) and two isolates inhibited the growth of Klebsiella oxytoca (MIC 64 μg/mL), Candida albicans and Candida tropicalis (MIC 64-128 μg/mL). Fourteen extracts at a concentration of 20 μg/mL showed antitumour activities against human breast cancer and human renal cancer cells, while two isolates showed anti-tumour activities against human melanoma cancer cells. Six extracts were able to reduce the proliferation of human peripheral blood mononuclear cells, indicating some degree of selective toxicity. Four isolates were able to inhibit Leishmania (Leishmania) amazonensis and one isolate inhibited Trypanosoma cruzi by at least 40% at 20 μg/mL. The trypanocidal extract obtained from Fusarium sp. [KF611679] culture was subjected to bioguided fractionation, which revealed beauvericin as the compound responsible for the observed toxicity of Fusarium sp. to T. cruzi. This depsipeptide showed a half maximal inhibitory concentration of 1.9 μg/mL (2.43 μM) in a T. cruzi cellular culture assay. PMID:25742265

  11. Glycolysis and glutaminolysis cooperatively control T cell function by limiting metabolite supply to N-glycosylation

    PubMed Central

    Araujo, Lindsey; Khim, Phillip; Mkhikian, Haik; Mortales, Christie-Lynn; Demetriou, Michael

    2017-01-01

    Rapidly proliferating cells switch from oxidative phosphorylation to aerobic glycolysis plus glutaminolysis, markedly increasing glucose and glutamine catabolism. Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer. DOI: http://dx.doi.org/10.7554/eLife.21330.001 PMID:28059703

  12. Medium modification to enhance the formation of bioactive metabolites in shake flask cultures of Antrodia cinnamomea by adding citrus peel extract.

    PubMed

    Yang, Fan-Chiang; Ma, Te-Wei; Chuang, Ya-Ting

    2012-10-01

    Antrodia cinnamomea has recently become a well-known medicinal mushroom in Taiwan. Bioactive compounds found in A. cinnamomea include: polysaccharide, sesquiterpene lactone, steroids and triterpenoids. The aim of this study was to evaluate the feasibility of adding citrus peel extract to enhance the formation of bioactive metabolites in the submerged culture of A. cinnamomea. With the exception of grapefruit, citrus peel extracts tested were proved to be beneficial to mycelial growth and to the production of intracellular polysaccharide. Lemon was the most effective for enhancing bioactive metabolite production. With an addition of 2% (v/v), the mycelium biomass concentration and intracellular polysaccharide content rose from 11.96 g DW/L of the control and 123.6 mg/g DW to 21.96 g DW/L and 230.8 mg/g DW, respectively, on day 8. The production of triterpenoids also increased from 86.7 to 282.9 mg/L. Moreover, this study also demonstrates that although the addition of peel extract could cause the lengthening of the exponential phase and reduce the specific growth rate, the production rate of biomass, intracellular polysaccharide and triterpenoids was still enhanced significantly.

  13. Identification of bioactive metabolites dihydrocanadensolide, Kojic acid, and vanillic acid in soy sauce using GC-MS, NMR spectroscopy, and single-crystal X-ray diffraction.

    PubMed

    Li, Ying; Teng, Zi; Parkin, Kirk L; Wang, Qin; Zhang, Qingli; Luo, Wei; Ma, Deyun; Zhao, Mouming

    2014-08-20

    Microbial transformations of intrinsic substrates offer immense potential for generating new bioactive compounds in fermented food products. The aim of this work was to characterize the secondary metabolites in soy sauce, one of the oldest fermented condiments. Ethyl acetate extract (EAE) of soy sauce was separated using flash column chromatography, crystallized, and analyzed by nuclear magnetic resonance (NMR), single-crystal X-ray diffraction (SC-XRD), and mass spectroscopy. Dihydrocanadensolide (DHC), an antiulcer agent, was identified in a food for the first time. The natural stereostructure of DHC, which remained controversial for several decades, was determined as (3S,3aS,6R,6aR)-6-butyl-3-methyltetrahydrofuro[3,4-b]furan-2,4-dione using SC-XRD analysis. Kojic acid (KA) and vanillic acid (VA) were also identified from EAE as bioactive metabolic products of fungi and yeasts. Moreover, a new polymorphic form of KA was determined by SC-XRD.

  14. Cytochromes P450 catalyze both steps of the major pathway of clopidogrel bioactivation, whereas paraoxonase catalyzes the formation of a minor thiol metabolite isomer.

    PubMed

    Dansette, Patrick M; Rosi, Julien; Bertho, Gildas; Mansuy, Daniel

    2012-02-20

    The mechanism generally admitted for the bioactivation of the antithrombotic prodrug, clopidogrel, is its two-step enzymatic conversion into a biologically active thiol metabolite. The first step is a classical cytochrome P450 (P450)-dependent monooxygenation of its thiophene ring leading to 2-oxo-clopidogrel, a thiolactone metabolite. The second step was described as a P450-dependent oxidative opening of the thiolactone ring of 2-oxo-clopidogrel, with intermediate formation of a reactive sulfenic acid metabolite that is eventually reduced to the corresponding thiol 4b. A very recent paper published in Nat. Med. (Bouman et al., (2011) 17, 110) reported that the second step of clopidogrel bioactivation was not catalyzed by P450 enzymes but by paraoxonase-1(PON-1) and that PON-1 was a major determinant of clopidogrel efficacy. The results described in the present article show that there are two metabolic pathways for the opening of the thiolactone ring of 2-oxo-clopidogrel. The major one, that was previously described, results from a P450-dependent redox bioactivation of 2-oxo-clopidogrel and leads to 4b cis, two previously reported thiol diastereomers bearing an exocyclic double bond. The second, minor one, results from a hydrolysis of 2-oxo-clopidogrel, which seems to be dependent on PON-1, and leads to an isomer of 4b cis, 4b "endo", in which the double bond has migrated from an exocyclic to an endocyclic position in the piperidine ring. These results were obtained from a detailed study of the metabolism of 2-oxo-clopidogrel by human liver microsomes and human sera and analysis by HPLC-MS under conditions allowing a complete separation of the thiol metabolite isomers, either as such or after derivatization with 3'-methoxy phenacyl bromide or N-ethyl maleimide (NEM). These results also show that the major bioactive thiol isomer found in the plasma of clopidogrel-treated patients derives from 2-oxo-clopidogrel by the P450-dependent pathway. Finally, chemical

  15. Submerged fermentation of the edible mushroom Pleurotus ostreatus in a batch stirred tank bioreactor as a promising alternative for the effective production of bioactive metabolites.

    PubMed

    Papaspyridi, Lefki-Maria; Aligiannis, Nektarios; Topakas, Evangelos; Christakopoulos, Paul; Skaltsounis, Alexandros-Leandros; Fokialakis, Nikolas

    2012-03-06

    The aim of this study was to investigate the potential of the submerged fermentation procedure in the production of bioactive metabolites of the common edible mushroom Pleurotus ostreatus. The biomass of the mushroom strain was produced by submerged fermentation in a batch stirred tank bioreactor and extracted by solvents of increasing polarity. The dichloromethane and methanol extract were fractioned by different techniques including Adsorption Chromatography and Fast Centrifugal Partition Chromatography (FCPC). The structures of pure compounds were elucidated with 1D/2D NMR-spectroscopic analyses, and chemical correlations combined with GC/MS and LC/MS experiments. Nineteen metabolites (e.g., fatty acids, phenolic metabolites, nucleotides and alkaloids) were isolated. Beyond the production of known metabolites, we report herein the production also of trans-3,4-dihydro-3,4,8-trihydroxynapthalen-1(2H)-one, indolo-3-carboxylic acid, 3-formylpyrrole and 4-hydroxybenzoic acid, that have pharmaceutical interest and are isolated for the first time from Pleurotus strains. This work indicates the great potential of the established bioprocess for the production of P. ostreatus mycelia with enhanced metabolic profile.

  16. Bioactive Plant Metabolites in the Management of Non-Communicable Metabolic Diseases: Looking at Opportunities beyond the Horizon

    PubMed Central

    Prasad, Chandan; Imrhan, Victorine; Juma, Shanil; Maziarz, Mindy; Prasad, Anand; Tiernan, Casey; Vijayagopal, Parakat

    2015-01-01

    There has been an unprecedented worldwide rise in non-communicable metabolic diseases (NCDs), particularly cardiovascular diseases (CVD) and diabetes. While modern pharmacotherapy has decreased the mortality in the existing population, it has failed to stem the rise. Furthermore, a large segment of the world population cannot afford expensive pharmacotherapy. Therefore, there is an urgent need for inexpensive preventive measures to control the rise in CVD and diabetes and associated co-morbidities. The purpose of this review is to explore the role of food bioactives in prevention of NCDs. To this end, we have critically analyzed the possible utility of three classes of food bioactives: (a) resistant starch, a metabolically resistant carbohydrate known to favorably modulate insulin secretion and glucose metabolism; (b) cyclo (His-Pro), a food-derived cyclic dipeptides; and (c) polyphenol-rich berries. Finally, we have also briefly outlined the strategies needed to prepare these food-bioactives for human use. PMID:26703752

  17. High-resolution MS, MS/MS, and UV database of fungal secondary metabolites as a dereplication protocol for bioactive natural products.

    PubMed

    El-Elimat, Tamam; Figueroa, Mario; Ehrmann, Brandie M; Cech, Nadja B; Pearce, Cedric J; Oberlies, Nicholas H

    2013-09-27

    A major problem in the discovery of new biologically active compounds from natural products is the reisolation of known compounds. Such reisolations waste time and resources, distracting chemists from more promising leads. To address this problem, dereplication strategies are needed that enable crude extracts to be screened for the presence of known compounds before isolation efforts are initiated. In a project to identify anticancer drug leads from filamentous fungi, a significant dereplication challenge arises, as the taxonomy of the source materials is rarely known, and, thus, the literature cannot be probed to identify likely known compounds. An ultraperformance liquid chromatography-photodiode array-high-resolution tandem mass spectrometric (UPLC-PDA-HRMS-MS/MS) method was developed for dereplication of fungal secondary metabolites in crude culture extracts. A database was constructed by recording HRMS and MS/MS spectra of fungal metabolites, utilizing both positive- and negative-ionization modes. Additional details, such as UV-absorption maxima and retention times, were also recorded. Small-scale cultures that showed cytotoxic activities were dereplicated before engaging in the scale-up or purification processes. Using these methods, approximately 50% of the cytotoxic extracts could be eliminated from further study after the confident identification of known compounds. The specific attributes of this dereplication methodology include a focus on bioactive secondary metabolites from fungi, the use of a 10 min chromatographic method, and the inclusion of both HRMS and MS/MS data.

  18. 4'-Demethylnobiletin, a bioactive metabolite of nobiletin enhancing PKA/ERK/CREB signaling, rescues learning impairment associated with NMDA receptor antagonism via stimulation of the ERK cascade.

    PubMed

    Al Rahim, Md; Nakajima, Akira; Saigusa, Daisuke; Tetsu, Naomi; Maruyama, Yuji; Shibuya, Masatoshi; Yamakoshi, Hiroyuki; Tomioka, Yoshihisa; Iwabuchi, Yoshiharu; Ohizumi, Yasushi; Yamakuni, Tohru

    2009-08-18

    The biochemical and pharmacological activities of nobiletin, including neurotrophic and memory-enhancing action, in both in vitro and in vivo systems are well established. However, whether its metabolites do have such beneficial effects like nobiletin remains to be examined. Here we, for the first time, report that 2-(4-hydroxy-3-methoxyphenyl)-5,6,7,8-tetramethoxychromen-4-one (4'-demethylnobiletin), a major metabolite of nobiletin identified in the urine of rats and mice, stimulates the phosphorylation of ERK and CREB and enhances CRE-mediated transcription by activating a PKA/MEK/ERK pathway, like nobiletin, in cultured hippocampal neurons. Since NMDA receptor-mediated ERK signaling is involved in memory processing, including associative memories, we also examined whether 4'-demethylnobiletin, by activating ERK signaling, could restore learning impairment. Chronic intraperitoneal (ip) treatment of the mice with 10 or 50 mg of 4'-demethylnobiletin/kg rescued the NMDA receptor antagonist MK-801-induced learning impairment, accompanied by improvement of the MK-801-induced decrease in the level of ERK phosphorylation in the hippocampus of the animals. Consistently, 4'-demethylnobiletin also restored MK-801-induced inhibition of NMDA-stimulated phosphorylation of not only ERK but also PKA substrates in cultured rat hippocampal neurons. Moreover, we actually detected 4'-demethylnobiletin in the brain of mice following acute ip administration, demonstrating that the metabolite can cross the blood-brain barrier to reach the brain and thereby exert its effects to reverse learning impairment. Therefore, these results suggest that 4'-demethylnobiletin, a bioactive metabolite of nobiletin, may serve as a potential therapeutic agent, at least, for memory disorders associated with a dysregulated NMDA receptor ERK signaling, like nobiletin.

  19. Bioactivation to an aldehyde metabolite--possible role in the onset of toxicity induced by the anti-HIV drug abacavir.

    PubMed

    Grilo, Nádia M; Charneira, Catarina; Pereira, Sofia A; Monteiro, Emília C; Marques, M Matilde; Antunes, Alexandra M M

    2014-01-30

    Aldehydes are highly reactive molecules, which can be generated during numerous physiological processes, including the biotransformation of drugs. Several non-P450 enzymes participate in their metabolism albeit alcohol dehydrogenase and aldehyde dehydrogenase are the ones most frequently involved in this process. Endogenous and exogenous aldehydes have been strongly implicated in multiple human pathologies. Their ability to react with biomacromolecules (e.g. proteins) yielding covalent adducts is suggested to be the common primary mechanism underlying the toxicity of these reactive species. Abacavir is one of the options for combined anti-HIV therapy. Although individual susceptibilities to adverse effects differ among patients, abacavir is associated with idiosyncratic hypersensitivity drug reactions and an increased risk of cardiac dysfunction. This review highlights the current knowledge on abacavir metabolism and discusses the potential role of bioactivation to an aldehyde metabolite, capable of forming protein adducts, in the onset of abacavir-induced toxic outcomes.

  20. Bioactive sulfur-containing sulochrin dimers and other metabolites from an Alternaria sp. isolate from a Hawaiian soil sample.

    PubMed

    Cai, Shengxin; King, Jarrod B; Du, Lin; Powell, Douglas R; Cichewicz, Robert H

    2014-10-24

    Polluxochrin (1) and dioschrin (2), two new dimers of sulochrin linked by thioether bonds, were purified from an Alternaria sp. isolate obtained from a Hawaiian soil sample. The structures of the two metabolites were established by NMR, mass spectrometry data, and X-ray analysis. Metabolite 1 was determined to be susceptible to intramolecular cyclization under aqueous conditions, resulting in the generation of 2 as well as another dimeric compound, castochrin (3). An additional nine new metabolites were also obtained, including four new pyrenochaetic acid derivatives (8-11), one new asterric acid analogue (13), and four new secalonic acid analogues (14-17). Bioassay analysis of these compounds revealed 1-3 displayed antimicrobial and weak cytotoxic activities.

  1. Short-term hypoxic vasodilation in vivo is mediated by bioactive nitric oxide metabolites, rather than free nitric oxide derived from haemoglobin-mediated nitrite reduction.

    PubMed

    Umbrello, Michele; Dyson, Alex; Pinto, Bernardo Bollen; Fernandez, Bernadette O; Simon, Verena; Feelisch, Martin; Singer, Mervyn

    2014-03-01

    Local increases in blood flow--'hypoxic vasodilation'--confer cellular protection in the face of reduced oxygen delivery. The physiological relevance of this response is well established, yet ongoing controversy surrounds its underlying mechanisms. We sought to confirm that early hypoxic vasodilation is a nitric oxide (NO)-mediated phenomenon and to study putative pathways for increased levels of NO, namely production from NO synthases, intravascular nitrite reduction, release from preformed stores and reduced deactivation by cytochrome c oxidase. Experiments were performed on spontaneously breathing, anaesthetized, male Wistar rats undergoing short-term systemic hypoxaemia, who received pharmacological inhibitors and activators of the various NO pathways. Arterial blood pressure, cardiac output, tissue oxygen tension and the circulating pool of NO metabolites (oxidation, nitrosation and nitrosylation products) were measured in plasma and erythrocytes. Hypoxaemia caused a rapid and sustained vasodilation, which was only partially reversed by non-selective NO synthase inhibition. This was associated with significantly lower plasma nitrite, and marginally elevated nitrate levels, suggestive of nitrite bioinactivation. Administration of sodium nitrite had little effect in normoxia, but produced significant vasodilation and increased nitrosylation during hypoxaemia that could not be reversed by NO scavenging. Methodological issues prevented assessment of the contribution, if any, of reduced deactivation of NO by cytochrome c oxidase. In conclusion, acute hypoxic vasodilation is an adaptive NO-mediated response conferred through bioactive metabolites rather than free NO from haemoglobin-mediated reduction of nitrite.

  2. Response surface methodology: A non-conventional statistical tool to maximize the throughput of Streptomyces species biomass and their bioactive metabolites.

    PubMed

    Latha, Selvanathan; Sivaranjani, Govindhan; Dhanasekaran, Dharumadurai

    2017-01-27

    Among diverse actinobacteria, Streptomyces is a renowned ongoing source for the production of a large number of secondary metabolites, furnishing immeasurable pharmacological and biological activities. Hence, to meet the demand of new lead compounds for human and animal use, research is constantly targeting the bioprospecting of Streptomyces. Optimization of media components and physicochemical parameters is a plausible approach for the exploration of intensified production of novel as well as existing bioactive metabolites from various microbes, which is usually achieved by a range of classical techniques including one factor at a time (OFAT). However, the major drawbacks of conventional optimization methods have directed the use of statistical optimization approaches in fermentation process development. Response surface methodology (RSM) is one of the empirical techniques extensively used for modeling, optimization and analysis of fermentation processes. To date, several researchers have implemented RSM in different bioprocess optimization accountable for the production of assorted natural substances from Streptomyces in which the results are very promising. This review summarizes some of the recent RSM adopted studies for the enhanced production of antibiotics, enzymes and probiotics using Streptomyces with the intention to highlight the significance of Streptomyces as well as RSM to the research community and industries.

  3. Bioactive brominated metabolites from the natural habitat and tank-maintained cuttings of the Jamaican sponge Aplysina fistularis.

    PubMed

    Gallimore, Winklet A

    2013-06-01

    Cut specimens of the common reef sponge of the Verongid family, Aplysina fistularis, were retained in flow-through seawater tanks over a six-week period to assess the metabolite profile of the sponge when subjected to stress, compare the profile with the source material, and assess the preliminary feasibility of the protocol for sponge culture. The living specimens were harvested, extracted with MeOH/CH₂Cl₂ 1:1, and subjected to column chromatography to identify metabolites. The brominated isoxazoline compounds, aerothionin (1) and 11-oxoaerothionin (2), along with aeroplysinin 2 (3) and 2-(3,5-dibromo-4-hydroxyphenol)acetamide (4), were detected in the cuttings from the tank-maintained sponge. An examination of the metabolite profile of the sponge from the natural habitat showed that the compounds 1 and 2 were present. The identities of all the compounds were ascertained by analysis of the mass-spectral data and NMR spectra (¹H, ¹³C, HMBC, and HSQC) of the compounds, which were compared with reported data. The survival rate was 44% with limited necrosis or exposed skeletal tissue being observed in eight of the 18 cuttings, suggesting that protocol modifications would be required for culturing the sponge.

  4. Pesticides and their metabolites in community water-supply wells of central and western New York, August 1999

    USGS Publications Warehouse

    Eckhardt, David A.V.; Hetcher, Kari K.; Phillips, Patrick J.; Miller, Todd S.

    2001-01-01

    Ten pesticides and pesticide metabolites were detected in ground-water samples collected from each of 32 community water-supply (CWS) systems in central and western New York in August 1999. The sampling sites consisted of 30 wells that ranged from 23 to 120 feet in depth, and 2 springwater infiltration galleries. All wells tapped unconfined sand and gravel aquifers except one, which was completed in karstic limestone. These systems were selected because they were deemed vulnerable to pesticide contamination; accordingly, the results are not considered representative of all CWS systems in New York.The samples were analyzed for 60 pesticides. Twenty-four of the 32 samples contained at least one pesticide, and one sample contained eight pesticides or pesticide metabolites. New York State and Federal water-quality standards were not exceeded in any sample collected in this study.All pesticides detected in the CWS wells are a specific class of herbicides that are used to control broadleaf weeds and undesirable grasses in agricultural fields, lawns, and other areas that require control of vegetation. The four compounds detected most frequently were the herbicides atrazine and metolachlor and their metabolites—deethylatrazine and metolachlor ESA. Maximum concentrations of the four compounds ranged from 0.088 micrograms per liter (μg/L) for deethylatrazine to 3.58 μg/L for metolachlor ESA.

  5. Quantification of main bioactive metabolites from saffron (Crocus sativus) stigmas by a micellar electrokinetic chromatographic (MEKC) method.

    PubMed

    Gonda, Sándor; Parizsa, Péter; Surányi, Gyula; Gyémánt, Gyöngyi; Vasas, Gábor

    2012-07-01

    Saffron is an expensive spice, cultivated in many regions of the world. Its chief metabolites include crocins, which are responsible for the coloring ability, safranal, which is the main essential oil constituent, and picrocrocin which is the main bitter constituent of the spice. A simple micellar capillary electrochromatographic (MEKC) method capable of quantifying all three types of main constituents was established. The pH, sodium dodecyl sulphate (SDS) content and electrolyte concentration of the background electrolyte was optimized. A simple extraction protocol was developed which can extract all metabolites of different polarity from the saffron stigmas. Optimal background electrolyte composed of 20 mM disodium phosphate, 5mM sodium tetraborate, 100 mM SDS, pH was set 9.5. Optimal extracting solvent was the background electrolyte, incubated with the sample for 60 min. The proposed method allows quantification of picrocrocin, safranal, crocetin- Di-(β-D-gentiobiosyl) ester and crocetin (β-D-glycosyl)-(β-D-gentiobiosyl) ester within 17.5 min, with limit of detection values ranging from 0.006 to 0.04 mg/ml, from a single stigma.

  6. Isolation and Characterization of Bioactive Metabolites from Fruiting Bodies and Mycelial Culture of Ganoderma oerstedii (Higher Basidiomycetes) from Mexico.

    PubMed

    Mendoza, Guillermo; Suárez-Medellín, Jorge; Espinoza, César; Ramos-Ligonio, Angel; Fernández, José J; Norte, Manuel; Trigos, Ángel

    2015-01-01

    Various species of the genus Ganoderma have been used for centuries according to oriental tradition as a source of medicines and nutrients. A chemical study of the fruiting bodies and mycelial culture of G. oerstedii was carried out with the idea of isolating and characterizing active natural components present to make use of their potential pharmaceutical application in Mexico. The fruiting bodies and mycelial culture of G. oesrtedii were lyophylized and extracted one after the other with hexane, chloroform, and methanol. Following this process, each substance was extracted separately by using column chromatography. From fruiting bodies eight metabolites, five sterols (ergosta-7,22-dien-3β-ol, ergosterol peroxide, ergosterol, cerevisterol, and ergosta-7,22-dien-3-one) as well as three terpene compounds (ganodermanondiol, ganoderic acid Sz, and ganoderitriol M) were obtained from fruiting bodies. From the mycelial culture three metabolites, two sterols (ergosterol and cerevisterol), and a new terpene compound (ganoderic acetate from the acid) were obtained. These structures were established based on a spectroscopic analysis mainly using nuclear magnetic resonance and a comparison with data already established.

  7. Cell-based assays in combination with ultra-high performance liquid chromatography-quadrupole time of flight tandem mass spectrometry for screening bioactive capilliposide C metabolites generated by rat intestinal microflora.

    PubMed

    Cheng, Zhongzhe; Huang, Meilin; Chen, Guiying; Yang, Guangjie; Zhou, Xin; Chen, Chang; Zhang, Yang; Xu, Yong; Feng, Yulin; Zhang, Lin; Jiang, Hongliang

    2016-02-05

    Many plant-derived glycosides are used as medications. It is common that these glycosides show poor intestinal absorption but their metabolites generated by intestinal microflora demonstrate strong bioactivity. Hence, it is crucial to develop a method for the identification and characterization of the metabolites, and consequently reveal the pathway in which the glycosides are processed in gut. In this study, cell-based assays in combination with ultra-high performance liquid chromatography-quadrupole time of flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) were developed for rapid discovery and evaluation of the metabolites of a glycoside compound, capilliposide C (LC-C). 92.7% of LC-C was biotransformed by rat intestinal microflora after 36-h incubation at 37°C. Human cancer cell lines HepG2, PC-3 and A549 was treated with metabolites pool, respectively, which was followed by cell viability assays and characterization of metabolites using UHPLC-QTOF-MS/MS. As a result, significant cytotoxicity was observed for the metabolites pool, from which six metabolites were identified. Based on the metabolites identified, deglycosylation and esterolysis were proposed as the major metabolic pathways of LC-C in rat intestinal microflora. In addition, M4, an esterolysis product of LC-C, was obtained and evaluated for its bioactivity in vitro. As a result, M4 exhibited a reduction in cell viability in HepG2 with an IC50 value of 17.46±1.55μg/mL.

  8. Interrogating the Bioactive Pharmacophore of the Latrunculin Chemotype by Investigating the Metabolites of Two Taxonomically Unrelated Sponges

    PubMed Central

    Amagata, Taro; Johnson, Tyler A.; Cichewicz, Robert H.; Tenney, Karen; Mooberry, Susan L.; Media, Joseph; Edelstein, Matthew; Valeriote, Frederick A.; Crews, Phillip

    2009-01-01

    This study involved a campaign to isolate and study additional latrunculin analogs from two taxonomically unrelated sponges, Cacospongia mycofijiensis and Negombata magnifica. A total of 13 latrunculin analogs were obtained by four different ways, reisolation (1–4), our repository (5–6), new derivatives (7–12), and a synthetic analog (7a). The structures of the new metabolites were elucidated based on a combination of comprehensive 1D and 2D NMR analysis, application of DFT calculations, and the preparation of acetonide derivative 7a. The cytotoxicities against both murine and human cancer cell lines observed for 1, 2, 7, 7a, 8, 9, and 12 were significant and the IC50 value range was 0.5–10 μM. Among the cytotoxic derivatives, compound 9 did not exhibit microfilament-disrupting activity at 5 μM. The implications of this observation and the value of further therapeutic study on key latrunculin derivatives are discussed. PMID:18942825

  9. Secondary metabolites of a deep sea derived fungus Aspergillus versicolor CXCTD-06-6a and their bioactivity

    NASA Astrophysics Data System (ADS)

    Kong, Xianglan; Cai, Shengxin; Zhu, Tianjiao; Gu, Qianqun; Li, Dehai; Luan, Yepeng

    2014-08-01

    In order to obtain novel secondary metabolites, a deep sea inhabiting fungus Aspergillus versicolor CXCTD-06-6a was investigated. One new diketopiperazine brevianamide W ( 1a), as well as five known diketopiperazine alkaloids, diketopiperazine V ( 1b), brevianamide Q ( 2), brevianamide R ( 3), brevianamide K ( 4), and brevianamide E ( 5), were isolated from the EtOAc extract of the fermentation broth. Their structures were elucidated by spectroscopy techniques (NMR, MS). The six compounds exhibited moderate radical scavenging activity against DPPH with clearance ratio of 55.0% ( 1a and 1b), 53.7% ( 2), 46.2% ( 3), 61.4% ( 4) and 19.3% ( 5) at a concentration of 13.9 μmol L-1, respectively; while the positive control ascorbic acid showed a ratio of 70.3% at the concentration of 28.4 μmol L-1.

  10. Optimization and Pharmacological Validation of a Leukocyte Migration Assay in Zebrafish Larvae for the Rapid In Vivo Bioactivity Analysis of Anti-Inflammatory Secondary Metabolites

    PubMed Central

    Vicet-Muro, Liliana; Wilches-Arizábala, Isabel María; Esguerra, Camila V.; de Witte, Peter A. M.; Crawford, Alexander D.

    2013-01-01

    Over the past decade, zebrafish (Danio rerio) have emerged as an attractive model for in vivo drug discovery. In this study, we explore the suitability of zebrafish larvae to rapidly evaluate the anti-inflammatory activity of natural products (NPs) and medicinal plants used in traditional medicine for the treatment of inflammatory disorders. First, we optimized a zebrafish assay for leukocyte migration. Inflammation was induced in four days post-fertilization (dpf) zebrafish larvae by tail transection and co-incubation with bacterial lipopolysaccharides (LPS), resulting in a robust recruitment of leukocytes to the zone of injury. Migrating zebrafish leukocytes were detected in situ by myeloperoxidase (MPO) staining, and anti-inflammatory activity was semi-quantitatively scored using a standardized scale of relative leukocyte migration (RLM). Pharmacological validation of this optimized assay was performed with a panel of anti-inflammatory drugs, demonstrating a concentration-responsive inhibition of leukocyte migration for both steroidal and non-steroidal anti-inflammatory drugs (SAIDs and NSAIDs). Subsequently, we evaluated the bioactivity of structurally diverse NPs with well-documented anti-inflammatory properties. Finally, we further used this zebrafish-based assay to quantify the anti-inflammatory activity in the aqueous and methanolic extracts of several medicinal plants. Our results indicate the suitability of this LPS-enhanced leukocyte migration assay in zebrafish larvae as a front-line screening platform in NP discovery, including for the bioassay-guided isolation of anti-inflammatory secondary metabolites from complex NP extracts. PMID:24124487

  11. Bioactive secondary metabolites of a marine Bacillus sp. inhibit superoxide generation and elastase release in human neutrophils by blocking formyl peptide receptor 1.

    PubMed

    Yang, Shun-Chin; Lin, Chwan-Fwu; Chang, Wen-Yi; Kuo, Jimmy; Huang, Yin-Ting; Chung, Pei-Jen; Hwang, Tsong-Long

    2013-06-03

    It is well known that overwhelming neutrophil activation is closely related to acute and chronic inflammatory injuries. Formyl peptide receptor 1 (FPR1) plays an important role in activation of neutrophils and may represent a potent therapeutic target in inflammatory diseases. In the present study, we demonstrated that IA-LBI07-1 (IA), an extract of bioactive secondary metabolites from a marine Bacillus sp., has anti-inflammatory effects in human neutrophils. IA significantly inhibited superoxide generation and elastase release in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-activated neutrophils, but failed to suppress the cell responses activated by non-FPR1 agonists. IA did not alter superoxide production and elastase activity in cell-free systems. IA also attenuated the downstream signaling from FPR1, such as the Ca2+, MAP kinases and AKT pathways. In addition, IA inhibited the binding of N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, a fluorescent analogue of FMLP, to FPR1 in human neutrophils and FPR1-transfected HEK293 cells. Taken together, these results show that the anti-inflammatory effects of IA in human neutrophils are through the inhibition of FPR1. Also, our data suggest that IA may have therapeutic potential to decrease tissue damage induced by human neutrophils.

  12. Enzyme-assistant extraction (EAE) of bioactive components: a useful approach for recovery of industrially important metabolites from seaweeds: a review.

    PubMed

    Wijesinghe, W A J P; Jeon, You-Jin

    2012-01-01

    Over the years, the biological activities of seaweeds could have gained a considerable research interest because of their specific functional compounds, which may not be available in land plants. Thus, efforts at discovery of novel metabolites from seaweeds over the past years have yielded a considerable amount of new active compounds. In addition, studies about the extraction of active compounds from natural products have attracted special attention in the last recent years. Potent biologically active compounds of seaweeds have been demonstrated to play a significant role in prevention of certain degenerative diseases such as cancer, inflammation, arthritis, diabetes and hypertension. Therefore, seaweed derived active components, whose immense biochemical diversity looks like to become a rich source of novel chemical entities for the use as functional ingredients in many industrial applications such as functional foods, pharmaceuticals and cosmeceuticals. Thus, the interest in the extraction of active compounds from seaweeds is obvious. However, the physical and chemical barriers of the plant material become the key drawbacks of such extraction process. Therefore, enhanced release and recovery of active compounds attached to the cells have been addressed. Taken together, the aim of this communication is to discuss the potential use of enzyme treatment as a tool to improve the extraction efficiency of bioactive compounds from seaweeds.

  13. Characterization of the bioactive metabolites from a plant growth-promoting rhizobacteria and their exploitation as antimicrobial and plant growth-promoting agents.

    PubMed

    George, Emrin; Kumar, S Nishanth; Jacob, Jubi; Bommasani, Bhaskara; Lankalapalli, Ravi S; Morang, P; Kumar, B S Dileep

    2015-05-01

    A plant growth-promoting bacterial strain, PM 105, isolated from a tea plantation soil from the North Eastern region of India was identified as Pseudomonas aeruginosa through classical and 16S ribosomal DNA (rDNA) gene sequencing. Further studies with this strain confirmed broad spectrum antifungal activity against ten human and plant pathogenic fungal pathogens viz. Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus tubingensis, Candida albicans, Colletotrichum gloeosporioides, Fusarium oxysporum, Pencillium expansum, Rhizoctonia solani, Trichophyton rubrum besides growth-promoting property in cowpea (Vigna unguiculata) and pigeon pea (Cajanus cajan). However, no antibacterial property was exhibited by this strain against the four test bacterial pathogens tested in agar overlay method. The crude bioactive metabolites produced by this strain were isolated with three different solvents that exhibited significant antimicrobial and plant growth-promoting activity. Chloroform extract recorded significant antimicrobial and plant growth-promoting activity. Three major compounds viz. 1-hydroxyphenazine, pyocyanin, and phenazine-1-carboxamide were purified and characterized from crude extracts of this strain by various spectral data. The purified compounds recorded prominent antimicrobial activity but failed to establish the plant growth promotion activity in test crop plants under gnotobiotic conditions. Pyocyanin recorded significant antimicrobial activity, and best activity was recorded against T. rubrum (29 mm), followed by P. expansum (28 mm). These results suggest the use of PM 105 as plant growth-promoting agent in crop plants after successful field trials.

  14. A novel stereo bioactive metabolite isolated from an endophytic fungus induces caspase dependent apoptosis and STAT-3 inhibition in human leukemia cells.

    PubMed

    Pathania, Anup Singh; Guru, Santosh Kumar; Ul Ashraf, Nissar; Riyaz-Ul-Hassan, Syed; Ali, Asif; Abdullah Tasduq, Sheikh; Malik, Fayaz; Bhushan, Shashi

    2015-10-15

    The present study describes the anti-leukemic potential of a novel stereo bioactive secondary metabolite, (R)-5-hydroxy-2-methylchroman-4-one (HMC) isolated from a novel endophytic fungus source (Cryptosporiopsis sp. H2-1, NFCCI-2856), associated with Clidemia hirta. HMC inhibited cell proliferation of different cancer cell lines with IC50 values in the range of 8-55 µg/ml. The cytotoxicity window of HMC was 6-12 times lower in normal cells as compared to susceptible leukemic HL-60, MOLT-4 and K-562 cells. It persuades apoptosis through both intrinsic and extrinsic pathways in above leukemic cell lines, which was evident through Hoechst staining, Annexin-V binding, cell cycle analysis, loss of mitochondrial membrane potential (Δψm), release of cytochrome c, Bax, Bid, over-expression of apical death receptors, activation of caspase-3,-8,-9 and PARP (poly ADP ribose polymerase) cleavage. HMC induced caspase dependent apoptosis and robustly attenuate transcription factor, p-STAT-3 in myeloid and lymphoid leukemia cells. The mechanism of HMC arbitrated inhibition of p-STAT-3 was due to the activation of ubiquitin dependent degradation of p-STAT-3. Therefore, our study not only describes the anti-leukemic potential of HMC but also provides insights into how endophytes can be useful in discovery and development of novel anticancer therapeutics.

  15. Development of a new high-performance liquid chromatography method with diode array and electrospray ionization-mass spectrometry detection for the metabolite fingerprinting of bioactive compounds in Humulus lupulus L.

    PubMed

    Prencipe, Francesco Pio; Brighenti, Virginia; Rodolfi, Margherita; Mongelli, Andrea; dall'Asta, Chiara; Ganino, Tommaso; Bruni, Renato; Pellati, Federica

    2014-07-04

    The study was aimed at developing a new analytical method for the metabolite fingerprinting of bioactive compounds in Humulus lupulus L. (hop), together with a simple extraction procedure. Different extraction techniques, including maceration, heat reflux extraction (HRE), ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE), were compared in order to obtain a high yield of the target analytes. Dynamic maceration for 30min with MeOH-HCOOH (99:1, v/v) as the extraction solvent provided the best result in terms of recovery of secondary metabolites. The analysis of hop constituents, including prenylflavonoids and prenylphloroglucinols (bitter acids), was carried out by means of HPLC-UV/DAD, HPLC-ESI-MS and MS(2), using an ion trap mass analyzer. An Ascentis Express C18 column (150mm×3.0mm I.D., 2.7μm) was used for the HPLC analysis, with a mobile phase composed of 0.25% formic acid in both water and acetonitrile, under gradient elution. The method validation was performed to show compliance with ICH guidelines. The validated technique was successfully applied to the phytochemical analysis of ten commercial cultivars and twenty-three wild Italian hop genotypes, thus demonstrating to be a reliable and useful tool for the comprehensive multi-component analysis of hop secondary metabolites.

  16. Advances in the study of the structures and bioactivities of metabolites isolated from mangrove-derived fungi in the South China Sea.

    PubMed

    Wang, Xin; Mao, Zhi-Gang; Song, Bing-Bing; Chen, Chun-Hua; Xiao, Wei-Wei; Hu, Bin; Wang, Ji-Wen; Jiang, Xiao-Bing; Zhu, Yong-Hong; Wang, Hai-Jun

    2013-09-30

    Many metabolites with novel structures and biological activities have been isolated from the mangrove fungi in the South China Sea, such as anthracenediones, xyloketals, sesquiterpenoids, chromones, lactones, coumarins and isocoumarin derivatives, xanthones, and peroxides. Some compounds have anticancer, antibacterial, antifungal and antiviral properties, but the biosynthesis of these compounds is still limited. This review summarizes the advances in the study of secondary metabolites from the mangrove-derived fungi in the South China Sea, and their biological activities reported between 2008 and mid-2013.

  17. Accurate dereplication of bioactive secondary metabolites from marine-derived fungi by UHPLC-DAD-QTOFMS and a MS/HRMS library.

    PubMed

    Kildgaard, Sara; Mansson, Maria; Dosen, Ina; Klitgaard, Andreas; Frisvad, Jens C; Larsen, Thomas O; Nielsen, Kristian F

    2014-06-20

    In drug discovery, reliable and fast dereplication of known compounds is essential for identification of novel bioactive compounds. Here, we show an integrated approach using ultra-high performance liquid chromatography-diode array detection-quadrupole time of flight mass spectrometry (UHPLC-DAD-QTOFMS) providing both accurate mass full-scan mass spectrometry (MS) and tandem high resolution MS (MS/HRMS) data. The methodology was demonstrated on compounds from bioactive marine-derived strains of Aspergillus, Penicillium, and Emericellopsis, including small polyketides, non-ribosomal peptides, terpenes, and meroterpenoids. The MS/HRMS data were then searched against an in-house MS/HRMS library of ~1300 compounds for unambiguous identification. The full scan MS data was used for dereplication of compounds not in the MS/HRMS library, combined with ultraviolet/visual (UV/Vis) and MS/HRMS data for faster exclusion of database search results. This led to the identification of four novel isomers of the known anticancer compound, asperphenamate. Except for very low intensity peaks, no false negatives were found using the MS/HRMS approach, which proved to be robust against poor data quality caused by system overload or loss of lock-mass. Only for small polyketides, like patulin, were both retention time and UV/Vis spectra necessary for unambiguous identification. For the ophiobolin family with many structurally similar analogues partly co-eluting, the peaks could be assigned correctly by combining MS/HRMS data and m/z of the [M + Na]+ ions.

  18. Composition and Bioactivity of Lipophilic Metabolites from Needles and Twigs of Korean and Siberian Pines (Pinus koraiensis Siebold & Zucc. and Pinus sibirica Du Tour).

    PubMed

    Shpatov, Alexander V; Popov, Sergey A; Salnikova, Olga I; Kukina, Tatyana P; Shmidt, Emma N; Um, Byung Hun

    2017-02-01

    Lipophilic extractive metabolites in different parts of the shoot system (needles and defoliated twigs) of Korean pine, Pinus koraiensis, and Siberian pine, Pinus sibirica, were studied by GC/MS. Korean pine needles comprised mainly bornyl p-coumarate, heterocyclic 15-O-functionalized labdane type acids (lambertianic acid), 10-nonacosanol, sterols and their esters. While Siberian pine needles contained less bornyl p-coumarate, lambertianic acid, sterols and their esters, but were richer in other 15-O-functionalized labdane type acids. The major components of the twig extract of P. koraiensis were lambertianic acid, abietane and isopimarane type acids, cembrane type alcohols, 8-O-functionalized labdanoids, sterols, sterol esters, and acylglycerols. The same extract of P. sibirica differed in larger amounts of other 15-O-functionalized labdane type acids and pinolenic acid glycerides, but in less quantities of cembranoids and 8-O-functionalized labdanoids. The labdane type pinusolic acid was detected for the first time in Korean pine. P. koraiensis was found to be unique in the genus for an ability to synthesize phyllocladane diterpenoids. The content of bound Δ(5) -unsaturated polymethylene-interrupted fatty acids in the twig extracts of the both pines was similar or superior to that in their seed oil. Among the pines' metabolites tested isocembrol was strongest in inhibition of both α-glucosidase (IC50 2.9 μg/ml) and NO production in activated macrophages (IC50 3.6 μg/ml).

  19. Advances in Marine Microbial Symbionts in the China Sea and Related Pharmaceutical Metabolites

    PubMed Central

    Li, Zhiyong

    2009-01-01

    Marine animals and plants such as sponges, sea squirts, corals, worms and algae host diverse and abundant symbiotic microorganisms. Marine microbial symbionts are possible the true producers or take part in the biosynthesis of some bioactive marine natural products isolated from the marine organism hosts. Investigation of the pharmaceutical metabolites may reveal the biosynthesis mechanisms of related natural products and solve the current problem of supply limitation in marine drug development. This paper reviews the advances in diversity revelation, biological activity and related pharmaceutical metabolites, and functional genes of marine microbial symbionts from the China Sea. PMID:19597576

  20. Preparative mass-spectrometry profiling of bioactive metabolites in Saudi-Arabian propolis fractionated by high-speed countercurrent chromatography and off-line atmospheric pressure chemical ionization mass-spectrometry injection.

    PubMed

    Jerz, Gerold; Elnakady, Yasser A; Braun, André; Jäckel, Kristin; Sasse, Florenz; Al Ghamdi, Ahmad A; Omar, Mohamed O M; Winterhalter, Peter

    2014-06-20

    Propolis is a glue material collected by honeybees which is used to seal cracks in beehives and to protect the bee population from infections. Propolis resins have a long history in medicinal use as a natural remedy. The multiple biological properties are related to variations in their chemical compositions. Geographical settings and availability of plant sources are important factors for the occurrence of specific natural products in propolis. A propolis ethylacetate extract (800mg) from Saudi Arabia (Al-Baha region) was separated by preparative scale high-speed countercurrent chromatography (HSCCC) using a non-aqueous solvent system n-hexane-ACN (1:1, v/v). For multiple metabolite detection, the resulting HSCCC-fractions were sequentially injected off-line into an atmospheric pressure chemical ionization mass-spectrometry (APCI-MS/MS) device, and a reconstituted mass spectrometry profile of the preparative run was visualized by selected ion traces. Best ion-intensities for detected compounds were obtained in the negative APCI mode and monitored occurring co-elution effects. HSCCC and successive purification steps resulted in the isolation and characterization of various bioactive natural products such as (12E)- and (12Z)-communic acid, sandaracopimaric acid, (+)-ferruginol, (+)-totarol, and 3β-acetoxy-19(29)-taraxasten-20a-ol using EI-, APCI-MS and 1D/2D-NMR. Cycloartenol-derivatives and triterpene acetates were isolated in mixtures and elucidated by EI-MS and 1D-NMR. Free fatty acids, and two labdane fatty acid esters were identified by APCI-MS/MS. In total 19 metabolites have been identified. The novel combination of HSCCC fractionation, and APCI-MS-target-guided molecular mass profiling improve efficiency of lead-structure identification.

  1. High throughput HPLC-ESI(-)-MS/MS methodology for mercapturic acid metabolites of 1,3-butadiene: Biomarkers of exposure and bioactivation.

    PubMed

    Kotapati, Srikanth; Esades, Amanda; Matter, Brock; Le, Chap; Tretyakova, Natalia

    2015-11-05

    1,3-Butadiene (BD) is an important industrial and environmental carcinogen present in cigarette smoke, automobile exhaust, and urban air. The major urinary metabolites of BD in humans are 2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene/1-(N-acetyl-L-cystein-S-yl)-2-hydroxybut-3-ene (MHBMA), 4-(N-acetyl-L-cystein-S-yl)-1,2-dihydroxybutane (DHBMA), and 4-(N-acetyl-L-cystein-S-yl)-1,2,3-trihydroxybutyl mercapturic acid (THBMA), which are formed from the electrophilic metabolites of BD, 3,4-epoxy-1-butene (EB), hydroxymethyl vinyl ketone (HMVK), and 3,4-epoxy-1,2-diol (EBD), respectively. In the present work, a sensitive high-throughput HPLC-ESI(-)-MS/MS method was developed for simultaneous quantification of MHBMA and DHBMA in small volumes of human urine (200 μl). The method employs a 96 well Oasis HLB SPE enrichment step, followed by isotope dilution HPLC-ESI(-)-MS/MS analysis on a triple quadrupole mass spectrometer. The validated method was used to quantify MHBMA and DHBMA in urine of workers from a BD monomer and styrene-butadiene rubber production facility (40 controls and 32 occupationally exposed to BD). Urinary THBMA concentrations were also determined in the same samples. The concentrations of all three BD-mercapturic acids and the metabolic ratio (MHBMA/(MHBMA+DHBMA+THBMA)) were significantly higher in the occupationally exposed group as compared to controls and correlated with BD exposure, with each other, and with BD-hemoglobin biomarkers. This improved high throughput methodology for MHBMA and DHBMA will be useful for future epidemiological studies in smokers and occupationally exposed workers.

  2. Healthy and adverse effects of plant-derived functional metabolites: the need of revealing their content and bioactivity in a complex food matrix.

    PubMed

    Lavecchia, Teresa; Rea, Giuseppina; Antonacci, Amina; Giardi, Maria T

    2013-01-01

    In recent years, both food quality and its effect on human health have become a fundamental issue all over the world. As a consequence of this new and increased awareness, American, European, and Asian policymakers have strongly encouraged the research programs on food quality and safety thematic. Attempts to improve human health and to satisfy people's desire for healthcare without intake of pharmaceuticals, has led the food industry to focus attention on functional or nutraceutical food. For a long time, compounds with nutraceutical activity have been produced chemically, but the new demands for a sustainable life have gradually led the food industry to move towards natural compounds, mainly those derived from plants. Many phytochemicals are known to promote good health, but, sometimes, undesirable effects are also reported. Furthermore, several products present on the market show few benefits and sometimes even the reverse - unhealthy effects; the evidence of efficacy is often unconvincing and epidemiological studies are necessary to prove the truth of their claims. Therefore, there is a need for reliable analytical control systems to measure the bioactivity, content, and quality of these additives in the complex food matrix. This review describes the most widespread nutraceutics and an analytical control of the same using recently developed biosensors which are promising candidates for routine control of functional foods.

  3. Healthy and Adverse Effects of Plant-Derived Functional Metabolites: The Need of Revealing their Content and Bioactivity in a Complex Food Matrix

    PubMed Central

    Lavecchia, Teresa; Rea, Giuseppina; Antonacci, Amina; Giardi, Maria T.

    2012-01-01

    In recent years, both food quality and its effect on human health have become a fundamental issue all over the world. As a consequence of this new and increased awareness, American, European, and Asian policymakers have strongly encouraged the research programs on food quality and safety thematic. Attempts to improve human health and to satisfy people's desire for healthcare without intake of pharmaceuticals, has led the food industry to focus attention on functional or nutraceutical food. For a long time, compounds with nutraceutical activity have been produced chemically, but the new demands for a sustainable life have gradually led the food industry to move towards natural compounds, mainly those derived from plants. Many phytochemicals are known to promote good health, but, sometimes, undesirable effects are also reported. Furthermore, several products present on the market show few benefits and sometimes even the reverse – unhealthy effects; the evidence of efficacy is often unconvincing and epidemiological studies are necessary to prove the truth of their claims. Therefore, there is a need for reliable analytical control systems to measure the bioactivity, content, and quality of these additives in the complex food matrix. This review describes the most widespread nutraceutics and an analytical control of the same using recently developed biosensors which are promising candidates for routine control of functional foods. PMID:23072533

  4. Induction of Diverse Bioactive Secondary Metabolites from the Mangrove Endophytic Fungus Trichoderma sp. (Strain 307) by Co-Cultivation with Acinetobacter johnsonii (Strain B2)

    PubMed Central

    Zhang, Liuhong; Niaz, Shah Iram; Khan, Dilfaraz; Wang, Zhen; Zhu, Yonghong; Zhou, Haiyun; Lin, Yongcheng; Li, Jing; Liu, Lan

    2017-01-01

    Two new sesquiterpenes, microsphaeropsisin B (1) and C (2), and two new de-O-methyllasiodiplodins, (3R, 7R)-7-hydroxy-de-O-methyllasiodiplodin (4) and (3R)-5-oxo-de-O-methyllasiodiplodin (5), together with one new natural product (6) and twelve known compounds (3, 7–17), were isolated from the co-cultivation of mangrove endophytic fungus Trichoderma sp. 307 and aquatic pathogenic bacterium Acinetobacter johnsonii B2. Their structures, including absolute configurations, were elucidated by extensive analysis of spectroscopic data, electronic circular dichroism, Mo2(AcO)4-induced circular dichroism, and comparison with reported data. All of the isolated compounds were tested for their α-glucosidase inhibitory activity and cytotoxicity. New compounds 4 and 5 exhibited potent α-glucosidase inhibitory activity with IC50 values of 25.8 and 54.6 µM, respectively, which were more potent than the positive control (acarbose, IC50 = 703.8 µM). The good results of the tested bioactivity allowed us to explore α-glucosidase inhibitors in lasiodiplodins. PMID:28208607

  5. Nanodiamonds coupled with 5,7-dimethoxycoumarin, a plant bioactive metabolite, interfere with the mitotic process in B16F10 cells altering the actin organization

    PubMed Central

    Gismondi, Angelo; Nanni, Valentina; Reina, Giacomo; Orlanducci, Silvia; Terranova, Maria Letizia; Canini, Antonella

    2016-01-01

    For the first time, we coupled reduced detonation nanodiamonds (NDs) with a plant secondary metabolite, citropten (5,7-dimethoxycoumarin), and demonstrated how this complex was able to reduce B16F10 tumor cell growth more effectively than treatment with the pure molecule. These results encouraged us to find out the specific mechanism underlying this phenomenon. Internalization kinetics and quantification of citropten in cells after treatment with its pure or ND-conjugated form were measured, and it was revealed that the coupling between NDs and citropten was essential for the biological properties of the complex. We showed that the adduct was not able to induce apoptosis, senescence, or differentiation, but it determined cell cycle arrest, morphological changes, and alteration of mRNA levels of the cytoskeletal-related genes. The identification of metaphasic nuclei and irregular disposition of β-actin in the cell cytoplasm supported the hypothesis that citropten conjugated with NDs showed antimitotic properties in B16F10 cells. This work can be considered a pioneering piece of research that could promote and support the biomedical use of plant drug-functionalized NDs in cancer therapy. PMID:26893562

  6. Bioactive terpenes from marine-derived fungi.

    PubMed

    Elissawy, Ahmed M; El-Shazly, Mohamed; Ebada, Sherif S; Singab, AbdelNasser B; Proksch, Peter

    2015-04-03

    Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years' reports on terpenoidal metabolites from marine-derived fungi with particular attention on those showing marked biological activities.

  7. Bioactive Terpenes from Marine-Derived Fungi

    PubMed Central

    Elissawy, Ahmed M.; El-Shazly, Mohamed; Ebada, Sherif S.; Singab, AbdelNasser B.; Proksch, Peter

    2015-01-01

    Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years’ reports on terpenoidal metabolites from marine-derived fungi with particular attention on those showing marked biological activities. PMID:25854644

  8. Bioactive deoxypreussomerins and dimeric naphthoquinones from Diospyros ehretioides fruits: deoxypreussomerins may not be plant metabolites but may be from fungal epiphytes or endophytes.

    PubMed

    Prajoubklang, Areerat; Sirithunyalug, Busaban; Charoenchai, Panarat; Suvannakad, Rapheephat; Sriubolmas, Nongluksna; Piyamongkol, Sirivipa; Kongsaeree, Palangpon; Kittakoop, Prasat

    2005-10-01

    Deoxypreussomerin derivatives, palmarumycins JC1 (1) and JC2 (2), and two dimeric naphthoquinones, isodiospyrin (3) and its new derivative isodiospyrol A (4), were isolated from dried fruits of Diospyros ehretioides. Structures of the isolated compounds were elucidated by spectroscopic analyses. Palmarumycins were not found in the extract of freshly collected fruits; however, they were present in dried fruit extract. The absence of palmarumycins in fresh fruits of D. ehretioides, together with the chemotaxonomic point of view, we proposed that palmarumycins JC1 (1) and JC2 (2) are more likely to be fungal metabolites, i.e., endophytes or epiphytes. The isolation of palmarumycins 1 and 2 from dried D. ehretioides fruits could be reproducible; both plant samples collected in the years 2002 and 2004 provided the same result, and, therefore, symbiont fungal strains should be specific to the plant host, D. ehretioides, and they can grow on the fruits during drying the sample. Palmarumycin JC1 (1) did not exhibit antimalarial, antifungal, antimycobacterial, and cytotoxic activities. Palmarumycin JC2 (2) exhibited antimalarial (IC50 4.5 microg/ml), antifungal (IC50 12.5 microg/ml), antimycobacterial (MIC 6.25 microg/ml), and cytotoxic (IC50 11.0 microg/ml for NCI-H187 cell line) activities. In our bioassay systems, isodiospyrin (3) did not exhibit antimycobacterial, antifungal, antimalarial, and cytotoxic activities. Isodiospyrol A (4) exhibited antimalarial (IC50 2.7 microg/ml) and antimycobacterial (MIC 50 microg/ml) activities, but was inactive towards Candida albicans. Compound 4 also exhibited cytotoxicity against BC cells (IC50 12.3 microg/ml), but not towards KB and Vero cell lines.

  9. Planctomycetes as Novel Source of Bioactive Molecules

    PubMed Central

    Graça, Ana P.; Calisto, Rita; Lage, Olga M.

    2016-01-01

    Marine environments are a fruitful source of bioactive compounds some of which are the newest leading drugs in medicinal therapeutics. Of particular importance are organisms like sponges and macroalgae and their associated microbiome. Planctomycetes, abundant in macroalgae biofilms, are promising producers of bioactive compounds since they share characteristics, like large genomes and complex life cycles, with the most bioactive bacteria, the Actinobacteria. Furthermore, genome mining revealed the presence of secondary metabolite pathway genes or clusters in 13 analyzed Planctomycetes genomes. In order to assess the antimicrobial production of a large and diverse collection of Planctomycetes isolated from macroalgae from the Portuguese coast, molecular, and bioactivity assays were performed in 40 bacteria from several taxa. Two genes commonly associated with the production of bioactive compounds, nonribosomal peptide synthetases (NRPS), and polyketide synthases (PKS) genes were screened. Molecular analysis revealed that 95% of the planctomycetes potentially have one or both secondary bioactive genes; 85% amplified with PKS-I primers and 55% with NRPS primers. Some of the amplified genes were confirmed to be involved in secondary metabolite pathways. Using bioinformatic tools their biosynthetic pathways were predicted. The secondary metabolite genomic potential of strains LF1, UC8, and FC18 was assessed using in silico analysis of their genomes. Aqueous and organic extracts of the Planctomycetes were evaluated for their antimicrobial activity against an environmental Escherichia coli, E. coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Bacillus subtilis ATCC 6633, and a clinical isolate of Candida albicans. The screening assays showed a high number of planctomycetes with bioactive extracts revealing antifungal (43%) and antibacterial (54%) activity against C. albicans and B. subtilis, respectively. Bioactivity was observed in

  10. Planctomycetes as Novel Source of Bioactive Molecules.

    PubMed

    Graça, Ana P; Calisto, Rita; Lage, Olga M

    2016-01-01

    Marine environments are a fruitful source of bioactive compounds some of which are the newest leading drugs in medicinal therapeutics. Of particular importance are organisms like sponges and macroalgae and their associated microbiome. Planctomycetes, abundant in macroalgae biofilms, are promising producers of bioactive compounds since they share characteristics, like large genomes and complex life cycles, with the most bioactive bacteria, the Actinobacteria. Furthermore, genome mining revealed the presence of secondary metabolite pathway genes or clusters in 13 analyzed Planctomycetes genomes. In order to assess the antimicrobial production of a large and diverse collection of Planctomycetes isolated from macroalgae from the Portuguese coast, molecular, and bioactivity assays were performed in 40 bacteria from several taxa. Two genes commonly associated with the production of bioactive compounds, nonribosomal peptide synthetases (NRPS), and polyketide synthases (PKS) genes were screened. Molecular analysis revealed that 95% of the planctomycetes potentially have one or both secondary bioactive genes; 85% amplified with PKS-I primers and 55% with NRPS primers. Some of the amplified genes were confirmed to be involved in secondary metabolite pathways. Using bioinformatic tools their biosynthetic pathways were predicted. The secondary metabolite genomic potential of strains LF1, UC8, and FC18 was assessed using in silico analysis of their genomes. Aqueous and organic extracts of the Planctomycetes were evaluated for their antimicrobial activity against an environmental Escherichia coli, E. coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Bacillus subtilis ATCC 6633, and a clinical isolate of Candida albicans. The screening assays showed a high number of planctomycetes with bioactive extracts revealing antifungal (43%) and antibacterial (54%) activity against C. albicans and B. subtilis, respectively. Bioactivity was observed in

  11. Bioactive glasses as accelerators of apatite bioactivity.

    PubMed

    Vallet-Regí, M; Rámila, A; Padilla, S; Muñoz, B

    2003-09-01

    Synthetic carbonatehydroxyapatite is the ceramic closest to the mineral component of human bone and seems, therefore, the optimum material to use in osseous implants. However, in vitro assays performed to determine its bioactivity have shown no positive results after 2 months of assay. With the aim of improving this bioactivity, a new biphasic material was synthesized composed mainly of synthetic carbonatehydroxyapatite and only 5% of a sol-gel bioactive glass. In vitro assays were assessed to determine the bioactive behavior of this new material and revealed that the addition of a minimal amount of bioactive glass is enough to induce bioactivity on synthetic carbonatehydroxyapatites.

  12. Secondary metabolite components of kiwifruit.

    PubMed

    McGhie, Tony K

    2013-01-01

    Both green and gold kiwifruit contain high concentrations of vitamin C, and much of the "health story" of kiwifruit involves this vitamin. Kiwifruit also contain other compounds that are bioactive and beneficial to health. In this chapter, the secondary metabolite composition of kiwifruit is presented. Although there are limited compositional data for kiwifruit published in the scientific literature, the concentrations of 42 compounds have been documented. Included are compounds that are often associated with "healthfulness," such as the vitamins (A, C, E, and K), carotenoids (lutein and β-carotene), folate, and antioxidant phenolic compounds. Metabolite discovery is advancing rapidly with the introduction of "metabolomic" studies where the goal is to identify and measure the complete metabolite composition of a sample. In a metabolomic experiment using liquid chromatography and high-resolution mass spectrometry, it was possible to measure more than 500 metabolites in kiwifruit extracts. The large number of detectable metabolites present suggests that there is an abundance of kiwifruit metabolites still to be discovered. Such studies will provide a more complete understanding of the metabolite composition of kiwifruit that will lead to new and improved hypotheses as to the function and effects of kiwifruit metabolites, including their relevance to human health.

  13. Anticancer properties of Monascus metabolites.

    PubMed

    Yang, Tao; Liu, Junwen; Luo, Feijun; Lin, Qinlu; Rosol, Thomas J; Deng, Xiyun

    2014-08-01

    This review provides up-to-date information on the anticancer properties of Monascus-fermented products. Topics covered include clinical evidence for the anticancer potential of Monascus metabolites, bioactive Monascus components with anticancer potential, mechanisms of the anticancer effects of Monascus metabolites, and existing problems as well as future perspectives. With the advancement of related fields, the development of novel anticancer Monascus food products and/or pharmaceuticals will be possible with the ultimate goal of decreasing the incidence and mortality of malignancies in humans.

  14. Secondary Metabolites from Polar Organisms

    PubMed Central

    Tian, Yuan; Li, Yan-Ling; Zhao, Feng-Chun

    2017-01-01

    Polar organisms have been found to develop unique defences against the extreme environment environment, leading to the biosynthesis of novel molecules with diverse bioactivities. This review covers the 219 novel natural products described since 2001, from the Arctic and the Antarctic microoganisms, lichen, moss and marine faunas. The structures of the new compounds and details of the source organism, along with any relevant biological activities are presented. Where reported, synthetic and biosynthetic studies on the polar metabolites have also been included. PMID:28241505

  15. Nutrient Supply and Simulated Herbivory Differentially Alter the Metabolite Pools and the Efficacy of the Glucosinolate-Based Defense System in Brassica Species.

    PubMed

    Almuziny, Makhdora; Decker, Charlotte; Wang, Dong; Gerard, Patrick; Tharayil, Nishanth

    2017-02-01

    Environmental stress hinders growth of plants and commonly results in the accumulation of carbon-based defense compounds. However, the dynamics of nitrogen (N)-containing defense compounds are less predictable under environmental stress. The impact of nutrient deficiency on plant defenses that require the metabolic conversion of a less toxic compound to a more potent toxin is even more poorly understood. We evaluated the effects of nitrogen (N) and potassium (K) deficiency and simulated herbivory on the concentration of metabolites including glucosinolates (GSLs), on the conversion of GSLs to more toxic isothiocyanates (ITCs), and on the activity of myrosinase (MYR) in leaves of Brassica juncea and Brassica nigra. Both species contained GSLs, predominantly sinigrin, but also derivatives of glucobrassicin. Compared to the control, N deficiency increased the sinigrin concentration in both species. Methyl jasmonate (MeJA) application increased sinigrin production in B. junceae, whereas in B. nigra MeJA increased sinigrin only under K-deficiency. Compared to the aliphatic-glucosinolates, MeJA application produced a greater compositional change in the profiles of indolic-glucosinolates. In both species the increase in sinigrin content of the tissue was associated with a decrease in its overall nutritive value as assessed by the content of sugars and amino acids. In B. juncea, application of MeJA decreased the conversion of sinigrin to allyl isothiocyanate (AITC) under both N and K deficiency. The potential activity of MYR decreased in both species under N deficiency. The reduced conversion of sinigrin to AITC and the lower activity of MYR suggest that the GSL-ITC defense system might have a limited efficiency in deterring generalist herbivores under environmental stress.

  16. A Simple Approach for Obtaining High Resolution, High Sensitivity ¹H NMR Metabolite Spectra of Biofluids with Limited Mass Supply

    SciTech Connect

    Hu, Jian Zhi; Rommereim, Donald N.; Wind, Robert A.; Minard, Kevin R.; Sears, Jesse A.

    2006-11-01

    A simple approach is reported that yields high resolution, high sensitivity ¹H NMR spectra of biofluids with limited mass supply. This is achieved by spinning a capillary sample tube containing a biofluid at the magic angle at a frequency of about 80Hz. A 2D pulse sequence called ¹H PASS is then used to produce a high-resolution ¹H NMR spectrum that is free from magnetic susceptibility induced line broadening. With this new approach a high resolution ¹H NMR spectrum of biofluids with a volume less than 1.0 µl can be easily achieved at a magnetic field strength as low as 7.05T. Furthermore, the methodology facilitates easy sample handling, i.e., the samples can be directly collected into inexpensive and disposable capillary tubes at the site of collection and subsequently used for NMR measurements. In addition, slow magic angle spinning improves magnetic field shimming and is especially suitable for high throughput investigations. In this paper first results are shown obtained in a magnetic field of 7.05T on urine samples collected from mice using a modified commercial NMR probe.

  17. Mitochondrial metabolites: undercover signalling molecules

    PubMed Central

    2017-01-01

    Mitochondria are one of most characterized metabolic hubs of the cell. Here, crucial biochemical reactions occur and most of the cellular adenosine triphosphate (ATP) is produced. In addition, mitochondria act as signalling platforms and communicate with the rest of the cell by modulating calcium fluxes, by producing free radicals, and by releasing bioactive proteins. It is emerging that mitochondrial metabolites can also act as second messengers and can elicit profound (epi)genetic changes. This review describes the many signalling functions of mitochondrial metabolites under normal and stress conditions, focusing on metabolites of the tricarboxylic acid cycle. We provide a new framework for understanding the role of mitochondrial metabolism in cellular pathophysiology. PMID:28382199

  18. Targeting high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance analysis with high-resolution radical scavenging profiles-Bioactive secondary metabolites from the endophytic fungus Penicillium namyslowskii.

    PubMed

    Wubshet, Sileshi G; Nyberg, Nils T; Tejesvi, Mysore V; Pirttilä, Anna Maria; Kajula, Marena; Mattila, Sampo; Staerk, Dan

    2013-08-09

    The high-resolution radical scavenging profile of an extract of the endophytic fungus Penicillium namyslowskii was used to target analysis by high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy, i.e., HPLC-HRMS-SPE-NMR, for identification of anti-oxidative secondary metabolites. This revealed the two chromatographic peaks with the highest relative response in the radical scavenging profile to be griseophenone C and peniprequinolone. The HPLC-HRMS-SPE-NMR analysis was performed in the tube-transfer mode using a cryogenically cooled NMR probe designed for 1.7mm NMR tubes. To further explore the potential of the above HPLC-HRMS-SPE-NMR platform for analysis of endophytic extracts, six peaks displaying no radical scavenging activity were also analyzed. This allowed unambiguous identification of six metabolites, i.e., dechlorogriseofulvin, dechlorodehydrogriseofulvin, griseofulvin, dehydrogriseofulvin, mevastatin acid, and mevastatin. The high mass sensitivity of the 1.7mm cryogenically cooled NMR probe allowed for the first time acquisition of direct detected (13)C NMR spectra of fungal metabolites, i.e., dechlorogriseofulvin and griseofulvin, directly from crude extract via HPLC-HRMS-SPE-NMR. Dechlorodehydrogriseofulvin was reported for the first time from nature.

  19. [Biologically active metabolites of the marine actinobacteria].

    PubMed

    Sobolevskaia, M P; Kuznetsova, T A

    2010-01-01

    This review systematically data on the chemical structure and biological activity of metabolites of obligate and facultative marine actinobacteria, published from 2000 to 2007. We discuss some structural features of the five groups of metabolites related to macrolides and compounds containing lactone, quinone and diketopiperazine residues, cyclic peptides, alkaloids, and compounds of mixed biosynthesis. Survey shows a large chemical diversity of metabolites actinobacteria isolated from marine environment. It is shown that, along with metabolites, identical to previously isolated from terrestrial actinobacteria, marine actinobacteria synthesize unknown compounds not found in other natural sources, including micro organisms. Perhaps the biosynthesis of new chemotypes bioactive compounds in marine actinobacteria is one manifestation of chemical adaptation of microorganisms to environmental conditions at sea. Review stresses the importance of the chemical study of metabolites of marine actinobacteria. These studies are aimed at obtaining new data on marine microorganisms producers of biologically active compounds and chemical structure and biological activity of new low-molecular bioregulators of natural origin.

  20. Human health benefits supplied by Mediterranean marine biodiversity.

    PubMed

    Lloret, Josep

    2010-10-01

    This paper summarizes the overall benefits supplied by Mediterranean marine biodiversity to human health and highlights the anthropogenic and environmental causes that are threatening these benefits. First, the Mediterranean Sea is a valuable source of seafood, which is an important component of the so-called "Mediterranean diet". This type of diet has several health benefits, including cardio and cancer protective effects, which are attributed to the high intake of seafood-derived n-3 (omega-3) fatty acids. Second, the Mediterranean marine organisms, particularly the benthic ones, have furnished a large variety of bioactive metabolites, some of which are being developed into new drugs to threat major human diseases such as cancer. Third, the Mediterranean coastal areas provide environments for practising maritime leisure activities that provide physical and psychological benefits to users. Despite all this, fishing, tourism, contamination and sea warming are deteriorating this rich marine ecosystem, which needs to be protected to assure human welfare.

  1. Ultrahigh resolution metabolomics for S-containing metabolites.

    PubMed

    Nakabayashi, Ryo; Saito, Kazuki

    2017-02-01

    The advent of the genome-editing era greatly increases the opportunities for synthetic biology research that aims to enhance production of potentially useful bioactive metabolites in heterologous hosts. A wide variety of sulfur (S)-containing metabolites (S-metabolites) are known to possess bioactivities and health-promoting properties, but finding them and their chemical assignment using mass spectrometry-based metabolomics has been difficult. In this review, we highlight recent advances on the targeted metabolomic analysis of S-metabolites (S-omics) in plants using ultrahigh resolution mass spectrometry. The use of exact mass and signal intensity differences between (32)S-containing monoisotopic ions and counterpart (34)S isotopic ions exploits an entirely new method to characterize S-metabolites. Finally, we discuss the availability of S-omics for synthetic biology.

  2. Bioactivation of myelotoxic xenobiotics by human neutrophil myeloperoxidase

    SciTech Connect

    Roy, R.R.

    1989-01-01

    Many environmental pollutants and drugs are toxic to the bone marrow. Some of these xenobiotics may initiate toxicity after undergoing bioactivation to free radicals and/or other reactive electrophiles. Peroxidases are a group of enzymes that catalyze the one-electron oxidative bioactivation of a variety of xenobiotics in vitro. Myeloperoxidase (MPO) is a peroxidative enzyme found in very high concentration in the neutrophils of human bone marrow. In this study, human MPO was evaluated to determine its ability to catalyze the in vitro bioactivation of known bone marrow toxicants that contain the aromatic hydroxyl (Ar-OH), aromatic amine (Ar-N-R{sub 2}), or heterocyclic tertiary amine ({double bond}N-R) moieties. The formation of free radical metabolites during the MPO-catalyzed bioactivation of hydroquinone and catechol (benzene metabolites), mitoxantrone and ametantrone (antitumor drugs), and chlorpromazine and promazine (antipsychotic drugs) was demonstrated by EPR spectroscopy. The reactivity of the products formed during the MPO catalyzed bioactivation of ({sup 14}C)hydroquinone and ({sup 14}C)catechol was shown by their covalent binding to protein and DNA in vitro. The covalently binding metabolite in each case is postulated to be the quinone form of the xenobiotic. In addition, both GSH and NADH were oxidized by the reactive intermediate(s) formed during the MPO-catalyzed bioactivation of many of the bone marrow toxicants tested. It was also shown that p,p-biphenol stimulated the MPO catalyzed bioactivation of both hydroquinone and catechol, while p-cresol stimulated the MPO-catalyzed bioactivation of catechol.

  3. Bioactivation of particles

    DOEpatents

    Pinaud, Fabien; King, David; Weiss, Shimon

    2011-08-16

    Particles are bioactivated by attaching bioactivation peptides to the particle surface. The bioactivation peptides are peptide-based compounds that impart one or more biologically important functions to the particles. Each bioactivation peptide includes a molecular or surface recognition part that binds with the surface of the particle and one or more functional parts. The surface recognition part includes an amino-end and a carboxy-end and is composed of one or more hydrophobic spacers and one or more binding clusters. The functional part(s) is attached to the surface recognition part at the amino-end and/or said carboxy-end.

  4. Immense essence of excellence: marine microbial bioactive compounds.

    PubMed

    Bhatnagar, Ira; Kim, Se-Kwon

    2010-10-15

    Oceans have borne most of the biological activities on our planet. A number of biologically active compounds with varying degrees of action, such as anti-tumor, anti-cancer, anti-microtubule, anti-proliferative, cytotoxic, photo protective, as well as antibiotic and antifouling properties, have been isolated to date from marine sources. The marine environment also represents a largely unexplored source for isolation of new microbes (bacteria, fungi, actinomycetes, microalgae-cyanobacteria and diatoms) that are potent producers of bioactive secondary metabolites. Extensive research has been done to unveil the bioactive potential of marine microbes (free living and symbiotic) and the results are amazingly diverse and productive. Some of these bioactive secondary metabolites of microbial origin with strong antibacterial and antifungal activities are being intensely used as antibiotics and may be effective against infectious diseases such as HIV, conditions of multiple bacterial infections (penicillin, cephalosporines, streptomycin, and vancomycin) or neuropsychiatric sequelae. Research is also being conducted on the general aspects of biophysical and biochemical properties, chemical structures and biotechnological applications of the bioactive substances derived from marine microorganisms, and their potential use as cosmeceuticals and nutraceuticals. This review is an attempt to consolidate the latest studies and critical research in this field, and to showcase the immense competence of marine microbial flora as bioactive metabolite producers. In addition, the present review addresses some effective and novel approaches of procuring marine microbial compounds utilizing the latest screening strategies of drug discovery.

  5. Construction of a metagenomic DNA library of sponge symbionts and screening of antibacterial metabolites

    NASA Astrophysics Data System (ADS)

    Chen, Juan; Zhu, Tianjiao; Li, Dehai; Cui, Chengbin; Fang, Yuchun; Liu, Hongbing; Liu, Peipei; Gu, Qianqun; Zhu, Weiming

    2006-04-01

    To study the bioactive metabolites produced by sponge-derived uncultured symbionts, a metagenomic DNA library of the symbionts of sponge Gelliodes gracilis was constructed. The average size of DNA inserts in the library was 20 kb. This library was screened for antibiotic activity using paper dise assaying. Two clones displayed the antibacterial activity against Micrococcus tetragenus. The metabolites of these two clones were analyzed through HPLC. The result showed that their metabolites were quite different from those of the host E. coli DH5α and the host containing vector pHZ132. This study may present a new approach to exploring bioactive metabolites of sponge symbionts.

  6. Pharmaceutically active secondary metabolites of marine actinobacteria.

    PubMed

    Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

    2014-04-01

    Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future.

  7. Biologically Active Metabolites Synthesized by Microalgae

    PubMed Central

    de Morais, Michele Greque; Vaz, Bruna da Silva; de Morais, Etiele Greque; Costa, Jorge Alberto Vieira

    2015-01-01

    Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences. PMID:26339647

  8. Marine actinomycetes as a source of novel secondary metabolites.

    PubMed

    Fiedler, Hans-Peter; Bruntner, Christina; Bull, Alan T; Ward, Alan C; Goodfellow, Michael; Potterat, Olivier; Puder, Carsten; Mihm, Gerhard

    2005-01-01

    A set of 600 actinomycetes strains which were isolated from marine sediments from various sites in the Pacific and Atlantic Oceans were screened for the production of bioactive secondary metabolites. Marine streptomycete strains were found to be producers of well known chemically diverse antibiotics isolated from terrestrial streptomycetes, as in the case of marine Micromonospora strains. New marine members of the rare genus Verrucosispora seem to be a promising source for novel bioactive secondary metabolites as shown in the case of the abyssomicin producing strain AB-18-032.

  9. Marine actinobacteria: an important source of bioactive natural products.

    PubMed

    Manivasagan, Panchanathan; Kang, Kyong-Hwa; Sivakumar, Kannan; Li-Chan, Eunice C Y; Oh, Hyun-Myung; Kim, Se-Kwon

    2014-07-01

    Marine environment is largely an untapped source for deriving actinobacteria, having potential to produce novel, bioactive natural products. Actinobacteria are the prolific producers of pharmaceutically active secondary metabolites, accounting for about 70% of the naturally derived compounds that are currently in clinical use. Among the various actinobacterial genera, Actinomadura, Actinoplanes, Amycolatopsis, Marinispora, Micromonospora, Nocardiopsis, Saccharopolyspora, Salinispora, Streptomyces and Verrucosispora are the major potential producers of commercially important bioactive natural products. In this respect, Streptomyces ranks first with a large number of bioactive natural products. Marine actinobacteria are unique enhancing quite different biological properties including antimicrobial, anticancer, antiviral, insecticidal and enzyme inhibitory activities. They have attracted global in the last ten years for their ability to produce pharmaceutically active compounds. In this review, we have focused attention on the bioactive natural products isolated from marine actinobacteria, possessing unique chemical structures that may form the basis for synthesis of novel drugs that could be used to combat resistant pathogenic microorganisms.

  10. Bioactive foods and ingredients for health.

    PubMed

    Weaver, Connie M

    2014-05-01

    Bioactive compounds in foods have been gaining interest, and processes to consider them for public health recommendations are being discussed. However, the evidence base is difficult to assemble. It is difficult to demonstrate causality, and there often is not a single compound-single effect relation. Furthermore, health benefits may be due to metabolites produced by the host or gut microbiome rather than the food constituent per se. Properties that can be measured in a food may not translate to in vivo health effects. Compounds that are being pursued may increase gut microbial diversity, improve endothelial function, improve cognitive function, reduce bone loss, and so forth. A new type of bioactive component is emerging from epigenetic modifications by our diet, including microRNA transfer from our diet, which can regulate expression of human genes. Policy processes are needed to establish the level of evidence needed to determine dietary advice and policy recommendations and to set research agendas.

  11. Bioactive Compounds from Marine Bacteria and Fungi

    PubMed Central

    Debbab, Abdessamad; Aly, Amal H.; Lin, Wen H.; Proksch, Peter

    2010-01-01

    Summary Marine bacteria and fungi are of considerable importance as new promising sources of a huge number of biologically active products. Some of these marine species live in a stressful habitat, under cold, lightless and high pressure conditions. Surprisingly, a large number of species with high diversity survive under such conditions and produce fascinating and structurally complex natural products. Up till now, only a small number of microorganisms have been investigated for bioactive metabolites, yet a huge number of active substances with some of them featuring unique structural skeletons have been isolated. This review covers new biologically active natural products published recently (2007–09) and highlights the chemical potential of marine microorganisms, with focus on bioactive products as well as on their mechanisms of action. PMID:21255352

  12. A nutrigenomics view of protein intake: macronutrient, bioactive peptides, and protein turnover.

    PubMed

    Chou, Chieh Jason; Affolter, Michael; Kussmann, Martin

    2012-01-01

    Proteins are needed for the development and sustainability of life. They are the molecular machines and building blocks in the human body that drive or exert most biological functions and confer structure and function to cell and tissue architecture. Dietary proteins provide essential amino acids and complement lipid and carbohydrate as a major source of energy. Therefore, humans must consume a sufficient amount and quality of proteins to stay healthy and avoid deficiencies. Even with a reasonable amount of intake, variability in protein consumption can result in measurable health consequences in specific conditions. This said, dietary protein delivers more than energy and building blocks to the human body: the pools of body, tissue, and cell proteins, peptides, and amino acids are under complex metabolic control, resulting in a highly dynamic protein turnover, that is, the interplay between synthesis and degradation. Proteins also contain peptide sequences that can be interpreted as bioactive precursors which can be liberated upon digestion to exert biological functions locally (e.g., in the gut) or systemically (i.e., via the bloodstream). In this chapter, we will first review holistic readouts of protein intake assessed by omics technologies such as gene expression, proteomics, and metabolite profiling. Second, we will look at protein benefits beyond macronutrient supply and describe how to generate, analyze, and leverage bioactive peptides. In the third part, we will discuss protein turnover as tackled by proteomics tools that allow single-protein resolution at proteome-wide scale.

  13. Volatile Metabolites

    PubMed Central

    Rowan, Daryl D.

    2011-01-01

    Volatile organic compounds (volatiles) comprise a chemically diverse class of low molecular weight organic compounds having an appreciable vapor pressure under ambient conditions. Volatiles produced by plants attract pollinators and seed dispersers, and provide defense against pests and pathogens. For insects, volatiles may act as pheromones directing social behavior or as cues for finding hosts or prey. For humans, volatiles are important as flavorants and as possible disease biomarkers. The marine environment is also a major source of halogenated and sulfur-containing volatiles which participate in the global cycling of these elements. While volatile analysis commonly measures a rather restricted set of analytes, the diverse and extreme physical properties of volatiles provide unique analytical challenges. Volatiles constitute only a small proportion of the total number of metabolites produced by living organisms, however, because of their roles as signaling molecules (semiochemicals) both within and between organisms, accurately measuring and determining the roles of these compounds is crucial to an integrated understanding of living systems. This review summarizes recent developments in volatile research from a metabolomics perspective with a focus on the role of recent technical innovation in developing new areas of volatile research and expanding the range of ecological interactions which may be mediated by volatile organic metabolites. PMID:24957243

  14. Marine bacterial sources of bioactive compounds.

    PubMed

    Jaiganesh, R; Sampath Kumar, N S

    2012-01-01

    Thousands of novel compounds have been isolated from various marine bacteria and tested for pharmacological properties, many of which are commercially available. Many more are being tested as potential bioactive compound at the preclinical and clinical stages. The growing interest in marine-derived antiviral compounds, along with the development of new technology in marine cultures and extraction, will significantly expedite the current exploration of the marine environment for compounds with significant pharmacological applications, which will continue to be a promising strategy and new trend for modern medicine. Marine actinomycetes and cyanobacteria are a prolific but underexploited source for the discovery of novel secondary metabolites.

  15. Dimethyl sulfoxide inhibits bioactivation of sulindac.

    PubMed

    Swanson, B N; Boppana, V K; Vlasses, P H; Rotmensch, H H; Ferguson, R K

    1983-07-01

    Sulindac, a nonsteroidal anti-inflammatory agent, is converted to a bioactive sulfide metabolite via reversible reduction of its sulfoxide moiety. To test whether DMSO can inhibit conversion of sulindac to its active form, eight healthy men received, in a randomized, crossover manner, 400 mg of sulindac, orally, either alone or 60 min after an oral dose of DMSO (30 ml, 70% solution). After the drug combination, mean plasma concentrations of the sulfide metabolite were significantly lower than in controls at 1.5, 2, 3, 4, and 8 hr after sulindac administration. The mean area under the plasma sulfide concentration-time curve for 0 to 12 hr was 30% (range 7% to 56%) lower after DMSO treatment. This study suggests that DMSO can inhibit metabolism of other sulfoxides in man and may antagonize the therapeutic efficacy of sulindac.

  16. Littoral lichens as a novel source of potentially bioactive Actinobacteria.

    PubMed

    Parrot, Delphine; Antony-Babu, Sanjay; Intertaglia, Laurent; Grube, Martin; Tomasi, Sophie; Suzuki, Marcelino T

    2015-10-30

    Cultivable Actinobacteria are the largest source of microbially derived bioactive molecules. The high demand for novel antibiotics highlights the need for exploring novel sources of these bacteria. Microbial symbioses with sessile macro-organisms, known to contain bioactive compounds likely of bacterial origin, represent an interesting and underexplored source of Actinobacteria. We studied the diversity and potential for bioactive-metabolite production of Actinobacteria associated with two marine lichens (Lichina confinis and L. pygmaea; from intertidal and subtidal zones) and one littoral lichen (Roccella fuciformis; from supratidal zone) from the Brittany coast (France), as well as the terrestrial lichen Collema auriforme (from a riparian zone, Austria). A total of 247 bacterial strains were isolated using two selective media. Isolates were identified and clustered into 101 OTUs (98% identity) including 51 actinobacterial OTUs. The actinobacterial families observed were: Brevibacteriaceae, Cellulomonadaceae, Gordoniaceae, Micrococcaceae, Mycobacteriaceae, Nocardioidaceae, Promicromonosporaceae, Pseudonocardiaceae, Sanguibacteraceae and Streptomycetaceae. Interestingly, the diversity was most influenced by the selective media rather than lichen species or the level of lichen thallus association. The potential for bioactive-metabolite biosynthesis of the isolates was confirmed by screening genes coding for polyketide synthases types I and II. These results show that littoral lichens are a source of diverse potentially bioactive Actinobacteria.

  17. Littoral lichens as a novel source of potentially bioactive Actinobacteria

    PubMed Central

    Parrot, Delphine; Antony-Babu, Sanjay; Intertaglia, Laurent; Grube, Martin; Tomasi, Sophie; Suzuki, Marcelino T.

    2015-01-01

    Cultivable Actinobacteria are the largest source of microbially derived bioactive molecules. The high demand for novel antibiotics highlights the need for exploring novel sources of these bacteria. Microbial symbioses with sessile macro-organisms, known to contain bioactive compounds likely of bacterial origin, represent an interesting and underexplored source of Actinobacteria. We studied the diversity and potential for bioactive-metabolite production of Actinobacteria associated with two marine lichens (Lichina confinis and L. pygmaea; from intertidal and subtidal zones) and one littoral lichen (Roccella fuciformis; from supratidal zone) from the Brittany coast (France), as well as the terrestrial lichen Collema auriforme (from a riparian zone, Austria). A total of 247 bacterial strains were isolated using two selective media. Isolates were identified and clustered into 101 OTUs (98% identity) including 51 actinobacterial OTUs. The actinobacterial families observed were: Brevibacteriaceae, Cellulomonadaceae, Gordoniaceae, Micrococcaceae, Mycobacteriaceae, Nocardioidaceae, Promicromonosporaceae, Pseudonocardiaceae, Sanguibacteraceae and Streptomycetaceae. Interestingly, the diversity was most influenced by the selective media rather than lichen species or the level of lichen thallus association. The potential for bioactive-metabolite biosynthesis of the isolates was confirmed by screening genes coding for polyketide synthases types I and II. These results show that littoral lichens are a source of diverse potentially bioactive Actinobacteria. PMID:26514347

  18. Phenolic plant metabolites as bioactive food and feed additives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Functional additives in food and animal feed formulations are gaining acceptance as consumers and producers recognize the health benefits associated with certain natural plant products. Phenolic compounds in particular have emerged as a class of compounds with antioxidant, antibacterial, and antifun...

  19. Triterpenoidal Saponins: Bioactive Secondary Metabolites from Zygophyllum coccineum

    DTIC Science & Technology

    2011-01-22

    of the publishers only Planta Medica Journal of Medicinal Plant and Natural Product Research www.thieme.de/fz/plantamedica l www.thieme-connect.com...insecticidal activity of compounds 1, 3, 5, 6, and 9. Amin E et al. Triterpenoidal Saponins: Bioactive… Planta Med Letters Th is is a co py of th e...Amin E et al. Triterpenoidal Saponins: Bioactive… Planta Med Letters Th is is a co py of th e au th or ʼs pe rs on al re pr in t Th is is a co py of th

  20. Using Molecular Networking for Microbial Secondary Metabolite Bioprospecting

    PubMed Central

    Purves, Kevin; Macintyre, Lynsey; Brennan, Debra; Hreggviðsson, Guðmundur Ó.; Kuttner, Eva; Ásgeirsdóttir, Margrét E.; Young, Louise C.; Green, David H.; Edrada-Ebel, Ruangelie; Duncan, Katherine R.

    2016-01-01

    The oceans represent an understudied resource for the isolation of bacteria with the potential to produce novel secondary metabolites. In particular, actinomyces are well known to produce chemically diverse metabolites with a wide range of biological activities. This study characterised spore-forming bacteria from both Scottish and Antarctic sediments to assess the influence of isolation location on secondary metabolite production. Due to the selective isolation method used, all 85 isolates belonged to the phyla Firmicutes and Actinobacteria, with the majority of isolates belonging to the genera Bacillus and Streptomyces. Based on morphology, thirty-eight isolates were chosen for chemical investigation. Molecular networking based on chemical profiles (HR-MS/MS) of fermentation extracts was used to compare complex metabolite extracts. The results revealed 40% and 42% of parent ions were produced by Antarctic and Scottish isolated bacteria, respectively, and only 8% of networked metabolites were shared between these locations, implying a high degree of biogeographic influence upon secondary metabolite production. The resulting molecular network contained over 3500 parent ions with a mass range of m/z 149–2558 illustrating the wealth of metabolites produced. Furthermore, seven fermentation extracts showed bioactivity against epithelial colon adenocarcinoma cells, demonstrating the potential for the discovery of novel bioactive compounds from these understudied locations. PMID:26761036

  1. Using Molecular Networking for Microbial Secondary Metabolite Bioprospecting.

    PubMed

    Purves, Kevin; Macintyre, Lynsey; Brennan, Debra; Hreggviðsson, Guðmundur Ó; Kuttner, Eva; Ásgeirsdóttir, Margrét E; Young, Louise C; Green, David H; Edrada-Ebel, Ruangelie; Duncan, Katherine R

    2016-01-08

    The oceans represent an understudied resource for the isolation of bacteria with the potential to produce novel secondary metabolites. In particular, actinomyces are well known to produce chemically diverse metabolites with a wide range of biological activities. This study characterised spore-forming bacteria from both Scottish and Antarctic sediments to assess the influence of isolation location on secondary metabolite production. Due to the selective isolation method used, all 85 isolates belonged to the phyla Firmicutes and Actinobacteria, with the majority of isolates belonging to the genera Bacillus and Streptomyces. Based on morphology, thirty-eight isolates were chosen for chemical investigation. Molecular networking based on chemical profiles (HR-MS/MS) of fermentation extracts was used to compare complex metabolite extracts. The results revealed 40% and 42% of parent ions were produced by Antarctic and Scottish isolated bacteria, respectively, and only 8% of networked metabolites were shared between these locations, implying a high degree of biogeographic influence upon secondary metabolite production. The resulting molecular network contained over 3500 parent ions with a mass range of m/z 149-2558 illustrating the wealth of metabolites produced. Furthermore, seven fermentation extracts showed bioactivity against epithelial colon adenocarcinoma cells, demonstrating the potential for the discovery of novel bioactive compounds from these understudied locations.

  2. Designing Bioactive Delivery Systems for Tissue Regeneration

    PubMed Central

    Davis, Hillary E.

    2010-01-01

    The direct infusion of macromolecules into defect sites generally does not impart adequate physiological responses. Without the protection of delivery systems, inductive molecules may likely redistribute away from their desired locale and are vulnerable to degradation. In order to achieve efficacy, large doses supplied at interval time periods are necessary, often at great expense and ensuing detrimental side effects. The selection of a delivery system plays an important role in the rate of re-growth and functionality of regenerating tissue: not only do the release kinetics of inductive molecules and their consequent bioactivities need to be considered, but also how the delivery system interacts and integrates with its surrounding host environment. In the current review, we describe the means of release of macromolecules from hydrogels, polymeric microspheres, and porous scaffolds along with the selection and utilization of bioactive delivery systems in a variety of tissue-engineering strategies. PMID:20676773

  3. Strategic Supply

    DTIC Science & Technology

    2005-01-01

    the potential to capitalize on more efficient and effective management of their respective supply chains . Supply Chain Management (SCM) is the...transformation efforts have the potential to create a more agile, flexible and resilient supply chain that is responsive to Commanders and sensitive to...optimizing their supply chain to remain viable and create competitive advantage. Supply Chain Management (SCM) is grounded in the field of logistics

  4. Bioactive benzopyrone derivatives from new recombinant fusant of marine Streptomyces.

    PubMed

    El-Gendy, Mervat M A; Shaaban, M; El-Bondkly, A M; Shaaban, K A

    2008-07-01

    In our searching program for bioactive secondary metabolites from marine Streptomycetes, three microbial benzopyrone derivatives (1-3), 7-methylcoumarin (1) and two flavonoides, rhamnazin (2) and cirsimaritin (3), were obtained during the working up of the ethyl acetate fraction of a marine Streptomyces fusant obtained from protoplast fusion between Streptomyces strains Merv 1996 and Merv 7409. The structures of the three compounds (1-3) were established by nuclear magnetic resonance, mass, UV spectra, and by comparison with literature data. Marine Streptomyces strains were identified based on their phenotypic and chemotypic characteristics as two different bioactive strains of the genus Streptomyces. We described here the fermentation, isolation, as well as the biological activity of these bioactive compounds. The isolated compounds (1-3) are reported here as microbial products for the first time.

  5. Chemical constituents and bioactivities of Clinacanthus nutans aerial parts.

    PubMed

    Tu, Shu-Fen; Liu, Rosa Huang; Cheng, Yuan-Bin; Hsu, Yu-Ming; Du, Ying-Chi; El-Shazly, Mohamed; Wu, Yang-Chang; Chang, Fang-Rong

    2014-12-05

    Four new sulfur-containing compounds, named clinamides A-C (1-3), and 2-cis-entadamide A (4), were isolated together with three known compounds from the bioactive ethanol extract of the aerial parts of Clinacanthus nutans. These secondary metabolites possess sulfur atoms and acrylamide functionalities. The structures of the isolated components were established by interpretation of their spectroscopic data, especially 1D and 2D NMR.

  6. New bioactive lipids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to the new compounds, 7,10-dihydroxy-8(E)-octad...

  7. New Bioactive Fatty Acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to new compounds, 7,10-dihydroxy-8(E)-octadecen...

  8. New bioactive fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to the new compounds, 7,10-dihydroxy-8(E)-octad...

  9. Porous bioactive materials

    NASA Astrophysics Data System (ADS)

    Zhang, Kai

    Bioactive materials chemically bond to tissues through the development of biologically active apatite. Porous structures in biomaterials are designed to enhance bioactivity, grow artificial tissues and achieve better integration with host tissues in the body. The goal of this research is to design, fabricate and characterize novel porous bioactive materials. 3D ordered macroporous bioactive glasses (3DOM-BGs, pore size: 200--1000 nm) were prepared using a sol-gel process and colloidal crystal templates. 3DOM-BGs are more bioactive and degradable than mesoporous (pore size <50 nm) sol-gel BGs in simulated body fluid (SBF). Apatite formation and 3DOM-BG degradation rates increased with the decrease of soaking ratio. Apatite induction time in SBF increased with 3DOM-BG calcination temperature (600--800°C). Apatite formation and 3DOMBG degradation were slightly enhanced for a phosphate containing composition. Large 3DOM-BG particles formed less apatite and degraded less completely as compared with small particles. An increase in macropore size slowed down 3DOM-BG degradation and apatite formation processes. After heating the converted apatite at a temperature higher than 700°C, highly crystalline hydroxyapatite and a minor tri-calcium phosphate phase formed. 3DOM-BGs have potential applications as bone/periodontal fillers, and drugs and biological factors delivery agents. Anchoring artificial soft tissues (e.g., cartilage) to native bone presents a challenge. Porous polymer/bioactive glass composites are candidate materials for engineering artificial soft tissue/bone interfaces. Porous composites consisting of polymer matrices (e.g., polysulfone, polylactide, and polyurethane) and bioactive glass particles were prepared by polymer phase separation techniques adapted to include ceramic particles. Composites (thickness: 200--500 mum) have asymmetric structures with dense top layers and porous structures beneath. Porous structures consist of large pores (>100 mum) in a

  10. Bioactivation potential of thiophene-containing drugs.

    PubMed

    Gramec, Darja; Peterlin Mašič, Lucija; Sollner Dolenc, Marija

    2014-08-18

    Thiophene is a five-membered, sulfur-containing heteroaromatic ring commonly used as a building block in drugs. It is considered to be a structural alert, as its metabolism can lead to the formation of reactive metabolites. Thiophene S-oxides and thiophene epoxides are highly reactive electrophilic thiophene metabolites whose formation is cytochrome P450-dependent. These reactive thiophene-based metabolites are quite often responsible for drug-induced hepatotoxicity. Tienilic acid is an example of a thiophene-based drug that was withdrawn from the market after only a few months of use, due to severe cases of immune hepatitis. However, inclusion of the thiophene moiety in drugs does not necessarily result in toxic effects. The presence of other, less toxic metabolic pathways, as well as an effective detoxification system in our body, protects us from the bioactivation potential of the thiophene ring. Thus, the presence of a structural alert itself is insufficient to predict a compound's toxicity. The question therefore arises as to which factors significantly influence the toxicity of thiophene-containing drugs. There is no easy way to answer this question. However, the findings presented here indicate that, for a number of reasons, daily dose and alternative metabolic pathways are important factors when predicting toxicity and will therefore be discussed together with examples.

  11. Detection of 191 Taxifolin Metabolites and Their Distribution in Rats Using HPLC-ESI-IT-TOF-MS(n).

    PubMed

    Yang, Ping; Xu, Feng; Li, Hong-Fu; Wang, Yi; Li, Feng-Chun; Shang, Ming-Ying; Liu, Guang-Xue; Wang, Xuan; Cai, Shao-Qing

    2016-09-13

    Taxifolin is a ubiquitous bioactive constituent of foods and herbs. To thoroughly explore its metabolism in vivo, an HPLC-ESI-IT-TOF-MS(n) method combined with specific metabolite detection strategy was used to detect and identify the metabolites of taxifolin in rats. Of the 191 metabolites tentatively identified, 154 were new metabolites, 69 were new compounds and 32 were dimers. This is the first report of the in vivo biotransformation of a single compound into more than 100 metabolites. Furthermore, acetylamination and pyroglutamic acid conjugation were identified as new metabolic reactions. Seventeen metabolites were found to have various taxifolin-related bioactivities. The potential targets of taxifolin and 63 metabolites were predicted using PharmMapper, with results showing that more than 60 metabolites have the same five targets. Metabolites with the same fragment pattern may have the same pharmacophore. Thus these metabolites may exert the same pharmacological effects as taxifolin through an additive effect on the same drug targets. This observation indicates that taxifolin is bioactive not only in the parent form, but also through its metabolites. These findings enhance understanding of the metabolism and effective forms of taxifolin and may provide further insight of the beneficial effects of taxifolin and its derivatives.

  12. Strategic Supply

    DTIC Science & Technology

    2006-01-01

    context of Supply Chain Management ( SCM ), it is quite apparent that Strategic Supply cannot be classified as a particular industry; but rather, as an...Management ( SCM ), it is quite apparent that Strategic Supply cannot be classified as a particular industry; but rather, as an enabler across all...advantage in the global marketplace. The Council of Supply Chain Management Professionals (CSCMP) has defined SCM as, “…encompassing the planning

  13. Extracellular Metabolites from Industrial Microalgae and Their Biotechnological Potential.

    PubMed

    Liu, Lu; Pohnert, Georg; Wei, Dong

    2016-10-20

    Industrial microalgae, as a big family of promising producers of renewable biomass feedstock, have been commercially exploited for functional food, living feed and feed additives, high-value chemicals in nutraceuticals, cosmeceuticals, and chemical reagents. Recently, microalgae have also been considered as a group that might play an important role in biofuel development and environmental protection. Almost all current products of industrial microalgae are derived from their biomass; however, large amounts of spent cell-free media are available from mass cultivation that is mostly unexploited. In this contribution we discuss that these media, which may contain a remarkable diversity of bioactive substances are worthy to be recovered for further use. Obviously, the extracellular metabolites from industrial microalgae have long been neglected in the development of production methods for valuable metabolites. With the advances in the last ten years, more and more structures and properties from extracellular metabolites have been identified, and the potential utilization over wide fields is attracting attention. Some of these extracellular metabolites can be potentially used as drugs, antioxidants, growth regulators or metal chelators. The purpose of this review is to provide an overview of the known extracellular metabolites from industrial microalgae which might be of commercial interest. The attention mainly focuses on the reports of extracellular bioactive metabolites and their potential application in biotechnology.

  14. Extracellular Metabolites from Industrial Microalgae and Their Biotechnological Potential

    PubMed Central

    Liu, Lu; Pohnert, Georg; Wei, Dong

    2016-01-01

    Industrial microalgae, as a big family of promising producers of renewable biomass feedstock, have been commercially exploited for functional food, living feed and feed additives, high-value chemicals in nutraceuticals, cosmeceuticals, and chemical reagents. Recently, microalgae have also been considered as a group that might play an important role in biofuel development and environmental protection. Almost all current products of industrial microalgae are derived from their biomass; however, large amounts of spent cell-free media are available from mass cultivation that is mostly unexploited. In this contribution we discuss that these media, which may contain a remarkable diversity of bioactive substances are worthy to be recovered for further use. Obviously, the extracellular metabolites from industrial microalgae have long been neglected in the development of production methods for valuable metabolites. With the advances in the last ten years, more and more structures and properties from extracellular metabolites have been identified, and the potential utilization over wide fields is attracting attention. Some of these extracellular metabolites can be potentially used as drugs, antioxidants, growth regulators or metal chelators. The purpose of this review is to provide an overview of the known extracellular metabolites from industrial microalgae which might be of commercial interest. The attention mainly focuses on the reports of extracellular bioactive metabolites and their potential application in biotechnology. PMID:27775594

  15. Synthesis of New Sulfated and Glucuronated Metabolites of Dietary Phenolic Compounds Identified in Human Biological Samples.

    PubMed

    Almeida, A Filipa; Santos, Cláudia N; Ventura, M Rita

    2017-02-23

    (Poly)phenols are a large group of dietary compounds present in fruits and vegetables; their consumption is associated with health beneficial effects. After ingestion, (poly)phenols suffer extensive metabolization, and the identification of their metabolites is an emerging area, because these metabolites are considered the effective bioactive molecules in the human organism. However, a lack of commercially available standards has hampered the study of metabolite bioactivity and the exact structural confirmation in biological samples. New (poly)phenol metabolites previously identified in human samples after the intake of berry juice were chemically synthesized. Efficient chemical reactions were performed with moderate to excellent yields and selectivities. These new compounds could be used as standard chemicals for confirmation of the structure of metabolites in biological samples and will also allow mechanistic studies in cellular models.

  16. Molecular Approaches to Screen Bioactive Compounds from Endophytic Fungi

    PubMed Central

    Vasundhara, M.; Kumar, Anil; Reddy, M. Sudhakara

    2016-01-01

    Endophytic fungi are capable of producing plant associated metabolites and their analogs with therapeutic value. In order to identify the potential endophytic isolates producing bioactive compounds, one need to screen all isolated endophytes, which may run into hundreds. Isolation of endophytic fungi is relatively a simple process; but screening of the isolated fungi for required metabolite production is a cumbersome process. Endophytic fungi producing plant associated metabolites may contain genes involved in the entire biosynthetic pathway(s). Therefore, ascertaining the presence of key enzymes of a particular biosynthetic pathway could serve as a molecular marker for screening of these endophytes to produce that metabolite. In absence of entire biosynthetic pathways in endophytic fungi, plant genes associated with that metabolic pathway could serve as markers. This review focuses on the impact of molecular approaches to screen the endophytic fungi for the production of bioactive compounds. An attempt has been made on screening of anticancer compounds like taxol (paclitaxel), podophyllotoxin, and camptothecin using molecular markers. The advantages of molecular approaches over conventional methods to screen endophytic fungi and also identification of endophytic fungi are discussed. PMID:27895623

  17. Mechanisms of Nitrite Bioactivation

    PubMed Central

    Kim-Shapiro, Daniel B.; Gladwin, Mark T.

    2014-01-01

    It is now accepted that the anion nitrite, once considered an inert oxidation product of nitric oxide (NO), contributes to hypoxic vasodilation, physiological blood pressure control, and redox signaling. As such, its application in therapeutics is being actively testing in pre-clinical models and in human phase I–II clinical trials. Major pathways for nitrite bioactivation involve its reduction to NO by members of the hemoglobin or molybdopterin family of proteins, or catalyzed dysproportionation. These conversions occur preferentially under hypoxic and acidic conditions. A number of enzymatic systems reduce nitrite to NO and their activity and importance are defined by oxygen tension, specific organ system and allosteric and redox effectors. In this work, we review different proposed mechanisms of nitrite bioactivation, focusing on analysis of kinetics and experimental evidence for the relevance of each mechanism under different conditions. PMID:24315961

  18. Bioactive glass in tissue engineering

    PubMed Central

    Rahaman, Mohamed N.; Day, Delbert E.; Bal, B. Sonny; Fu, Qiang; Jung, Steven B.; Bonewald, Lynda F.; Tomsia, Antoni P.

    2011-01-01

    This review focuses on recent advances in the development and use of bioactive glass for tissue engineering applications. Despite its inherent brittleness, bioactive glass has several appealing characteristics as a scaffold material for bone tissue engineering. New bioactive glasses based on borate and borosilicate compositions have shown the ability to enhance new bone formation when compared to silicate bioactive glass. Borate-based bioactive glasses also have controllable degradation rates, so the degradation of the bioactive glass implant can be more closely matched to the rate of new bone formation. Bioactive glasses can be doped with trace quantities of elements such as Cu, Zn and Sr, which are known to be beneficial for healthy bone growth. In addition to the new bioactive glasses, recent advances in biomaterials processing have resulted in the creation of scaffold architectures with a range of mechanical properties suitable for the substitution of loaded as well as non-loaded bone. While bioactive glass has been extensively investigated for bone repair, there has been relatively little research on the application of bioactive glass to the repair of soft tissues. However, recent work has shown the ability of bioactive glass to promote angiogenesis, which is critical to numerous applications in tissue regeneration, such as neovascularization for bone regeneration and the healing of soft tissue wounds. Bioactive glass has also been shown to enhance neocartilage formation during in vitro culture of chondrocyte-seeded hydrogels, and to serve as a subchondral substrate for tissue-engineered osteochondral constructs. Methods used to manipulate the structure and performance of bioactive glass in these tissue engineering applications are analyzed. PMID:21421084

  19. Complete genome sequence of Streptomyces venezuelae ATCC 15439, a promising cell factory for production of secondary metabolites.

    PubMed

    Song, Ju Yeon; Yoo, Young Ji; Lim, Si-Kyu; Cha, Sun Ho; Kim, Ji-Eun; Roe, Jung-Hye; Kim, Jihyun F; Yoon, Yeo Joon

    2016-02-10

    Streptomyces venezuelae ATCC 15439, which produces 12- and 14-membered ring macrolide antibiotics, is a platform strain for heterologous expression of secondary metabolites. Its 9.05-Mb genome sequence revealed an abundance of genes involved in the biosynthesis of secondary metabolites and their precursors, which should be useful for the production of bioactive compounds.

  20. Strategies for metabolite profiling based on liquid chromatography.

    PubMed

    Saurina, Javier; Sentellas, Sonia

    2017-02-15

    This paper aims at covering the principal strategies based on liquid chromatography (LC) for metabolite profiling in the field of drug discovery and development. The identification of metabolites generated in the organism is an important task during the early stages of preclinical research to define the most proper strategy for optimizing, adjusting metabolic clearance and minimizing bioactivation. An early assessment of the metabolite profile may be critical since metabolites can contribute to pharmacological and/or toxicological effects. The study of metabolites first involves their synthesis/generation and their further characterization and structural elucidation. For such a purpose, both in vitro and in vivo methods are commonly used for the generation of the corresponding metabolites. Next, analytical methods are used to tackle identification and characterization studies. Among the arsenal of techniques available in our labs, we will focus on LC, especially coupled to mass spectrometry (LC-MS), as one of the most powerful approaches for metabolite identification, characterization and quantification. Here, the topic of metabolite profiling based on LC will be addressed and representative examples of different possibilities will be discussed.

  1. Enhanced production of phenazine-like metabolite produced by Streptomyces aurantiogriseus VSMGT1014 against rice pathogen, Rhizoctonia solani.

    PubMed

    Harikrishnan, Hariharan; Shanmugaiah, Vellasamy; Nithya, Karmegham; Balasubramanian, Natesan; Sharma, Mahaveer P; Gachomo, Emma W; Kotchoni, Simeon O

    2016-02-01

    The efficacy of a rhizobacterium Streptomyces aurantiogriseus VSMGT1014 for the production of bioactive metabolites with antifungal properties was evaluated under in vitro conditions. The production of bioactive metabolites by S. aurantiogriseus VSMGT1014 in International Streptomyces Project-2 (ISP-2) broth, supplemented with glucose and ammonium acetate was found to be the most suitable carbon and nitrogen sources for the maximum production of bioactive metabolites against rice pathogen, Rhizoctonia solani. The zone of inhibition range from 23.5 to 28.5 mm and 10.3 to 18.3 mm for glucose and ammonium acetate supplemented media, respectively. The culture filtrate of S. aurantiogriseus VSMGT1014 at pH 7.5, 37 °C at 120 rpm in 6 days of incubation showed the maximum production of bioactive metabolites with antagonistic potential. The crude metabolite was characterized by different spectral studies such as Ultraviolet spectrum, infrared-spectrum and based on the different analytical techniques, including thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) with the retention time 29.4 and the bioactive metabolite was identified as phenazine, which was confirmed by pure phenazine compound as positive control.

  2. Pharmacokinetics of Tyrosol Metabolites in Rats.

    PubMed

    Lee, Da-Hye; Kim, Yang-Ji; Kim, Min Jung; Ahn, Jiyun; Ha, Tae-Youl; Lee, Sang Hee; Jang, Young Jin; Jung, Chang Hwa

    2016-01-21

    Tyrosol is considered a potential antioxidant; however, little is known regarding the pharmacokinetics of its metabolites. To study the pharmacokinetics of tyrosol-derived metabolites after oral administration of a single dose of tyrosol, we attempted to identify tyrosol metabolites in rat plasma by using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Two tyrosol metabolites (M1 and M2) were detected in the plasma. M1 was identified as tyrosol-4-sulfate (T4S) with an [M - H](-) ion at m/z 217. While M2 showed an [M - H](-) ion at m/z 151.0, its metabolite was not identified. Pharmacokinetic analysis of T4S and M2 showed rapid uptake after oral administration of tyrosol within 1 h. The metabolites were rapidly distributed in most organs and tissues and eliminated within 4 h. The greatest T4S deposition by tissue weight was observed in the liver, followed by the kidney and spleen, while M2 was most concentrated in the kidney followed by the liver and spleen. These findings indicate that T4S and M2 were distributed mainly in tissues with an abundant blood supply and were rapidly excreted in urine.

  3. Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health.

    PubMed

    Lv, Xinmiao; Zhao, Siyu; Ning, Zhangchi; Zeng, Honglian; Shu, Yisong; Tao, Ou; Xiao, Cheng; Lu, Cheng; Liu, Yuanyan

    2015-01-01

    Citrus fruits, which are cultivated worldwide, have been recognized as some of the most high-consumption fruits in terms of energy, nutrients and health supplements. What is more, a number of these fruits have been used as traditional medicinal herbs to cure diseases in several Asian countries. Numerous studies have focused on Citrus secondary metabolites as well as bioactivities and have been intended to develop new chemotherapeutic or complementary medicine in recent decades. Citrus-derived secondary metabolites, including flavonoids, alkaloids, limonoids, coumarins, carotenoids, phenolic acids and essential oils, are of vital importance to human health due to their active properties. These characteristics include anti-oxidative, anti-inflammatory, anti-cancer, as well as cardiovascular protective effects, neuroprotective effects, etc. This review summarizes the global distribution and taxonomy, numerous secondary metabolites and bioactivities of Citrus fruits to provide a reference for further study. Flavonoids as characteristic bioactive metabolites in Citrus fruits are mainly introduced.

  4. Marine microorganism-invertebrate assemblages: perspectives to solve the "supply problem" in the initial steps of drug discovery.

    PubMed

    Leal, Miguel Costa; Sheridan, Christopher; Osinga, Ronald; Dionísio, Gisela; Rocha, Rui Jorge Miranda; Silva, Bruna; Rosa, Rui; Calado, Ricardo

    2014-06-30

    The chemical diversity associated with marine natural products (MNP) is unanimously acknowledged as the "blue gold" in the urgent quest for new drugs. Consequently, a significant increase in the discovery of MNP published in the literature has been observed in the past decades, particularly from marine invertebrates. However, it remains unclear whether target metabolites originate from the marine invertebrates themselves or from their microbial symbionts. This issue underlines critical challenges associated with the lack of biomass required to supply the early stages of the drug discovery pipeline. The present review discusses potential solutions for such challenges, with particular emphasis on innovative approaches to culture invertebrate holobionts (microorganism-invertebrate assemblages) through in toto aquaculture, together with methods for the discovery and initial production of bioactive compounds from these microbial symbionts.

  5. Marine Microorganism-Invertebrate Assemblages: Perspectives to Solve the “Supply Problem” in the Initial Steps of Drug Discovery

    PubMed Central

    Leal, Miguel Costa; Sheridan, Christopher; Osinga, Ronald; Dionísio, Gisela; Rocha, Rui Jorge Miranda; Silva, Bruna; Rosa, Rui; Calado, Ricardo

    2014-01-01

    The chemical diversity associated with marine natural products (MNP) is unanimously acknowledged as the “blue gold” in the urgent quest for new drugs. Consequently, a significant increase in the discovery of MNP published in the literature has been observed in the past decades, particularly from marine invertebrates. However, it remains unclear whether target metabolites originate from the marine invertebrates themselves or from their microbial symbionts. This issue underlines critical challenges associated with the lack of biomass required to supply the early stages of the drug discovery pipeline. The present review discusses potential solutions for such challenges, with particular emphasis on innovative approaches to culture invertebrate holobionts (microorganism-invertebrate assemblages) through in toto aquaculture, together with methods for the discovery and initial production of bioactive compounds from these microbial symbionts. PMID:24983638

  6. Preparation method: structure-bioactivity correlation in mesoporous bioactive glass

    NASA Astrophysics Data System (ADS)

    Shih, Shao-Ju; Chou, Yu-Jen; Borisenko, Konstantin B.

    2013-06-01

    Mesoporous bioactive glasses (MBGs) are receiving increased attention because of their superior bioactive properties and possible applications as drug-releasing carriers, bone implants and sealing materials in dentistry. We report here the results of investigation of structures and bioactivities of two types of MBG particles prepared by two different techniques, the sol-gel method and spray pyrolysis (SP). In this study, we used transmission electron microscopy and selected area electron diffraction to characterize particle morphology and atomistic structures of the particles correlating these observations with nitrogen adsorption measurements to determine surface areas of the particles and in vitro bioactivity tests. It is found that the preparation method can influence the final composition of the particles and that SP method offers a better control over the composition. The SP particles have higher bioactivity than the sol-gel particles due to their higher surface area and possibly more favourable atomistic structure for promoting deposition of pure hydroxyl apatite phase.

  7. Cytochromes P450 in the bioactivation of chemicals.

    PubMed

    Ioannides, Costas; Lewis, David F V

    2004-01-01

    The initial view that the cytochrome P450 enzyme system functions simply in the deactivation of xenobiotics is anachronistic on the face of mounting evidence that this system can also transform many innocuous chemicals to toxic products. However, not all xenobiotic-metabolising cytochrome P450 subfamilies show the same propensity in the bioactivation of chemicals. For example, the CYP2C, 2B and 2D subfamilies play virtually no role in the bioactivation of toxic and carcinogenic chemicals, whereas the CYP1A, 1B and 2E subfamilies are responsible for the bioactivation of the majority of xenobiotics. Electronic and molecular structural features of organic chemicals appear to predispose them to either bioactivation by one cytochrome P450 enzyme or deactivation by another. Consequently, the fate of a chemical in the body is largely dependent on the cytochrome P450 profile at the time of exposure. Any factor that modulates the enzymes involved in the metabolism of a certain chemical will also influence its toxicity and carcinogenicity. For example, many chemical carcinogens bioactivated by CYP1, on repeated administration, selectively induce this family, thus exacerbating their carcinogenicity. CYP1 induction potency by chemicals appears to be determined by a combination of their molecular shape and electron activation. The function of cytochromes P450 in the bioactivation of chemicals is currently being exploited to design systems that can be used clinically to facilitate the metabolic conversion of prodrugs to their biologically-active metabolites in cells that poorly express them, such as tumour cells, in the so-called gene-directed prodrug therapy.

  8. Bioactive peptides derived from food.

    PubMed

    Rutherfurd-Markwick, Kay J; Moughan, Paul J

    2005-01-01

    As interest in the ability of functional foods to impact on human health has grown over the past decade, so has the volume of knowledge detailing the beneficial roles of food-derived bioactive peptides. Bioactive peptides from both plant and animal proteins have been discovered, with to date, by far the most being isolated from milk-based products. A wide range of activities has been described, including antimicrobial and antifungal properties, blood pressure-lowering effects, cholesterol-lowering ability, antithrombotic effects, enhancement of mineral absorption, immunomodulatory effects, and localized effects on the gut. Although there is still considerable research to be performed in the area of food-derived bioactive peptides, it is clear that the generation of bioactive peptides from dietary proteins during the normal digestive process is of importance. Therefore, it will become necessary when determining dietary protein quality to consider the potential effects of latent bioactive peptides that are released during digestion of the protein.

  9. Anti-fouling bioactive surfaces.

    PubMed

    Yu, Qian; Zhang, Yanxia; Wang, Hongwei; Brash, John; Chen, Hong

    2011-04-01

    Bioactive surfaces refer to surfaces with immobilized bioactive molecules aimed specifically at promoting or supporting particular interactions. Such surfaces are of great importance for various biomedical and biomaterials applications. In the past few years, considerable effort has been made to create bioactive surfaces by forming specific biomolecule-modified surfaces on a non-biofouling "base" or "background". Hydrophilic and bioinert polymers have been widely used as anti-fouling layers that resist non-specific protein interactions. They can also serve as "spacers" to effectively move the immobilized biomolecule away from the surface, thus enhancing its bioactivity. In this review we summarize several successful approaches for the design and preparation of bioactive surfaces based on different types of anti-fouling/spacer materials. Some perspectives on future research in this area are also presented.

  10. A High-Resolution LC-MS-Based Secondary Metabolite Fingerprint Database of Marine Bacteria

    PubMed Central

    Lu, Liang; Wang, Jijie; Xu, Ying; Wang, Kailing; Hu, Yingwei; Tian, Renmao; Yang, Bo; Lai, Qiliang; Li, Yongxin; Zhang, Weipeng; Shao, Zongze; Lam, Henry; Qian, Pei-Yuan

    2014-01-01

    Marine bacteria are the most widely distributed organisms in the ocean environment and produce a wide variety of secondary metabolites. However, traditional screening for bioactive natural compounds is greatly hindered by the lack of a systematic way of cataloguing the chemical profiles of bacterial strains found in nature. Here we present a chemical fingerprint database of marine bacteria based on their secondary metabolite profiles, acquired by high-resolution LC-MS. Till now, 1,430 bacterial strains spanning 168 known species collected from different marine environments were cultured and profiled. Using this database, we demonstrated that secondary metabolite profile similarity is approximately, but not always, correlated with taxonomical similarity. We also validated the ability of this database to find species-specific metabolites, as well as to discover known bioactive compounds from previously unknown sources. An online interface to this database, as well as the accompanying software, is provided freely for the community to use. PMID:25298017

  11. A high-resolution LC-MS-based secondary metabolite fingerprint database of marine bacteria.

    PubMed

    Lu, Liang; Wang, Jijie; Xu, Ying; Wang, Kailing; Hu, Yingwei; Tian, Renmao; Yang, Bo; Lai, Qiliang; Li, Yongxin; Zhang, Weipeng; Shao, Zongze; Lam, Henry; Qian, Pei-Yuan

    2014-10-09

    Marine bacteria are the most widely distributed organisms in the ocean environment and produce a wide variety of secondary metabolites. However, traditional screening for bioactive natural compounds is greatly hindered by the lack of a systematic way of cataloguing the chemical profiles of bacterial strains found in nature. Here we present a chemical fingerprint database of marine bacteria based on their secondary metabolite profiles, acquired by high-resolution LC-MS. Till now, 1,430 bacterial strains spanning 168 known species collected from different marine environments were cultured and profiled. Using this database, we demonstrated that secondary metabolite profile similarity is approximately, but not always, correlated with taxonomical similarity. We also validated the ability of this database to find species-specific metabolites, as well as to discover known bioactive compounds from previously unknown sources. An online interface to this database, as well as the accompanying software, is provided freely for the community to use.

  12. Bioactive peptides and proteins from foods: indication for health effects.

    PubMed

    Möller, Niels Peter; Scholz-Ahrens, Katharina Elisabeth; Roos, Nils; Schrezenmeir, Jürgen

    2008-06-01

    Some dietary proteins cause specific effects going beyond nutrient supply. A number of proteins seem to act directly in the intestine, such as IGFs, lactoferrin and immunoglobulins. Many substances, however, are peptides encrypted in intact molecules and are released from their encrypted position by enzymes during gastrointestinal transit or by fermentation or ripening during food processing. Among food-derived bioactive proteins and peptides from plants and animals, those obtained from milk are known in particular. Numerous effects have been described after in vitro and animal trials for bioactive proteins and peptides, such as immunomodulating, antihypertensive, osteoprotective, antilipemic, opiate, antioxidative and antimicrobial. This article reviews the current knowledge of the existence of bioactive proteins and of in vitro bioactivity and the present evidence of health effects exerted by such substances or products containing bioactive compounds. For example, there is evidence for the antihypertensive effects of milk products fermented with Lactobacillus helveticus containing the tripeptides IPP and VPP, which inhibit angiotensin converting enzyme, and for osteoprotective effects by milk basic protein. There is less profound evidence on the immunomodulating effects of lactoferrin and postprandial triglyceride reduction by a hydrolysate of bovine hemoglobin.

  13. Nursing Supplies

    MedlinePlus

    ... Stages Listen Español Text Size Email Print Share Nursing Supplies Page Content Article Body Throughout most of ... budget. (Nursing equipment also makes wonderful baby gifts.) Nursing Bras A well-made nursing bra that comfortably ...

  14. Study on bioactive compounds from Streptomyces sp. ANU 6277.

    PubMed

    Narayana, Kolla J P; Prabhakar, Peddikotla; Vijayalakshmi, Muvva; Venkateswarlu, Yenamandra; Krishna, Palakodety S J

    2008-01-01

    An attempt was made to study the bioactive compounds from a terrestrial Streptomyces sp. ANU 6277 isolated from laterite soil. Four active fractions were recovered from the solvent extracts obtained from the culture broth of five day-old strain. Three bioactive compounds were purified and identified as 3-phenylpropionic acid, anthracene-9,10-quinone and 8-hydroxyquinoline. The components of the partially purified fourth active fraction were analyzed by gas chromatography-mass spectrometry and identified as benzyl alcohol, phenylethyl alcohol and 2H-1, 4-benzoxazin-3 (4H)-one. Four active fractions were screened for antimicrobial activity against Gram-positive and Gram-negative bacteria, and fungi including phytopathogenic, toxigenic and dermatophytic genera. Among these metabolites, 8-hydroxyquinoline exhibited strong antibacterial and antifungal activity as compared to 3-phenylpropionic acid and anthracene-9,10-quinone.

  15. Bioactive materials in endodontics.

    PubMed

    Enkel, Bénédicte; Dupas, Cécile; Armengol, Valérie; Akpe Adou, Jonas; Bosco, Julia; Daculsi, Guy; Jean, Alain; Laboux, Olivier; LeGeros, Racquel Z; Weiss, Pierre

    2008-07-01

    Endodontic treatment in dentistry is a delicate procedure and many treatment attempts fail. Despite constant development of new root canal filling techniques, the clinician is confronted with both a complex root canal system and the use of filling materials that are harmful for periapical tissues. This paper evaluates reported studies on biomaterials used in endodontics, including calcium hydroxide, mineral trioxide aggregate, calcium phosphate ceramics and calcium phosphate cements. Special emphasis is made on promising new biomaterials, such as injectable bone substitute and injectable calcium phosphate cements. These materials, which combine biocompatibility, bioactivity and rheological properties, could be good alternatives in endodontics as root canal fillers. They could also be used as drug-delivery vehicles (e.g., for antibiotics and growth factors) or as scaffolds in pulp tissue engineering.

  16. Bioactivities from Marine Algae of the Genus Gracilaria

    PubMed Central

    de Almeida, Cynthia Layse F.; Falcão, Heloina de S.; Lima, Gedson R. de M.; Montenegro, Camila de A.; Lira, Narlize S.; de Athayde-Filho, Petrônio F.; Rodrigues, Luis C.; de Souza, Maria de Fátima V.; Barbosa-Filho, José M.; Batista, Leônia M.

    2011-01-01

    Seaweeds are an important source of bioactive metabolites for the pharmaceutical industry in drug development. Many of these compounds are used to treat diseases like cancer, acquired immune-deficiency syndrome (AIDS), inflammation, pain, arthritis, as well as viral, bacterial, and fungal infections. This paper offers a survey of the literature for Gracilaria algae extracts with biological activity, and identifies avenues for future research. Nineteen species of this genus that were tested for antibacterial, antiviral, antifungal, antihypertensive, cytotoxic, spermicidal, embriotoxic, and anti-inflammatory activities are cited from the 121 references consulted. PMID:21845096

  17. Bioactivity of Fungal Endophytes as a Function of Endophyte Taxonomy and the Taxonomy and Distribution of Their Host Plants

    PubMed Central

    Higginbotham, Sarah J.; Arnold, A. Elizabeth; Ibañez, Alicia; Spadafora, Carmenza; Coley, Phyllis D.; Kursar, Thomas A.

    2013-01-01

    Fungal endophytes – fungi that grow within plant tissues without causing immediate signs of disease – are abundant and diverse producers of bioactive secondary metabolites. Endophytes associated with leaves of tropical plants are an especially exciting and relatively untapped source of novel compounds. However, one major challenge in drug discovery lies in developing strategies to efficiently recover highly bioactive strains. As part of a 15-year drug discovery project, foliar endophytes were isolated from 3198 plant samples (51 orders, 105 families and at least 232 genera of angiosperms and ferns) collected in nine geographically distinct regions of Panama. Extracts from culture supernatants of >2700 isolates were tested for bioactivity (in vitro percent inhibition of growth, % IG) against a human breast cancer cell line (MCF-7) and the causative agents of malaria, leishmaniasis, and Chagas' disease. Overall, 32.7% of endophyte isolates were highly active in at least one bioassay, including representatives of diverse fungal lineages, host lineages, and collection sites. Up to 17% of isolates tested per assay were highly active. Most bioactive strains were active in only one assay. Fungal lineages differed in the incidence and degree of bioactivity, as did fungi from particular plant taxa, and greater bioactivity was observed in endophytes isolated from plants in cloud forests vs. lowland forests. Our results suggest that using host taxonomy and forest type to tailor plant collections, and selecting endophytes from specific orders or families for cultivation, will markedly increase the efficiency and efficacy of discovering bioactive metabolites for particular pharmaceutical targets. PMID:24066037

  18. Bioactive Glass for Large Bone Repair.

    PubMed

    Jia, Weitao; Lau, Grace Y; Huang, Wenhai; Zhang, Changqing; Tomsia, Antoni P; Fu, Qiang

    2015-12-30

    There has been an ongoing quest for new biomedical materials for the repair and regeneration of large segmental bone defects caused by disease or trauma. Autologous bone graft (ABG) remains the gold standard for bone repair despite their limited supply and donor-site morbidity. The current tissue engineering approach with synthetically derived bone grafts requires a bioactive ceramic or polymeric scaffold loaded with growth factors for osteoinduction and angiogenesis, and bone marrow stromal cells (BMSCs) for osteogenic properties. Unfortunately, this approach has serious drawbacks: the low mechanical strength of scaffolds, the high cost of growth factors, and a lack of optimal strategies for growth-factor delivery. Here, it is shown that, for the first time, a synthetic material alone can repair large bone defects as efficiently as the gold standard ABG. Through the use of strong and resorbable bioactive glass scaffolds, complete bone healing, and defect bridging can be achieved in a rabbit femur segmental defect model without growth factors or BMSCs. New bone and blood vessel formation, in both inner and peripheral scaffolds, demonstrates the excellent osteoinductive and osteogenic properties of these scaffolds similar as ABG.

  19. Elicitation: a tool for enriching the bioactive composition of foods.

    PubMed

    Baenas, Nieves; García-Viguera, Cristina; Moreno, Diego A

    2014-09-01

    Elicitation is a good strategy to induce physiological changes and stimulate defense or stress-induced responses in plants. The elicitor treatments trigger the synthesis of phytochemical compounds in fruits, vegetables and herbs. These metabolites have been widely investigated as bioactive compounds responsible of plant cell adaptation to the environment, specific organoleptic properties of foods, and protective effects in human cells against oxidative processes in the development of neurodegenerative and cardiovascular diseases and certain types of cancer. Biotic (biological origin), abiotic (chemical or physical origin) elicitors and phytohormones have been applied alone or in combinations, in hydroponic solutions or sprays, and in different selected time points of the plant growth or during post-harvest. Understanding how plant tissues and their specific secondary metabolic pathways respond to specific treatments with elicitors would be the basis for designing protocols to enhance the production of secondary metabolites, in order to produce quality and healthy fresh foods.

  20. Richness and bioactivity of culturable soil fungi from the Fildes Peninsula, Antarctica.

    PubMed

    Ding, Zhuang; Li, Liyuan; Che, Qian; Li, Dehai; Gu, Qianqun; Zhu, Tianjiao

    2016-07-01

    Since the discovery of penicillin, fungi have been an important source of bioactive natural products. However, as a specific resource, the bioactive potentiality and specificity of fungal metabolites from the Antarctic region have had little attention. In this paper, we investigated the diversity patterns and biological activities of cultivable fungi isolated from soil samples in Fildes Peninsula, King George Island, Antarctica. Fungal communities showed low abundance and diversity; a total of 150 cultivable fungi were isolated from eight soil samples. After being dereplicated by morphological characteristics and chemical fingerprints, 47 fungal isolates were identified by ITS-rDNA sequencing. We confirmed that these isolates belonged to at least 11 different genera and clustered into nine groups corresponding to taxonomic orders in the phylogenetic analysis. Using two different fermentation conditions, 94 crude extracts acquired from the abovementioned different metabolite characteristic isolates were screened by bioactivity assay and 18 isolates produced biologically active compounds. Compared with HPLC-DAD-UV fingerprint analysis of culture extracts and standard compounds, two bioactive components secalonic acid and chetracins were identified. Our research suggests that the abundance and diversity of Antarctic cultivable fungal communities exhibit unique ecological characteristics and potential producers of novel natural bioactive products.

  1. Modulation of antimicrobial metabolites production by the fungus Aspergillus parasiticus

    PubMed Central

    Bracarense, Adriana A.P.; Takahashi, Jacqueline A.

    2014-01-01

    Biosynthesis of active secondary metabolites by fungi occurs as a specific response to the different growing environments. Changes in this environment alter the chemical and biological profiles leading to metabolites diversification and consequently to novel pharmacological applications. In this work, it was studied the influence of three parameters (fermentation length, medium composition and aeration) in the biosyntheses of antimicrobial metabolites by the fungus Aspergillus parasiticus in 10 distinct fermentation periods. Metabolism modulation in two culturing media, CYA and YES was evaluated by a 22 full factorial planning (ANOVA) and on a 23 factorial planning, role of aeration, medium composition and carbohydrate concentration were also evaluated. In overall, 120 different extracts were prepared, their HPLC profiles were obtained and the antimicrobial activity against A. flavus, C. albicans, E. coli and S. aureus of all extracts was evaluated by microdilution bioassay. Yield of kojic acid, a fine chemical produced by the fungus A. parasiticus was determined in all extracts. Statistical analyses pointed thirteen conditions able to modulate the production of bioactive metabolites by A. parasiticus. Effect of carbon source in metabolites diversification was significant as shown by the changes in the HPLC profiles of the extracts. Most of the extracts presented inhibition rates higher than that of kojic acid as for the extract obtained after 6 days of fermentation in YES medium under stirring. Kojic acid was not the only metabolite responsible for the activity since some highly active extracts showed to possess low amounts of this compound, as determined by HPLC. PMID:24948950

  2. Bioactive Glasses: Frontiers and Challenges

    PubMed Central

    Hench, Larry L.; Jones, Julian R.

    2015-01-01

    Bioactive glasses were discovered in 1969 and provided for the first time an alternative to nearly inert implant materials. Bioglass formed a rapid, strong, and stable bond with host tissues. This article examines the frontiers of research crossed to achieve clinical use of bioactive glasses and glass–ceramics. In the 1980s, it was discovered that bioactive glasses could be used in particulate form to stimulate osteogenesis, which thereby led to the concept of regeneration of tissues. Later, it was discovered that the dissolution ions from the glasses behaved like growth factors, providing signals to the cells. This article summarizes the frontiers of knowledge crossed during four eras of development of bioactive glasses that have led from concept of bioactivity to widespread clinical and commercial use, with emphasis on the first composition, 45S5 Bioglass®. The four eras are (a) discovery, (b) clinical application, (c) tissue regeneration, and (d) innovation. Questions still to be answered for the fourth era are included to stimulate innovation in the field and exploration of new frontiers that can be the basis for a general theory of bioactive stimulation of regeneration of tissues and application to numerous clinical needs. PMID:26649290

  3. Bioactive Glasses: Frontiers and Challenges.

    PubMed

    Hench, Larry L; Jones, Julian R

    2015-01-01

    Bioactive glasses were discovered in 1969 and provided for the first time an alternative to nearly inert implant materials. Bioglass formed a rapid, strong, and stable bond with host tissues. This article examines the frontiers of research crossed to achieve clinical use of bioactive glasses and glass-ceramics. In the 1980s, it was discovered that bioactive glasses could be used in particulate form to stimulate osteogenesis, which thereby led to the concept of regeneration of tissues. Later, it was discovered that the dissolution ions from the glasses behaved like growth factors, providing signals to the cells. This article summarizes the frontiers of knowledge crossed during four eras of development of bioactive glasses that have led from concept of bioactivity to widespread clinical and commercial use, with emphasis on the first composition, 45S5 Bioglass(®). The four eras are (a) discovery, (b) clinical application, (c) tissue regeneration, and (d) innovation. Questions still to be answered for the fourth era are included to stimulate innovation in the field and exploration of new frontiers that can be the basis for a general theory of bioactive stimulation of regeneration of tissues and application to numerous clinical needs.

  4. Power supply

    DOEpatents

    Yakymyshyn, Christopher Paul; Hamilton, Pamela Jane; Brubaker, Michael Allen

    2007-12-04

    A modular, low weight impedance dropping power supply with battery backup is disclosed that can be connected to a high voltage AC source and provide electrical power at a lower voltage. The design can be scaled over a wide range of input voltages and over a wide range of output voltages and delivered power.

  5. Glucosinolates in broccoli sprouts (Brassica oleracea var. italica) as conditioned by sulphate supply during germination.

    PubMed

    Pérez-Balibrea, Santiago; Moreno, Diego A; García-Viguera, Cristina

    2010-10-01

    Sulphur (S) fertilization is essential for primary and secondary metabolism in cruciferous foods. Deficient, suboptimal, or excessive S affects the growth and biosynthesis of secondary metabolites in adult plants. Nevertheless, there is little information regarding the influence of S fertilization on sprouts and seedlings. An experiment was set up to evaluate the effect of S fertilization, supplied as K(2)SO(4) at 0, 15, 30, and 60 mg/L, on the glucosinolate content of broccoli sprouts during the germination course of 3, 6, 9, and 12 d after sowing. Glucosinolate concentration was strongly influenced by germination, causing a rapid increase during the first 3 d after sowing, and decreasing afterwards. The S supply increased aliphatic and total glucosinolate content at the end of the monitored sprouting period. S-treated sprouts, with S(15), S(30), and S(60) at 9 and 12 d after sowing presented enhanced glucosinolate content. Overall, both germination time and S fertilization were key factors in maximizing the bioactive health-promoting phytochemicals of broccoli. Practical Application: Germination with sulphate is a simple and inexpensive way to obtain sprouts that contain much higher levels of glucosinolates (health promoting compounds), than the corresponding florets from the same seeds.

  6. Enhanced metabolite generation

    DOEpatents

    Chidambaram, Devicharan [Middle Island, NY

    2012-03-27

    The present invention relates to the enhanced production of metabolites by a process whereby a carbon source is oxidized with a fermentative microbe in a compartment having a portal. An electron acceptor is added to the compartment to assist the microbe in the removal of excess electrons. The electron acceptor accepts electrons from the microbe after oxidation of the carbon source. Other transfers of electrons can take place to enhance the production of the metabolite, such as acids, biofuels or brewed beverages.

  7. Major Australian tropical fruits biodiversity: bioactive compounds and their bioactivities.

    PubMed

    Pierson, Jean T; Dietzgen, Ralf G; Shaw, Paul N; Roberts-Thomson, Sarah J; Monteith, Gregory R; Gidley, Michael J

    2012-03-01

    The plant kingdom harbours many diverse bioactive molecules of pharmacological relevance. Temperate fruits and vegetables have been highly studied in this regard, but there have been fewer studies of fruits and vegetables from the tropics. As global consumers demand and are prepared to pay for new appealing and exotic foods, tropical fruits are now being more intensively investigated. Polyphenols and major classes of compounds like flavonoids or carotenoids are ubiquitously present in these fruits, as they are in the temperate ones, but particular classes of compounds are unique to tropical fruits and other plant parts. Bioactivity studies of compounds specific to tropical fruit plants may lead to new drug discoveries, while the synergistic action of the wide range of diverse compounds contained in plant extracts underlies nutritional and health properties of tropical fruits and vegetables. The evidence for in vitro and animal bioactivities is a strong indicator of the pharmacological promise shown in tropical fruit plant biodiversity. In this review, we will discuss both the occurrence of potential bioactive compounds isolated and identified from a selection of tropical fruit plants of importance in Australia, as well as recent studies of bioactivity associated with such fruits and other fruit plant parts.

  8. In silico prediction and automatic LC-MS(n) annotation of green tea metabolites in urine.

    PubMed

    Ridder, Lars; van der Hooft, Justin J J; Verhoeven, Stefan; de Vos, Ric C H; Vervoort, Jacques; Bino, Raoul J

    2014-05-20

    The colonic breakdown and human biotransformation of small molecules present in food can give rise to a large variety of potentially bioactive metabolites in the human body. However, the absence of reference data for many of these components limits their identification in complex biological samples, such as plasma and urine. We present an in silico workflow for automatic chemical annotation of metabolite profiling data from liquid chromatography coupled with multistage accurate mass spectrometry (LC-MS(n)), which we used to systematically screen for the presence of tea-derived metabolites in human urine samples after green tea consumption. Reaction rules for intestinal degradation and human biotransformation were systematically applied to chemical structures of 75 green tea components, resulting in a virtual library of 27,245 potential metabolites. All matching precursor ions in the urine LC-MS(n) data sets, as well as the corresponding fragment ions, were automatically annotated by in silico generated (sub)structures. The results were evaluated based on 74 previously identified urinary metabolites and lead to the putative identification of 26 additional green tea-derived metabolites. A total of 77% of all annotated metabolites were not present in the Pubchem database, demonstrating the benefit of in silico metabolite prediction for the automatic annotation of yet unknown metabolites in LC-MS(n) data from nutritional metabolite profiling experiments.

  9. Power supply

    DOEpatents

    Hart, Edward J.; Leeman, James E.; MacDougall, Hugh R.; Marron, John J.; Smith, Calvin C.

    1976-01-01

    An electric power supply employs a striking means to initiate ferroelectric elements which provide electrical energy output which subsequently initiates an explosive charge which initiates a second ferroelectric current generator to deliver current to the coil of a magnetic field current generator, creating a magnetic field around the coil. Continued detonation effects compression of the magnetic field and subsequent generation and delivery of a large output current to appropriate output loads.

  10. Influence of abiotic stress signals on secondary metabolites in plants

    PubMed Central

    Ramakrishna, Akula; Ravishankar, Gokare Aswathanarayana

    2011-01-01

    Plant secondary metabolites are unique sources for pharmaceuticals, food additives, flavors, and industrially important biochemicals. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. Secondary metabolites play a major role in the adaptation of plants to the environment and in overcoming stress conditions. Environmental factors viz. temperature, humidity, light intensity, the supply of water, minerals, and CO2 influence the growth of a plant and secondary metabolite production. Drought, high salinity, and freezing temperatures are environmental conditions that cause adverse effects on the growth of plants and the productivity of crops. Plant cell culture technologies have been effective tools for both studying and producing plant secondary metabolites under in vitro conditions and for plant improvement. This brief review summarizes the influence of different abiotic factors include salt, drought, light, heavy metals, frost etc. on secondary metabolites in plants. The focus of the present review is the influence of abiotic factors on secondary metabolite production and some of important plant pharmaceuticals. Also, we describe the results of in vitro cultures and production of some important secondary metabolites obtained in our laboratory. PMID:22041989

  11. Secondary metabolites of endophytic Xylaria species with potential applications in medicine and agriculture.

    PubMed

    Macías-Rubalcava, Martha Lydia; Sánchez-Fernández, Rosa Elvira

    2017-01-01

    Fungal endophytes are important sources of bioactive secondary metabolites. The genus Xylaria Hill (ex Schrank, 1789, Xylariaceae) comprises various endophytic species associated to both vascular and non vascular plants. The secondary metabolites produced by Xylaria species include a variety of volatile and non-volatile compounds. Examples of the former are sesquiterpenoids, esters, and alcohols, among others; and of the latter we find terpenoids, cytochalasins, mellein, alkaloids, polyketides, and aromatic compounds. Some of these metabolites have shown potential activity as herbicides, fungicides, and insecticides; others possess antibacterial, antimalarial, and antifungal activities, or α-glucosidase inhibitory activity. Thus metabolites from Xylaria are promising compounds for applications in agriculture for plague control as biopesticides, and biocontrol agents; and in medicine, for example as drugs for the treatment of infectious and non-infectious diseases. This review seeks to show the great value of the secondary metabolites of Xylaria, particularly in the agriculture and medicine fields.

  12. Isolation and characterization of bioactive fungi from shark Carcharodon carcharias' gill with biopharmaceutical prospects

    NASA Astrophysics Data System (ADS)

    Zhang, Yi; Han, Jinyuan; Feng, Yan; Mu, Jun; Bao, Haiyan; Kulik, Andreas; Grond, Stephanie

    2016-01-01

    Until recently, little was known about the fungi found in shark gills and their biomedicinal potential. In this article, we described the isolation, bioactivity, diversity, and secondary metabolites of bioactive fungi from the gill of a shark ( Carcharodon carcharias). A total of 115 isolates were obtained and grown in 12 culture media. Fifty-eight of these isolates demonstrated significant activity in four antimicrobial, pesticidal, and cytotoxic bioassay models. Four randomly selected bioactive isolates inhibited human cancer cell proliferation during re-screening. These active isolates were segregated into 6 genera using the internal transcribed spacer-large subunit (ITS-LSU) rDNA-sequence BLAST comparison. Four genera, Penicillium, Aspergillus, Mucor, and Chaetomium were the dominant taxa. A phylogenic tree illustrated their intergenera and intragenera genetic diversity. HPLC-DAD-HRMS analysis and subsequent database searching revealed that nine representative strains produced diverse bioactive compound profiles. These results detail the broad range of bioactive fungi found in a shark's gills, revealing their biopharmaceutical potential. To the best of our knowledge, this is the first study characterizing shark gill fungi and their bioactivity.

  13. Preliminary Study on the In vitro and In vivo Effects of Asparagopsis taxiformis Bioactive Phycoderivates on Teleosts

    PubMed Central

    Marino, Fabio; Di Caro, Gianfranco; Gugliandolo, Concetta; Spanò, Antonio; Faggio, Caterina; Genovese, Giuseppa; Morabito, Marina; Russo, Annamaria; Barreca, Davide; Fazio, Francesco; Santulli, Andrea

    2016-01-01

    Several compounds from marine organisms have been studied for their potential use in aquaculture. Among the red algae, Asparagopsis taxiformis is considered one of the most promising species for the production of bioactive metabolites with numerous proposed applications. Here, the in vitro antibacterial activity, the easy handling and the absence of adverse effects on marine fish species are reported. Depending on the seasonal period of sampling, ethanol extracts of A. taxiformis exhibited significantly different inhibitory activity against fish pathogenic bacteria. The extract obtained in late spring showed strong antibacterial activity against Aeromonas salmonicida subsp. salmonicida, Vibrio alginolyticus, and V. vulnificus, and moderate activity against Photobacterium damselae subsp. damselae, P. damselae subsp. piscicida, V. harveyi and V. parahaemolyticus. Sea bass and gilthead sea bream were fed with pellets supplied with the alga and algal extracts. The absence of undesired effects on fish was demonstrated. Hematological and biochemical investigations allowed to confirm that the whole alga and its extracts could be proposed for a future application in aquaculture. PMID:27826246

  14. Preliminary Study on the In vitro and In vivo Effects of Asparagopsis taxiformis Bioactive Phycoderivates on Teleosts.

    PubMed

    Marino, Fabio; Di Caro, Gianfranco; Gugliandolo, Concetta; Spanò, Antonio; Faggio, Caterina; Genovese, Giuseppa; Morabito, Marina; Russo, Annamaria; Barreca, Davide; Fazio, Francesco; Santulli, Andrea

    2016-01-01

    Several compounds from marine organisms have been studied for their potential use in aquaculture. Among the red algae, Asparagopsis taxiformis is considered one of the most promising species for the production of bioactive metabolites with numerous proposed applications. Here, the in vitro antibacterial activity, the easy handling and the absence of adverse effects on marine fish species are reported. Depending on the seasonal period of sampling, ethanol extracts of A. taxiformis exhibited significantly different inhibitory activity against fish pathogenic bacteria. The extract obtained in late spring showed strong antibacterial activity against Aeromonas salmonicida subsp. salmonicida, Vibrio alginolyticus, and V. vulnificus, and moderate activity against Photobacterium damselae subsp. damselae, P. damselae subsp. piscicida, V. harveyi and V. parahaemolyticus. Sea bass and gilthead sea bream were fed with pellets supplied with the alga and algal extracts. The absence of undesired effects on fish was demonstrated. Hematological and biochemical investigations allowed to confirm that the whole alga and its extracts could be proposed for a future application in aquaculture.

  15. Transportable hyperpolarized metabolites

    NASA Astrophysics Data System (ADS)

    Ji, Xiao; Bornet, Aurélien; Vuichoud, Basile; Milani, Jonas; Gajan, David; Rossini, Aaron J.; Emsley, Lyndon; Bodenhausen, Geoffrey; Jannin, Sami

    2017-01-01

    Nuclear spin hyperpolarization of 13C-labelled metabolites by dissolution dynamic nuclear polarization can enhance the NMR signals of metabolites by several orders of magnitude, which has enabled in vivo metabolic imaging by MRI. However, because of the short lifetime of the hyperpolarized magnetization (typically <1 min), the polarization process must be carried out close to the point of use. Here we introduce a concept that markedly extends hyperpolarization lifetimes and enables the transportation of hyperpolarized metabolites. The hyperpolarized sample can thus be removed from the polarizer and stored or transported for use at remote MRI or NMR sites. We show that hyperpolarization in alanine and glycine survives 16 h storage and transport, maintaining overall polarization enhancements of up to three orders of magnitude.

  16. Transportable hyperpolarized metabolites

    PubMed Central

    Ji, Xiao; Bornet, Aurélien; Vuichoud, Basile; Milani, Jonas; Gajan, David; Rossini, Aaron J.; Emsley, Lyndon; Bodenhausen, Geoffrey; Jannin, Sami

    2017-01-01

    Nuclear spin hyperpolarization of 13C-labelled metabolites by dissolution dynamic nuclear polarization can enhance the NMR signals of metabolites by several orders of magnitude, which has enabled in vivo metabolic imaging by MRI. However, because of the short lifetime of the hyperpolarized magnetization (typically <1 min), the polarization process must be carried out close to the point of use. Here we introduce a concept that markedly extends hyperpolarization lifetimes and enables the transportation of hyperpolarized metabolites. The hyperpolarized sample can thus be removed from the polarizer and stored or transported for use at remote MRI or NMR sites. We show that hyperpolarization in alanine and glycine survives 16 h storage and transport, maintaining overall polarization enhancements of up to three orders of magnitude. PMID:28072398

  17. Brain-targeted proanthocyanidin metabolites for Alzheimer's disease treatment.

    PubMed

    Wang, Jun; Ferruzzi, Mario G; Ho, Lap; Blount, Jack; Janle, Elsa M; Gong, Bing; Pan, Yong; Gowda, G A Nagana; Raftery, Daniel; Arrieta-Cruz, Isabel; Sharma, Vaishali; Cooper, Bruce; Lobo, Jessica; Simon, James E; Zhang, Chungfen; Cheng, Alice; Qian, Xianjuan; Ono, Kenjiro; Teplow, David B; Pavlides, Constantine; Dixon, Richard A; Pasinetti, Giulio M

    2012-04-11

    While polyphenolic compounds have many health benefits, the potential development of polyphenols for the prevention/treatment of neurological disorders is largely hindered by their complexity as well as by limited knowledge regarding their bioavailability, metabolism, and bioactivity, especially in the brain. We recently demonstrated that dietary supplementation with a specific grape-derived polyphenolic preparation (GP) significantly improves cognitive function in a mouse model of Alzheimer's disease (AD). GP is comprised of the proanthocyanidin (PAC) catechin and epicatechin in monomeric (Mo), oligomeric, and polymeric forms. In this study, we report that following oral administration of the independent GP forms, only Mo is able to improve cognitive function and only Mo metabolites can selectively reach and accumulate in the brain at a concentration of ∼400 nM. Most importantly, we report for the first time that a biosynthetic epicatechin metabolite, 3'-O-methyl-epicatechin-5-O-β-glucuronide (3'-O-Me-EC-Gluc), one of the PAC metabolites identified in the brain following Mo treatment, promotes basal synaptic transmission and long-term potentiation at physiologically relevant concentrations in hippocampus slices through mechanisms associated with cAMP response element binding protein (CREB) signaling. Our studies suggest that select brain-targeted PAC metabolites benefit cognition by improving synaptic plasticity in the brain, and provide impetus to develop 3'-O-Me-EC-Gluc and other brain-targeted PAC metabolites to promote learning and memory in AD and other forms of dementia.

  18. Current approaches toward production of secondary plant metabolites

    PubMed Central

    Hussain, Md. Sarfaraj; Fareed, Sheeba; Ansari, Saba; Rahman, Md. Akhlaquer; Ahmad, Iffat Zareen; Saeed, Mohd.

    2012-01-01

    Plants are the tremendous source for the discovery of new products with medicinal importance in drug development. Today several distinct chemicals derived from plants are important drugs, which are currently used in one or more countries in the world. Secondary metabolites are economically important as drugs, flavor and fragrances, dye and pigments, pesticides, and food additives. Many of the drugs sold today are simple synthetic modifications or copies of the naturally obtained substances. The evolving commercial importance of secondary metabolites has in recent years resulted in a great interest in secondary metabolism, particularly in the possibility of altering the production of bioactive plant metabolites by means of tissue culture technology. Plant cell and tissue culture technologies can be established routinely under sterile conditions from explants, such as plant leaves, stems, roots, and meristems for both the ways for multiplication and extraction of secondary metabolites. In vitro production of secondary metabolite in plant cell suspension cultures has been reported from various medicinal plants, and bioreactors are the key step for their commercial production. Based on this lime light, the present review is aimed to cover phytotherapeutic application and recent advancement for the production of some important plant pharmaceuticals. PMID:22368394

  19. Natural Products from Deep-Sea-Derived Fungi ̶ a New Source of Novel Bioactive Compounds?

    PubMed

    Daletos, Georgios; Ebrahim, Weaam; Ancheeva, Elena; El-Neketi, Mona; Proksch, Peter

    2017-03-14

    Over the last two decades, deep-sea-derived fungi are considered to be a new source of pharmacologically active secondary metabolites for drug discovery mainly based on the underlying assumption that the uniqueness of the deep sea will give rise to equally unprecedented natural products. Indeed, up to now over 200 new metabolites have been identified from deep-sea fungi, which is in support of the statement made above. This review will summarize the new and/or bioactive compounds reported from deep-sea-derived fungi in the last six years (2010 - present) and will critically evaluate whether the data published so far really support the notion that these fungi are a promising source of new bioactive chemical entities.

  20. Quinones as toxic metabolites of benzene

    SciTech Connect

    Irons, R.D.

    1985-01-01

    Occupational exposure to benzene has long been associated with toxicity to the blood and bone marrow, including lymphocytopenia, pancytopenia, aplastic anemia, acute myelogenous leukemia, and possible lymphoma. A variety of studies have established that benzene itself is not the toxic species but requires metabolism to reactive intermediates. The bioactivation of benzene is complex. Both primary and secondary oxidation of benzene and its metabolites are mediated via cytochrome P-450 in the liver, although the role of secondary metabolism in the bone marrow is not clear. Toxicity is associated with the dihydroxy metabolites, hydroquinone and catechol, which concentrate in bone marrow. Hydroquinone and its terminal oxidation product, p-benzoquinone, have been demonstrated to be potent suppressors of cell growth in culture. Suppression of lymphocyte blastogenesis by these compounds is a sulfhydryl-dependent process and occurs at concentrations that do not result in cell death, or in detectable alterations in energy metabolism, intracellular glutathione concentration, or protein synthesis. Recent studies suggest that these compounds and other membrane-penetrating sulfyhdryl alkylating agents, such as N-ethylmaleimide and cytochalasin A, and endogenous regulatory molecules, such as soluble immune response suppressor (SIRS), interfere with microtubule assembly in vitro and selectively interfere with microtubule-dependent cell functions at identical concentrations. These agents appear to react with nucleophilic sulfhydryl groups essential for guanosine triphosphate binding to tubulin that are particularly sensitive to sulfhydryl-alkylating agents.

  1. Novel Approach to Classify Plants Based on Metabolite-Content Similarity

    PubMed Central

    Abdullah, Azian Azamimi; Huang, Ming; Nishioka, Takaaki

    2017-01-01

    Secondary metabolites are bioactive substances with diverse chemical structures. Depending on the ecological environment within which they are living, higher plants use different combinations of secondary metabolites for adaptation (e.g., defense against attacks by herbivores or pathogenic microbes). This suggests that the similarity in metabolite content is applicable to assess phylogenic similarity of higher plants. However, such a chemical taxonomic approach has limitations of incomplete metabolomics data. We propose an approach for successfully classifying 216 plants based on their known incomplete metabolite content. Structurally similar metabolites have been clustered using the network clustering algorithm DPClus. Plants have been represented as binary vectors, implying relations with structurally similar metabolite groups, and classified using Ward's method of hierarchical clustering. Despite incomplete data, the resulting plant clusters are consistent with the known evolutional relations of plants. This finding reveals the significance of metabolite content as a taxonomic marker. We also discuss the predictive power of metabolite content in exploring nutritional and medicinal properties in plants. As a byproduct of our analysis, we could predict some currently unknown species-metabolite relations. PMID:28164123

  2. Novel Approach to Classify Plants Based on Metabolite-Content Similarity.

    PubMed

    Liu, Kang; Abdullah, Azian Azamimi; Huang, Ming; Nishioka, Takaaki; Altaf-Ul-Amin, Md; Kanaya, Shigehiko

    2017-01-01

    Secondary metabolites are bioactive substances with diverse chemical structures. Depending on the ecological environment within which they are living, higher plants use different combinations of secondary metabolites for adaptation (e.g., defense against attacks by herbivores or pathogenic microbes). This suggests that the similarity in metabolite content is applicable to assess phylogenic similarity of higher plants. However, such a chemical taxonomic approach has limitations of incomplete metabolomics data. We propose an approach for successfully classifying 216 plants based on their known incomplete metabolite content. Structurally similar metabolites have been clustered using the network clustering algorithm DPClus. Plants have been represented as binary vectors, implying relations with structurally similar metabolite groups, and classified using Ward's method of hierarchical clustering. Despite incomplete data, the resulting plant clusters are consistent with the known evolutional relations of plants. This finding reveals the significance of metabolite content as a taxonomic marker. We also discuss the predictive power of metabolite content in exploring nutritional and medicinal properties in plants. As a byproduct of our analysis, we could predict some currently unknown species-metabolite relations.

  3. Excretion of berberine and its metabolites in oral administration in rats.

    PubMed

    Ma, Jing-Yi; Feng, Ru; Tan, Xiang-Shan; Ma, Chao; Shou, Jia-Wen; Fu, Jie; Huang, Min; He, Chi-Yu; Chen, Shuo-Nan; Zhao, Zhen-Xiong; He, Wen-Yi; Wang, Yan; Jiang, Jian-Dong

    2013-11-01

    Berberine (BBR) has been confirmed to show extensive bioactivities for the treatments of diabetes and hypercholesterolemia in clinic. However, there are few pharmacokinetic studies to elucidate the excretions of BBR and its metabolites. Our research studied the excretions of BBR and its metabolites in rats after oral administration (200 mg/kg). Metabolites in bile, urine, and feces were detected by liquid chromatography coupled to ion trap time-of-flight mass spectrometry; meanwhile, a validated liquid chromatography coupled with tandem mass spectrometry method was developed for their quantifications. Sixteen metabolites, including 10 Phase I and six Phase II metabolites were identified and clarified after dosing in vivo. Total recovered rate of BBR was 22.83% (19.07% of prototype and 3.76% of its metabolites) with 9.2 × 10(-6) % in bile (24 h), 0.0939% in urine (48 h), and 22.74% in feces (48 h), respectively. 83% of BBR was excreted as thalifendine (M1) from bile, whereas thalifendine (M1) and berberrubine (M2) were the major metabolites occupying 78% of urine excretion. Most of BBR and its metabolites were found in feces containing 84% of prototype. In summary, we provided excretion profiles of BBR and its metabolites after oral administration in rats in vivo.

  4. Statistical research on the bioactivity of new marine natural products discovered during the 28 years from 1985 to 2012.

    PubMed

    Hu, Yiwen; Chen, Jiahui; Hu, Guping; Yu, Jianchen; Zhu, Xun; Lin, Yongcheng; Chen, Shengping; Yuan, Jie

    2015-01-07

    Every year, hundreds of new compounds are discovered from the metabolites of marine organisms. Finding new and useful compounds is one of the crucial drivers for this field of research. Here we describe the statistics of bioactive compounds discovered from marine organisms from 1985 to 2012. This work is based on our database, which contains information on more than 15,000 chemical substances including 4196 bioactive marine natural products. We performed a comprehensive statistical analysis to understand the characteristics of the novel bioactive compounds and detail temporal trends, chemical structures, species distribution, and research progress. We hope this meta-analysis will provide useful information for research into the bioactivity of marine natural products and drug development.

  5. Statistical Research on the Bioactivity of New Marine Natural Products Discovered during the 28 Years from 1985 to 2012

    PubMed Central

    Hu, Yiwen; Chen, Jiahui; Hu, Guping; Yu, Jianchen; Zhu, Xun; Lin, Yongcheng; Chen, Shengping; Yuan, Jie

    2015-01-01

    Every year, hundreds of new compounds are discovered from the metabolites of marine organisms. Finding new and useful compounds is one of the crucial drivers for this field of research. Here we describe the statistics of bioactive compounds discovered from marine organisms from 1985 to 2012. This work is based on our database, which contains information on more than 15,000 chemical substances including 4196 bioactive marine natural products. We performed a comprehensive statistical analysis to understand the characteristics of the novel bioactive compounds and detail temporal trends, chemical structures, species distribution, and research progress. We hope this meta-analysis will provide useful information for research into the bioactivity of marine natural products and drug development. PMID:25574736

  6. Application of cellular biosensors for detection of atypical toxic bioactivity in microcystin-containing cyanobacterial extracts.

    PubMed

    Mankiewicz-Boczek, Joanna; Karwaciak, Iwona; Ratajewski, Marcin; Gągała, Ilona; Jurczak, Tomasz; Zalewski, Maciej; Pułaski, Łukasz

    2015-11-01

    Despite the focus of most ecotoxicological studies on cyanobacteria on a select group of cyanotoxins, especially microcystins, a growing body of evidence points to the involvement of other cyanobacterial metabolites in deleterious health effects. In the present study, original, self-developed reporter gene-based cellular biosensors, detecting activation of the main human xenobiotic stress response pathways, PXR and NFkappaB, were applied to detect novel potentially toxic bioactivities in extracts from freshwater microcystin-producing cyanobacterial blooms. Crude and purified extracts from cyanobacteria containing varying levels of microcystins, and standard microcystin-LR were tested. Two cellular biosensor types applied in this study, called NHRTOX (detecting PXR activation) and OXIBIOS (detecting NFkappaB activation), successfully detected potentially toxic or immunomodulating bioactivities in cyanobacterial extracts. The level of biosensor activation was comparable to control cognate environmental toxins. Despite the fact that extracts were derived from microcystin-producing cyanobacterial blooms and contained active microcystins, biosensor-detected bioactivities were shown to be unrelated to microcystin levels. Experimental results suggest the involvement of environmental toxins (causing a response in NHRTOX) and lipopolysaccharides (LPS) or other cell wall components (causing a response in OXIBIOS) in the potentially harmful bioactivity of investigated extracts. These results demonstrate the need for further identification of cyanobacterial metabolites other than commonly studied cyanotoxins as sources of health risk, show the usefulness of cellular biosensors for this purpose and suggest a novel, more holistic approach to environmental monitoring.

  7. Bare Bones of Bioactive Glass

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Paul Ducheyne, a principal investigator in the microgravity materials science program and head of the University of Pernsylvania's Center for Bioactive Materials and Tissue Engineering, is leading the trio as they use simulated microgravity to determine the optimal characteristics of tiny glass particles for growing bone tissue. The result could make possible a much broader range of synthetic bone-grafting applications. Even in normal gravity, bioactive glass particles enhance bone growth in laboratory tests with flat tissue cultures. Ducheyne and his team believe that using the bioactive microcarriers in a rotating bioreactor in microgravity will produce improved, three-dimensional tissue cultures. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Credit: NASA and University of Pennsylvania Center for Bioactive Materials and Tissue Engineering.

  8. Role of electrostatic potential in the in silico prediction of molecular bioactivation and mutagenesis.

    PubMed

    Ford, Kevin A

    2013-04-01

    Electrostatic potential (ESP) is a useful physicochemical property of a molecule that provides insights into inter- and intramolecular associations, as well as prediction of likely sites of electrophilic and nucleophilic metabolic attack. Knowledge of sites of metabolic attack is of paramount importance in DMPK research since drugs frequently fail in clinical trials due to the formation of bioactivated metabolites which are often difficult to measure experimentally due to their reactive nature and relatively short half-lives. Computational chemistry methods have proven invaluable in recent years as a means to predict and study bioactivated metabolites without the need for chemical syntheses, or testing on experimental animals. Additional molecular properties (heat of formation, heat of solvation and E(LUMO) - E(HOMO)) are discussed in this paper as complementary indicators of the behavior of metabolites in vivo. Five diverse examples are presented (acetaminophen, aniline/phenylamines, imidacloprid, nefazodone and vinyl chloride) which illustrate the utility of this multidimensional approach in predicting bioactivation, and in each case the predicted data agreed with experimental data described in the scientific literature. A further example of the usefulness of calculating ESP, in combination with the molecular properties mentioned above, is provided by an examination of the use of these parameters in providing an explanation for the sites of nucleophilic attack of the nucleic acid cytosine. Exploration of sites of nucleophilic attack of nucleic acids is important as adducts of DNA have the potential to result in mutagenesis.

  9. Human colon microbiota transform polycyclic aromatic hydrocarbons to estrogenic metabolites.

    PubMed

    Van de Wiele, Tom; Vanhaecke, Lynn; Boeckaert, Charlotte; Peru, Kerry; Headley, John; Verstraete, Willy; Siciliano, Steven

    2005-01-01

    Ingestion is an important exposure route for polycyclic aromatic hydrocarbons (PAHs) to enter the human body. Although the formation of hazardous PAH metabolites by human biotransformation enzymes is well documented, nothing is known about the PAH transformation potency of human intestinal microbiota. Using a gastrointestinal simulator, we show that human intestinal microbiota can also bioactivate PAHs, more in particular to estrogenic metabolites. PAH compounds are not estrogenic, and indeed, stomach and small intestine digestions of 62.5 nmol naphthalene, phenanthrene, pyrene, and benzo(a)pyrene showed no estrogenic effects in the human estrogen receptor bioassay. In contrast, colon digests of these PAH compounds displayed estrogenicity, equivalent to 0.31, 2.14, 2.70, and 1.48 nmol 17alpha-ethynylestradiol (EE2), respectively. Inactivating the colon microbiota eliminated these estrogenic effects. Liquid chromatography-mass spectrometry analysis confirmed the microbial PAH transformation by the detection of PAH metabolites 1-hydroxypyrene and 7-hydroxybenzo(a)pyrene in colon digests of pyrene and benzo(a)pyrene. Furthermore, we show that colon digests of a PAH-contaminated soil (simulated ingestion dose of 5 g/day) displayed estrogenic activity equivalent to 0.58 nmol EE2, whereas stomach or small intestine digests did not. Although the matrix in which PAHs are ingested may result in lower exposure concentrations in the gut, our results imply that the PAH bioactivation potency of colon microbiota is not eliminated by the presence of soil. Moreover, because PAH toxicity is also linked to estrogenicity of the compounds, the PAH bioactivation potency of colon microbiota suggests that current risk assessment may underestimate the risk from ingested PAHs.

  10. Neutrophil- and myeloperoxidase-mediated metabolism of reduced nimesulide: evidence for bioactivation.

    PubMed

    Yang, Min; Chordia, Mahendra D; Li, Fengping; Huang, Tao; Linden, Joel; Macdonald, Timothy L

    2010-11-15

    Nimesulide, a widely used nonsteroidal anti-inflammatory drug (NSAID), has been associated with rare idiosyncratic hepatotoxicity. The chemical mechanisms underlying the liver injury remain unknown. We have undertaken the detailed study of the metabolic pathways of nimesulide in an effort to identify potential reactive metabolites. A previous report from this laboratory has demonstrated that one of the known nimesulide metabolites, termed reduced nimesulide (M1), is further bioactivated by human liver microsomes (HLMs) to form a reactive diiminoquinone species M2. The formation of M2 was confirmed indirectly by trapping with N-acetylcysteine (NAC). The aim of this study was to explore the fate of M1 in an inflammatory environment created by the recruitment of leukocytes. Leukocytes upon activation produce hydrogen peroxide (H(2)O(2)) and other myeloperoxidase (MPO) products, such as hypochlorous acid (HOCl), that are capable of metabolite oxidation. We demonstrate here that the reduced nimesulide, M1, undergoes a facile oxidation with activated neutrophils or with MPO in the presence of H(2)O(2) or HOCl to produce a variety of reactive as well as stable metabolites. One major metabolite, M3, was also produced by HLM as determined by trapping with NAC. Other metabolites, for example, M6, M8, and M9, were unique to the myeloperoxidase, because of their mode of formation from activation of the amino group of reduced nimesulide. The structures of some of these reactive metabolites were proposed on the basis of liquid chromatography-tandem mass spectrometry analyses and established by their comparison with synthetic standards. Metabolite M6 is interesting because it provides clear evidence of amine activation and indicates the potential of the reactive intermediate of M1 to conjugate with protein nucleophiles. In summary, our results demonstrate that a known nimesulide metabolite could be bioactivated by MPO through a pathway distinct from HLM-mediated pathways and that

  11. Microalgal metabolites: a new perspective.

    PubMed

    Shimizu, Y

    1996-01-01

    Occurrence of secondary metabolites in microalgae (protoctista) is discussed with respect to the phylogenic or taxonomic relationships of organisms. Biosynthetic mechanisms of certain metabolites such as paralytic shellfish poisoning toxins and polyether toxins are also discussed, and genetic aspects of the secondary metabolite production as well.

  12. Secondary metabolites in plants: transport and self-tolerance mechanisms.

    PubMed

    Shitan, Nobukazu

    2016-07-01

    Plants produce a host of secondary metabolites with a wide range of biological activities, including potential toxicity to eukaryotic cells. Plants generally manage these compounds by transport to the apoplast or specific organelles such as the vacuole, or other self-tolerance mechanisms. For efficient production of such bioactive compounds in plants or microbes, transport and self-tolerance mechanisms should function cooperatively with the corresponding biosynthetic enzymes. Intensive studies have identified and characterized the proteins responsible for transport and self-tolerance. In particular, many transporters have been isolated and their physiological functions have been proposed. This review describes recent progress in studies of transport and self-tolerance and provides an updated inventory of transporters according to their substrates. Application of such knowledge to synthetic biology might enable efficient production of valuable secondary metabolites in the future.

  13. Integrating mass spectrometry and genomics for cyanobacterial metabolite discovery.

    PubMed

    Moss, Nathan A; Bertin, Matthew J; Kleigrewe, Karin; Leão, Tiago F; Gerwick, Lena; Gerwick, William H

    2016-03-01

    Filamentous marine cyanobacteria produce bioactive natural products with both potential therapeutic value and capacity to be harmful to human health. Genome sequencing has revealed that cyanobacteria have the capacity to produce many more secondary metabolites than have been characterized. The biosynthetic pathways that encode cyanobacterial natural products are mostly uncharacterized, and lack of cyanobacterial genetic tools has largely prevented their heterologous expression. Hence, a combination of cutting edge and traditional techniques has been required to elucidate their secondary metabolite biosynthetic pathways. Here, we review the discovery and refined biochemical understanding of the olefin synthase and fatty acid ACP reductase/aldehyde deformylating oxygenase pathways to hydrocarbons, and the curacin A, jamaicamide A, lyngbyabellin, columbamide, and a trans-acyltransferase macrolactone pathway encoding phormidolide. We integrate into this discussion the use of genomics, mass spectrometric networking, biochemical characterization, and isolation and structure elucidation techniques.

  14. Integrating mass spectrometry and genomics for cyanobacterial metabolite discovery

    PubMed Central

    Bertin, Matthew J.; Kleigrewe, Karin; Leão, Tiago F.; Gerwick, Lena

    2016-01-01

    Filamentous marine cyanobacteria produce bioactive natural products with both potential therapeutic value and capacity to be harmful to human health. Genome sequencing has revealed that cyanobacteria have the capacity to produce many more secondary metabolites than have been characterized. The biosynthetic pathways that encode cyanobacterial natural products are mostly uncharacterized, and lack of cyanobacterial genetic tools has largely prevented their heterologous expression. Hence, a combination of cutting edge and traditional techniques has been required to elucidate their secondary metabolite biosynthetic pathways. Here, we review the discovery and refined biochemical understanding of the olefin synthase and fatty acid ACP reductase/aldehyde deformylating oxygenase pathways to hydrocarbons, and the curacin A, jamaicamide A, lyngbyabellin, columbamide, and a trans-acyltransferase macrolactone pathway encoding phormidolide. We integrate into this discussion the use of genomics, mass spectrometric networking, biochemical characterization, and isolation and structure elucidation techniques. PMID:26578313

  15. Comparative UPLC-QTOF-MS-based metabolomics and bioactivities analyses of Garcinia oblongifolia.

    PubMed

    Li, Ping; AnandhiSenthilkumar, Harini; Wu, Shi-biao; Liu, Bo; Guo, Zhi-yong; Fata, Jimmie E; Kennelly, Edward J; Long, Chun-lin

    2016-02-01

    Garcinia oblongifolia Champ. ex Benth. (Clusiaceae) is a well-known medicinal plant from southern China, with edible fruits. However, the phytochemistry and bioactivity of the different plant parts of G. oblongifolia have not been studied extensively. Comparative metabolic profiling and bioactivities of the leaf, branch, and fruit of G. oblongifolia were investigated. A total of 40 compounds such as biflavonoids, xanthones, and benzophenones were identified using UPLC-QTOF-MS and MS(E), including 15 compounds reported for the first time from this species. Heatmap analyses found that benzophenones, xanthones, and biflavonoids were predominately found in branches, with benzophenones present in relatively high concentrations in all three plant parts. Xanthones were found to have limited distribution in fruit while biflavonoids were present at only low levels in leaves. In addition, the cytotoxic (MCF-7 breast cancer cell line) and antioxidant (ABTS and DPPH chemical tests) activities of the crude extracts of G. oblongifolia indicate that the branch extract exhibits greater bioactivity than either the leaf or the fruit extracts. Orthogonal partial least squares discriminate analysis was used to find 12 marker compounds, mainly xanthones, from the branches, including well-known antioxidants and cytotoxic agents. These G. oblongifolia results revealed that the variation in metabolite profiles can be correlated to the differences in bioactivity of the three plant parts investigated. This UPLC-QTOF-MS strategy can be useful to identify bioactive constituents expressed differentially in the various plant parts of a single species.

  16. Emerging Strategies and Integrated Systems Microbiology Technologies for Biodiscovery of Marine Bioactive Compounds

    PubMed Central

    Rocha-Martin, Javier; Harrington, Catriona; Dobson, Alan D.W.; O’Gara, Fergal

    2014-01-01

    Marine microorganisms continue to be a source of structurally and biologically novel compounds with potential use in the biotechnology industry. The unique physiochemical properties of the marine environment (such as pH, pressure, temperature, osmolarity) and uncommon functional groups (such as isonitrile, dichloroimine, isocyanate, and halogenated functional groups) are frequently found in marine metabolites. These facts have resulted in the production of bioactive substances with different properties than those found in terrestrial habitats. In fact, the marine environment contains a relatively untapped reservoir of bioactivity. Recent advances in genomics, metagenomics, proteomics, combinatorial biosynthesis, synthetic biology, screening methods, expression systems, bioinformatics, and the ever increasing availability of sequenced genomes provides us with more opportunities than ever in the discovery of novel bioactive compounds and biocatalysts. The combination of these advanced techniques with traditional techniques, together with the use of dereplication strategies to eliminate known compounds, provides a powerful tool in the discovery of novel marine bioactive compounds. This review outlines and discusses the emerging strategies for the biodiscovery of these bioactive compounds. PMID:24918453

  17. Bioactivation, protein haptenation, and toxicity of sulfamethoxazole and dapsone in normal human dermal fibroblasts

    SciTech Connect

    Bhaiya, Payal; Roychowdhury, Sanjoy; Vyas, Piyush M.; Doll, Mark A.; Hein, David W.; Svensson, Craig K. . E-mail: craig-svensson@uiowa.edu

    2006-09-01

    Cutaneous drug reactions (CDRs) associated with sulfonamides are believed to be mediated through the formation of reactive metabolites that result in cellular toxicity and protein haptenation. We evaluated the bioactivation and toxicity of sulfamethoxazole (SMX) and dapsone (DDS) in normal human dermal fibroblasts (NHDF). Incubation of cells with DDS or its metabolite (D-NOH) resulted in protein haptenation readily detected by confocal microscopy and ELISA. While the metabolite of SMX (S-NOH) haptenated intracellular proteins, adducts were not evident in incubations with SMX. Cells expressed abundant N-acetyltransferase-1 (NAT1) mRNA and activity, but little NAT2 mRNA or activity. Neither NAT1 nor NAT2 protein was detected. Incubation of NHDF with S-NOH or D-NOH increased reactive oxygen species formation and reduced glutathione content. NHDF were less susceptible to the cytotoxic effect of S-NOH and D-NOH than are keratinocytes. Our studies provide the novel observation that NHDF are able to acetylate both arylamine compounds and bioactivate the sulfone DDS, giving rise to haptenated proteins. The reactive metabolites of SMX and DDS also provoke oxidative stress in these cells in a time- and concentration-dependent fashion. Further work is needed to determine the role of the observed toxicity in mediating CDRs observed with these agents.

  18. Dung-inhabiting fungi: a potential reservoir of novel secondary metabolites for the control of plant pathogens.

    PubMed

    Sarrocco, Sabrina

    2016-04-01

    Coprophilous fungi are a large group of saprotrophic fungi mostly found in herbivore dung. The number of these fungi undergoing investigation is continually increasing, and new species and genera continue to be described. Dung-inhabiting fungi play an important ecological role in decomposing and recycling nutrients from animal dung. They produce a large array of bioactive secondary metabolites and have a potent enzymatic arsenal able to utilise even complex molecules. Bioactive secondary metabolites are actively involved in interaction with and defence against other organisms whose growth can be inhibited, resulting in an enhanced ecological fitness of producer strains. Currently, these antibiotics and bioactive secondary metabolites are of interest in medicine in particular, while very little information is available concerning their potential use in agriculture. This review introduces the ecology of dung-inhabiting fungi, with particular emphasis on the production of antibiotic compounds as a means to compete with other microorganisms. Owing to the fast pace of technological progress, new approaches to predicting the biosynthesis of bioactive metabolites are proposed. Coprophilous fungi should be considered as elite candidate organisms for the discovery of novel antifungal compounds, above all in view of their exploitation for crop protection.

  19. Marine Peptides: Bioactivities and Applications

    PubMed Central

    Cheung, Randy Chi Fai; Ng, Tzi Bun; Wong, Jack Ho

    2015-01-01

    Peptides are important bioactive natural products which are present in many marine species. These marine peptides have high potential nutraceutical and medicinal values because of their broad spectra of bioactivities. Their antimicrobial, antiviral, antitumor, antioxidative, cardioprotective (antihypertensive, antiatherosclerotic and anticoagulant), immunomodulatory, analgesic, anxiolytic anti-diabetic, appetite suppressing and neuroprotective activities have attracted the attention of the pharmaceutical industry, which attempts to design them for use in the treatment or prevention of various diseases. Some marine peptides or their derivatives have high commercial values and had reached the pharmaceutical and nutraceutical markets. A large number of them are already in different phases of the clinical and preclinical pipeline. This review highlights the recent research in marine peptides and the trends and prospects for the future, with special emphasis on nutraceutical and pharmaceutical development into marketed products. PMID:26132844

  20. Bioactive natural products from Lysobacter

    PubMed Central

    Xie, Yunxuan; Wright, Stephen; Shen, Yuemao

    2012-01-01

    The gliding Gram-negative Lysobacter bacteria are emerging as a promising source of new bioactive natural products. These ubiquitous freshwater and soil microorganisms are fast growing, simple to use and maintain, and genetically amenable for biosynthetic engineering. This Highlight reviews a group of biologically active and structurally distinct natural products from the genus Lysobacter, with a focus on their biosyntheses. Although Lysobacter sp. are known as prolific producers of bioactive natural products, detailed molecular mechanistic studies of their enzymatic assembly have been surprisingly scarce. We hope to provide a snapshot of the important work done on the lysobacterial natural products and to provide useful information for future biosynthetic engineering of novel antibiotics in Lysobacter. PMID:22898908

  1. Bare Bones of Bioactive Glass

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Paul Ducheyne, a principal investigator in the microgravity materials science program and head of the University of Pernsylvania's Center for Bioactive Materials and Tissue Engineering, is leading the trio as they use simulated microgravity to determine the optimal characteristics of tiny glass particles for growing bone tissue. The result could make possible a much broader range of synthetic bone-grafting applications. Bioactive glass particles (left) with a microporous surface (right) are widely accepted as a synthetic material for periodontal procedures. Using the particles to grow three-dimensional tissue cultures may one day result in developing an improved, more rugged bone tissue that may be used to correct skeletal disorders and bone defects. The work is sponsored by NASA's Office of Biological and Physical Research.

  2. [Recent progress of potential effects and mechanisms of chlorogenic acid and its intestinal metabolites on central nervous system diseases].

    PubMed

    Xing, Li-na; Zhou, Ming-mei; Li, Yun; Shi, Xiao-wen; Jia, Wei

    2015-03-01

    Chlorogenic acid displays several important roles in the therapeutic properties of many herbs, such as antioxidant activity, antibacterial, antiviral, scavenging free radicals and exciting central nervous system. Only about one-third of chlorogenic acid was absorbed in its prototype, therefore, its gut metabolites play a more important role in the therapeutic properties of chlorogenic acid. It is necessary to consider not only the bioactivities of chlorogenic acid but also its gut metabolites. This review focuses on the potential activities and mechanisms of chlorogenic acid and its gut metabolites on central nervous system diseases.

  3. Microbial biotransformation of cryptotanshinone by Cunninghamella elegans and its application for metabolite identification in rat bile.

    PubMed

    Sun, Jiang-Hao; Yang, Min; Ma, Xiao-Chi; Kang, Jie; Han, Jian; Guo, De-An

    2009-06-01

    Cryptotanshinone (1) is one of the major bioactive constituents in Salvia miltiorrhiza Bunge. Preparative-scale biotransformation of cryptotanshinone by Cunninghamella elegans (AS 3.2082) produced three new products, which were identified as (3R,15R)-3-hydroxycryptotanshinone (2), (3S,15R)-3-hydroxycryptotanshinone (3), and (4S,15R)-18-hydroxycryptotanshinone (4), respectively. The structural elucidation was based primarily on 1D and 2D NMR and HR-ESI-MS analyses. The absolute configuration of these three products was confirmed by comparison of their circular dichroism spectra with those of the known compounds. These biotransformed metabolites were used as for the comparison of in vivo metabolites in rat bile sample after intravenous administration and they are identical to three of the minor hydroxylated metabolites in vivo, which suggested that microbial biotransformation model was a useful and feasible approach for the preparation of mammalian metabolites in trace.

  4. Covalent Modification of Microsomal Lipids by Thiobenzamide Metabolites in Vivo

    PubMed Central

    Ji, Tao; Ikehata, Keisuke; Koen, Yakov M.; Esch, Steven W.; Williams, Todd D.; Hanzlik, Robert P.

    2008-01-01

    Thiobenzamide (TB) is hepatotoxic in rats causing centrolobular necrosis, steatosis, cholestasis and hyperbilirubinemia. It serves as a model compound for a number of thiocarbonyl compounds that undergo oxidative bioactivation to chemically reactive metabolites. The hepatotoxicity of TB is strongly dependent on the electronic character of substituents in the meta- and para- positions, with Hammett rho values ranging from −4 to −2. On the other hand ortho substituents which hinder nucleophilic addition to the benzylic carbon of S-oxidized TB metabolites abrogate the toxicity and protein covalent binding of TB. This strong linkage between the chemistry of TB and its metabolites and their toxicity suggests that this model is a good one for probing the overall mechanism of chemically-induced biological responses. While investigating the protein covalent binding of TB metabolites we noticed an unusually large amount of radioactivity associated with the lipid fraction of rat liver microsomes. Thin layer chromatography showed that most of the radioactivity was contained in a single spot more polar than the neutral lipids but less polar than the phospholipid fractions. Mass spectral analyses aided by the use of synthetic standards identified the material as N-benzimidoyl derivatives of typical microsomal phosphatidylethanolamine (PE) lipids. Quantitative analysis indicated that up to 25% of total microsomal PE became modified within 5 h after a hepatotoxic dose of TB. Further studies will be required to determine the contribution of lipid modification to the hepatotoxicity of thiobenzamide. PMID:17381136

  5. Aeroplysinin-1, a Sponge-Derived Multi-Targeted Bioactive Marine Drug

    PubMed Central

    García-Vilas, Javier A.; Martínez-Poveda, Beatriz; Quesada, Ana R.; Medina, Miguel Ángel

    2015-01-01

    Organisms lacking external defense mechanisms have developed chemical defense strategies, particularly through the production of secondary metabolites with antibiotic or repellent effects. Secondary metabolites from marine organisms have proven to be an exceptionally rich source of small molecules with pharmacological activities potentially beneficial to human health. (+)-Aeroplysinin-1 is a secondary metabolite isolated from marine sponges with a wide spectrum of bio-activities. (+)-Aeroplysinin-1 has potent antibiotic effects on Gram-positive bacteria and several dinoflagellate microalgae causing toxic blooms. In preclinical studies, (+)-aeroplysinin-1 has been shown to have promising anti-inflammatory, anti-angiogenic and anti-tumor effects. Due to its versatility, (+)-aeroplysinin-1 might have a pharmaceutical interest for the treatment of different pathologies. PMID:26703630

  6. Bioactivation of bis[p-nitrophenyl]phosphate by phosphoesterases of the earthworm, Lumbricus terrestris.

    PubMed

    Park, S C; Smith, T J; Bisesi, M S

    1993-01-01

    In view of the ability of several phosphoesterases to hydrolyze organophosphates to toxic phenols, the bioactivation of bis[p-nitrophenyl]phosphate (BNPP) by the earthworm Lumbricus terrestris was investigated. In a contact toxicity test, BNPP was was less toxic than the metabolite p-nitrophenol (PNP), but more toxic than the metabolite p-nitrophenylphosphate (PNPP). Results from an artificial soil test (soil containing BNPP) revealed that the phosphomonoesterase and phosphodiesterase activities from the enteric tissue of the annelid could be selectively depressed without significant reduction of these activities in other tissues. Since these esterase activities are 5 to 7 fold higher in the enteric tissue, these results suggest that the phosphoesterases in the annelid participate in the activation of BNPP to the more toxic metabolite, p-nitrophenol.

  7. Aeroplysinin-1, a Sponge-Derived Multi-Targeted Bioactive Marine Drug.

    PubMed

    García-Vilas, Javier A; Martínez-Poveda, Beatriz; Quesada, Ana R; Medina, Miguel Ángel

    2015-12-22

    Organisms lacking external defense mechanisms have developed chemical defense strategies, particularly through the production of secondary metabolites with antibiotic or repellent effects. Secondary metabolites from marine organisms have proven to be an exceptionally rich source of small molecules with pharmacological activities potentially beneficial to human health. (+)-Aeroplysinin-1 is a secondary metabolite isolated from marine sponges with a wide spectrum of bio-activities. (+)-Aeroplysinin-1 has potent antibiotic effects on Gram-positive bacteria and several dinoflagellate microalgae causing toxic blooms. In preclinical studies, (+)-aeroplysinin-1 has been shown to have promising anti-inflammatory, anti-angiogenic and anti-tumor effects. Due to its versatility, (+)-aeroplysinin-1 might have a pharmaceutical interest for the treatment of different pathologies.

  8. Sage in vitro cultures: a promising tool for the production of bioactive terpenes and phenolic substances.

    PubMed

    Marchev, Andrey; Haas, Christiane; Schulz, Sibylle; Georgiev, Vasil; Steingroewer, Juliane; Bley, Thomas; Pavlov, Atanas

    2014-02-01

    Extracts of Salvia species are used in traditional medicine to treat various diseases. The economic importance of this genus has increased in recent years due to evidence that some of its secondary metabolites have valuable pharmaceutical and nutraceutical properties.The bioactivity of sage extracts is mainly due to their content of terpenes and polyphenols. The increasing demand for sage products combined with environmental, ecological and climatic limitations on the production of sage metabolites from field-grown plants have led to extensive investigations into biotechnological approaches for the production of Salvia phytochemicals. The purpose of this review is to evaluate recent progress in investigations of sage in vitro systems as tools for producing important terpenoids and polyphenols and in development of methods for manipulating regulatory processes to enhance secondary metabolite production in such systems.

  9. Identification of Echinacoside Metabolites Produced by Human Intestinal Bacteria Using Ultraperformance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry.

    PubMed

    Li, Yang; Zhou, Guisheng; Xing, Shihua; Tu, Pengfei; Li, Xiaobo

    2015-08-05

    Echinacoside (ECH) is one of the representative phenylethanoid glycosides. It is widely present in plants and exhibits various bioactivities. However, the extremely low oral bioavailability of ECH in rats implies that ECH may go through multiple hydrolysis steps in the gastrointestinal tract prior to its absorption into the blood. Therefore, the gastrointestinal metabolites of ECH are more likely to be the bioactive components. This study established an approach combining ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) with MS(E) technology and MetaboLynx software for rapid analysis of the ECH metabolic profile produced by human intestinal bacteria. As a result, 13 ECH metabolites and 5 possible metabolic pathways (including deglycosylation, dehydroxylation, reduction, hydroxylation, and acetylation) were identified. Furthermore, hydroxytyrosol (HT) and 3-hydroxyphenylpropionic acid (3-HPP) were found to be the two bioactive metabolites of ECH produced by human intestinal bacteria.

  10. Mining Bacterial Genomes for Secondary Metabolite Gene Clusters.

    PubMed

    Adamek, Martina; Spohn, Marius; Stegmann, Evi; Ziemert, Nadine

    2017-01-01

    With the emergence of bacterial resistance against frequently used antibiotics, novel antibacterial compounds are urgently needed. Traditional bioactivity-guided drug discovery strategies involve laborious screening efforts and display high rediscovery rates. With the progress in next generation sequencing methods and the knowledge that the majority of antibiotics in clinical use are produced as secondary metabolites by bacteria, mining bacterial genomes for secondary metabolites with antimicrobial activity is a promising approach, which can guide a more time and cost-effective identification of novel compounds. However, what sounds easy to accomplish, comes with several challenges. To date, several tools for the prediction of secondary metabolite gene clusters are available, some of which are based on the detection of signature genes, while others are searching for specific patterns in gene content or regulation.Apart from the mere identification of gene clusters, several other factors such as determining cluster boundaries and assessing the novelty of the detected cluster are important. For this purpose, comparison of the predicted secondary metabolite genes with different cluster and compound databases is necessary. Furthermore, it is advisable to classify detected clusters into gene cluster families. So far, there is no standardized procedure for genome mining; however, different approaches to overcome all of these challenges exist and are addressed in this chapter. We give practical guidance on the workflow for secondary metabolite gene cluster identification, which includes the determination of gene cluster boundaries, addresses problems occurring with the use of draft genomes, and gives an outlook on the different methods for gene cluster classification. Based on comprehensible examples a protocol is set, which should enable the readers to mine their own genome data for interesting secondary metabolites.

  11. Herbal bioactivation: the good, the bad and the ugly.

    PubMed

    Zhou, Shufeng; Koh, Hwee-Ling; Gao, Yihuai; Gong, Zhi-yuan; Lee, Edmund Jon Deoon

    2004-01-09

    It has been well established that the formation of reactive metabolites of drugs is associated with drug toxicity. Similarly, there are accumulating data suggesting the role of the formation of reactive metabolites/intermediates through bioactivation in herbal toxicity and carcinogenicity. It has been hypothesized that the resultant reactive metabolites following herbal bioactivation covalently bind to cellular proteins and DNA, leading to toxicity via multiple mechanisms such as direct cytotoxicity, oncogene activation, and hypersensitivity reactions. This is exemplified by aristolochic acids present in Aristolochia spp, undergoing reduction of the nitro group by hepatic cytochrome P450 (CYP1A1/2) or peroxidases in extrahepatic tissues to reactive cyclic nitrenium ion. The latter was capable of reacting with DNA and proteins, resulting in activation of H-ras oncogene, gene mutation and finally carcinogenesis. Other examples are pulegone present in essential oils from many mint species; and teucrin A, a diterpenoid found in germander (Teuchrium chamaedrys) used as an adjuvant to slimming diets. Extensive pulegone metabolism generated p-cresol that was a glutathione depletory, and the furan ring of the diterpenoids in germander was oxidized by CYP3A4 to reactive epoxide which reacts with proteins such as CYP3A and epoxide hydrolase. On the other hand, some herbal/dietary constituents were shown to form reactive intermediates capable of irreversibly inhibiting various CYPs. The resultant metabolites lead to CYP inactivation by chemical modification of the heme, the apoprotein, or both as a result of covalent binding of modified heme to the apoprotein. Some examples include bergamottin, a furanocoumarin of grapefruit juice; capsaicin from chili peppers; glabridin, an isoflavan from licorice root; isothiocyanates found in all cruciferous vegetables; oleuropein rich in olive oil; dially sulfone found in garlic; and resveratrol, a constituent of red wine. CYPs have been

  12. Bioactive natural products from Chinese marine flora and fauna.

    PubMed

    Zhou, Zhen-Fang; Guo, Yue-Wei

    2012-09-01

    In recent decades, the pharmaceutical application potential of marine natural products has attracted much interest from both natural product chemists and pharmacologists. Our group has long been engaged in the search for bioactive natural products from Chinese marine flora (such as mangroves and algae) and fauna (including sponges, soft corals, and mollusks), resulting in the isolation and characterization of numerous novel secondary metabolites spanning a wide range of structural classes and various biosynthetic origins. Of particular interest is the fact that many of these compounds show promising biological activities, including cytotoxic, antibacterial, and enzyme inhibitory effects. By describing representative studies, this review presents a comprehensive summary regarding the achievements and progress made by our group in the past decade. Several interesting examples are discussed in detail.

  13. Bioactive Pigments from Marine Bacteria: Applications and Physiological Roles

    PubMed Central

    Soliev, Azamjon B.; Hosokawa, Kakushi; Enomoto, Keiichi

    2011-01-01

    Research into natural products from the marine environment, including microorganisms, has rapidly increased over the past two decades. Despite the enormous difficulty in isolating and harvesting marine bacteria, microbial metabolites are increasingly attractive to science because of their broad-ranging pharmacological activities, especially those with unique color pigments. This current review paper gives an overview of the pigmented natural compounds isolated from bacteria of marine origin, based on accumulated data in the literature. We review the biological activities of marine compounds, including recent advances in the study of pharmacological effects and other commercial applications, in addition to the biosynthesis and physiological roles of associated pigments. Chemical structures of the bioactive compounds discussed are also presented. PMID:21961023

  14. Endophytes: A Treasure House of Bioactive Compounds of Medicinal Importance

    PubMed Central

    Gouda, Sushanto; Das, Gitishree; Sen, Sandeep K.; Shin, Han-Seung; Patra, Jayanta Kumar

    2016-01-01

    Endophytes are an endosymbiotic group of microorganisms that colonize in plants and microbes that can be readily isolated from any microbial or plant growth medium. They act as reservoirs of novel bioactive secondary metabolites, such as alkaloids, phenolic acids, quinones, steroids, saponins, tannins, and terpenoids that serve as a potential candidate for antimicrobial, anti-insect, anticancer and many more properties. While plant sources are being extensively explored for new chemical entities for therapeutic purposes, endophytic microbes also constitute an important source for drug discovery. This review aims to comprehend the contribution and uses of endophytes as an impending source of drugs against various forms of diseases and other possible medicinal use. PMID:27746767

  15. Predominately Uncultured Microbes as Sources of Bioactive Agents

    PubMed Central

    Newman, David J.

    2016-01-01

    In this short review, I am discussing the relatively recent awareness of the role of symbionts in plant, marine-invertebrates and fungal areas. It is now quite obvious that in marine-invertebrates, a majority of compounds found are from either as yet unculturable or poorly culturable microbes, and techniques involving “state of the art” genomic analyses and subsequent computerized analyses are required to investigate these interactions. In the plant kingdom evidence is amassing that endophytes (mainly fungal in nature) are heavily involved in secondary metabolite production and that mimicking the microbial interactions of fermentable microbes leads to involvement of previously unrecognized gene clusters (cryptic clusters is one name used), that when activated, produce previously unknown bioactive molecules. PMID:27917159

  16. Implications of bioactive solute transfer from hosts to parasitic plants.

    PubMed

    Smith, Jason D; Mescher, Mark C; De Moraes, Consuelo M

    2013-08-01

    Parasitic plants--which make their living by extracting nutrients and other resources from other plants--are important components of many natural ecosystems; and some parasitic species are also devastating agricultural pests. To date, most research on plant parasitism has focused on nutrient transfer from host to parasite and the impacts of parasites on host plants. Far less work has addressed potential effects of the translocation of bioactive non-nutrient solutes-such as phytohormones, secondary metabolites, RNAs, and proteins-on the development and physiology of parasitic plants and on their subsequent interactions with other organisms such as insect herbivores. A growing number of recent studies document the transfer of such molecules from hosts to parasites and suggest that they may have significant impacts on parasite physiology and ecology. We review this literature and discuss potential implications for management and priorities for future research.

  17. Fast determination of bioactive compounds from Lycopersicon esculentum Mill. leaves.

    PubMed

    Taveira, Marcos; Ferreres, Federico; Gil-Izquierdo, Angel; Oliveira, Luísa; Valentão, Patrícia; Andrade, Paula B

    2012-11-15

    Lycopersicon esculentum leaves, usually considered as a by-product of tomato production, present several bioactive compounds of interest for industries like food, pharmaceutical and cosmetics. Nevertheless, before industrial application, suitable methods to identify and quantify those metabolites should be developed. In this study agitation with aqueous methanol was used for phenolic compounds extraction. Solid-phase extraction (SPE) was performed as the purification step before alkaloids analysis. Among the SPE sorbents tested, sulphonic acid bonded silica with H(+) counterion (SCX) proved to be the most efficient one for removing interfering components. Fifteen phenolics and four steroidic alkaloids were identified in 35 and 20 min analysis, respectively. The optimised methods were validated, revealing to be accurate, fast, simple and sensitive. Thus, these methods represent an easy and fast analytical approach, using equipment available in almost laboratory, which render them to be appropriate for routine analysis.

  18. Characterization of oxygenated metabolites of ginsenoside Rg1 in plasma and urine of rat.

    PubMed

    Wang, Jing-Rong; Tong, Tian-Tian; Yau, Lee-Fong; Chen, Cheng-Yu; Bai, Li-Ping; Ma, Jing; Hu, Ming; Liu, Liang; Jiang, Zhi-Hong

    2016-07-15

    This study describes the characterization of oxygenated metabolites of ginsenoside Rg1 in rat urine and plasma. These in vivo metabolites were profiled by using UHPLC-QTOF MS-based method. On the basis of high-resolution MS/MS data, and comparison with chemically synthesized authentic compounds, nine oxygenated metabolites of Rg1 were characterized as vinaginsenosides 21 and 22 (M1 and M2), vinaginsenoside R15 (M3), 6-O-(β-d-glucopyranosyl)-20-O-(β-d-glucopyranosyl) 3β, 6α, 12β, 20(S)-tetrahydroxy-24ξ-hydroxydammar-25-ene (M4 and M5), floralginsenoside A (M7 and M8), floralginsenoside B (M9) and epoxyginsenoside Rg1 (M13), respectively. Among these metabolites, M4, M5 and M13 are new ginsenosides and others were detected as in vivo metabolites of Rg1 for the first time. In addition, a series of oxygenated metabolites of Rh1 and deglycosylated metabolite of Rg1, were observed and characterized by comparing with compounds synthesized by us, which revealed an association between C-20 configuration and the extent of oxidation metabolism. Appearance of all these metabolites in blood stream and urine after i.v. dosing and oral administration of Rg1 was further examined, which clearly showed that mono-oxygenated metabolites of Rg1 were major circulating metabolites at the early stage after dosing. Characterization of exact chemical structures of these circulating metabolites contribute greatly to our understanding of chemical exposure after consumption of ginseng products, and provide valuable information for explaining multiple bioactivities of ginseng products.

  19. Metabolomic tools for secondary metabolite discovery from marine microbial symbionts.

    PubMed

    Macintyre, Lynsey; Zhang, Tong; Viegelmann, Christina; Martinez, Ignacio Juarez; Cheng, Cheng; Dowdells, Catherine; Abdelmohsen, Usama Ramadam; Gernert, Christine; Hentschel, Ute; Edrada-Ebel, RuAngelie

    2014-06-05

    Marine invertebrate-associated symbiotic bacteria produce a plethora of novel secondary metabolites which may be structurally unique with interesting pharmacological properties. Selection of strains usually relies on literature searching, genetic screening and bioactivity results, often without considering the chemical novelty and abundance of secondary metabolites being produced by the microorganism until the time-consuming bioassay-guided isolation stages. To fast track the selection process, metabolomic tools were used to aid strain selection by investigating differences in the chemical profiles of 77 bacterial extracts isolated from cold water marine invertebrates from Orkney, Scotland using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Following mass spectrometric analysis and dereplication using an Excel macro developed in-house, principal component analysis (PCA) was employed to differentiate the bacterial strains based on their chemical profiles. NMR 1H and correlation spectroscopy (COSY) were also employed to obtain a chemical fingerprint of each bacterial strain and to confirm the presence of functional groups and spin systems. These results were then combined with taxonomic identification and bioassay screening data to identify three bacterial strains, namely Bacillus sp. 4117, Rhodococcus sp. ZS402 and Vibrio splendidus strain LGP32, to prioritize for scale-up based on their chemically interesting secondary metabolomes, established through dereplication and interesting bioactivities, determined from bioassay screening.

  20. Metabolomic Tools for Secondary Metabolite Discovery from Marine Microbial Symbionts

    PubMed Central

    Macintyre, Lynsey; Zhang, Tong; Viegelmann, Christina; Juarez Martinez, Ignacio; Cheng, Cheng; Dowdells, Catherine; Abdelmohsen, Usama Ramadan; Gernert, Christine; Hentschel, Ute; Edrada-Ebel, RuAngelie

    2014-01-01

    Marine invertebrate-associated symbiotic bacteria produce a plethora of novel secondary metabolites which may be structurally unique with interesting pharmacological properties. Selection of strains usually relies on literature searching, genetic screening and bioactivity results, often without considering the chemical novelty and abundance of secondary metabolites being produced by the microorganism until the time-consuming bioassay-guided isolation stages. To fast track the selection process, metabolomic tools were used to aid strain selection by investigating differences in the chemical profiles of 77 bacterial extracts isolated from cold water marine invertebrates from Orkney, Scotland using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Following mass spectrometric analysis and dereplication using an Excel macro developed in-house, principal component analysis (PCA) was employed to differentiate the bacterial strains based on their chemical profiles. NMR 1H and correlation spectroscopy (COSY) were also employed to obtain a chemical fingerprint of each bacterial strain and to confirm the presence of functional groups and spin systems. These results were then combined with taxonomic identification and bioassay screening data to identify three bacterial strains, namely Bacillus sp. 4117, Rhodococcus sp. ZS402 and Vibrio splendidus strain LGP32, to prioritize for scale-up based on their chemically interesting secondary metabolomes, established through dereplication and interesting bioactivities, determined from bioassay screening. PMID:24905482

  1. Mangrove rare actinobacteria: taxonomy, natural compound, and discovery of bioactivity.

    PubMed

    Azman, Adzzie-Shazleen; Othman, Iekhsan; Velu, Saraswati S; Chan, Kok-Gan; Lee, Learn-Han

    2015-01-01

    Actinobacteria are one of the most important and efficient groups of natural metabolite producers. The genus Streptomyces have been recognized as prolific producers of useful natural compounds as they produced more than half of the naturally-occurring antibiotics isolated to-date and continue as the primary source of new bioactive compounds. Lately, Streptomyces groups isolated from different environments produced the same types of compound, possibly due to frequent genetic exchanges between species. As a result, there is a dramatic increase in demand to look for new compounds which have pharmacological properties from another group of Actinobacteria, known as rare actinobacteria; which is isolated from special environments such as mangrove. Recently, mangrove ecosystem is becoming a hot spot for studies of bioactivities and the discovery of natural products. Many novel compounds discovered from the novel rare actinobacteria have been proven as potential new drugs in medical and pharmaceutical industries such as antibiotics, antimicrobials, antibacterials, anticancer, and antifungals. This review article highlights the latest studies on the discovery of natural compounds from the novel mangrove rare actinobacteria and provides insight on the impact of these findings.

  2. Mangrove rare actinobacteria: taxonomy, natural compound, and discovery of bioactivity

    PubMed Central

    Azman, Adzzie-Shazleen; Othman, Iekhsan; Velu, Saraswati S.; Chan, Kok-Gan; Lee, Learn-Han

    2015-01-01

    Actinobacteria are one of the most important and efficient groups of natural metabolite producers. The genus Streptomyces have been recognized as prolific producers of useful natural compounds as they produced more than half of the naturally-occurring antibiotics isolated to-date and continue as the primary source of new bioactive compounds. Lately, Streptomyces groups isolated from different environments produced the same types of compound, possibly due to frequent genetic exchanges between species. As a result, there is a dramatic increase in demand to look for new compounds which have pharmacological properties from another group of Actinobacteria, known as rare actinobacteria; which is isolated from special environments such as mangrove. Recently, mangrove ecosystem is becoming a hot spot for studies of bioactivities and the discovery of natural products. Many novel compounds discovered from the novel rare actinobacteria have been proven as potential new drugs in medical and pharmaceutical industries such as antibiotics, antimicrobials, antibacterials, anticancer, and antifungals. This review article highlights the latest studies on the discovery of natural compounds from the novel mangrove rare actinobacteria and provides insight on the impact of these findings. PMID:26347734

  3. A genome-wide survey of the secondary metabolite biosynthesis genes in the wheat pathogen Parastagonospora nodorum.

    PubMed

    Chooi, Yit-Heng; Muria-Gonzalez, Mariano Jordi; Solomon, Peter S

    2014-07-03

    The model pathogen Parastagonospora nodorum is a necrotroph and the causal agent of the wheat disease Septoria nodorum blotch (SNB). The sequenced P. nodorum genome has revealed that the fungus harbours a large number of secondary metabolite genes. Secondary metabolites are known to play important roles in the virulence of plant pathogens, but limited knowledge is available about the SM repertoire of this wheat pathogen. Here, we review the secondary metabolites that have been isolated from P. nodorum and related species of the same genus and provide an in-depth genome-wide overview of the secondary metabolite gene clusters encoded in the P. nodorum genome. The secondary metabolite gene survey reveals that P. nodorum is capable of producing a diverse range of small molecules and exciting prospects exist for discovery of novel virulence factors and bioactive molecules.

  4. A genome-wide survey of the secondary metabolite biosynthesis genes in the wheat pathogen Parastagonospora nodorum

    PubMed Central

    Chooi, Yit-Heng; Muria-Gonzalez, Mariano Jordi; Solomon, Peter S.

    2014-01-01

    The model pathogen Parastagonospora nodorum is a necrotroph and the causal agent of the wheat disease Septoria nodorum blotch (SNB). The sequenced P. nodorum genome has revealed that the fungus harbours a large number of secondary metabolite genes. Secondary metabolites are known to play important roles in the virulence of plant pathogens, but limited knowledge is available about the SM repertoire of this wheat pathogen. Here, we review the secondary metabolites that have been isolated from P. nodorum and related species of the same genus and provide an in-depth genome-wide overview of the secondary metabolite gene clusters encoded in the P. nodorum genome. The secondary metabolite gene survey reveals that P. nodorum is capable of producing a diverse range of small molecules and exciting prospects exist for discovery of novel virulence factors and bioactive molecules. PMID:25379341

  5. Mutagenic azide metabolite is azidoalanine

    SciTech Connect

    Owais, W.M.; Rosichan, J.L.; Ronald, R.C.; Kleinhofs, A.; Nilan, R.A.

    1981-01-01

    Sodium axide produces high mutation rates in a number of species. Azide mutagenicity is mediated through a metabolite in barley and bacteria. Many studies showed that azide affects the L-cysteine biosynthesis pathway. Cell-free extracts of Salmonella typhimurium convert azide and O-acetylserine to the mutagenic metabolite. O-acetylserine sulfhydrylase was identified as the enzyme responsible for the metabolite biosynthesis. To confirm the conclusion that the azide metabolite is formed through the ..beta..-substitution pathway of L-cysteine, we radioactively labeled the azide metabolite using /sup 14/C-labeled precursors. Moreover, the mutagenic azide metabolite was purified and identified as azidoalanine based on mass spectroscopy and elemental analysis. 26 refs., 3 figs., 1 tab.

  6. Are dietary bioactives ready for recommended intakes?

    PubMed

    Gaine, P Courtney; Balentine, Douglas A; Erdman, John W; Dwyer, Johanna T; Ellwood, Kathleen C; Hu, Frank B; Russell, Robert M

    2013-09-01

    Research has shown that numerous dietary bioactive components that are not considered essential may still be beneficial to health. The dietary reference intake (DRI) process has been applied to nonessential nutrients, such as fiber, yet the majority of bioactive components await a recommended intake. Despite a plethora of new research over the past several years on the health effects of bioactives, it is possible that the field may never reach a point where the current DRI framework is suitable for these food components. If bioactives are to move toward dietary guidance, they will likely require an alternative path to get there.

  7. Screening botanical extracts for quinoid metabolites.

    PubMed

    Johnson, B M; Bolton, J L; van Breemen, R B

    2001-11-01

    Botanical dietary supplements represent a significant share of the growing market for alternative medicine in the USA, where current regulations do not require assessment of their safety. To help ensure the safety of such products, an in vitro assay using pulsed ultrafiltration and LC-MS-MS has been developed to screen botanical extracts for the formation of electrophilic and potentially toxic quinoid species upon bioactivation by hepatic cytochromes P450. Rat liver microsomes were trapped in a flow-through chamber by an ultrafiltration membrane, and samples containing botanical extracts, GSH and NADP(H), were flow-injected into the chamber. Botanical compounds that were metabolized to reactive intermediates formed stable GSH adducts mimicking a common in vivo detoxification pathway. If present in the ultrafiltrate, GSH conjugates were detected using LC-MS-MS with precursor ion scanning followed by additional characterization using product ion scanning and comparison to standard compounds. As expected, no GSH adducts of reactive metabolites were found in extracts of Trifolium pratense L. (red clover), which are under investigation as botanical dietary supplements for the management of menopause. However, extracts of Sassafras albidum (Nutt.) Nees (sassafras), Symphytum officinale L. (comfrey), and Rosmarinus officinalis L. (rosemary), all of which are known to contain compounds that are either carcinogenic or toxic to mammals, produced GSH adducts during this screening assay. Several compounds that formed GSH conjugates including novel metabolites of rosmarinic acid were identified using database searching and additional LC-MS-MS studies. This assay should be useful as a preliminary toxicity screen during the development of botanical dietary supplements. A positive test suggests that additional toxicological studies are warranted before human consumption of a botanical product.

  8. Rapamycin regulates biochemical metabolites

    PubMed Central

    Tucci, Paola; Porta, Giovanni; Agostini, Massimiliano; Antonov, Alexey; Garabadgiu, Alexander Vasilievich; Melino, Gerry; Willis, Anne E

    2013-01-01

    The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth, and deregulation of this pathway is associated with tumorigenesis. p53, and its less investigated family member p73, have been shown to interact closely with mTOR pathways through the transcriptional regulation of different target genes. To investigate the metabolic changes that occur upon inhibition of the mTOR pathway and the role of p73 in this response primary mouse embryonic fibroblast from control and TAp73−/− were treated with the macrocyclic lactone rapamycin. Extensive gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS) analysis were used to obtain a rapamycin-dependent global metabolome profile from control or TAp73−/− cells. In total 289 metabolites involved in selective pathways were identified; 39 biochemical metabolites were found to be significantly altered, many of which are known to be associated with the cellular stress response. PMID:23839040

  9. Cleaning supplies and equipment

    MedlinePlus

    ... gov/ency/patientinstructions/000443.htm Cleaning supplies and equipment To use the sharing features on this page, ... to clean supplies and equipment. Disinfecting Supplies and Equipment Start by wearing the right personal protective equipment ( ...

  10. Quinone and Hydroquinone Metabolites from the Ascidians of the Genus Aplidium

    PubMed Central

    Bertanha, Camila Spereta; Januário, Ana Helena; Alvarenga, Tavane Aparecida; Pimenta, Letícia Pereira; e Silva, Márcio Luis Andrade; Cunha, Wilson Roberto; Pauletti, Patrícia Mendonça

    2014-01-01

    Ascidians of the genus Aplidium are recognized as an important source of chemical diversity and bioactive natural products. Among the compounds produced by this genus are non-nitrogenous metabolites, mainly prenylated quinones and hydroquinones. This review discusses the isolation, structural elucidation, and biological activities of quinones, hydroquinones, rossinones, longithorones, longithorols, floresolides, scabellones, conicaquinones, aplidinones, thiaplidiaquinones, and conithiaquinones. A compilation of the 13C-NMR spectral data of these compounds is also presented. PMID:24927227

  11. Quinazoline derivatives: synthesis and bioactivities

    PubMed Central

    2013-01-01

    Owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. This review summarizes the recent advances in the synthesis and biological activities investigations of quinazoline derivatives. According to the main method the authors adopted in their research design, those synthetic methods were divided into five main classifications, including Aza-reaction, Microwave-assisted reaction, Metal-mediated reaction, Ultrasound-promoted reaction and Phase-transfer catalysis reaction. The biological activities of the synthesized quinazoline derivatives also are discussed. PMID:23731671

  12. Toward bioactive yet antibacterial surfaces.

    PubMed

    Sukhorukova, I V; Sheveyko, A N; Kiryukhantsev-Korneev, Ph V; Zhitnyak, I Y; Gloushankova, N A; Denisenko, E A; Filippovich, S Yu; Ignatov, S G; Shtansky, D V

    2015-11-01

    The fabrication of antibacterial yet biocompatible and bioactive surfaces is a challenge that biological and biomedical community has faced for many years, while no "dream material" has been developed so far. The primary goal of this study was to establish an optimal range of Ag concentration and its state of agglomeration in bioactive nanocomposite TiCaPCON films which would provide a strong bactericidal effect without compromising the material biocompatibility and bioactivity. To obtain samples with different Ag content and redistribution, two different methods were employed: (i) TiCaPCON films deposition by magnetron sputtering of composite TiС0.5-Ca3(РО4)2 target followed by Ag(+) ion implantation and (ii) Ag-doped TiCaPCON films obtained by co-sputtering of composite TiС0.5-Ca3(РО4)2 and Ag targets. In order to reveal the antibacterial role of Ag nanoparticles and Ag(+) ions, both separate and in synergy, part of the samples from the first and second groups was subjected to additional ion etching to remove an Ag rich surface layer heavily populated with Ag nanoparticles. All resultant films were characterized with respect to surface morphology, chemical composition, surface roughness, wettability, and Ag(+) ion release. The antibacterial and antifungal effects of the Ag-doped TiCaPCON films were evaluated against clinically isolated Escherichia coli O78 (E. coli) and Neurospora crassa wt-987 spores. The influence of the surface chemistry on spreading, proliferation, and early stages of MC3T3-E1 osteoblastic cell differentiation was also studied. Our data demonstrated that under optimal conditions in terms of Ag content and agglomeration, the Ag-doped TiCaPCON films are highly efficient against E. coli bacteria and, at the same time, provide good adhesion, spreading, proliferation and differentiation of osteoblastic cells which reflect high level of biocompatibility and bioactivity of the films. The influence of Ag(+) ions and nanoparticles on the MC3T3-E

  13. The importance of drug metabolites synthesis: the case-study of cardiotoxic anticancer drugs.

    PubMed

    Hrynchak, Ivanna; Sousa, Emília; Pinto, Madalena; Costa, Vera Marisa

    2017-04-10

    Anticancer drugs are presently guarantying more survivors as a result of more powerful drugs or combinations of drugs used in therapy. Thus, it has become more crucial to study and overcome the side effects of these therapies. Cardiotoxicity is one of the most relevant side effect on the long-term cancer survivors, because of its high social and economic impact. Drug metabolism can result in active metabolites or toxic metabolites that can lead to important side effects. The metabolites of anticancer drugs are possible culprits of cardiotoxicity; however, the cardiotoxicity of many of the metabolites in several drug classes was not yet suitably studied so far. On the other hand, the use of prodrugs that are bioactivated through metabolism can be a good alternative to obtain more cardio safe drugs. In this review, the methods to obtain and study metabolites are summarized and their application to the study of a group of anticancer drugs with acknowledged cardiotoxicity is highlighted. In this group of drugs, doxorubicin (DOX, 1), mitoxantrone (MTX, 2), cyclophosphamide (CTX, 3), and 5-fluorouracil (5-FU, 4) are included, as well as the tyrosine kinase inhibitors, such as imatinib (5), sunitinib (6), and sorafenib (7). Only with the synthesis and purification of considerable amounts of the metabolites can reliable studies be performed, either in vitro or in vivo that allow accurate conclusions regarding the cardiotoxicity of anticancer drug metabolites and then pharmacological prevention or treatment of the cardiac side effects can be done.

  14. Bioactive properties and potentials cosmeceutical applications of phlorotannins isolated from brown seaweeds: A review.

    PubMed

    Sanjeewa, Kalu Kapuge Asanka; Kim, Eun-A; Son, Kwang-Tae; Jeon, You-Jin

    2016-09-01

    Currently, natural ingredients are becoming more attractive for the industries such as functional food, nutraceuticals, cosmeceutical and pharmaceutical industries as people starting to believe naturally occurring compounds are safer to humans than artificial compounds. Seaweeds are one of the most interesting organisms found in oceans around the earth, which are carrying great ecological importance and contribute to increase the biodiversity of ecosystems where they were originated and habitat. Within last few decades, discovery of secondary metabolites with biological activities from seaweeds has been significantly increased. Further, the unique secondary metabolites isolated from seaweeds including polysaccharides, carotenoids and polyphenols possess range of bioactive properties that make them potential ingredient for many industrial applications. Among those groups of compounds phlorotannins isolated from brown seaweeds have shown interesting bioactive properties including anti-cancer, anti-inflammation, anti-oxidant, anti-allergic, anti-wrinkling and hair growth promotion properties. Moreover, these properties associated with phlorotannins make them an ideal compounds to use as a functional ingredient in cosmeceutical products. Up to now no report has been reviewed about discuss properties of phlorotannins related to the cosmeceutical application. In the present review primary attention is given to the collect scientific data published about bioactive properties of brown algal phlorotannins related to the cosmeceutical industry.

  15. Merging Chemical Ecology with Bacterial Genome Mining for Secondary Metabolite Discovery

    PubMed Central

    Vizcaino, Maria I.; Guo, Xun; Crawford, Jason M.

    2013-01-01

    The integration of chemical ecology and bacterial genome mining can enhance the discovery of structurally diverse natural products in functional contexts. By examining bacterial secondary metabolism in the framework of its ecological niche, insights can be drawn for the upregulation of orphan biosynthetic pathways and the enhancement of enzyme substrate supply to illuminate new secondary metabolic pathways that would otherwise be silent or undetected under typical laboratory cultivation conditions. Access to these new natural products (i.e., the chemotypes) facilitates experimental genotype-to-phenotype linkages. Here, we describe select functional natural products produced by Xenorhabdus and Photorhabdus bacteria, with experimentally linked biosynthetic gene clusters, as illustrative examples of synergy between chemical ecology and bacterial genome mining in connecting genotypes to phenotypes through chemotype characterization. These Gammaproteobacteria share a mutualistic relationship with nematodes and a pathogenic relationship with insects, and in select cases, humans. The natural products encoded by these bacteria distinguish their interactions with animal hosts and other microorganisms in their multipartite symbiotic lifestyles. Though both genera have similar lifestyles, their genetic, chemical, and physiological attributes are distinct. Both undergo phenotypic variation and produce a profuse number of bioactive secondary metabolites. We provide further detail in the context of regulation, production, processing, and function of these genetically encoded small molecules with respect to their roles in mutualism and pathogenicity. These collective insights more widely promote the discovery of atypical orphan biosynthetic pathways encoding novel small molecules in symbiotic systems, which could open new avenues for investigating and exploiting microbial chemical signaling in host-bacteria interactions. PMID:24127069

  16. Bioactivity of plasma implanted biomaterials

    NASA Astrophysics Data System (ADS)

    Chu, Paul K.

    2006-01-01

    Plasma immersion ion implantation and deposition (PIII&D) is an effective technique to enhance the surface bioactivity of materials. In this paper, recent progress made in our laboratory on plasma surface modification of biomedical materials is described. NiTi alloys have unique super-elastic and shape memory properties and are suitable for orthopedic implants but the leaching of toxic Ni may pose health hazards in humans. We have recently investigated the use of acetylene, oxygen and nitrogen PIII&D to prevent out-diffusion of nickel and good results have been obtained. Silicon is the most important material in the microelectronics industry but its surface biocompatibility has not been investigated in details. We have recently performed hydrogen PIII into silicon to improve the surface bioactivity and observed biomimetic growth of apatite on the surface in simulated body fluids. Diamond-like carbon (DLC) is widely used in the industry due to its excellent mechanical properties and chemical inertness and by incorporation of elements such as nitrogen and phosphorus, the surface blood compatibility can be improved. The properties as well as in vitro biological test results are discussed in this article.

  17. Bioactive Egg Components and Inflammation

    PubMed Central

    Andersen, Catherine J.

    2015-01-01

    Inflammation is a normal acute response of the immune system to pathogens and tissue injury. However, chronic inflammation is known to play a significant role in the pathophysiology of numerous chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and cancer. Thus, the impact of dietary factors on inflammation may provide key insight into mitigating chronic disease risk. Eggs are recognized as a functional food that contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways. Interestingly, the effects of egg consumption on inflammation varies across different populations, including those that are classified as healthy, overweight, metabolic syndrome, and type 2 diabetic. The following review will discuss the pro- and anti-inflammatory properties of egg components, with a focus on egg phospholipids, cholesterol, the carotenoids lutein and zeaxanthin, and bioactive proteins. The effects of egg consumption of inflammation across human populations will additionally be presented. Together, these findings have implications for population-specific dietary recommendations and chronic disease risk. PMID:26389951

  18. Bioactive Components in Fish Venoms

    PubMed Central

    Ziegman, Rebekah; Alewood, Paul

    2015-01-01

    Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules. PMID:25941767

  19. Top-down Targeted Metabolomics Reveals a Sulfur-Containing Metabolite with Inhibitory Activity against Angiotensin-Converting Enzyme in Asparagus officinalis.

    PubMed

    Nakabayashi, Ryo; Yang, Zhigang; Nishizawa, Tomoko; Mori, Tetsuya; Saito, Kazuki

    2015-05-22

    The discovery of bioactive natural compounds containing sulfur, which is crucial for inhibitory activity against angiotensin-converting enzyme (ACE), is a challenging task in metabolomics. Herein, a new S-containing metabolite, asparaptine (1), was discovered in the spears of Asparagus officinalis by targeted metabolomics using mass spectrometry for S-containing metabolites. The contribution ratio (2.2%) to the IC50 value in the crude extract showed that asparaptine (1) is a new ACE inhibitor.

  20. Laser cladding of bioactive glass coatings.

    PubMed

    Comesaña, R; Quintero, F; Lusquiños, F; Pascual, M J; Boutinguiza, M; Durán, A; Pou, J

    2010-03-01

    Laser cladding by powder injection has been used to produce bioactive glass coatings on titanium alloy (Ti6Al4V) substrates. Bioactive glass compositions alternative to 45S5 Bioglass were demonstrated to exhibit a gradual wetting angle-temperature evolution and therefore a more homogeneous deposition of the coating over the substrate was achieved. Among the different compositions studied, the S520 bioactive glass showed smoother wetting angle-temperature behavior and was successfully used as precursor material to produce bioactive coatings. Coatings processed using a Nd:YAG laser presented calcium silicate crystallization at the surface, with a uniform composition along the coating cross-section, and no significant dilution of the titanium alloy was observed. These coatings maintain similar bioactivity to that of the precursor material as demonstrated by immersion in simulated body fluid.

  1. Surface modification of bioactive glasses and preparation of PDLLA/bioactive glass composite films.

    PubMed

    Gao, Yuan; Chang, Jiang

    2009-08-01

    In order to improve the homogeneous dispersion of particles in the polymeric matrix, 45S5, mesoporous 58S, and 58S bioactive glasses were surface modified by esterification reactions with dodecyl alcohol at reflux temperature of 260 degrees C (named as m-45S5, m-mesoporous 58S, and m-58S, respectively). The modified particles showed better hydrophobicity and longer time of suspension in organic matrix. The PDLLA/bioactive glass composite films were fabricated using surface modified bioactive glass particles through solvent casting-evaporation method. Surface morphology, mechanical property, and bioactivity were investigated. The results revealed that the inorganic particle distribution and tensile strength of the composite films with modified bioactive glass particles were significantly improved while great bioactive properties were maintained. Scanning electron microscopy (SEM) observation illustrated that the modified bioactive glass particles were homogeneously dispersed in the PDLLA matrix. The maximum tensile strengths of composite films with modified bioactive glass particles were higher than that of composite films with unmodified bioactive glass particles. The bioactivity of the composite films were evaluated by being soaked in the simulated body fluid (SBF) and the SEM observation of the films suggested that the modified composite films were still bioactive in that they could induce the formation of HAp on its surface and the distribution of HAp was even more homogeneous on the film. The results mentioned above indicated that the surface modification of bioactive glasses with dodecyl alcohol was an effective method to prepare PDLLA/bioactive glass composites with enhanced properties. By studying the comparisons of modification effects among the three types of bioactive glasses, we could get the conclusion that the size and morphology of the inorganic particles would greatly affect the modification effects and the properties of composites.

  2. Food proteins as a source of bioactive peptides with diverse functions.

    PubMed

    Rutherfurd-Markwick, Kay J

    2012-08-01

    In addition to supplying essential nutrients, some food proteins can confer additional health benefits beyond nutrition. The presence of bioactive proteins and peptides in different foods is a factor not currently taken into consideration when assessing the dietary quality of food proteins. The range of described physiological benefits attributed to bioactive proteins and peptides is diverse. Multiple factors can potentially impact on the ability of a bioactive peptide or protein to elicit an effect. Although some food proteins act directly in their intact form to elicit their effects, generally it is peptides derived from digestion, hydrolysis or fermentation that are of most interest. The levels of bioactive peptides generated must be sufficient to elicit a response, but should not be so high as to be unsafe, thus causing negative effects. In addition, some peptides cause systemic effects and therefore must be absorbed, again in sufficient amounts to elicit their action. Many studies to date have been carried out in vitro; therefore it is important that further trials are conducted in vivo to assess efficacy, dose response and safety of the peptides, particularly if health related claims are to be made. Therefore, methods must be developed and standardised that enable the measurement of health benefits and also the level of bioactive peptides which are absorbed into the bloodstream. Once standardised, such methods may provide a new perspective and an additional mechanism for analysing protein quality which is currently not encompassed by the use of the protein digestibility-corrected amino acid score (PDCAAS).

  3. Health supply chain management.

    PubMed

    Zimmerman, Rolf; Gallagher, Pat

    2010-01-01

    This chapter gives an educational overview of: * The actual application of supply chain practice and disciplines required for service delivery improvement within the current health environment. * A rationale for the application of Supply Chain Management (SCM) approaches to the Health sector. * The tools and methods available for supply chain analysis and benchmarking. * Key supply chain success factors.

  4. Sustainable production of bioactive compounds by sponges--cell culture and gene cluster approach: a review.

    PubMed

    Müller, Werner E G; Grebenjuk, Vladislav A; Le Pennec, Gaël; Schröder, Heinz- C; Brümmer, Franz; Hentschel, Ute; Müller, Isabel M; Breter, Hans- J

    2004-01-01

    Sponges (phylum Porifera) are sessile marine filter feeders that have developed efficient defense mechanisms against foreign attackers such as viruses, bacteria, or eukaryotic organisms. Protected by a highly complex immune system, as well as by the capacity to produce efficient antiviral compounds (e.g., nucleoside analogues), antimicrobial compounds (e.g., polyketides), and cytostatic compounds (e.g., avarol), they have not become extinct during the last 600 million years. It can be assumed that during this long period of time, bacteria and microorganisms coevolved with sponges, and thus acquired a complex common metabolism. It is suggested that (at least) some of the bioactive secondary metabolites isolated from sponges are produced by functional enzyme clusters, which originated from the sponges and their associated microorganisms. As a consequence, both the host cells and the microorganisms lost the ability to grow independently from each other. Therefore, it was--until recently--impossible to culture sponge cells in vitro. Also the predominant number of "symbiotic bacteria" proved to be nonculturable. In order to exploit the bioactive potential of both the sponge and the "symbionts," a 3D-aggregate primmorph culture system was established; also it was proved that one bioactive compound, avarol/avarone, is produced by the sponge Dysidea avara. Another promising way to utilize the bioactive potential of the microorganisms is the cloning and heterologous expression of enzymes involved in secondary metabolism, such as the polyketide synthases.

  5. Effects of Actinomycete Secondary Metabolites on Sediment Microbial Communities.

    PubMed

    Patin, Nastassia V; Schorn, Michelle; Aguinaldo, Kristen; Lincecum, Tommie; Moore, Bradley S; Jensen, Paul R

    2017-02-15

    Marine sediments harbor complex microbial communities that remain poorly studied relative to other biomes such as seawater. Moreover, bacteria in these communities produce antibiotics and other bioactive secondary metabolites, yet little is known about how these compounds affect microbial community structure. In this study, we used next-generation amplicon sequencing to assess native microbial community composition in shallow tropical marine sediments. The results revealed complex communities comprised of largely uncultured taxa, with considerable spatial heterogeneity and known antibiotic producers comprising only a small fraction of the total diversity. Organic extracts from cultured strains of the sediment-dwelling actinomycete genus Salinispora were then used in mesocosm studies to address how secondary metabolites shape sediment community composition. We identified predatory bacteria and other taxa that were consistently reduced in the extract-treated mesocosms, suggesting that they may be the targets of allelopathic interactions. We tested related taxa for extract sensitivity and found general agreement with the culture-independent results. Conversely, several taxa were enriched in the extract-treated mesocosms, suggesting that some bacteria benefited from the interactions. The results provide evidence that bacterial secondary metabolites can have complex and significant effects on sediment microbial communities.

  6. Marine actinobacterial metabolites: current status and future perspectives.

    PubMed

    Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

    2013-07-19

    Marine actinobacteriology is one of the major emerging areas of research in tropics. Marine actinobacteria are the most economically as well as biotechnologically valuable prokaryotes. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Among the actinobacteria, streptomycetes group are considered economically important because out of the approximately more than 10,000 known antibiotics, 50-55% are produced by this genus. The ecological role of actinobacteria in the marine ecosystem is largely neglected and various assumptions meant there was little incentive to isolate marine strains for search and discovery of new drugs. The search for and discovery of novel actinobacteria are of significant interest to drug discovery due to a growing need for the development of new and potent therapeutic agents. In this review an evaluation is made on the present state of research on marine actinobacterial metabolites and its perspectives. The highlights include the production and biotechnological applications of metabolites such as antibiotics, anticancer compounds, melanins, enzymes and enzyme inhibitors, single cell protein and as probiotics in aquaculture. With increasing advancement in science and technology, there would be greater demands in future for new bioactive compounds synthesized by actinobacteria from various marine sources.

  7. Metabolite transport across the mammalian and insect brain diffusion barriers.

    PubMed

    Weiler, Astrid; Volkenhoff, Anne; Hertenstein, Helen; Schirmeier, Stefanie

    2017-02-24

    The nervous system in higher vertebrates is separated from the circulation by a layer of specialized endothelial cells. It protects the sensitive neurons from harmful blood-derived substances, high and fluctuating ion concentrations, xenobiotics or even pathogens. To this end, the brain endothelial cells and their interlinking tight junctions build an efficient diffusion barrier. A structurally analogous diffusion barrier exists in insects, where glial cell layers separate the hemolymph from the neural cells. Both types of diffusion barriers, of course, also prevent influx of metabolites from the circulation. Because neuronal function consumes vast amounts of energy and necessitates influx of diverse substrates and metabolites, tightly regulated transport systems must ensure a constant metabolite supply. Here, we review the current knowledge about transport systems that carry key metabolites, amino acids, lipids and carbohydrates into the vertebrate and Drosophila brain and how this transport is regulated. Blood-brain and hemolymph-brain transport functions are conserved and we can thus use a simple, genetically accessible model system to learn more about features and dynamics of metabolite transport into the brain.

  8. The profiling and identification of the metabolites of (+)-catechin and study on their distribution in rats by HPLC-DAD-ESI-IT-TOF-MS(n) technique.

    PubMed

    Liang, Jing; Xu, Feng; Zhang, Ya-Zhou; Zang, Xin-Yu; Wang, Dan; Shang, Ming-Ying; Wang, Xuan; Chui, De-Hua; Cai, Shao-Qing

    2014-03-01

    (+)-Catechin, a potential beneficial compound to human health, is widely distributed in plants and foods. A high-performance liquid chromatography with diode array detector and combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry method was applied to profile and identify the metabolites of (+)-catechin in rats and to study the distribution of these metabolites in rat organs for the first time. In total, 51 phase II metabolites (44 new) and three phase I metabolites were tentatively identified, comprising 16 (+)-catechin conjugates, 14 diarylpropan-2-ol metabolites, 6 phenyl valerolactone metabolites and 18 aromatic acid metabolites. Further, 19 phase II metabolites were new compounds. The in vivo metabolic reactions of (+)-catechin in rats were found to be ring-cleavage, sulfation, glucuronidation, methylation, dehydroxylation and dehydrogenation. The numbers of detected metabolites in urine, plasma, small intestine, kidney, liver, lung, heart, brain and spleen were 53, 23, 27, 9, 7, 5, 3, 2 and 1, respectively. This indicated that small intestine, kidney and liver were the major organs for the distribution of (+)-catechin metabolites. In addition, eight metabolites were found to possess bioactivities according to literature. These results are very helpful for better comprehension of the in vivo metabolism of (+)-catechin and its pharmacological actions, and also can give strong indications on the effective forms of (+)-catechin in vivo.

  9. Diversity and bioactive potentials of culturable heterotrophic bacteria from the surficial sediments of the Arabian Sea.

    PubMed

    Anas, Abdulaziz; Nilayangod, Charulatha; Jasmin, C; Vinothkumar, Saradavey; Parameswaran, P S; Nair, Shanta

    2016-12-01

    Marine sediments accommodate plethora of diverse microorganisms with varying ecological functions. In the present study, we isolated bacteria from surficial sediments of south east Arabian Sea (AS) and evaluated their bioactive potentials. A total of 131 isolates belonging to the phylum: γ-Proteobacteria (63%), Bacillales (34%) and Micrococcaceae (3%) were isolated. Among these, about 40% of the isolates showed the presence of secondary metabolite biosynthetic genes such as PKS or NRPS or both. Organic extracts of nearly 50% of these organisms were cytotoxic to human breast cancer MCF-7 cells and were bactericidal to human pathogens, Escherichia coli and Pseudomonas sp., while 20-30% of them were bactericidal to Vibrio sp. and Staphylococcus sp. too. In all, 8 isolates, belonging to Pseudomonas spp., Bacillus sp. and/or Lysinibacillus sp. displayed high level of bactericidal/cytotoxic properties. The study proposes AS sediment as a rich source for microorganisms with prospective bioactive molecules.

  10. Bioactivity Enhancement of Herbal Supplements by Intestinal Microbiota Focusing on the Ginsenosides

    PubMed Central

    Wang, Huai-You; Qi, Lian-Wen; Wang, Chong-Zhi; Li, Ping

    2012-01-01

    Intestinal microbiota contributes to diverse mammalian processes including the metabolic function of drugs. It is a potential new territory for drug targeting, especially for dietary herbal products. Because most of herbal drugs are orally administered, the chemical profile and corresponding bioactivities of herbal medicines may be altered by intestinal microbiota. Ginseng is one of the most commonly used herb and it is always an attractive natural product to understand. In this review, after briefly introduce the interactions of herbal products and gut microbiota, we discussed the microbiota-mediated metabolism of ginsenosides in ginseng and red ginseng. In particular, the major metabolite Compound K and its pharmacological advances are commented including anticancer, antidiabetic and antiinflammatory effects. In summary, the intestinal microbiota may play an important role in mediating the metabolism and enhancement of bioactivity of herbal medicines. PMID:22083984

  11. Culturable endophytes of medicinal plants and the genetic basis for their bioactivity.

    PubMed

    Miller, Kristin I; Qing, Chen; Sze, Daniel Man-Yuen; Roufogalis, Basil D; Neilan, Brett A

    2012-08-01

    The bioactive compounds of medicinal plants are products of the plant itself or of endophytes living inside the plant. Endophytes isolated from eight different anticancer plants collected in Yunnan, China, were characterized by diverse 16S and 18S rRNA gene phylogenies. A functional gene-based molecular screening strategy was used to target nonribosomal peptide synthetase (NRPS) and type I polyketide synthase (PKS) genes in endophytes. Bioinformatic analysis of these biosynthetic pathways facilitated inference of the potential bioactivity of endophyte natural products, suggesting that the isolated endophytes are capable of producing a plethora of secondary metabolites. All of the endophyte culture broth extracts demonstrated antiproliferative effects in at least one test assay, either cytotoxic, antibacterial or antifungal. From the perspective of natural product discovery, this study confirms the potential for endophytes from medicinal plants to produce anticancer, antibacterial and antifungal compounds. In addition, PKS and NRPS gene screening is a valuable method for screening isolates of biosynthetic potential.

  12. Endogenous cross-talk of fungal metabolites

    PubMed Central

    Sheridan, Kevin J.; Dolan, Stephen K.; Doyle, Sean

    2015-01-01

    Non-ribosomal peptide (NRP) synthesis in fungi requires a ready supply of proteogenic and non-proteogenic amino acids which are subsequently incorporated into the nascent NRP via a thiotemplate mechanism catalyzed by NRP synthetases. Substrate amino acids can be modified prior to or during incorporation into the NRP, or following incorporation into an early stage amino acid-containing biosynthetic intermediate. These post-incorporation modifications involve a range of additional enzymatic activities including but not exclusively, monooxygenases, methyltransferases, epimerases, oxidoreductases, and glutathione S-transferases which are essential to effect biosynthesis of the final NRP. Likewise, polyketide biosynthesis is directly by polyketide synthase megaenzymes and cluster-encoded ancillary decorating enzymes. Additionally, a suite of additional primary metabolites, for example: coenzyme A (CoA), acetyl CoA, S-adenosylmethionine, glutathione (GSH), NADPH, malonyl CoA, and molecular oxygen, amongst others are required for NRP and polyketide synthesis (PKS). Clearly these processes must involve exquisite orchestration to facilitate the simultaneous biosynthesis of different types of NRPs, polyketides, and related metabolites requiring identical or similar biosynthetic precursors or co-factors. Moreover, the near identical structures of many natural products within a given family (e.g., ergot alkaloids), along with localization to similar regions within fungi (e.g., conidia) suggests that cross-talk may exist, in terms of biosynthesis and functionality. Finally, we speculate if certain biosynthetic steps involved in NRP and PKS play a role in cellular protection or environmental adaptation, and wonder if these enzymatic reactions are of equivalent importance to the actual biosynthesis of the final metabolite. PMID:25601857

  13. Bioactive glasses and glass-ceramics.

    PubMed

    Rawlings, R D

    1993-01-01

    Bioactive materials are designed to induce a specific biological activity; in most cases the desired biological activity is one that will give strong bonding to bone. A range of materials has been assessed as being capable of bonding to bone, but this paper is solely concerned with bioactive glasses and glass-ceramics. Firstly, the structure and processing of glasses and glass-ceramics are described, as a basic knowledge is essential for the understanding of the development and properties of the bioactive materials. The effect of composition and structure on the bioactivity is then discussed, and it will be shown that bioactivity is associated with the formation of an apatite layer on the surface of the implant. A survey of mechanical performance demonstrates that the structure and mechanical properties of glass-ceramics depend upon whether the processing involves casting or sintering and that the strength and toughness of glass-ceramics are superior to those of glasses. Attempts to further improve the mechanical performance by the use of non-monolithic components, i.e. bioactive coatings on metal substrates and glass and glass-ceramic matrix composites, are also reviewed and are shown to have varying degrees of success. Finally, some miscellaneous applications, namely bioactive bone cements and bone fillers, are briefly covered.

  14. Isoflavone metabolism and bone-sparing effects of daidzein-metabolites

    PubMed Central

    Uehara, Mariko

    2013-01-01

    Several dietary phytochemicals exhibit anti-oxidative, anti-inflammatory and anti-osteoporotic activities relevant to prevention of chronic diseases, including lifestyle-related diseases. Soybean isoflavones are similar in structure to estrogen and have received considerable attention as potential alternatives to hormone replacement therapy. Daidzein, a major isoflavone found in soybean, is metabolized to equol by intestinal microflora; this metabolite exhibits stronger estrogenic activity than daidzein. Recent studies suggest that the clinical effectiveness of isoflavones might be due to their ability to produce equol in the gut. This review focused on the metabolic pathway of equol and possible bioactivities of equol and O-desmethylangolensin, another metabolite of daidzein, with regard to bone metabolism and the status of intestinal microflora. Furthermore, we considered risk-benefit analyses of isoflavones and their metabolites. PMID:23704808

  15. Extraction and purification of high-value metabolites from microalgae: essential lipids, astaxanthin and phycobiliproteins.

    PubMed

    Cuellar-Bermudez, Sara P; Aguilar-Hernandez, Iris; Cardenas-Chavez, Diana L; Ornelas-Soto, Nancy; Romero-Ogawa, Miguel A; Parra-Saldivar, Roberto

    2015-03-01

    The marked trend and consumers growing interest in natural and healthy products have forced researches and industry to develop novel products with functional ingredients. Microalgae have been recognized as source of functional ingredients with positive health effects since these microorganisms produce polyunsaturated fatty acids, polysaccharides, natural pigments, essential minerals, vitamins, enzymes and bioactive peptides. For this reason, the manuscript reviews two of the main high-value metabolites which can be obtained from microalgae: pigments and essential lipids. Therefore, the extraction and purification methods for polyunsaturated fatty acids, astaxanthin, phycoerythrin and phycocyanin are described. Also, the effect that environmental growth conditions have in the production of these metabolites is described. This review summarizes the existing methods to extract and purify such metabolites in order to develop a feasible and sustainable algae industry.

  16. Construction of a natural product library containing secondary metabolites produced by actinomycetes.

    PubMed

    Takagi, Motoki; Shin-Ya, Kazuo

    2012-09-01

    To construct a natural product library for drug screening, we isolated secondary metabolites from a wide variety of actinomycetes cultured from marine sponges. The results suggested that marine sponges are a promising source of actinomycetes with the potential to produce new metabolites. Furthermore, we evaluated the chemical space occupied by our natural product library (CB library) by multidimensional principal component analysis and compared it with a commercially available compound library (ZINC library), which was randomly selected from the ZINC library (approximately 30 000 000 compounds). The CB library occupied a wider chemical space than the ZINC library. Bioactive compounds in the CB library possessed a wide chemical space that was not covered by ZINC library. These results indicate that the CB library mainly comprises secondary metabolites from actinomycetes, and it has great potential as a source of compounds for drug screening.

  17. Extraction and purification of high-value metabolites from microalgae: essential lipids, astaxanthin and phycobiliproteins

    PubMed Central

    Cuellar-Bermudez, Sara P; Aguilar-Hernandez, Iris; Cardenas-Chavez, Diana L; Ornelas-Soto, Nancy; Romero-Ogawa, Miguel A; Parra-Saldivar, Roberto

    2015-01-01

    The marked trend and consumers growing interest in natural and healthy products have forced researches and industry to develop novel products with functional ingredients. Microalgae have been recognized as source of functional ingredients with positive health effects since these microorganisms produce polyunsaturated fatty acids, polysaccharides, natural pigments, essential minerals, vitamins, enzymes and bioactive peptides. For this reason, the manuscript reviews two of the main high-value metabolites which can be obtained from microalgae: pigments and essential lipids. Therefore, the extraction and purification methods for polyunsaturated fatty acids, astaxanthin, phycoerythrin and phycocyanin are described. Also, the effect that environmental growth conditions have in the production of these metabolites is described. This review summarizes the existing methods to extract and purify such metabolites in order to develop a feasible and sustainable algae industry. PMID:25223877

  18. Production of specialized metabolites by Streptomyces coelicolor A3(2).

    PubMed

    van Keulen, Geertje; Dyson, Paul J

    2014-01-01

    The actinomycetes are well-known bioactive natural product producers, comprising the Streptomycetes, the richest drug-prolific family in all kingdoms, producing therapeutic compounds for the areas of infection, cancer, circulation, and immunity. Completion and annotation of many actinomycete genomes has highlighted further how proficient these bacteria are in specialized metabolism, which have been largely underexploited in traditional screening programs. The genome sequence of the model strain Streptomyces coelicolor A3(2), and subsequent development of genomics-driven approaches to understand its large specialized metabolome, has been key in unlocking the high potential of specialized metabolites for natural product genomics-based drug discovery. This review discusses systematically the biochemistry and genetics of each of the specialized metabolites of S. coelicolor and describes metabolite transport processes for excretion and complex regulatory patterns controlling biosynthesis.

  19. Rethinking cycad metabolite research.

    PubMed

    Snyder, Laura R; Marler, Thomas E

    2011-01-01

    Cycads are among the most ancient of extant Spermatophytes, and are known for their numerous pharmacologically active compounds. One compound in particular, β-methylamino-L-alanine (BMAA), has been implicated as the cause of amyotrophic lateral sclerosis/Parkinson dementia complex (ALS/PDC) on Guam. Previous studies allege that BMAA is produced exclusively by cyanobacteria, and is transferred to cycads through the symbiotic relationship between these cyanobacteria and the roots of cycads. We recently published data showing that Cycas micronesica seedlings grown without endophytic cyanobacteria do in fact increase in BMAA, invalidating the foundation of the BMAA hypothesis. We use this example to suggest that the frenzy centered on BMAA and other single putative toxins has hindered progress. The long list of cycad-specific compounds may have important roles in signaling or communication, but these possibilities have been neglected during decades of attempts to force single metabolites into a supposed anti-herbivory function. We propose that an unbiased, comprehensive approach may be a more appropriate means of proceeding with cycad biochemistry research.

  20. Synthesis Of Labeled Metabolites

    DOEpatents

    Martinez, Rodolfo A.; Silks, III, Louis A.; Unkefer, Clifford J.; Atcher, Robert

    2004-03-23

    The present invention is directed to labeled compounds, for example, isotopically enriched mustard gas metabolites including: [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1,1'-sulfonylbis[2-(methylthio); [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1-[[2-(methylsulfinyl)ethyl]sulfonyl]-2-(methylthio); [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1,1'-sulfonylbis[2-(methylsulfinyl)]; and, 2,2'-sulfinylbis([1,2-.sup.13 C.sub.2 ]ethanol of the general formula ##STR1## where Q.sup.1 is selected from the group consisting of sulfide (--S--), sulfone (--S(O)--), sulfoxide (--S(O.sub.2)--) and oxide (--O--), at least one C* is .sup.13 C, X is selected from the group consisting of hydrogen and deuterium, and Z is selected from the group consisting of hydroxide (--OH), and --Q.sup.2 --R where Q.sup.2 is selected from the group consisting of sulfide (--S--), sulfone(--S(O)--), sulfoxide (--S(O.sub.2)--) and oxide (--O--), and R is selected from the group consisting of hydrogen, a C.sub.1 to C.sub.4 lower alkyl, and amino acid moieties, with the proviso that when Z is a hydroxide and Q.sup.1 is a sulfide, then at least one X is deuterium.

  1. Quantitative bioluminescence imaging--a method for the detection of metabolite distributions in frozen tissues

    NASA Astrophysics Data System (ADS)

    Mueller-Klieser, Wolfgang; Walenta, Stefan; Schwickert, Georg

    1994-02-01

    A novel technique allows for measurement of metabolite distributions in tissue cryosections at a microscopic level using bioluminescence, single photon imaging, and computerized image analysis. Metabolites, such as ATP, glucose and lactate are registered in absolute concentration units, and the respective images can be correlated with each other and with histological structures by specific algorithms. One striking difference between malignant tumors and normal tissue is the pronounced heterogeneity of metabolite distributions in malignancies contrasted by rather homogeneous patterns obtained in many normal organs. The heterogeneous distribution of metabolites in solid tumors reflects the chaotic organization of the histological architecture and of the microvascular supply in cancerous tissue. Pixel-to-pixel comparison of metabolite distributions measured in cervix cancers of patients revealed a negative linear correlation between glucose and ATP concentrations at identical locations. In contrast, local lactate concentration was positively correlated with ATP.

  2. Bioactivities and Health Benefits of Wild Fruits

    PubMed Central

    Li, Ya; Zhang, Jiao-Jiao; Xu, Dong-Ping; Zhou, Tong; Zhou, Yue; Li, Sha; Li, Hua-Bin

    2016-01-01

    Wild fruits are exotic or underutilized. Wild fruits contain many bioactive compounds, such as anthocyanins and flavonoids. Many studies have shown that wild fruits possess various bioactivities and health benefits, such as free radical scavenging, antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. Therefore, wild fruits have the potential to be developed into functional foods or pharmaceuticals to prevent and treat several chronic diseases. In the present article, we review current knowledge about the bioactivities and health benefits of wild fruits, which is valuable for the exploitation and utilization of wild fruits. PMID:27527154

  3. Bioactivities and Health Benefits of Wild Fruits.

    PubMed

    Li, Ya; Zhang, Jiao-Jiao; Xu, Dong-Ping; Zhou, Tong; Zhou, Yue; Li, Sha; Li, Hua-Bin

    2016-08-04

    Wild fruits are exotic or underutilized. Wild fruits contain many bioactive compounds, such as anthocyanins and flavonoids. Many studies have shown that wild fruits possess various bioactivities and health benefits, such as free radical scavenging, antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. Therefore, wild fruits have the potential to be developed into functional foods or pharmaceuticals to prevent and treat several chronic diseases. In the present article, we review current knowledge about the bioactivities and health benefits of wild fruits, which is valuable for the exploitation and utilization of wild fruits.

  4. Towards microbial fermentation metabolites as markers for health benefits of prebiotics.

    PubMed

    Verbeke, Kristin A; Boobis, Alan R; Chiodini, Alessandro; Edwards, Christine A; Franck, Anne; Kleerebezem, Michiel; Nauta, Arjen; Raes, Jeroen; van Tol, Eric A F; Tuohy, Kieran M

    2015-06-01

    Available evidence on the bioactive, nutritional and putative detrimental properties of gut microbial metabolites has been evaluated to support a more integrated view of how prebiotics might affect host health throughout life. The present literature inventory targeted evidence for the physiological and nutritional effects of metabolites, for example, SCFA, the potential toxicity of other metabolites and attempted to determine normal concentration ranges. Furthermore, the biological relevance of more holistic approaches like faecal water toxicity assays and metabolomics and the limitations of faecal measurements were addressed. Existing literature indicates that protein fermentation metabolites (phenol, p-cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects are expected either locally or following systemic absorption. The endproducts of saccharolytic fermentation, SCFA, may have effects on colonic health, host physiology, immunity, lipid and protein metabolism and appetite control. However, measuring SCFA concentrations in faeces is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature on the usefulness of faecal water toxicity measures as indicators of cancer risk seems limited. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but adequate tools for data integration and interpretation are currently lacking. Similarly, studies measuring metabolite fluxes in different body compartments to provide a more accurate picture of their nutrikinetics are needed.

  5. Structures of bioactive carexanes from the roots of Carex distachya Desf.

    PubMed

    Fiorentino, Antonio; D'Abrosca, Brigida; Pacifico, Severina; Natale, Angela; Monaco, Pietro

    2006-05-01

    Four metabolites, named carexanes I-L, have been isolated from the roots of Carex distachya Desf, an herbaceous plant living in the Mediterranean maquis, together with three known compounds, already isolated from the aerial part of the plant. All the compounds have been characterized on the basis of their spectroscopic properties. Carexane I derived from the lose of a proton from the C-18 carbon of an intermediate isopropyl cation. Its stereostructure has been elucidated by Mosher's method, NOESY/ROESY experiments and computational calculations. The bioactivity on seed germination and root/shoot growth of Lactuca sativa L. of all the isolated compounds is also reported.

  6. Natural Products from Plant-associated Microorganisms: Distribution, Structural Diversity, Bioactivity, and Implications of Their Occurrence⊥

    PubMed Central

    Gunatilaka, A. A. Leslie

    2012-01-01

    A growing body of evidence suggests that plant-associated microorganisms, especially endophytic and rhizosphere bacteria and fungi, represent a huge and largely untapped resource of natural products with chemical structures that have been optimized by evolution for biological and ecological relevance. A diverse array of bioactive small molecule natural products has been encountered in these microorganisms. The structures of over 230 metabolites isolated and characterized from over 70 plant-associated microbial strains during the past four years are presented with information on their hosts, culture conditions, and biological activities. Some significant biological and ecological implications of their occurrence are also reviewed. PMID:16562864

  7. Low molecular weight phenols from the bioactive aqueous fraction of Cestrum parqui.

    PubMed

    D'Abrosca, Brigida; DellaGreca, Marina; Fiorentino, Antonio; Monaco, Pietro; Zarrelli, Armando

    2004-06-30

    The aqueous fraction of fresh leaves of Cestrum parqui and its organic fractions have been assayed for their phytotoxicity on Lactuca sativa, Lycopersicon esculentum, and Allium cepa. The tests showed that the bioactivity was retained in the organic fractions. Chromatographic processes led to isolation and characterization of the N-(p-carboxymethylphenyl)-p-hydroxybenzamide together with 17 low molecular weight phenols and 2 flavones. The phytotoxicity tests showed a good activity of these compounds on the target species. Comparison of some metabolites with commercial herbicides revealed a major activity of the natural compounds at lower concentrations.

  8. Potential Pharmacological Resources: Natural Bioactive Compounds from Marine-Derived Fungi

    PubMed Central

    Jin, Liming; Quan, Chunshan; Hou, Xiyan; Fan, Shengdi

    2016-01-01

    In recent years, a considerable number of structurally unique metabolites with biological and pharmacological activities have been isolated from the marine-derived fungi, such as polyketides, alkaloids, peptides, lactones, terpenoids and steroids. Some of these compounds have anticancer, antibacterial, antifungal, antiviral, anti-inflammatory, antioxidant, antibiotic and cytotoxic properties. This review partially summarizes the new bioactive compounds from marine-derived fungi with classification according to the sources of fungi and their biological activities. Those fungi found from 2014 to the present are discussed. PMID:27110799

  9. Sol-gel derived porous bioactive nanocomposites: Synthesis and in vitro bioactivity

    NASA Astrophysics Data System (ADS)

    Shankhwar, Nisha; Kothiyal, G. P.; Srinivasan, A.

    2013-06-01

    Porous bioactive composites consisting of SiO2-CaO-Na2O-P2O5 bioactive glass-ceramic and synthetic water soluble polymer Polyvinylpyrrolidone [PVP (C6H9NO)n, MW˜40000 g/mol] have been synthesized by sol-gel route. As-prepared polymeric composites were characterized by X-ray diffraction (XRD) technique. Two major bone mineral phases, viz., hydroxyapatite [Ca10(PO4)6(OH)2] and wollastonite [calcium silicate (CaSiO3)] have been identified in the XRD patterns of the composites. Presence of these bone minerals indicates the bioactive nature of the composites. In vitro bioactivity tests confirm bioactivity in the porous composites. The flexibility offered by these bioactive polymer composites is advantageous for its application as implant material.

  10. Prospects and challenges for industrial production of seaweed bioactives.

    PubMed

    Hafting, Jeff T; Craigie, James S; Stengel, Dagmar B; Loureiro, Rafael R; Buschmann, Alejandro H; Yarish, Charles; Edwards, Maeve D; Critchley, Alan T

    2015-10-01

    Large-scale seaweed cultivation has been instrumental in globalizing the seaweed industry since the 1950s. The domestication of seaweed cultivars (begun in the 1940s) ended the reliance on natural cycles of raw material availability for some species, with efforts driven by consumer demands that far exceeded the available supplies. Currently, seaweed cultivation is unrivaled in mariculture with 94% of annual seaweed biomass utilized globally being derived from cultivated sources. In the last decade, research has confirmed seaweeds as rich sources of potentially valuable, health-promoting compounds. Most existing seaweed cultivars and current cultivation techniques have been developed for producing commoditized biomass, and may not necessarily be optimized for the production of valuable bioactive compounds. The future of the seaweed industry will include the development of high value markets for functional foods, cosmeceuticals, nutraceuticals, and pharmaceuticals. Entry into these markets will require a level of standardization, efficacy, and traceability that has not previously been demanded of seaweed products. Both internal concentrations and composition of bioactive compounds can fluctuate seasonally, geographically, bathymetrically, and according to genetic variability even within individual species, especially where life history stages can be important. History shows that successful expansion of seaweed products into new markets requires the cultivation of domesticated seaweed cultivars. Demands of an evolving new industry based upon efficacy and standardization will require the selection of improved cultivars, the domestication of new species, and a refinement of existing cultivation techniques to improve quality control and traceability of products.

  11. Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities

    PubMed Central

    Hayes, Maria; Tiwari, Brijesh K.

    2015-01-01

    Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these. PMID:26393573

  12. Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities.

    PubMed

    Hayes, Maria; Tiwari, Brijesh K

    2015-09-17

    Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these.

  13. TNT metabolites in animal tissues

    SciTech Connect

    Shugart, L.R.

    1990-01-01

    The overall objectives of this project are: to provide quantitative analytical procedures for the analysis of TNT and at least eight of its metabolites in animal tissues; and to obtain representative samples of tissues from animals from designated Army sites, and to determine the presence or absence of TNT and its metabolites in these samples. The study is divided into two Phases corresponding to the stated overall objectives of the project. 5 figs., 4 tabs.

  14. Bioactive compounds derived from the yeast metabolism of aromatic amino acids during alcoholic fermentation.

    PubMed

    Mas, Albert; Guillamon, Jose Manuel; Torija, Maria Jesus; Beltran, Gemma; Cerezo, Ana B; Troncoso, Ana M; Garcia-Parrilla, M Carmen

    2014-01-01

    Metabolites resulting from nitrogen metabolism in yeast are currently found in some fermented beverages such as wine and beer. Their study has recently attracted the attention of researchers. Some metabolites derived from aromatic amino acids are bioactive compounds that can behave as hormones or even mimic their role in humans and may also act as regulators in yeast. Although the metabolic pathways for their formation are well known, the physiological significance is still far from being understood. The understanding of this relevance will be a key element in managing the production of these compounds under controlled conditions, to offer fermented food with specific enrichment in these compounds or even to use the yeast as nutritional complements.

  15. Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

    PubMed Central

    Guillamon, Jose Manuel; Torija, Maria Jesus; Beltran, Gemma; Troncoso, Ana M.; Garcia-Parrilla, M. Carmen

    2014-01-01

    Metabolites resulting from nitrogen metabolism in yeast are currently found in some fermented beverages such as wine and beer. Their study has recently attracted the attention of researchers. Some metabolites derived from aromatic amino acids are bioactive compounds that can behave as hormones or even mimic their role in humans and may also act as regulators in yeast. Although the metabolic pathways for their formation are well known, the physiological significance is still far from being understood. The understanding of this relevance will be a key element in managing the production of these compounds under controlled conditions, to offer fermented food with specific enrichment in these compounds or even to use the yeast as nutritional complements. PMID:24895623

  16. Feedstock Supply System Logistics

    SciTech Connect

    2006-06-01

    Feedstock supply is a significant cost component in the production of biobased fuels, products, and power. The uncertainty of the biomass feedstock supply chain and associated risks are major barriers to procuring capital funding for start-up biorefineries.

  17. Neuropeptides: metabolism to bioactive fragments and the pharmacology of their receptors.

    PubMed

    Hallberg, Mathias

    2015-05-01

    The proteolytic processing of neuropeptides has an important regulatory function and the peptide fragments resulting from the enzymatic degradation often exert essential physiological roles. The proteolytic processing generates, not only biologically inactive fragments, but also bioactive fragments that modulate or even counteract the response of their parent peptides. Frequently, these peptide fragments interact with receptors that are not recognized by the parent peptides. This review discusses tachykinins, opioid peptides, angiotensins, bradykinins, and neuropeptide Y that are present in the central nervous system and their processing to bioactive degradation products. These well-known neuropeptide systems have been selected since they provide illustrative examples that proteolytic degradation of parent peptides can lead to bioactive metabolites with different biological activities as compared to their parent peptides. For example, substance P, dynorphin A, angiotensin I and II, bradykinin, and neuropeptide Y are all degraded to bioactive fragments with pharmacological profiles that differ considerably from those of the parent peptides. The review discusses a selection of the large number of drug-like molecules that act as agonists or antagonists at receptors of neuropeptides. It focuses in particular on the efforts to identify selective drug-like agonists and antagonists mimicking the effects of the endogenous peptide fragments formed. As exemplified in this review, many common neuropeptides are degraded to a variety of smaller fragments but many of the fragments generated have not yet been examined in detail with regard to their potential biological activities. Since these bioactive fragments contain a small number of amino acid residues, they provide an ideal starting point for the development of drug-like substances with ability to mimic the effects of the degradation products. Thus, these substances could provide a rich source of new pharmaceuticals

  18. Human Intestinal Raf Kinase Inhibitor Protein (RKIP) Catalyzes Prasugrel as a Bioactivation Hydrolase.

    PubMed

    Kazui, Miho; Ogura, Yuji; Hagihara, Katsunobu; Kubota, Kazuishi; Kurihara, Atsushi

    2016-01-01

    Prasugrel is a thienopyridine antiplatelet prodrug that undergoes rapid hydrolysis in vivo to a thiolactone metabolite by human carboxylesterase-2 (hCE2) during gastrointestinal absorption. The thiolactone metabolite is further converted to a pharmacologically active metabolite by cytochrome P450 isoforms. The aim of the current study was to elucidate hydrolases other than hCE2 involved in the bioactivation step of prasugrel in human intestine. Using size-exclusion column chromatography of a human small intestinal S9 fraction, another peak besides the hCE2 peak was observed to have prasugrel hydrolyzing activity, and this protein was found to have a molecular weight of about 20 kDa. This prasugrel hydrolyzing protein was successfully purified from a monkey small intestinal cytosolic fraction by successive four-step column chromatography and identified as Raf-1 kinase inhibitor protein (RKIP) by liquid chromatography-tandem mass spectrometry. Second, we evaluated the enzymatic kinetic parameters for prasugrel hydrolysis using recombinant human RKIP and hCE2 and estimated the contributions of these two hydrolyzing enzymes to the prasugrel hydrolysis reaction in human intestine, which were approximately 40% for hRKIP and 60% for hCE2. Moreover, prasugrel hydrolysis was inhibited by anti-hRKIP antibody and carboxylesterase-specific chemical inhibitor (bis p-nitrophenyl phosphate) by 30% and 60%, respectively. In conclusion, another protein capable of hydrolyzing prasugrel to its thiolactone metabolite was identified as RKIP, and this protein may play a significant role with hCE2 in prasugrel bioactivation in human intestine. RKIP is known to have diverse functions in many intracellular signaling cascades, but this is the first report describing RKIP as a hydrolase involved in drug metabolism.

  19. From genome mining to phenotypic microarrays: Planctomycetes as source for novel bioactive molecules.

    PubMed

    Jeske, Olga; Jogler, Mareike; Petersen, Jörn; Sikorski, Johannes; Jogler, Christian

    2013-10-01

    Most members of the phylum Planctomycetes share many unusual traits that are unique for bacteria, since they divide independent of FtsZ through asymmetric budding, possess a complex life cycle and comprise a compartmentalized cell plan. Besides their complex cell biological features Planctomycetes are environmentally important and play major roles in global matter fluxes. Such features have been successfully employed in biotechnological applications such as the anaerobic oxidation of ammonium in wastewater treatment plants or the utilization of enzymes for biotechnological processes. However, little is known about planctomycetal secondary metabolites. This is surprising as Planctomycetes have several key features in common with known producers of small bioactive molecules such as Streptomycetes or Myxobacteria: a complex life style and large genome sizes. Planctomycetal genomes with an average size of 6.9 MB appear as tempting targets for drug discovery approaches. To enable the hunt for bioactive molecules from Planctomycetes, we performed a comprehensive genome mining approach employing the antiSMASH secondary metabolite identification pipeline and found 102 candidate genes or clusters within the analyzed 13 genomes. However, as most genes and operons related to secondary metabolite production are exclusively expressed under certain environmental conditions, we optimized Phenotype MicroArray protocols for Rhodopirellula baltica and Planctomyces limnophilus to allow high throughput screening of putative stimulating carbon sources. Our results point towards a previously postulated relationship of Planctomycetes with algae or plants, which secrete compounds that might serve as trigger to stimulate the secondary metabolite production in Planctomycetes. Thus, this study provides the necessary starting point to explore planctomycetal small molecules for drug development.

  20. Ability of the gut microbiota to produce PUFA-derived bacterial metabolites: proof of concept in germ-free versus conventionalized mice

    PubMed Central

    Druart, Céline; Bindels, Laure B.; Schmaltz, Robert; Neyrinck, Audrey M.; Cani, Patrice D.; Walter, Jens; Ramer-Tait, Amanda E.; Delzenne, Nathalie M.

    2015-01-01

    Scope The gut microbiota is able to modulate host physiology through the production of bioactive metabolites. Our recent studies suggest that changes in gut microbiota composition upon prebiotics supplementation alter tissue levels of PUFA-derived metabolites in mice. However, in vivo evidence that gut microbes produces PUFA-derived metabolites is lacking. This study aimed to decipher the contribution of gut microbes versus that of the host in PUFA-derived metabolite production. Methods and results To achieve this goal, we compared the proportion of PUFA-derived metabolites and the expression of fatty acid desaturases in germ-free (GF) and conventionalized (CONV) mice fed either a low fat or Western diet. Higher concentrations of PUFA-derived metabolites were found in the colonic contents of CONV mice compared to GF mice. The abundance of these metabolites in host tissues was modulated by dietary treatments but not by microbial status. Although microbial status did significantly influence desaturase expression, no correlations between host enzymes and tissue PUFA-derived metabolite levels were observed. Conclusion Together, these results highlight the ability of the gut microbiota to produce PUFA-derived metabolites from dietary PUFA. However, microbial production of these metabolites in colonic contents is not necessarily associated with modifications of their concentration in host tissues. PMID:25820326

  1. Novel bioactive compounds from actinomycetes.

    PubMed

    Sanglier, J J; Wellington, E M; Behal, V; Fiedler, H P; Ellouz Ghorbel, R; Finance, C; Hacene, M; Kamoun, A; Kelly, C; Mercer, D K

    1993-10-01

    Actinomycetes form an enormous reservoir of secondary metabolites and enzymes. The potential for exploiting rare actinomycetes is highlighted by the discovery of novel compounds from strains of Spirillospora and Nocardioides. Novel compounds of well known classes of antibiotics, such as polyenes, continue to be discovered. For compounds containing a chromophore, the analysis by high-performance liquid chromatography coupled with a diode-array detector enables the elimination of producers of known compounds and facilitates the discovery of novel compounds or derivatives. The complexity of the regulatory mechanisms is illustrated by glutamine synthetase. The characterization of thermostable amylolytic, lignolytic, peroxidase and neuramidase activities, and the isolation of novel cellulolytic actinomycetes clearly demonstrate the potential of Actinomycetes as producers of enzymes.

  2. Pursuing supply chain gains.

    PubMed

    Long, Gene

    2005-09-01

    Five hallmarks of an effective supply chain are: A strong relationship is developed with a single GPO. Physicians are involved in supply standardization. Supply contracts are routinely reviewed at time of renewal. Freight costs are understood and negotiated effectively. Products are distributed through an in-house distribution center.

  3. Advances on Bioactive Polysaccharides from Medicinal Plants.

    PubMed

    Xie, Jian-Hua; Jin, Ming-Liang; Morris, Gordon A; Zha, Xue-Qiang; Chen, Han-Qing; Yi, Yang; Li, Jing-En; Wang, Zhi-Jun; Gao, Jie; Nie, Shao-Ping; Shang, Peng; Xie, Ming-Yong

    2016-07-29

    In recent decades, the polysaccharides from the medicinal plants have attracted a lot of attention due to their significant bioactivities, such as anti-tumor activity, antioxidant activity, anticoagulant activity, antidiabetic activity, radioprotection effect, anti-viral activity, hypolipidemic and immunomodulatory activities, which make them suitable for medicinal applications. Previous studies have also shown that medicinal plant polysaccharides are non-toxic and show no side effects. Based on these encouraging observations, most researches have been focusing on the isolation and identification of polysaccharides, as well as their bioactivities. A large number of bioactive polysaccharides with different structural features and biological effects from medicinal plants have been purified and characterized. This review provides a comprehensive summary of the most recent developments in physiochemical, structural features and biological activities of bioactive polysaccharides from a number of important medicinal plants, such as polysaccharides from Astragalus membranaceus, Dendrobium plants, Bupleurum, Cactus fruits, Acanthopanax senticosus, Angelica sinensis (Oliv.) Diels, Aloe barbadensis Miller, and Dimocarpus longan Lour. Moreover, the paper has also been focused on the applications of bioactive polysaccharides for medicinal applications. Recent studies have provided evidence that polysaccharides from medicinal plants can play a vital role in bioactivities. The contents and data will serve as a useful reference material for further investigation, production, and application of these polysaccharides in functional foods and therapeutic agents.

  4. Biomolecule immobilization techniques for bioactive paper fabrication.

    PubMed

    Kong, Fanzhi; Hu, Yim Fun

    2012-04-01

    Research into paper-based sensors or functional materials that can perform analytical functions with active recognition capabilities is rapidly expanding, and significant research effort has been made into the design and fabrication of bioactive paper at the biosensor level to detect potential health hazards. A key step in the fabrication of bioactive paper is the design of the experimental and operational procedures for the immobilization of biomolecules such as antibodies, enzymes, phages, cells, proteins, synthetic polymers and DNA aptamers on a suitably prepared paper membrane. The immobilization methods are concisely categorized into physical absorption, bioactive ink entrapment, bioaffinity attachment and covalent chemical bonding immobilization. Each method has individual immobilization characteristics. Although every biomolecule-paper combination has to be optimized before use, the bioactive ink entrapment method is the most commonly used approach owing to its general applicability and biocompatibility. Currently, there are four common applications of bioactive paper: (1) paper-based bioassay or paper-based analytical devices for sample conditioning; (2) counterfeiting and countertempering in the packaging and construction industries; (3) pathogen detection for food and water quality monitoring; and (4) deactivation of pathogenic bacteria using antimicrobial paper. This article reviews and compares the different biomolecule immobilization techniques and discusses current trends. Current, emerging and future applications of bioactive paper are also discussed.

  5. Secondary metabolite arsenal of an opportunistic pathogenic fungus.

    PubMed

    Bignell, Elaine; Cairns, Timothy C; Throckmorton, Kurt; Nierman, William C; Keller, Nancy P

    2016-12-05

    Aspergillus fumigatus is a versatile fungus able to successfully exploit diverse environments from mammalian lungs to agricultural waste products. Among its many fitness attributes are dozens of genetic loci containing biosynthetic gene clusters (BGCs) producing bioactive small molecules (often referred to as secondary metabolites or natural products) that provide growth advantages to the fungus dependent on environment. Here we summarize the current knowledge of these BGCs-18 of which can be named to product-their expression profiles in vivo, and which BGCs may enhance virulence of this opportunistic human pathogen. Furthermore, we find extensive evidence for the presence of many of these BGCs, or similar BGCs, in distantly related genera including the emerging pathogen Pseudogymnoascus destructans, the causative agent of white-nose syndrome in bats, and suggest such BGCs may be predictive of pathogenic potential in other fungi.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.

  6. Controlling supply expenses through capitated supply contracting.

    PubMed

    Kowalski, J C

    1997-07-01

    Some providers dealing with the financial challenges of managed care are attempting to control supply expenses through capitated supply contracting and similar risk/reward sharing arrangements. Under such arrangements, a supplier sells products and services to a provider for a fixed, prospective price in exchange for the provider's exclusive business. If expenses exceed the prospectively established amount, the supplier and provider share the loss. Conversely, if expenses are less than the fixed amount, they share the savings. For a capitated supply arrangement to be successful, providers must be able to identify and track supply expense drivers, such as clinical pathways, technology utilization, and product selection and utilization. Sophisticated information systems are needed to capture data, such as total and per-transaction product usage/volume; unit price per item; average and cost per item; average and total cost per transaction; and total cost per outcome. Providers also will need to establish mutually cooperative relationships with the suppliers with whom they contract.

  7. Bioactive Constituents of Indigofera spicata

    PubMed Central

    Pérez, Lynette Bueno; Li, Jie; Lantvit, Daniel D.; Pan, Li; Ninh, Tran Ngoc; Chai, Hee-Byung; Soejarto, Djaja Djendoel; Swanson, Steven M.; Lucas, David M.; Kinghorn, A. Douglas

    2013-01-01

    Four new flavanones, designated as (+)−5″-deacetylpurpurin (1), (+)−5-methoxypurpurin (2), (2S)-2,3-dihydrotephroglabrin (3), and (2S)-2,3-dihydrotephroapollin C (4), together with two known flavanones (5 and 6), three known rotenoids (7–9), and one known chalcone (10) were isolated from a chloroform-soluble partition of a methanol extract from the combined flowers, fruits, leaves, and twigs of Indigofera spicata, collected in Vietnam. The compounds were obtained by bioactivity-guided isolation using HT-29 human colon cancer, 697 human acute lymphoblastic leukemia, and Raji human Burkitt’s lymphoma cell lines. The structures of 1–4 were established by extensive 1D- and 2D-NMR experiments and the absolute configurations were determined by the measurement of specific rotations and CD spectra. The cytotoxic activities of the isolated compounds were tested against the HT-29, 697, Raji and the CCD-112CoN human normal colon cells. Also, the quinone reductase induction activities of the isolates were determined using the Hepa 1c1c7 murine hepatoma cell line. In addition, cis-6aβ−12aβ-hydroxyrotenone (7) was evaluated in an in vivo hollow fiber bioassay using HT-29, MCF-7 human breast cancer, and MDA-MB-435 human melanoma cells. PMID:23895019

  8. Nonoxidative ethanol metabolism in humans-from biomarkers to bioactive lipids.

    PubMed

    Heier, Christoph; Xie, Hao; Zimmermann, Robert

    2016-12-01

    Ethanol is a widely used psychoactive drug whose chronic abuse is associated with organ dysfunction and disease. Although the prevalent metabolic fate of ethanol in the human body is oxidation a smaller fraction undergoes nonoxidative metabolism yielding ethyl glucuronide, ethyl sulfate, phosphatidylethanol and fatty acid ethyl esters. Nonoxidative ethanol metabolites persist in tissues and body fluids for much longer than ethanol itself and represent biomarkers for the assessment of ethanol intake in clinical and forensic settings. Of note, the nonoxidative reaction of ethanol with phospholipids and fatty acids yields bioactive compounds that affect cellular signaling pathways and organelle function and may contribute to ethanol toxicity. Thus, despite low quantitative contributions of nonoxidative pathways to overall ethanol metabolism the resultant ethanol metabolites have important biological implications. In this review we summarize the current knowledge about the enzymatic formation of nonoxidative ethanol metabolites in humans and discuss the implications of nonoxidative ethanol metabolites as biomarkers of ethanol intake and mediators of ethanol toxicity. © 2016 IUBMB Life, 68(12):916-923, 2016.

  9. Nonoxidative ethanol metabolism in humans—from biomarkers to bioactive lipids

    PubMed Central

    Xie, Hao; Zimmermann, Robert

    2016-01-01

    Abstract Ethanol is a widely used psychoactive drug whose chronic abuse is associated with organ dysfunction and disease. Although the prevalent metabolic fate of ethanol in the human body is oxidation a smaller fraction undergoes nonoxidative metabolism yielding ethyl glucuronide, ethyl sulfate, phosphatidylethanol and fatty acid ethyl esters. Nonoxidative ethanol metabolites persist in tissues and body fluids for much longer than ethanol itself and represent biomarkers for the assessment of ethanol intake in clinical and forensic settings. Of note, the nonoxidative reaction of ethanol with phospholipids and fatty acids yields bioactive compounds that affect cellular signaling pathways and organelle function and may contribute to ethanol toxicity. Thus, despite low quantitative contributions of nonoxidative pathways to overall ethanol metabolism the resultant ethanol metabolites have important biological implications. In this review we summarize the current knowledge about the enzymatic formation of nonoxidative ethanol metabolites in humans and discuss the implications of nonoxidative ethanol metabolites as biomarkers of ethanol intake and mediators of ethanol toxicity. © 2016 IUBMB Life, 68(12):916–923, 2016 PMID:27714979

  10. Green tea catechins and their metabolites in human skin before and after exposure to ultraviolet radiation.

    PubMed

    Clarke, Kayleigh A; Dew, Tristan P; Watson, Rachel E B; Farrar, Mark D; Osman, Joanne E; Nicolaou, Anna; Rhodes, Lesley E; Williamson, Gary

    2016-01-01

    Dietary flavonoids may protect against sunburn inflammation in skin. Preliminary reports using less complete analysis suggest that certain catechins and their metabolites are found in skin biopsies and blister fluid after consumption of green tea; however, it is not known if they are affected by solar-simulated ultraviolet radiation (UVR) or whether conjugated forms, with consequently altered bioactivity, are present. The present study tested the hypothesis that UVR affects the catechin levels in the skin of healthy volunteers after consumption of green tea and how catechins in the plasma are related to their presence in skin tissue samples. In an open oral intervention study, 11 subjects consumed green tea and vitamin C supplements daily for 3months. Presupplementation and postsupplementation plasma samples, suction blister fluid and skin biopsies were collected; the latter two samples were collected both before and after UVR. A sensitive high-performance liquid chromatography/mass spectrometric assay was used to measure the intact catechin metabolites, conjugates and free forms. Seven green tea catechins and their corresponding metabolites were identified postsupplementation in skin biopsies, 20 in blister fluid and 26 in plasma, with 15 green tea catechin metabolites present in both blister fluid and plasma. The valerolactone, O-methyl-M4-O-sulfate, a gut microbiota metabolite of catechins, was significantly increased 1.6-fold by UVR in blister fluid samples. In conclusion, there were some common catechin metabolites in the plasma and blister fluid, and the concentration was always higher in plasma. The results suggest that green tea catechins and metabolites are bioavailable in skin and provide a novel link between catechin metabolites derived from the skin and gut microbiota.

  11. Herbal bioactivation, molecular targets and the toxicity relevance.

    PubMed

    Chen, Xiao-Wu; Serag, Erini S; Sneed, Kevin B; Zhou, Shu-Feng

    2011-07-15

    There have been increasing reports on the adverse reactions associated with herbal consumption. For many of these adverse reactions, the underlying biochemical mechanisms are unknown, but bioactivation of herbal compounds to generate reactive intermediates have been implicated. This minireview updates our knowledge on metabolic activation of herbal compounds, molecular targets and the toxicity relevance. A number of studies have documented that some herbal compounds can be converted to toxic or even carcinogenic metabolites by Phase I [e.g. cytochrome P450s (CYPs)] and less frequently by Phase II enzymes. For example, aristolochic acids (AAs) in Aristolochia spp, which undergo reduction of the nitro group by hepatic CYP1A1/2 or peroxidases in extrahepatic tissues to generate highly reactive cyclic nitrenium ions. The latter can react with macromolecules (DNA and protein), resulting in activation of H-ras and myc oncogenes and gene mutation in renal cells and finally carcinogenesis of the kidneys. Teucrin A and teuchamaedryn A, two diterpenoids found in germander (Teuchrium chamaedrys) used as an adjuvant to slimming herbal supplements that caused severe hepatotoxicity, are converted by CYP3A4 to reactive epoxide which reacts with proteins such as CYP3A and epoxide hydrolase and inactivate them. Some naturally occurring alkenylbenzenes (e.g. safrole, methyleugenol and estragole) and flavonoids (e.g. quercetin) can undergo bioactivation by sequential 1-hydroxylation and sulfation, resulting in reactive intermediates capable of forming DNA adducts. Extensive pulegone metabolism generated p-cresol that is a glutathione depletory. The hepatotoxicity of kava is possibly due to intracellular glutathione depletion and/or quinone formation. Moreover, several herbal compounds including capsaicin from chili peppers, dially sulfone in garlic, methysticin and dihydromethysticin in kava, oleuropein in olive oil, and resveratrol found in grape seeds are mechanism-based (suicide

  12. Activation of the silent secondary metabolite production by introducing neomycin-resistance in a marine-derived Penicillium purpurogenum G59.

    PubMed

    Wu, Chang-Jing; Yi, Le; Cui, Cheng-Bin; Li, Chang-Wei; Wang, Nan; Han, Xiao

    2015-04-22

    Introduction of neomycin-resistance into a marine-derived, wild-type Penicillium purpurogenum G59 resulted in activation of silent biosynthetic pathways for the secondary metabolite production. Upon treatment of G59 spores with neomycin and dimethyl sulfoxide (DMSO), a total of 56 mutants were obtained by single colony isolation. The acquired resistance of mutants to neomycin was testified by the resistance test. In contrast to the G59 strain, the EtOAc extracts of 28 mutants inhibited the human cancer K562 cells, indicating that the 28 mutants have acquired the capability to produce bioactive metabolites. HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses further indicated that diverse secondary metabolites have been newly produced in the bioactive mutant extracts. Followed isolation and characterization demonstrated that five bioactive secondary metabolites, curvularin (1), citrinin (2), penicitrinone A (3), erythro-23-O-methylneocyclocitrinol (4) and 22E-7α-methoxy-5α, 6α-epoxyergosta-8(14),22-dien-3β-ol (5), were newly produced by a mutant, 4-30, compared to the G59 strain. All 1-5 were also not yet found in the secondary metabolites of other wild type P. purpurogenum strains. Compounds 1-5 inhibited human cancer K562, HL-60, HeLa and BGC-823 cells to varying extents. Both present bioassays and chemical investigations demonstrated that the introduction of neomycin-resistance into the marine-derived fungal G59 strain could activate silent secondary metabolite production. The present work not only extended the previous DMSO-mediated method for introducing drug-resistance in fungi both in DMSO concentrations and antibiotics, but also additionally exemplified effectiveness of this method for activating silent fungal secondary metabolites. This method could be applied to other fungal isolates to elicit their metabolic potentials to investigate secondary metabolites from silent biosynthetic pathways.

  13. Microbial metabolism Part 12 isolation characterization and bioactivity evaluation of eighteen microbial metabolites of 4'-hydroxyflavanone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fermentation of 4'-hydroxyflavanone (1) with fungal cultures, Beauveria bassiana (ATCC 13144 and ATCC 7159) yielded 6,3',4'-trihydroxyflavanone (2), 3',4'-dihydroxyflavanone 6-O-B-D-4-methoxyglucopyranoside (3), 4'-hydroxyflavanone 3'-sulfate (4), 6,4'-dihydroxyflavanone 3'-sulfate (5) and 4'-hydrox...

  14. A Review of Cyanobacterial Odorous and Bioactive Metabolites: Impacts and Management Alternatives in Aquaculture

    DTIC Science & Technology

    2008-05-06

    comments regarding this burden estimate or any other aspect of this collection of information, including suggesstions for reducing this burden, to...Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any oenalty for failing to comply with...2008.05.007 Contents lists available at ScienceDirect Aquaculture j ourna l homepage: www.e lsev ie r.com/ locate /aqua- on l ine 4.3. Neurotoxins

  15. Microbial metabolism Part 14 Isolation and bioactivity evaluation of microbial metabolites of resveratrol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fungi, Beauveria bassiana (ATCC 13144) and Penicillium chrysogenium (ATCC 9480) transformed resveratrol (1) to resveratrol-3-O-sulfate (4). The former, in addition, gave 5-methoxyresveratrol-3-O-ß-glucoside (2) with the latter yielding 5-methoxyresveratrol-3-O-sulfate (3). The structures were es...

  16. Bioactive Secondary Metabolites with Unique Aromatic and Heterocyclic Structures Obtained from Terrestrial Actinomycetes Species.

    PubMed

    Abdelfattah, Mohamed S; Arai, Midori A; Ishibashi, Masami

    2016-07-01

    Natural products from actinomycetes are important and valuable sources for drug discovery and the development of biological tools. The present review describes our recent study on the isolation of new natural products mainly possessing heterocyclic and aromatic ring structures with biological effects on cancer-related cellular pathways such as tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) and Wnt signaling.

  17. Mentha L. species (Lamiaceae) as promising sources of bioactive secondary metabolites.

    PubMed

    Mimica-Dukic, N; Bozin, B

    2008-01-01

    The use of mint species in traditional and conventional medicine is mostly due to the presence of two classes of secondary bimolecules: monoterpenoids in essential oils and different structural types of phenolic compounds. Essential oils are known to act as antimicrobial, antispasmodic, carminative, and antiviral agents. In addition, essential oils of several mint species have been recently qualified as natural antioxidants. However, since oil composition is highly variable, the pharmacological activity strongly depends on certain chemorace. On the contrary, composition of phenolic constituents is relatively stable within species. The most important phenolic compounds in Mentha species are flavonoids. Mints are characterized by the presence of specific lipophilic flavonoids. Phenolic compounds of mints are found to poses a wide range of pharmacological activity: antioxidant, antiulcer, cytoprotective, heptoprotective, cholagogue, chemopreventive, anti-inflammatory, antidiabetogenic etc. However, besides healing properties some mint species can exhibit an adverse effect on human health. Here we report on botany, chemistry and activity of Mentha species with special respect to their significance for the modern phytotherapy.

  18. Isolation and characterization of novel marine-derived actinomycete taxa rich in bioactive metabolites.

    PubMed

    Magarvey, Nathan A; Keller, Jessica M; Bernan, Valerie; Dworkin, Martin; Sherman, David H

    2004-12-01

    A unique selective enrichment procedure has resulted in the isolation and identification of two new genera of marine-derived actinobacteria. Approximately 90% of the microorganisms cultured by using the presented method were from the prospective new genera, a result indicative of its high selectivity. In this study, 102 actinomycetes were isolated from subtidal marine sediments collected from the Bismarck Sea and the Solomon Sea off the coast of Papua New Guinea. A combination of physiological parameters, chemotaxonomic characteristics, distinguishing 16S rRNA gene sequences, and phylogenetic analysis based on 16S rRNA genes provided strong evidence for the two new genera (represented by strains of the PNG1 clade and strain UMM518) within the family Micromonosporaceae. Biological activity testing of fermentation products from the new marine-derived actinomycetes revealed that several had activities against multidrug-resistant gram-positive pathogens, malignant cells, and vaccinia virus replication.

  19. New secondary metabolites from bioactive extracts of the fungus Armillaria tabescens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ethyl acetate extracts of Armillaria tabescens (strain JNB-OZ344) mycelium showed significant fungistatic and bacteristatic activities against several major human pathogens including Candida albicans, Cryptococcus neoformans, Escherichia coli and Mycobacterium intracellulare. Chemical analysis of th...

  20. New Metabolites and Bioactive Chlorinated Benzophenone Derivatives Produced by a Marine-Derived Fungus Pestalotiopsis heterocornis

    PubMed Central

    Lei, Hui; Lin, Xiuping; Han, Li; Ma, Jian; Ma, Qingjuan; Zhong, Jialiang; Liu, Yonghong; Sun, Tiemin; Wang, Jinhui; Huang, Xueshi

    2017-01-01

    Four new compounds, including two isocoumarins, pestaloisocoumarins A and B (1, 2), one sesquiterpenoid degradation, isopolisin B (4), and one furan derivative, pestalotiol A (5), together with one known isocoumarin, gamahorin (3), and three chlorinated benzophenone derivatives, pestalachloride B (6), pestalachloride E (7) and a mixture of pestalalactone atropisomers (8a/8b), were isolated from a culture of the fungus Pestalotiopsis heterocornis associated with sponge Phakellia fusca. These new chemical structures were established using NMR and MS spectroscopic data, as well as single-crystal X-ray crystallographic analysis and CD Cotton effects. All of the isolated compounds were evaluated for their antimicrobial and cytotoxic activities. Isocoumarins 1–3, showed antibacterial activities against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis with MIC values ranging from 25 to 100 μg/mL and weak antifungal activities. Chlorinated benzophenone derivatives 6–8 exhibited antibacterial activities against S. aureus and B. subtilis with MIC values ranging from 3.0 to 50 μg/mL and cytotoxicities against four human cancer cell lines with IC50 values of 6.8–87.8 μM. PMID:28335391

  1. Vitamin D metabolites and bioactive parathyroid hormone levels during Spacelab 2

    NASA Technical Reports Server (NTRS)

    Morey-Holton, Emily R.; Schnoes, Heinrich K.; Deluca, Hector F.; Phelps, Mary E.; Klein, Robert F.

    1988-01-01

    The effect of an 8-day space flight (Spacelab mission 2) on plasma levels of the vitamin D and parathyroid hormones is investigated experimentally in four crew members. The results are presented in tables and graphs and briefly characterized. Parathyroid hormone levels remained normal throughout the flight, whereas vitamin D hormone levels increased significantly on day 1 but returned to normal by day 7.

  2. HPLC-DAD-MS identification of bioactive secondary metabolites from Ferula communis roots.

    PubMed

    Arnoldi, Lolita; Ballero, Mauro; Fuzzati, Nicola; Maxia, Andrea; Mercalli, Enrico; Pagni, Luca

    2004-06-01

    A simple HPLC method was developed to distinguish between 'poisonous' and 'non-poisonous' chemotypes of Ferula communis. The method was performed on a C8 reverse phase analytical column using a binary eluent (aqueous TFA 0.01%-TFA 0.01% in acetonitrile) under gradient condition. The two chemotypes showed different fingerprints. The identification of five coumarins and eleven daucane derivatives by HPLC-diode array detection (HPLC-DAD) and HPLC-MS is described. A coumarin, not yet described, was detected.

  3. Bioactive natural products from fungicolous Hawaiian isolates: Secondary metabolites from a Phialemoniopsis sp.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chemical investigations of two fungal isolates initially identified as members of the genus Phialemonium are described. Both isolates were obtained as colonists of other fungi collected on the island of Hawaii and were later assigned as P. curvatum. However, P. curvatum has recently been reclassifie...

  4. Bioactivity of polycrystalline silicon layers.

    PubMed

    Pramatarova, Lilyana; Pecheva, Emilia; Montgomery, Paul; Dimova-Malinovska, Doriana; Petrov, Todor; Toth, Attila L; Dimitrova, Magdalena

    2008-02-01

    After oxygen, silicon is the second most abundant element in the environment and is present as an impurity in most materials. The widespread occurrence of siliceous biominerals as structural elements in lower plants and animals suggests that Si plays a role in the production and maintenance of connective tissue in higher organisms. It has been shown that the presence of Si is necessary in bones, cartilage and in the formation of connective tissue, as well as in some important metabolic processes. In this work, polycrystalline silicon layers are tested in terms of bioactivity, i.e., their ability to induce hydroxyapatite formation from simulated body fluid. Hydroxyapatite is a biologically compatible material with chemical similarity to the inorganic part of bones and teeth. Polycrystalline silicon layers are obtained by aluminum induced crystallization of Al and amorphous Si thin films deposited sequentially on glass substrates by radio-frequency magnetron sputtering and subsequently annealed in different atmospheres. The hydroxyapatite formation is induced by applying a method of laser-liquid-solid interaction. The method consists of irradiating the samples with laser light while immersed in a solution that is supersaturated with respect to Ca and P. As a result, heterogeneous porous sponge-like carbonate-containing hydroxyapatite is grown on the polysilicon surfaces. Crystals that are spherical in shape, containing Ca, P and O, Na, Cl, Mg, Al, Si and S, as well as well-faceted NaCl crystals are embedded in the hydroxyapatite layer. Enhancement of the hydroxyapatite growth and increased crystallinity is observed due to the applied laser-liquid-solid interaction.

  5. Toxicological significance of dihydrodiol metabolites

    SciTech Connect

    Hsia, M.T.

    1982-01-01

    Dihydrodiols are often found as the major organic-extractable metabolites of various olefinic or aromatic xenobiotics in many biological samples. Studies on the chemistry of dihydrodiol metabolites have provided insight into the pharmacokinetic behavior and the mode of action of the parent compound. The toxicology of dihydrodiol is more complex than what can be deduced solely on the basis of diminished bioavailability of the epoxide precursor, and the increased hydrophilicity associated with the dihydrodiol moiety. Dihydrodiols can be intrinsically toxic and may even represent metabolically activated species. Some of the dihydrodiol metabolites may still retain sufficient lipophilic character to serve again as substrates for microsomal oxygenases. Because of the tremendous chemical and biological diversity that existed among the various dihydrodiols, more mechanistic studies are needed to examine the toxicological properties of these compounds. It may be premature to conclude dihydrodiol formation as purely a detoxification route for xenobioties.

  6. MS-Based Metabolite Profiling of Aboveground and Root Components of Zingiber mioga and Officinale.

    PubMed

    Han, Ji Soo; Lee, Sunmin; Kim, Hyang Yeon; Lee, Choong Hwan

    2015-09-03

    Zingiber species are members of the Zingiberaceae family, and are widely used for medicinal and food purposes. In this study aboveground and root parts of Zingiber mioga and Zingiber officinale were subjected to metabolite profiling by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) in order to characterize them by species and parts and also to measure bioactivities. Both primary and secondary metabolites showed clear discrimination in the PCA score plot and PLS-DA by species and parts. Tetrahydrocurcumin, diarylheptanoid, 8-gingerol, and 8-paradol were discriminating metabolites between Z. mioga and Z. officinale that were present in different quantities. Eleven flavonoids, six amino acids, six organic acids, four fatty acids, and gingerenone A were higher in the aboveground parts than the root parts. Antioxidant activities were measured and were highest in the root part of Z. officinale. The relatively high contents of tetrahydrocurcumin, diarylheptanoid, and galanganol C in the root part of Z. officinale showed highly positive correlation with bioactivities based on correlation assay. On the basis of these results, we can suggest different usages of structurally different parts of Zingiber species as food plants.

  7. Development of a Biosensor Concept to Detect the Production of Cluster-Specific Secondary Metabolites.

    PubMed

    Sun, Yi-Qian; Busche, Tobias; Rückert, Christian; Paulus, Constanze; Rebets, Yuriy; Novakova, Renata; Kalinowski, Jörn; Luzhetskyy, Andriy; Kormanec, Jan; Sekurova, Olga N; Zotchev, Sergey B

    2017-03-03

    Genome mining of actinomycete bacteria aims at the discovery of novel bioactive secondary metabolites that can be developed into drugs. A new repressor-based biosensor to detect activated secondary metabolite biosynthesis gene clusters in Streptomyces was developed. Biosynthetic gene clusters for undecylprodigiosin and coelimycin in the genome of Streptomyces lividans TK24, which encoded TetR-like repressors and appeared to be almost "silent" based on the RNA-seq data, were chosen for the proof-of-principle studies. The bpsA reporter gene for indigoidine synthetase was placed under control of the promotor/operator regions presumed to be controlled by the cluster-associated TetR-like repressors. While the biosensor for undecylprodigiosin turned out to be nonfunctional, the coelimycin biosensor was shown to perform as expected, turning on biosynthesis of indigoidine in response to the concomitant production of coelimycin. The developed reporter system concept can be applied to those cryptic gene clusters that encode metabolite-sensing repressors to speed up discovery of novel bioactive compounds in Streptomyces.

  8. Countercurrent assisted quantitative recovery of metabolites from plant-associated natural deep eutectic solvents.

    PubMed

    Liu, Yang; Garzon, Jahir; Friesen, J Brent; Zhang, Yu; McAlpine, James B; Lankin, David C; Chen, Shao-Nong; Pauli, Guido F

    2016-07-01

    NAtural Deep Eutectic Solvents (NADES) are chemically simple but physiologically important plant constituents that exhibit unique solubilizing properties of other metabolites, including bioactive constituents. The high polarity of NADES introduces a challenge in the ability of conventional solid-support based chromatography to recover potential bioactive metabolites. This complicates the systematic explanation of the NADES' functions in botanical extracts. The present study utilizes countercurrent separation (CCS) methodology to overcome the recovery challenge. To demonstrate its feasibility, Glucose-Choline chloride-Water (GCWat, 2:5:5, mole/mole) served as a model NADES, and four widely used marker flavonoids with different polarities (rutin, quercetin, kaempferol, and daidzein) were chosen as model target analytes. In order to prepare GCWat with high consistency, a water drying study was performed. The unique capabilities of the recently introduced CherryOne system, offering volumetric phase metering, were used to monitor the CCS operations. The collected fractions were analyzed using UHPLC and NMR/quantitative NMR. CCS was able to recover the analytes from the NADES matrix with quantitative recoveries of 95.7%, 94.6%, 97.0%, and 96.7% for rutin, quercetin, kaempferol, and daidzein respectively. The CCS strategy enables recovery of target metabolites from NADES-containing crude extracts as well as from other chemical mixtures, and moreover offers a means of using NADES as environmentally friendly extraction solvents.

  9. Bioactive Compounds from Vitex leptobotrys#

    PubMed Central

    Pan, Wenhui; Liu, Kanglun; Guan, Yifu; Tan, Ghee Teng; Hung, Nguyen Van; Cuong, Nguyen Manh; Soejarto, D. Doel; Pezzuto, John M.; Fong, Harry H.S.; Zhang, Hongjie

    2014-01-01

    A new lignan, vitexkarinol (1), as well as a known lignan, neopaulownin (2), a known chalcone, 3-(4-hydroxyphenyl)-1-(2,4,6-trimethoxyphenyl)-2-propen-1-one (3), two known dehydroflavones, tsugafolin (4) and alpinetin (5), two known dipeptides, aurantiamide and aurantiamide acetate, a known sesquiterpene, vemopolyanthofuran, and five known carotenoid metabolites, vomifoliol, dihydrovomifoliol, dehydrovomifoliol, loliolide and isololiolide, were isolated from the leaves and twigs of Vitex leptobotrys through bioassay-guided fractionation. The chalcone (3) was found to inhibit HIV-1 replication by 77% at 15.9 µM, and the two dehydroflavones (4 and 5) showed weak anti-HIV activity with IC50 values of 118 and 130 µM, respectively, while being devoid of cytotoxicity at 150 µM. A chlorophyll-enriched fraction of V. leptobotrys, containing pheophorbide a, was found to inhibit the replication of HIV-1 by 80% at a concentration of 10 µg/mL. Compounds 1 and 3 were further selected to be evaluated against 21 viral targets available at NIAID (National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD). PMID:24404757

  10. Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus

    PubMed Central

    Throckmorton, Kurt; Lim, Fang Yun; Kontoyiannis, Dimitrios P.; Zheng, Weifa; Keller, Nancy P.

    2016-01-01

    Summary Filamentous fungi are renowned for the production of bioactive secondary metabolites. Typically, one distinct metabolite is generated from a specific secondary metabolite cluster. Here, we characterize the newly described trypacidin (tpc) cluster in the opportunistic human pathogen Aspergillus fumigatus. We find that this cluster as well as the previously characterized endocrocin (enc) cluster both contribute to the production of the spore metabolite endocrocin. Whereas trypacidin is eliminated when only tpc cluster genes are deleted, endocrocin production is only eliminated when both the tpc and enc non-reducing polyketide synthase-encoding genes, tpcC and encA, respectively, are deleted. EncC, an anthrone oxidase, converts the product released from EncA to endocrocin as a final product. In contrast, endocrocin synthesis by the tpc cluster likely results from incomplete catalysis by TpcK (a putative decarboxylase), as its deletion results in a nearly 10-fold increase in endocrocin production. We suggest endocrocin is likely a shunt product in all related non-reducing polyketide synthase clusters containing homologues of TpcK and TpcL (a putative anthrone oxidase), e.g. geodin and monodictyphenone. This finding represents an unusual example of two physically discrete secondary metabolite clusters generating the same natural product in one fungal species by distinct routes. PMID:26242966

  11. Microbial production of primary metabolites

    NASA Astrophysics Data System (ADS)

    Demain, Arnold L.

    1980-12-01

    Microbial production of primary metabolites contributes significantly to the quality of life. Through fermentation, microorganisms growing on inexpensive carbon sources can produce valuable products such as amino acids, nucleotides, organic acids, and vitamins which can be added to food to enhance its flavor or increase its nutritive value. The contribution of microorganisms will go well beyond the food industry with the renewed interest in solvent fermentations. Microorganisms have the potential to provide many petroleum-derived products as well as the ethanol necessary for liquid fuel. The role of primary metabolites and the microbes which produce them will certainly increase in importance.

  12. Enriching screening libraries with bioactive fragment space.

    PubMed

    Zhang, Na; Zhao, Hongtao

    2016-08-01

    By deconvoluting 238,073 bioactive molecules in the ChEMBL library into extended Murcko ring systems, we identified a set of 2245 ring systems present in at least 10 molecules. These ring systems belong to 2221 clusters by ECFP4 fingerprints with a minimum intracluster similarity of 0.8. Their overlap with ring systems in commercial libraries was further quantified. Our findings suggest that success of a small fragment library is driven by the convergence of effective coverage of bioactive ring systems (e.g., 10% coverage by 1000 fragments vs. 40% by 2million HTS compounds), high enrichment of bioactive ring systems, and low molecular complexity enhancing the probability of a match with the protein targets. Reconciling with the previous studies, bioactive ring systems are underrepresented in screening libraries. As such, we propose a library of virtual fragments with key functionalities via fragmentation of bioactive molecules. Its utility is exemplified by a prospective application on protein kinase CK2, resulting in the discovery of a series of novel inhibitors with the most potent compound having an IC50 of 0.5μM and a ligand efficiency of 0.41kcal/mol per heavy atom.

  13. Bioactive proteins from Solanaceae as quorum sensing inhibitors against virulence in Pseudomonas aeruginosa.

    PubMed

    Singh, Gurpreet; Tamboli, Ekant; Acharya, Aurovind; Kumarasamy, Chellan; Mala, Kanchana; Raman, Pachaiappan

    2015-06-01

    Cell-to-cell communication or quorum sensing (QS) is a generic event in bacteria that is used to coordinate gene expression among local populations. The phenomenon of QS depends on the fact that presence of sufficient bacteria ascertains a threshold level of autoinducer concentration that allows bacteria to sense a critical cell mass and to activate or repress target genes. Thus, QS has been an attractive target for the development of anti-infective strategies that are not based on the use of antibiotics. Several anti-QS approaches have been demonstrated including natural products from plant-based secondary metabolites. However, the role of plant bioactive proteins as an anti-QS peptide is yet to be deciphered. Against a backdrop of ever-increasing antibiotic resistant pathogens, there is a strong need for development of alternative therapeutic strategies. Thus, our hypothesis is that bioactive proteins from the plant family Solanaceae are quorum quenching molecules that can be exploited to develop a therapeutic strategy against virulence. We presume that bioactive proteins will inactivate or inhibit or degrade QS signals from bacteria to prevent cell-to-cell communication and thus inhibit development of virulence in Pseudomonas aeruginosa. Further, the use of proteins as quorum quenchers will delay the bacteria to develop resistance against these quenching molecules.

  14. Berry Leaves: An Alternative Source of Bioactive Natural Products of Nutritional and Medicinal Value†

    PubMed Central

    Ferlemi, Anastasia-Varvara; Lamari, Fotini N.

    2016-01-01

    Berry fruits are recognized, worldwide, as “superfoods” due to the high content of bioactive natural products and the health benefits deriving from their consumption. Berry leaves are byproducts of berry cultivation; their traditional therapeutic use against several diseases, such as the common cold, inflammation, diabetes, and ocular dysfunction, has been almost forgotten nowadays. Nevertheless, the scientific interest regarding the leaf composition and beneficial properties grows, documenting that berry leaves may be considered an alternative source of bioactives. The main bioactive compounds in berry leaves are similar as in berry fruits, i.e., phenolic acids and esters, flavonols, anthocyanins, and procyanidins. The leaves are one of the richest sources of chlorogenic acid. In various studies, these secondary metabolites have demonstrated antioxidant, anti-inflammatory, cardioprotective, and neuroprotective properties. This review focuses on the phytochemical composition of the leaves of the commonest berry species, i.e., blackcurrant, blackberry, raspberry, bilberry, blueberry, cranberry, and lingonberry leaves, and presents their traditional medicinal uses and their biological activities in vitro and in vivo. PMID:27258314

  15. Berry Leaves: An Alternative Source of Bioactive Natural Products of Nutritional and Medicinal Value.

    PubMed

    Ferlemi, Anastasia-Varvara; Lamari, Fotini N

    2016-06-01

    Berry fruits are recognized, worldwide, as "superfoods" due to the high content of bioactive natural products and the health benefits deriving from their consumption. Berry leaves are byproducts of berry cultivation; their traditional therapeutic use against several diseases, such as the common cold, inflammation, diabetes, and ocular dysfunction, has been almost forgotten nowadays. Nevertheless, the scientific interest regarding the leaf composition and beneficial properties grows, documenting that berry leaves may be considered an alternative source of bioactives. The main bioactive compounds in berry leaves are similar as in berry fruits, i.e., phenolic acids and esters, flavonols, anthocyanins, and procyanidins. The leaves are one of the richest sources of chlorogenic acid. In various studies, these secondary metabolites have demonstrated antioxidant, anti-inflammatory, cardioprotective, and neuroprotective properties. This review focuses on the phytochemical composition of the leaves of the commonest berry species, i.e., blackcurrant, blackberry, raspberry, bilberry, blueberry, cranberry, and lingonberry leaves, and presents their traditional medicinal uses and their biological activities in vitro and in vivo.

  16. Bioactive Sesterterpenes and Triterpenes from Marine Sponges: Occurrence and Pharmacological Significance

    PubMed Central

    Ebada, Sherif S.; Lin, WenHan; Proksch, Peter

    2010-01-01

    Marine ecosystems (>70% of the planet’s surface) comprise a continuous resource of immeasurable biological activities and immense chemical entities. This diversity has provided a unique source of chemical compounds with potential bioactivities that could lead to potential new drug candidates. Many marine-living organisms are soft bodied and/or sessile. Consequently, they have developed toxic secondary metabolites or obtained them from microorganisms to defend themselves against predators [1]. For the last 30–40 years, marine invertebrates have been an attractive research topic for scientists all over the world. A relatively small number of marine plants, animals and microbes have yielded more than 15,000 natural products including numerous compounds with potential pharmaceutical potential. Some of these have already been launched on the pharmaceutical market such as Prialt® (ziconotide; potent analgesic) and Yondelis® (trabectedin or ET-743; antitumor) while others have entered clinical trials, e.g., alpidin and kahalalide F. Amongst the vast array of marine natural products, the terpenoids are one of the more commonly reported and discovered to date. Sesterterpenoids (C25) and triterpenoids (C30) are of frequent occurrence, particularly in marine sponges, and they show prominent bioactivities. In this review, we survey sesterterpenoids and triterpenoids obtained from marine sponges and highlight their bioactivities. PMID:20390108

  17. Integrative Approach to Analyze Biodiversity and Anti-Inflammatory Bioactivity of Wedelia Medicinal Plants

    PubMed Central

    Chen, Yung-Hsiang; Hsiao, Pei-Wen; Liao, Jiunn-Wang; Peng, Ching-I; Yang, Ning-Sun

    2015-01-01

    For the development of “medical foods” and/or botanical drugs as defined USA FDA, clear and systemic characterizations of the taxonomy, index phytochemical components, and the functional or medicinal bioactivities of the reputed or candidate medicinal plant are needed. In this study, we used an integrative approach, including macroscopic and microscopic examination, marker gene analysis, and chemical fingerprinting, to authenticate and validate various species/varieties of Wedelia, a reputed medicinal plant that grows naturally and commonly used in Asian countries. The anti-inflammatory bioactivities of Wedelia extracts were then evaluated in a DSS-induced murine colitis model. Different species/varieties of Wedelia exhibited distinguishable morphology and histological structures. Analysis of the ribosomal DNA internal transcribed spacer (ITS) region revealed significant differences among these plants. Chemical profiling of test Wedelia species demonstrated candidate index compounds and distinguishable secondary metabolites, such as caffeic acid derivatives, which may serve as phytochemical markers or index for quality control and identification of specific Wedelia species. In assessing their effect on treating DSS induced-murine colitis, we observed that only the phytoextract from W. chinensis species exhibited significant anti-inflammatory bioactivity on DSS-induced murine colitis among the various Wedelia species commonly found in Taiwan. Our results provide a translational research approach that may serve as a useful reference platform for biotechnological applications of traditional phytomedicines. Our findings indicate that specific Wedelia species warrant further investigation for potential treatment of human inflammatory bowel disease. PMID:26042672

  18. Bioactive Peptides and Depsipeptides with Anticancer Potential: Sources from Marine Animals

    PubMed Central

    Suarez-Jimenez, Guadalupe-Miroslava; Burgos-Hernandez, Armando; Ezquerra-Brauer, Josafat-Marina

    2012-01-01

    Biologically active compounds with different modes of action, such as, antiproliferative, antioxidant, antimicrotubule, have been isolated from marine sources, specifically algae and cyanobacteria. Recently research has been focused on peptides from marine animal sources, since they have been found as secondary metabolites from sponges, ascidians, tunicates, and mollusks. The structural characteristics of these peptides include various unusual amino acid residues which may be responsible for their bioactivity. Moreover, protein hydrolysates formed by the enzymatic digestion of aquatic and marine by-products are an important source of bioactive peptides. Purified peptides from these sources have been shown to have antioxidant activity and cytotoxic effect on several human cancer cell lines such as HeLa, AGS, and DLD-1. These characteristics imply that the use of peptides from marine sources has potential for the prevention and treatment of cancer, and that they might also be useful as molecular models in anticancer drug research. This review focuses on the latest studies and critical research in this field, and evidences the immense potential of marine animals as bioactive peptide sources. PMID:22822350

  19. Profiling a gut microbiota-generated catechin metabolite's fate in human blood cells using a metabolomic approach.

    PubMed

    Mülek, Melanie; Fekete, Agnes; Wiest, Johannes; Holzgrabe, Ulrike; Mueller, Martin J; Högger, Petra

    2015-10-10

    The microbial catechin metabolite δ-(3,4-dihydroxy-phenyl)-γ-valerolactone (M1) has been found in human plasma samples after intake of maritime pine bark extract (Pycnogenol). M1 has been previously shown to accumulate in endothelial and blood cells in vitro after facilitated uptake and to exhibit anti-inflammatory activity. The purpose of the present research approach was to systematically and comprehensively analyze the metabolism of M1 in human blood cells in vitro and in vivo. A metabolomic approach that had been successfully applied for drug metabolite profiling was chosen to detect 19 metabolite peaks of M1 which were subsequently further analyzed and validated. The metabolites were categorized into three levels of identification according to the Metabolomics Standards Initiative with six compounds each confirmed at levels 1 and 2 and seven putative metabolites at level 3. The predominant metabolites were glutathione conjugates which were rapidly formed and revealed prolonged presence within the cells. Although a formation of an intracellular conjugate of M1 and glutathione (M1-GSH) was already known two GSH conjugate isomers, M1-S-GSH and M1-N-GSH were observed in the current study. Additionally detected organosulfur metabolites were conjugates with oxidized glutathione and cysteine. Other biotransformation products constituted the open-chained ester form of M1 and a methylated M1. Six of the metabolites determined in in vitro assays were also detected in blood cells in vivo after ingestion of the pine bark extract by two volunteers. The present study provides the first evidence that multiple and structurally heterogeneous polyphenol metabolites can be generated in human blood cells. The bioactivity of the M1 metabolites and their contribution to the previously determined anti-inflammatory effects of M1 now need to be elucidated.

  20. Control limits for accumulation of plant metabolites: brute force is no substitute for understanding.

    PubMed

    Morandini, Piero

    2013-02-01

    Which factors limit metabolite accumulation in plant cells? Are theories on flux control effective at explaining the results? Many biotechnologists cling to the idea that every pathway has a rate limiting enzyme and target such enzymes first in order to modulate fluxes. This often translates into large effects on metabolite concentration, but disappointing small increases in flux. Rate limiting enzymes do exist, but are rare and quite opposite to what predicted by biochemistry. In many cases however, flux control is shared among many enzymes. Flux control and concentration control can (and must) be distinguished and quantified for effective manipulation. Flux control for several 'building blocks' of metabolism is placed on the demand side, and therefore increasing demand can be very successful. Tampering with supply, particularly desensitizing supply enzymes, is usually not very effective, if not dangerous, because supply regulatory mechanisms function to control metabolite homeostasis. Some important, but usually unnoticed, metabolic constraints shape the responses of metabolic systems to manipulation: mass conservation, cellular resource allocation and, most prominently, energy supply, particularly in heterotrophic tissues. The theoretical basis for this view shall be explored with recent examples gathered from the manipulation of several metabolites (vitamins, carotenoids, amino acids, sugars, fatty acids, polyhydroxyalkanoates, fructans and sugar alcohols). Some guiding principles are suggested for an even more successful engineering of plant metabolism.

  1. Diverse and bioactive endophytic Aspergilli inhabit Cupressaceae plant family.

    PubMed

    Soltani, Jalal; Moghaddam, Mahdieh S Hosseyni

    2014-09-01

    Aspergilli are filamentous, cosmopolitan and ubiquitous fungi which have significant impact on human, animal and plant welfare worldwide. Due to their extraordinary metabolic diversity, Aspergillus species are used in biotechnology for the production of a vast array of biomolecules. However, little is known about Aspergillus species that are able to adapt an endophytic lifestyle in Cupressaceae plant family and are capable of producing cytotoxic, antifungal and antibacterial metabolites. In this work, we report a possible ecological niche for pathogenic fungi such as Aspergillus fumigatus and Aspergillus flavus. Indeed, our findings indicate that A. fumigatus, A. flavus, Aspergillus niger var. niger and A. niger var. awamori adapt an endophytic lifestyle inside the Cupressaceous plants including Cupressus arizonica, Cupressus sempervirens var. fastigiata, Cupressus semipervirens var. cereiformis, and Thuja orientalis. In addition, we found that extracts of endophytic Aspergilli showed significant growth inhibition and cytotoxicity against the model fungus Pyricularia oryzae and bacteria such as Bacillus sp., Erwinia amylovora and Pseudomonas syringae. These endophytic Aspergilli also showed in vitro antifungal effects on the cypress fungal phytopathogens including Diplodia seriata, Phaeobotryon cupressi and Spencermartinsia viticola. In conclusion, our findings clearly support the endophytic association of Aspergilli with Cupressaceae plants and their possible role in protection of host plants against biotic stresses. Observed bioactivities of such endophytic Aspergilli may represent a significant potential for bioindustry and biocontrol applications.

  2. Bioactive heterocycles containing endocyclic N-hydroxy groups.

    PubMed

    Rani, Reshma; Granchi, Carlotta

    2015-06-05

    Drug-likeness rules consider N-O single bonds as "structural alerts" which should not be present in a perspective drug candidate. In most cases this concern is correct, since it is known that N-hydroxy metabolites of branded drugs produce reactive species that cause serious side effects. However, this dangerous reactivity of the N-OH species generally takes place when the nitrogen atom is not comprised in a cyclic moiety. In fact, the same type of metabolic behavior should not be expected when the nitrogen atom is included in the ring of an aromatic heterocyclic scaffold. Nevertheless, heterocycles bearing endocyclic N-hydroxy portions have so far been poorly studied as chemical classes that may provide new therapeutic agents. This review provides an overview of N-OH-containing heterocycles with reported bioactivities that may be considered as therapeutically relevant and, therefore, may extend the chemical space available for the future development of novel pharmaceuticals. A systematic treatment of the various chemical classes belonging to this particular family of molecules is described along with a discussion of the biological activities associated to the most important examples.

  3. Bioactivity characterization of Lactobacillus strains isolated from dairy products.

    PubMed

    Haghshenas, Babak; Nami, Yousef; Haghshenas, Minoo; Abdullah, Norhafizah; Rosli, Rozita; Radiah, Dayang; Khosroushahi, Ahmad Yari

    2015-10-01

    This study aimed to find candidate strains of Lactobacillus isolated from sheep dairy products (yogurt and ewe colostrum) with probiotic and anticancer activity. A total of 100 samples were randomly collected from yogurt and colostrum and 125 lactic acid bacteria were isolated. Of these, 17 Lactobacillus strains belonging to five species (L. delbrueckii, L. plantarum, L. rhamnosus, L. paracasei, and L. casei) were identified. L. plantarum 17C and 13C, which isolated from colostrums, demonstrated remarkable results such as resistant to low pH and high concentrations of bile salts, susceptible to some antibiotics and good antimicrobial activity that candidate them as potential probiotics. Seven strains (1C, 5C, 12C, 13C, 17C, 7M, and 40M), the most resistant to simulated digestion, were further investigated to evaluate their capability to adhere to human intestinal Caco-2 cells. L. plantarum 17C was the most adherent strain. The bioactivity assessment of L. plantarum 17C showed anticancer effects via the induction of apoptosis on HT-29 human cancer cells and negligible side effects on one human epithelial normal cell line (FHs 74). The metabolites produced by this strain can be used as alternative pharmaceutical compounds with promising therapeutic indices because they are not cytotoxic to normal mammalian cells.

  4. Bioactivity characterization of Lactobacillus strains isolated from dairy products

    PubMed Central

    Haghshenas, Babak; Nami, Yousef; Haghshenas, Minoo; Abdullah, Norhafizah; Rosli, Rozita; Radiah, Dayang; Yari Khosroushahi, Ahmad

    2015-01-01

    This study aimed to find candidate strains of Lactobacillus isolated from sheep dairy products (yogurt and ewe colostrum) with probiotic and anticancer activity. A total of 100 samples were randomly collected from yogurt and colostrum and 125 lactic acid bacteria were isolated. Of these, 17 Lactobacillus strains belonging to five species (L. delbrueckii, L. plantarum, L. rhamnosus, L. paracasei, and L. casei) were identified. L. plantarum 17C and 13C, which isolated from colostrums, demonstrated remarkable results such as resistant to low pH and high concentrations of bile salts, susceptible to some antibiotics and good antimicrobial activity that candidate them as potential probiotics. Seven strains (1C, 5C, 12C, 13C, 17C, 7M, and 40M), the most resistant to simulated digestion, were further investigated to evaluate their capability to adhere to human intestinal Caco-2 cells. L. plantarum 17C was the most adherent strain. The bioactivity assessment of L. plantarum 17C showed anticancer effects via the induction of apoptosis on HT-29 human cancer cells and negligible side effects on one human epithelial normal cell line (FHs 74). The metabolites produced by this strain can be used as alternative pharmaceutical compounds with promising therapeutic indices because they are not cytotoxic to normal mammalian cells. PMID:26219634

  5. Alhagi: a plant genus rich in bioactives for pharmaceuticals.

    PubMed

    Muhammad, Gulzar; Hussain, Muhammad Ajaz; Anwar, Farooq; Ashraf, Muhammad; Gilani, Anwarul-Hassan

    2015-01-01

    Alhagi, a plant genus from family Fabaceae, is widely distributed in many countries of Asia, Australia and Europe. Commonly known as camel thorn, Alhagi has many species famous for feed and folk medicinal uses. Different species of Alhagi such as Alhagi pseudalhagi, A. graecorum, A. sparsifolia, A. kirgisorum, A. maurorum, A. camelorum and A. persarum have been explored for their antioxidant potential and nutritive value along with various medicinal properties. A wide array of pharmacologically active secondary metabolites such as flavonoids, alkaloids (alhacidin and alhacin), steroids, pseudalhagin A, phospholipids and polysaccharides have been reported from different parts of Alhagi species. A broad range of biological activities such as antioxidant, cardiovascular, anti-ulcer, hepatoprotective, antispasmodic, antidiarrheal, antinociceptive, antipyretic, anti-inflammatory, anti-rheumatic, antibacterial and antifungal have been ascribed to different parts of Alhagi. In addition, Alhagi plants are also valued as a rich source of digestible protein and important minerals. This review focuses on the medicinal applications and detailed profile of high-value bioactive phytochemicals along with pharmacological attributes and therapeutic potential of these multi-purpose plants.

  6. Bioactive heterocycles containing endocyclic N-hydroxy groups

    PubMed Central

    Rani, Reshma; Granchi, Carlotta

    2014-01-01

    Drug-likeness rules consider N-O single bonds as “structural alerts” which should not be present in a perspective drug candidate. In most cases this concern is correct, since it is known that N-hydroxy metabolites of branded drugs produce reactive species that cause serious side effects. However, this dangerous reactivity of the N-OH species generally takes place when the nitrogen atom is not comprised in a cyclic moiety. In fact, the same type of metabolic behavior should not be expected when the nitrogen atom is included in the ring of an aromatic heterocyclic scaffold. Nevertheless, heterocycles bearing endocyclic N-hydroxy portions have so far been poorly studied as chemical classes that may provide new therapeutic agents. This review provides an overview of N-OH-containing heterocycles with reported bioactivities that may be considered as therapeutically relevant and, therefore, may extend the chemical space available for the future development of novel pharmaceuticals. A systematic treatment of the various chemical classes belonging to this particular family of molecules is described along with a discussion of the biological activities associated to the most important examples. PMID:25466924

  7. Microbial biotransformation of bioactive flavonoids.

    PubMed

    Cao, Hui; Chen, Xiaoqing; Jassbi, Amir Reza; Xiao, Jianbo

    2015-01-01

    The bioactive flavonoids are considered as the most important phytochemicals in food, which exert a wide range of biological benefits for human being. Microbial biotransformation strategies for production of flavonoids have attracted considerable interest because they allow yielding novel flavonoids, which do not exist in nature. In this review, we summarize the existing knowledge on the production and biotransformation of flavonoids by various microbes. The main reactions during microbial biotransformation are hydroxylation, dehydroxylation, O-methylation, O-demethylation, glycosylation, deglycosylation, dehydrogenation, hydrogenation, C ring cleavage of the benzo-γ-pyrone system, cyclization, and carbonyl reduction. Cunninghamella, Penicillium, and Aspergillus strains are very popular to biotransform flavonoids and they can perform almost all the reactions with excellent yields. Aspergillus niger is one of the most applied microorganisms in the flavonoids' biotransformation; for example, A. niger can transfer flavanone to flavan-4-ol, 2'-hydroxydihydrochalcone, flavone, 3-hydroxyflavone, 6-hydroxyflavanone, and 4'-hydroxyflavanone. The hydroxylation of flavones by microbes usually happens on the ortho position of hydroxyl group on the A ring and C-4' position of the B ring and microbes commonly hydroxylate flavonols at the C-8 position. The microorganisms tend to hydroxylate flavanones at the C-5, 6, and 4' positions; however, for prenylated flavanones, dihydroxylation often takes place on the C4α=C5α double bond on the prenyl group (the side chain of A ring). Isoflavones are usually hydroxylated at the C-3' position of the B ring by microorganisms. The microbes convert flavonoids to their 7-O-glycosides and 3-O-glycosides (when flavonoids have a hydroxyl moiety at the C-3 position). The demethylation of multimethoxyl flavonoids by microbes tends to happen at the C-3' and C-4' positions of the B ring. Multimethoxyl flavanones and isoflavone are demethylated at

  8. SAR analysis and bioactive potentials of freshwater and terrestrial cyanobacterial compounds: a review.

    PubMed

    Nagarajan, M; Maruthanayagam, V; Sundararaman, M

    2013-05-01

    Freshwater and terrestrial cyanobacteria resemble the marine forms in producing divergent chemicals such as linear, cyclic and azole containing peptides, alkaloids, cyclophanes, terpenes, lactones, etc. These metabolites have wider biomedical potentials in targeting proteases, cancers, parasites, pathogens and other cyanobacteria and algae (allelopathy). Among the various families of non-marine cyanobacterial peptides reported, many of them are acting as serine protease inhibitors. While the micropeptin family has a preference for chymotrypsin inhibition rather than other serine proteases, the aeruginosin family targets trypsin and thrombin. In addition, cyanobacterial compounds such as scytonemide A, lyngbyazothrins C and D and cylindrocyclophanes were found to inhibit 20S proteosome. Apart from proteases, metabolites blocking the other targets of cancer pathways may exhibit cytotoxic effect. Colon and rectum, breast, lung and prostate are the worst affecting cancers in humans and are deduced to be inhibited by both peptidic and non-peptidic compounds. Moreover, the growth of infections causing parasites such as Plasmodium, Leishmania and Trypanosoma are well controlled by peptides: aerucyclamides A-D, tychonamides and alkaloids: nostocarboline and calothrixins. Likewise, varieties of cyanobacterial compounds tend to inhibit serious infectious disease causing bacterial, fungal and viral agents. Interestingly, portoamides, spiroidesin, nostocyclamide and kasumigamide are the allelopathic peptides determined to suppress the growth of toxic cyanobacteria and nuisance algae. Thus cyanobacterial compounds have a broad bioactive spectrum; the analysis of SAR studies will not only assist to find out the mode of action but also reveal bioactive key components. Thereby, developing the drugs bearing these bioactive skeletons to treat various illnesses is wide open.

  9. Tantalum—A bioactive metal for implants

    NASA Astrophysics Data System (ADS)

    Balla, Vamsi Krishna; Bose, Susmita; Davies, Neal M.; Bandyopadhyay, Amit

    2010-07-01

    Metallic biomaterials currently in use for load-bearing orthopedic applications are mostly bioinert and therefore lack sufficient osseointegration. Although bioactive ceramics such as hydroxyapatite (HA) can spontaneously bond to living bone tissue, low fracture toughness of HA limits their use as a bone substitute for load-bearing applications. Surface modification techniques such as HA coating on metals are current options to improve osseointegration in load-bearing metal implants. Over the last few decades researchers have attempted to find a bioactive metal with high mechanical strength and excellent fatigue resistance that can bond chemically with surrounding bone for orthopedic applications. Recent in vitro, in vivo, and clinical studies demonstrated that tantalum is a promising metal that is bioactive. However, tantalum applications in biomedical devices have been limited by processing challenges rather than biological performances. In this article, we provide an overview of processing aspects and biological properties of tantalum for load-bearing orthopedic applications.

  10. Bioactive scaffolds for bone and ligament tissue.

    PubMed

    Guarino, Vincenzo; Causa, Filippo; Ambrosio, Luigi

    2007-05-01

    Bone and ligament injuries present the greatest challenges in connective tissue regeneration. The design of materials for these applications lies at the forefront of material science and is the epitome of its current ambition. Indeed, its goal is to design and fabricate reproducible, bioactive and bioresorbable 3D scaffolds with tailored properties that are able to maintain their structure and integrity for predictable times, even under load-bearing conditions. Unfortunately, the mechanical properties of today's available porous scaffolds fall short of those exhibited by complex human tissues, such as bone and ligament. The manipulation of structural parameters in the design of scaffolds and their bioactivation, through the incorporation of soluble and insoluble signals capable of promoting cell activities, are discussed as possible strategies to improve the formation of new tissues both in vitro and in vivo. This review focuses on the different approaches adopted to develop bioactive composite systems for use as temporary scaffolds for bone and anterior ligament regeneration.

  11. Bioactive Proteins and Peptides from Soybeans.

    PubMed

    Agyei, Dominic

    2015-01-01

    Dietary proteins from soybeans have been shown to offer health benefits in vivo and/or in vitro either as intact proteins or in partially digested forms also called bioactive peptides. Upon oral administration and absorption, soy-derived bioactive peptides may induce several physiological responses such as antioxidative, antimicrobial, antihypertensive, anticancer and immunomodulatory effects. There has therefore been a mounting research interest in the therapeutic potential of soy protein hydrolysates and their subsequent incorporation in functional foods and 'Food for Specified Health Uses' (FOSHU) related products where their biological activities may assist in the promotion of good health or in the control and prevention of diseases. This mini review discusses relevant patents and gives an overview on bioactive proteins and peptides obtainable from soybeans. Processes for the production and formulation of these peptides are given, together with specific examples of their therapeutic potential and possible areas of application.

  12. Enhanced bioactivity, biocompatibility and mechanical behavior of strontium substituted bioactive glasses.

    PubMed

    Arepalli, Sampath Kumar; Tripathi, Himanshu; Hira, Sumit Kumar; Manna, Partha Pratim; Pyare, Ram; S P Singh

    2016-12-01

    Strontium contained biomaterials have been reported as a potential bioactive material for bone regeneration, as it reduces bone resorption and stimulates bone formation. In the present investigation, the bioactive glasses were designed to partially substitute SrO for SiO2 in Na2O-CaO-SrO-P2O5-SiO2 system. This work demonstrates that the substitution of SrO for SiO2 has got significant benefit than substitution for CaO in the bioactive glass. Bioactivity was assessed by the immersion of the samples in simulated body fluid for different intervals. The formation of hydroxy carbonate apatite layer was identified by X-ray diffractometry, scanning electron microscopy (SEM) and energy dispersive spectroscopy. The elastic modulus of the bioactive glasses was measured and found to increase with increasing SrO for SiO2. The blood compatibility of the samples was evaluated. In vitro cell culture studies of the samples were performed using human osteosarcoma U2-OS cell lines and found a significant improvement in cell viability and proliferation. The investigation showed enhancement in bioactivity, mechanical and biological properties of the strontia substituted for silica in glasses. Thus, these bioactive glasses would be highly potential for bone regeneration.

  13. Bioactive proteins and peptides in foods.

    PubMed

    Walther, Barbara; Sieber, Robert

    2011-03-01

    Increasing amounts of data demonstrate a bioactive role of proteins and peptides above and beyond their nutritional impact. The focus of the investigations has mainly been on vitamin- and mineral-binding proteins, on antimicrobial, immunosuppressing/-modulatory proteins, and on proteins with enzyme inhibitory activity as well as on hormones and growth factors from different food proteins; most research has been performed on milk proteins. Because of their molecular size, intact absorption of proteins in the human gastrointestinal tract is limited. Therefore, most of the proteins with biological functions show physiological activity in the gastrointestinal tract by enhancing nutrient absorption, inhibiting enzymes, and modulating the immune system to defend against pathogens. Peptides are released during fermentation or digestion from food proteins by proteolytic enzymes; such peptides have been found mainly in milk. Some of these released peptides exert biological activities such as opiate-like, antihypertensive, mineral-binding, antioxidative, antimicrobial, immuno-, and cytomodulating activity. Intact absorption of these smaller peptides is more likely than that of the larger proteins. Consequently, other organs than the gastrointestinal tract are possible targets for their biological functions. Bioactive proteins as well as bioactive peptides are part of a balanced diet. It is possible to accumulate bioactive peptides in food, for example by using specific microorganisms in fermented dairy products. Although bioactive peptides have been the subject of several studies in vitro and in vivo, their health potential is still under investigation. Up to now, the Commission of European Communities has not (yet) authorized any health claims for bioactive proteins and peptides from food.

  14. Natural products: Hunting microbial metabolites

    NASA Astrophysics Data System (ADS)

    Schmidt, Eric W.

    2015-05-01

    Symbiotic bacteria synthesize many specialized small molecules; however, establishing the role these chemicals play in human health and disease has been difficult. Now, the chemical structure and mechanism of the Escherichia coli product colibactin provides insight into the link between this secondary metabolite and colorectal cancer.

  15. Automated analysis of oxidative metabolites

    NASA Technical Reports Server (NTRS)

    Furner, R. L. (Inventor)

    1974-01-01

    An automated system for the study of drug metabolism is described. The system monitors the oxidative metabolites of aromatic amines and of compounds which produce formaldehyde on oxidative dealkylation. It includes color developing compositions suitable for detecting hyroxylated aromatic amines and formaldehyde.

  16. Primary expectations of secondary metabolites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant secondary metabolites (e.g., phenolics) are important for human health, in addition to the organoleptic properties they impart to fresh and processed foods. Consumer expectations such as appearance, taste, or texture influence their purchasing decisions. Thorough identification of phenolic com...

  17. Primary expectations of secondary metabolites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    My program examines the plant secondary metabolites (i.e. phenolics) important for human health, and which impart the organoleptic properties that are quality indicators for fresh and processed foods. Consumer expectations such as appearance, taste, or texture influence their purchasing decisions; a...

  18. Trapping Methylglyoxal by Genistein and Its Metabolites in Mice.

    PubMed

    Wang, Pei; Chen, Huadong; Sang, Shengmin

    2016-03-21

    Increasing evidence supports dicarbonyl stress such as methylglyoxal (MGO) as one of the major pathogenic links between hyperglycemia and diabetic complications. In vitro studies have shown that dietary flavonoids can inhibit the formation of advanced glycation end products (AGEs) by trapping MGO. However, whether flavonoids can trap MGO in vivo and whether biotransformation limits the trapping capacity of flavonoids remain virtually unknown. In this study, we investigated whether genistein (GEN), the major soy isoflavone, could trap MGO in mice by promoting the formation of MGO adducts of GEN and its metabolites. Two different mouse studies were conducted. In the acute study, a single dose of MGO and GEN were administered to mice via oral gavage. In the chronic study, MGO was given to mice in drinking water for 1 month and then GEN was given to mice for 4 consecutive days via oral gavage. Two mono-MGO adducts of GEN and six mono-MGO adducts of GEN phase I and microbial metabolites were identified in mouse urine samples from these studies using liquid chromatography/electrospray ionization tandem mass spectrometry. The structures of these MGO adducts were confirmed by analyzing their MS(n) (n = 1-4) spectra as well as by comparing them with the tandem mass spectra of authentic standards. All of the MGO adducts presented in their phase II conjugated forms in mouse urine samples in the acute and chronic studies. To our knowledge, this is the first in vivo evidence to demonstrate the trapping efficacy of GEN in mice and to show that the metabolites of GEN remain bioactive.

  19. Marine Microbial Secondary Metabolites: Pathways, Evolution and Physiological Roles.

    PubMed

    Giordano, Daniela; Coppola, Daniela; Russo, Roberta; Denaro, Renata; Giuliano, Laura; Lauro, Federico M; di Prisco, Guido; Verde, Cinzia

    2015-01-01

    Microbes produce a huge array of secondary metabolites endowed with important ecological functions. These molecules, which can be catalogued as natural products, have long been exploited in medical fields as antibiotics, anticancer and anti-infective agents. Recent years have seen considerable advances in elucidating natural-product biosynthesis and many drugs used today are natural products or natural-product derivatives. The major contribution to recent knowledge came from application of genomics to secondary metabolism and was facilitated by all relevant genes being organised in a contiguous DNA segment known as gene cluster. Clustering of genes regulating biosynthesis in bacteria is virtually universal. Modular gene clusters can be mixed and matched during evolution to generate structural diversity in natural products. Biosynthesis of many natural products requires the participation of complex molecular machines known as polyketide synthases and non-ribosomal peptide synthetases. Discovery of new evolutionary links between the polyketide synthase and fatty acid synthase pathways may help to understand the selective advantages that led to evolution of secondary-metabolite biosynthesis within bacteria. Secondary metabolites confer selective advantages, either as antibiotics or by providing a chemical language that allows communication among species, with other organisms and their environment. Herewith, we discuss these aspects focusing on the most clinically relevant bioactive molecules, the thiotemplated modular systems that include polyketide synthases, non-ribosomal peptide synthetases and fatty acid synthases. We begin by describing the evolutionary and physiological role of marine natural products, their structural/functional features, mechanisms of action and biosynthesis, then turn to genomic and metagenomic approaches, highlighting how the growing body of information on microbial natural products can be used to address fundamental problems in

  20. Involvement of CYP 2E1 enzyme in ovotoxicity caused by 4-vinylcyclohexene and its metabolites

    SciTech Connect

    Rajapaksa, Kathila S.; Cannady, Ellen A.; Sipes, I. Glenn; Hoyer, Patricia B. . E-mail: hoyer@u.arizona.edu

    2007-06-01

    4-Vinylcyclohexene (VCH) is bioactivated by hepatic CYP 2A and 2B to a monoepoxide (VCM) and subsequently to an ovotoxic diepoxide metabolite (VCD). Studies suggest that the ovary can directly bioactivate VCH via CYP 2E1. The current study was designed to evaluate the role of ovarian CYP 2E1 in VCM-induced ovotoxicity. Postnatal day 4 B6C3F{sub 1} and CYP 2E1 wild-type (+/+) and null (-/-) mouse ovaries were cultured (15 days) with VCD (30 {mu}M), 1,2-VCM (125-1000 {mu}M), or vehicle. Twenty-eight days female CYP 2E1 +/+ and -/- mice were dosed daily (15 days; ip) with VCH, 1,2-VCM, VCD or vehicle. Following culture or in vivo dosing, ovaries were histologically evaluated. In culture, VCD decreased (p < 0.05) primordial and primary follicles in ovaries from all three groups of mice. 1,2-VCM decreased (p < 0.05) primordial follicles in B6C3F{sub 1} and CYP 2E1 +/+ ovaries, but not in CYP 2E1 -/- ovaries in culture. 1,2-VCM did not affect primary follicles in any group of mouse ovaries. Conversely, following in vivo dosing, primordial and primary follicles were reduced (p < 0.05) by VCD and VCM in CYP2E1 +/+ and -/-, and by VCH in +/+ mice. The data demonstrate that, whereas in vitro ovarian bioactivation of VCM requires CYP 2E1 enzyme, in vivo CYP 2E1 plays a minimal role. Thus, the findings support that hepatic metabolism dominates the contribution made by the ovary in bioactivation of VCM to its ovotoxic metabolite, VCD. This study also demonstrates the use of a novel ovarian culture system to evaluate ovary-specific metabolism of xenobiotics.

  1. Integrating Dynamic Positron Emission Tomography and Conventional Pharmacokinetic Studies to Delineate Plasma and Tumor Pharmacokinetics of FAU, a Prodrug Bioactivated by Thymidylate Synthase.

    PubMed

    Li, Jing; Kim, Seongho; Shields, Anthony F; Douglas, Kirk A; McHugh, Christopher I; Lawhorn-Crews, Jawana M; Wu, Jianmei; Mangner, Thomas J; LoRusso, Patricia M

    2016-11-01

    FAU, a pyrimidine nucleotide analogue, is a prodrug bioactivated by intracellular thymidylate synthase to form FMAU, which is incorporated into DNA, causing cell death. This study presents a model-based approach to integrating dynamic positron emission tomography (PET) and conventional plasma pharmacokinetic studies to characterize the plasma and tissue pharmacokinetics of FAU and FMAU. Twelve cancer patients were enrolled into a phase 1 study, where conventional plasma pharmacokinetic evaluation of therapeutic FAU (50-1600 mg/m(2) ) and dynamic PET assessment of (18) F-FAU were performed. A parent-metabolite population pharmacokinetic model was developed to simultaneously fit PET-derived tissue data and conventional plasma pharmacokinetic data. The developed model enabled separation of PET-derived total tissue concentrations into the parent drug and metabolite components. The model provides quantitative, mechanistic insights into the bioactivation of FAU and retention of FMAU in normal and tumor tissues and has potential utility to predict tumor responsiveness to FAU treatment.

  2. Exploring in vitro, in vivo metabolism of mogroside V and distribution of its metabolites in rats by HPLC-ESI-IT-TOF-MS(n).

    PubMed

    Xu, Feng; Li, Dian-Peng; Huang, Zhen-Cong; Lu, Feng-Lai; Wang, Lei; Huang, Yong-Lin; Wang, Ru-Feng; Liu, Guang-Xue; Shang, Ming-Ying; Cai, Shao-Qing

    2015-11-10

    Mogroside V, a cucurbitane-type saponin, is not only the major bioactive constituent of traditional Chinese medicine Siraitiae Fructus, but also a widely used sweetener. To clarify its biotransformation process and identify its effective forms in vivo, we studied its metabolism in a human intestinal bacteria incubation system, a rat hepatic 9000g supernatant (S9) incubation system, and rats. Meanwhile, the distribution of mogroside V and its metabolites was also reported firstly. Seventy-seven new metabolites, including 52 oxidation products formed by mono- to tetra- hydroxylation/dehydrogenation, were identified with the aid of HPLC in tandem with ESI ion trap (IT) TOF multistage mass spectrometry (HPLC-ESI-IT-TOF-MS(n)). Specifically, 14 metabolites were identified in human intestinal bacteria incubation system, 4 in hepatic S9 incubation system, 58 in faeces, 29 in urine, 14 in plasma, 34 in heart, 33 in liver, 39 in spleen, 39 in lungs, 42 in kidneys, 45 in stomach, and 51 in small intestine. The metabolic pathways of mogroside V were proposed and the identified metabolic reactions were deglycosylation, hydroxylation, dehydrogenation, isomerization, glucosylation, and methylation. Mogroside V and its metabolites were distributed unevenly in the organs of treated rats. Seven bioactive metabolites of mogroside V were identified, among which mogroside IIE was abundant in heart, liver, spleen and lung, suggesting that it may contribute to the bioactivities of mogroside V. Mogroside V was mainly excreted in urine, whereas its metabolites were mainly excreted in faeces. To our knowledge, this is the first report that a plant constituent can be biotransformed into more than 65 metabolites in vivo. These findings will improve understanding of the in vivo metabolism, distribution, and effective forms of mogroside V and congeneric molecules.

  3. Competing for supply.

    PubMed

    Stolle, B

    2001-02-01

    The Internet was supposed to make it possible for anybody anywhere to get anything anytime. Instead, it's magnified suppliers' miscalculations into global shortages. But if the Net caused these supply chain woes, it's also the solution, says the CEO of a supply-chain software manufacturer.

  4. A physiologically based biokinetic (PBBK) model for estragole bioactivation and detoxification in rat

    SciTech Connect

    Punt, Ans Freidig, Andreas P.; Delatour, Thierry; Scholz, Gabriele; Boersma, Marelle G.; Schilter, Benoit; Bladeren, Peter J. van; Rietjens, Ivonne M.C.M.

    2008-09-01

    The present study defines a physiologically based biokinetic (PBBK) model for the alkenylbenzene estragole in rat based on in vitro metabolic parameters determined using relevant tissue fractions, in silico derived partition coefficients, and physiological parameters derived from the literature. The model consists of eight compartments including liver, lung and kidney as metabolizing compartments, and additional compartments for fat, arterial blood, venous blood, rapidly perfused tissue and slowly perfused tissue. Evaluation of the model was performed by comparing the PBBK predicted dose-dependent formation of the estragole metabolites 4-allylphenol and 1'-hydroxyestragole glucuronide to literature reported levels of these metabolites, which were demonstrated to be in the same order of magnitude. With the model obtained the relative extent of bioactivation and detoxification of estragole at different oral doses was examined. At low doses formation of 4-allylphenol, leading to detoxification, is observed to be the major metabolic pathway, occurring mainly in the lung and kidney due to formation of this metabolite with high affinity in these organs. Saturation of this metabolic pathway in the lung and kidney leads to a relative increase in formation of the proximate carcinogenic metabolite 1'-hydroxyestragole, occurring mainly in the liver. This relative increase in formation of 1'-hydroxyestragole leads to a relative increase in formation of 1'-hydroxyestragole glucuronide and 1'-sulfooxyestragole the latter being the ultimate carcinogenic metabolite of estragole. These results indicate that the relative importance of different metabolic pathways of estragole may vary in a dose-dependent way, leading to a relative increase in bioactiviation of estragole at higher doses.

  5. Power supply conditioning circuit

    NASA Technical Reports Server (NTRS)

    Primas, L. E.; Loveland, R.

    1987-01-01

    A power supply conditioning circuit that can reduce Periodic and Random Deviations (PARD) on the output voltages of dc power supplies to -150 dBV from dc to several KHz with no measurable periodic deviations is described. The PARD for a typical commercial low noise power supply is -74 dBV for frequencies above 20 Hz and is often much worse at frequencies below 20 Hz. The power supply conditioning circuit described here relies on the large differences in the dynamic impedances of a constant current diode and a zener diode to establish a dc voltage with low PARD. Power supplies with low PARD are especially important in circuitry involving ultrastable frequencies for the Deep Space Network.

  6. Spatial Data Supply Chains

    NASA Astrophysics Data System (ADS)

    Varadharajulu, P.; Azeem Saqiq, M.; Yu, F.; McMeekin, D. A.; West, G.; Arnold, L.; Moncrieff, S.

    2015-06-01

    This paper describes current research into the supply of spatial data to the end user in as close to real time as possible via the World Wide Web. The Spatial Data Infrastructure paradigm has been discussed since the early 1990s. The concept has evolved significantly since then but has almost always examined data from the perspective of the supplier. It has been a supplier driven focus rather than a user driven focus. The current research being conducted is making a paradigm shift and looking at the supply of spatial data as a supply chain, similar to a manufacturing supply chain in which users play a significant part. A comprehensive consultation process took place within Australia and New Zealand incorporating a large number of stakeholders. Three research projects that have arisen from this consultation process are examining Spatial Data Supply Chains within Australia and New Zealand and are discussed within this paper.

  7. Methods of Manufacturing Bioactive Gels from Extracellular Matrix Material

    NASA Technical Reports Server (NTRS)

    Kentner, Kimberly A. (Inventor); Stuart, Katherine A. (Inventor); Janis, Abram D. (Inventor)

    2015-01-01

    The present invention is directed to methods of manufacturing bioactive gels from ECM material, i.e., gels which retain bioactivity, and can serve as scaffolds for preclinical and clinical tissue engineering and regenerative medicine approaches to tissue reconstruction. The manufacturing methods take advantage of a new recognition that bioactive gels from ECM material can be created by digesting particularized ECM material in an alkaline environment and neutralizing to provide bioactive gels.

  8. Methods of Manufacturing Bioactive Gels from Extracellular Matrix Material

    NASA Technical Reports Server (NTRS)

    Kentner, Kimberly A. (Inventor); Stuart, Katherine A. (Inventor); Janis, Abram D. (Inventor)

    2014-01-01

    The present invention is directed to methods of manufacturing bioactive gels from ECM material, i.e., gels which retain bioactivity, and can serve as scaffolds for preclinical and clinical tissue engineering and regenerative medicine approaches to tissue reconstruction. The manufacturing methods take advantage of a new recognition that bioactive gels from ECM material can be created by digesting particularized ECM material in an alkaline environment and neutralizing to provide bioactive gels.

  9. Methods of Manufacturing Bioactive Gels from Extracellular Matrix Material

    NASA Technical Reports Server (NTRS)

    Kentner, Kimberly A. (Inventor); Stuart, Katherine A. (Inventor); Janis, Abram D. (Inventor)

    2016-01-01

    The present invention is directed to methods of manufacturing bioactive gels from ECM material, i.e., gels which retain bioactivity, and can serve as scaffolds for preclinical and clinical tissue engineering and regenerative medicine approaches to tissue reconstruction. The manufacturing methods take advantage of a new recognition that bioactive gels from ECM material can be created by digesting particularized ECM material in an alkaline environment and neutralizing to provide bioactive gels.

  10. Recent advances in genome mining of secondary metabolites in Aspergillus terreus

    PubMed Central

    Guo, Chun-Jun; Wang, Clay C. C.

    2014-01-01

    Filamentous fungi are rich resources of secondary metabolites (SMs) with a variety of interesting biological activities. Recent advances in genome sequencing and techniques in genetic manipulation have enabled researchers to study the biosynthetic genes of these SMs. Aspergillus terreus is the well-known producer of lovastatin, a cholesterol-lowering drug. This fungus also produces other SMs, including acetylaranotin, butyrolactones, and territram, with interesting bioactivities. This review will cover recent progress in genome mining of SMs identified in this fungus. The identification and characterization of the gene cluster for these SMs, as well as the proposed biosynthetic pathways, will be discussed in depth. PMID:25566227

  11. Biochemometrics for Natural Products Research: Comparison of Data Analysis Approaches and Application to Identification of Bioactive Compounds

    PubMed Central

    Kellogg, Joshua J.; Todd, Daniel A.; Egan, Joseph M.; Raja, Huzefa A.; Oberlies, Nicholas H.; Kvalheim, Olav M.; Cech, Nadja B.

    2016-01-01

    A central challenge of natural products research is assigning bioactive compounds from complex mixtures. The gold standard approach to address this challenge, bioassay-guided fractionation, is often biased towards abundant, rather than bioactive, mixture components. This study evaluated the combination of bioassay-guided fractionation with untargeted metabolite profiling to improve active component identification early in the fractionation process. Key to this methodology was statistical modeling of the integrated biological and chemical datasets (biochemometric analysis). Three data analysis approaches for biochemometric analysis were compared, namely, partial least squares loading vectors, S-plots, and the selectivity ratio. Extracts from the endophytic fungi Alternaria sp. and Pyrenochaeta sp. with antimicrobial activity against Staphylococcus aureus served as test cases. Biochemometric analysis incorporating the selectivity ratio performed best in identifying bioactive ions from these extracts early in the fractionation process, yielding altersetin (3, MIC 0.23 μg/mL) and macrosphelide A (4, MIC 75 μg/mL) as antibacterial constituents from Alternaria sp. and Pyrenochaeta sp., respectively. This study demonstrates the potential of biochemometrics coupled with bioassay-guided fractionation to identify bioactive mixture components. A benefit of this approach is the ability to integrate multiple stages of fractionation and bioassay data into a single analysis. PMID:26841051

  12. Establishing high temperature gas chromatographic profiles of non-polar metabolites for quality assessment of African traditional herbal medicinal products.

    PubMed

    Bony, Nicaise F; Libong, Danielle; Solgadi, Audrey; Bleton, Jean; Champy, Pierre; Malan, Anglade K; Chaminade, Pierre

    2014-01-01

    The quality assessment of African traditional herbal medicinal products is a difficult challenge since they are complex mixtures of several herbal drug or herbal drug preparations. The plant source is also often unknown and/or highly variable. Plant metabolites chromatographic profiling is therefore an important tool for quality control of such herbal products. The objective of this work is to propose a protocol for sample preparation and gas chromatographic profiling of non-polar metabolites for quality control of African traditional herbal medicinal products. The methodology is based on the chemometric assessment of chromatographic profiles of non-polar metabolites issued from several batches of leaves of Combretum micranthum and Mitracarpus scaber by high temperature gas chromatography coupled to mass spectrometry, performed on extracts obtained in refluxed dichloromethane, after removal of chlorophyll pigments. The method using high temperature gas chromatography after dichloromethane extraction allows detection of most non-polar bioactive and non-bioactive metabolites already identified in leaves of both species. Chemometric data analysis using Principal Component Analysis and Partial Least Squares after Orthogonal Signal Correction applied to chromatographic profiles of leaves of Combretum micranthum and Mitracarpus scaber showed slight batch to batch differences, and allowed clear differentiation of the two herbal extracts.

  13. Marine bioactives and potential application in sports.

    PubMed

    Gammone, Maria Alessandra; Gemello, Eugenio; Riccioni, Graziano; D'Orazio, Nicolantonio

    2014-04-30

    An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB), macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS) production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports.

  14. Interaction between bioactive glasses and human dentin.

    PubMed

    Efflandt, S E; Magne, P; Douglas, W H; Francis, L F

    2002-06-01

    This study explores the interaction between bioactive glasses and dentin from extracted human teeth in simulated oral conditions. Bioactive glasses in the Na(2)O-CaO-P(2)O(5)-SiO(2) and MgO-CaO-P(2)O(5)-SiO(2) systems were prepared as polished disks. Teeth were prepared by grinding to expose dentin and etching with phosphoric acid. A layer of saliva was placed between the two, and the pair was secured with an elastic band and immersed in saliva at 37 degrees C for 5, 21 or 42 days. The bioactive glasses adhered to dentin, while controls showed no such interaction. A continuous interface between the bioactive glass and dentin was imaged using cryogenic-scanning electron microscopy (SEM). However, after alcohol dehydration and critical point drying, fracture occurred due to stresses from dentin shrinkage. SEM investigations showed a microstructurally different material at the fractured interface. Chemical analyses revealed that ions from the glass penetrated into the dentin and that the surface of the glass in contact with the dentin was modified. Microdiffractometry showed the presence of apatite at the interface. Bonding appears to be due to an affinity of collagen for the glass surface and chemical interaction between the dentin and glass, leading to apatite formation at the interface.

  15. Bromophenols in Marine Algae and Their Bioactivities

    PubMed Central

    Liu, Ming; Hansen, Poul Erik; Lin, Xiukun

    2011-01-01

    Marine algae contain various bromophenols that have been shown to possess a variety of biological activities, including antioxidant, antimicrobial, anticancer, anti-diabetic, and anti-thrombotic effects. Here, we briefly review the recent progress of these marine algal biomaterials, with respect to structure, bioactivities, and their potential application as pharmaceuticals. PMID:21822416

  16. Citrus Limonoids: Analysis, Bioactivity, and Biomedical Prospects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This publication is a review of the chemistry, biochemistry and bioactivity of limonoids occurring in citrus. The review chronologically relates the evolution of research in citrus limonoids beginning with their association with bitterness development in citrus juices. The chemical and biochemical...

  17. Five new bioactive compounds from Chenopodium ambrosioides.

    PubMed

    Song, Kun; Zhang, Jian; Zhang, Peng; Wang, Hong-Qing; Liu, Chao; Li, Bao-Ming; Kang, Jie; Chen, Ruo-Yun

    2015-05-01

    Five new bioactive compounds, chenopodiumamines A-D (1-4) and chenopodiumoside A (5), were isolated from the ethanol extract of Chenopodium ambrosioides. The structures of these compounds were elucidated by various spectroscopic means (UV, IR, HR-ESI-MS, 1D and 2D NMR). Compounds 1-3 had moderate antioxidant and anti-inflammatory activities.

  18. Marine Bioactives and Potential Application in Sports

    PubMed Central

    Gammone, Maria Alessandra; Gemello, Eugenio; Riccioni, Graziano; D’Orazio, Nicolantonio

    2014-01-01

    An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB), macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS) production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports. PMID:24796298

  19. UV-B induced changes in the secondary metabolites of Morus alba L. leaves.

    PubMed

    Gu, Xi-Da; Sun, Ming-Yao; Zhang, Lin; Fu, Hong-Wei; Cui, Lei; Chen, Run-Ze; Zhang, Da-Wei; Tian, Jing-Kui

    2010-04-27

    Ultraviolet-B (UV-B) radiation is harmful to plants and human beings. Many secondary metabolites, like flavonoids, alkaloids, and lignin, are UV-B absorbing compounds, which can protect the genetic material of plants. Furthermore, they are active components of herbal drugs. UV-B radiation can activate the self-protective secondary metabolism system. The results of this paper provide a method to induce bioactive secondary metabolites from mulberry leaves (Morus alba L.) by UV-B irradiation in vitro. Five significantly different chromatographic peaks were found by HPLC fingerprint after induction, from which two active compounds were identified: One was chalcomoracin, a natural Diels-Alder type adduct with antibacterial activity; the other one was moracin N, which is a precursor of chalcomoracin. Their contents were 0.818 mg/g and 0.352 mg/g by dry weight, respectively.

  20. Quantitative metabolite profiling of edible onion species by NMR and HPLC-MS.

    PubMed

    Soininen, Tuula H; Jukarainen, Niko; Auriola, Seppo O K; Julkunen-Tiitto, Riitta; Karjalainen, Reijo; Vepsäläinen, Jouko J

    2014-12-15

    Allium genus is a treasure trove of valuable bioactive compounds with potentially therapeutically important properties. This work utilises HPLC-MS and a constrained total-line-shape (CTLS) approach applied to (1)H NMR spectra to quantify metabolites present in onion species to reveal important inter-species differences. Extensive differences were detected between the sugar concentrations in onion species. Yellow onion contained the highest and red onion the lowest amounts of amino acids. The main flavonol-glucosides were quercetin 3,4'-diglucoside and quercetin 4'-glucoside. In general, the levels of flavonols were, higher in yellow onions than in red onions, and garlic and leek contained a lower amount of flavonols than the other Allium species. Our results highlight how (1)H NMR together with HPLC-MS can be useful in the quantification and the identification of the most abundant metabolites, representing an efficient means to pinpoint important functional food ingredients from Allium species.

  1. Preparation and bioactive properties of nano bioactive glass and segmented polyurethane composites.

    PubMed

    Aguilar-Pérez, Fernando J; Vargas-Coronado, Rossana F; Cervantes-Uc, Jose M; Cauich-Rodríguez, Juan V; Covarrubias, Cristian; Pedram-Yazdani, Merhdad

    2016-04-01

    Composites of glutamine-based segmented polyurethanes with 5 to 25 wt.% bioactive glass nanoparticles were prepared, characterized, and their mineralization potential was evaluated in simulated body fluid. Biocompatibility with dental pulp stem cells was assessed by MTS to an extended range of compositions (1 to 25 wt.% of bioactive glass nanoparticles). Physicochemical characterization showed that composites retained many of the matrix properties, i.e. those corresponding to semicrystalline elastomeric polymers as they exhibited a glass transition temperature (Tg) between -41 and -36℃ and a melting temperature (Tm) between 46 and 49℃ in agreement with X-ray reflections at 23.6° and 21.3°. However, with bioactive glass nanoparticles addition, tensile strength and strain were reduced from 22.2 to 12.2 MPa and 667.2 to 457.8%, respectively with 25 wt.% of bioactive glass nanoparticles. Although Fourier transform infrared spectroscopy did not show evidence of mineralization after conditioning of these composites in simulated body fluid, X-ray diffraction, scanning electron microscopy, and energy dispersive X-ray microanalysis showed the formation of an apatite layer on the surface which increased with higher bioactive glass concentrations and longer conditioning time. Dental pulp stem cells proliferation at day 5 was improved in bioactive glass nanoparticles composites containing lower amounts of the filler (1-2.5 wt.%) but it was compromised at day 9 in composites containing high contents of nBG (5, 15, 25 wt.%). However, Runx2 gene expression was particularly upregulated for the dental pulp stem cells cultured with composites loaded with 15 and 25 wt.% of bioactive glass nanoparticles. In conclusion, low content bioactive glass nanoparticles and segmented polyurethanes composites deserve further investigation for applications such as guided bone regeneration membranes, where osteoconductivity is desirable but not a demanding mechanical performance.

  2. Hydrogen supply system

    SciTech Connect

    Teitel, R.J.

    1981-11-24

    A system for supplying hydrogen to an apparatus which utilizes hydrogen contains a metal hydride hydrogen supply component and a microcavity hydrogen storage hydrogen supply component which in tandem supply hydrogen for the apparatus. The metal hydride hydrogen supply component includes a first storage tank filled with a composition which is capable of forming a metal hydride of such a nature that the hydride will release hydrogen when heated but will absorb hydrogen when cooled. This first storage tank is equipped with a heat exchanger for both adding heat to and extracting heat from the composition to regulate the absorption/deabsorption of hydrogen from the composition. The microcavity hydrogen storage hydrogen supply component includes a second tank containing the microcavity hydrogen supply. The microcavity hydrogen storage contains hydrogen held under high pressure within individual microcavities. The hydrogen is released from the microcavities by heating the cavities. This heating is accomplished by including within the tank for the microcavity hydrogen storage a heating element.

  3. Automating power supply checkout

    SciTech Connect

    Laster, J.; Bruno, D.; D'Ottavio, T.; Drozd, J.; Marr, G.; Mi, C.

    2011-03-28

    Power Supply checkout is a necessary, pre-beam, time-critical function. At odds are the desire to decrease the amount of time to perform the checkout while at the same time maximizing the number and types of checks that can be performed and analyzing the results quickly (in case any problems exist that must be addressed). Controls and Power Supply Group personnel have worked together to develop tools to accomplish these goals. Power Supply checkouts are now accomplished in a time-frame of hours rather than days, reducing the number of person-hours needed to accomplish the checkout and making the system available more quickly for beam development. The goal of the Collider-Accelerator Department (CAD) at Brookhaven National Laboratory is to provide experimenters with collisions of heavy-ions and polarized protons. The Relativistic Heavy-Ion Collider (RHIC) magnets are controlled by 100's of varying types of power supplies. There is a concentrated effort to perform routine maintenance on the supplies during shutdown periods. There is an effort at RHIC to streamline the time needed for system checkout in order to quickly arrive at a period of beam operations for RHIC. This time-critical period is when the checkout of the power supplies is performed as the RHIC ring becomes cold and the supplies are connected to their physical magnets. The checkout process is used to identify problems in voltage and current regulation by examining data signals related to each for problems in settling and regulation (ripple).

  4. Supply chain planning classification

    NASA Astrophysics Data System (ADS)

    Hvolby, Hans-Henrik; Trienekens, Jacques; Bonde, Hans

    2001-10-01

    Industry experience a need to shift in focus from internal production planning towards planning in the supply network. In this respect customer oriented thinking becomes almost a common good amongst companies in the supply network. An increase in the use of information technology is needed to enable companies to better tune their production planning with customers and suppliers. Information technology opportunities and supply chain planning systems facilitate companies to monitor and control their supplier network. In spite if these developments, most links in today's supply chains make individual plans, because the real demand information is not available throughout the chain. The current systems and processes of the supply chains are not designed to meet the requirements now placed upon them. For long term relationships with suppliers and customers, an integrated decision-making process is needed in order to obtain a satisfactory result for all parties. Especially when customized production and short lead-time is in focus. An effective value chain makes inventory available and visible among the value chain members, minimizes response time and optimizes total inventory value held throughout the chain. In this paper a supply chain planning classification grid is presented based current manufacturing classifications and supply chain planning initiatives.

  5. Bioactive Organocopper Compound from Pseudomonas aeruginosa Inhibits the Growth of Xanthomonas citri subsp. citri

    PubMed Central

    de Oliveira, Admilton G.; Spago, Flavia R.; Simionato, Ane S.; Navarro, Miguel O. P.; da Silva, Caroline S.; Barazetti, André R.; Cely, Martha V. T.; Tischer, Cesar A.; San Martin, Juca A. B.; de Jesus Andrade, Célia G. T.; Novello, Cláudio R.; Mello, João C. P.; Andrade, Galdino

    2016-01-01

    Citrus canker is a very destructive disease of citrus species. The challenge is to find new compounds that show strong antibiotic activity and low toxicity to plants and the environment. The objectives of the present study were (1) to extract, purify and evaluate the secondary metabolites with antibiotic activity produced by Pseudomonas aeruginosa LV strain in vitro against Xanthomonas citri subsp. citri (strain 306), (2) to determine the potential of semi-purified secondary metabolites in foliar application to control citrus canker under greenhouse conditions, and (3) to identify antibiotic activity in orange leaf mesophyll infected with strain 306, by electron microscopy. Two pure bioactive compounds were isolated, an organocopper antibiotic compound (OAC) and phenazine-1-carboxamide. Phenazine-1-carboxamide did not show any antibiotic activity under the experimental conditions used in this study. The OAC showed a high level of antibiotic activity with a minimum inhibitory concentration of 0.12 μg mL-1. In greenhouse tests for control of citrus canker in orange trees, the semi-purified fraction F3d reduced lesion formation by about 97%. The concentration used was 500 times lower than that for the recommended commercial copper-based product. Electron microscopy showed that F3d altered the exopolysaccharide matrix and caused cell lysis of the pathogen inside the citrus canker lesions. These results suggest that secondary metabolites produced by inducing P. aeruginosa LV strain have a high potential to be used as a bioproduct to control citrus canker. PMID:26903992

  6. Bioactive Organocopper Compound from Pseudomonas aeruginosa Inhibits the Growth of Xanthomonas citri subsp. citri.

    PubMed

    de Oliveira, Admilton G; Spago, Flavia R; Simionato, Ane S; Navarro, Miguel O P; da Silva, Caroline S; Barazetti, André R; Cely, Martha V T; Tischer, Cesar A; San Martin, Juca A B; de Jesus Andrade, Célia G T; Novello, Cláudio R; Mello, João C P; Andrade, Galdino

    2016-01-01

    Citrus canker is a very destructive disease of citrus species. The challenge is to find new compounds that show strong antibiotic activity and low toxicity to plants and the environment. The objectives of the present study were (1) to extract, purify and evaluate the secondary metabolites with antibiotic activity produced by Pseudomonas aeruginosa LV strain in vitro against Xanthomonas citri subsp. citri (strain 306), (2) to determine the potential of semi-purified secondary metabolites in foliar application to control citrus canker under greenhouse conditions, and (3) to identify antibiotic activity in orange leaf mesophyll infected with strain 306, by electron microscopy. Two pure bioactive compounds were isolated, an organocopper antibiotic compound (OAC) and phenazine-1-carboxamide. Phenazine-1-carboxamide did not show any antibiotic activity under the experimental conditions used in this study. The OAC showed a high level of antibiotic activity with a minimum inhibitory concentration of 0.12 μg mL(-1). In greenhouse tests for control of citrus canker in orange trees, the semi-purified fraction F3d reduced lesion formation by about 97%. The concentration used was 500 times lower than that for the recommended commercial copper-based product. Electron microscopy showed that F3d altered the exopolysaccharide matrix and caused cell lysis of the pathogen inside the citrus canker lesions. These results suggest that secondary metabolites produced by inducing P. aeruginosa LV strain have a high potential to be used as a bioproduct to control citrus canker.

  7. Effect of nanoparticulate bioactive glass particles on bioactivity and cytocompatibility of poly(3-hydroxybutyrate) composites.

    PubMed

    Misra, Superb K; Ansari, Tahera; Mohn, Dirk; Valappil, Sabeel P; Brunner, Tobias J; Stark, Wendelin J; Roy, Ipsita; Knowles, Jonathan C; Sibbons, Paul D; Jones, Eugenia Valsami; Boccaccini, Aldo R; Salih, Vehid

    2010-03-06

    This work investigated the effect of adding nanoparticulate (29 nm) bioactive glass particles on the bioactivity, degradation and in vitro cytocompatibility of poly(3-hydroxybutyrate) (P(3HB)) composites/nano-sized bioactive glass (n-BG). Two different concentrations (10 and 20 wt %) of nanoscale bioactive glass particles of 45S5 Bioglass composition were used to prepare composite films. Several techniques (Raman spectroscopy, scanning electron microscopy, atomic force microscopy, energy dispersive X-ray) were used to monitor their surface and bioreactivity over a 45-day period of immersion in simulated body fluid (SBF). All results suggested the P(3HB)/n-BG composites to be highly bioactive, confirmed by the formation of hydroxyapatite on material surfaces upon immersion in SBF. The weight loss and water uptake were found to increase on increasing bioactive glass content. Cytocompatibility study (cell proliferation, cell attachment, alkaline phosphatase activity and osteocalcin production) using human MG-63 osteoblast-like cells in osteogenic and non-osteogenic medium showed that the composite substrates are suitable for cell attachment, proliferation and differentiation.

  8. Thermal analysis and in vitro bioactivity of bioactive glass-alumina composites

    SciTech Connect

    Chatzistavrou, Xanthippi; Kantiranis, Nikolaos; Kontonasaki, Eleana; Chrissafis, Konstantinos; Papadopoulou, Labrini; Koidis, Petros; Boccaccini, Aldo R.; Paraskevopoulos, Konstantinos M.

    2011-01-15

    Bioactive glass-alumina composite (BA) pellets were fabricated in the range 95/5-60/40 wt.% respectively and were heat-treated under a specific thermal treatment up to 950 {sup o}C. Control (unheated) and heat-treated pellets were immersed in Simulated Body Fluid (SBF) for bioactivity testing. All pellets before and after immersion in SBF were studied by Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM-EDS) and X-ray Diffraction (XRD) analysis. All composite pellets presented bioactive response. On the surface of the heat-treated pellets the development of a rich biological hydroxyapatite (HAp) layer was delayed for one day, compared to the respective control pellets. Independent of the proportion of the two components, all composites of each group (control and heat-treated) presented the same bioactive response as a function of immersion time in SBF. It was found that by the applied methodology, Al{sub 2}O{sub 3} can be successfully applied in bioactive glass composites without obstructing their bioactive response. - Research Highlights: {yields} Isostatically pressed glass-alumina composites presented apatite-forming ability. {yields} The interaction with SBF resulted in an aluminium phosphate phase formation. {yields} The formation of an aluminium phosphate phase enhanced the in vitro apatite growth.

  9. Bioactive macroporous titanium implants highly interconnected.

    PubMed

    Caparrós, Cristina; Ortiz-Hernandez, Mónica; Molmeneu, Meritxell; Punset, Miguel; Calero, José Antonio; Aparicio, Conrado; Fernández-Fairén, Mariano; Perez, Román; Gil, Francisco Javier

    2016-10-01

    Intervertebral implants should be designed with low load requirements, high friction coefficient and low elastic modulus in order to avoid the stress shielding effect on bone. Furthermore, the presence of a highly interconnected porous structure allows stimulating bone in-growth and enhancing implant-bone fixation. The aim of this study was to obtain bioactive porous titanium implants with highly interconnected pores with a total porosity of approximately 57 %. Porous Titanium implants were produced by powder sintering route using the space holder technique with a binder phase and were then evaluated in an in vivo study. The size of the interconnection diameter between the macropores was about 210 μm in order to guarantee bone in-growth through osteblastic cell penetration. Surface roughness and mechanical properties were analyzed. Stiffness was reduced as a result of the powder sintering technique which allowed the formation of a porous network. Compression and fatigue tests exhibited suitable properties in order to guarantee a proper compromise between mechanical properties and pore interconnectivity. Bioactivity treatment effect in novel sintered porous titanium materials was studied by thermo-chemical treatments and were compared with the same material that had undergone different bioactive treatments. Bioactive thermo-chemical treatment was confirmed by the presence of sodium titanates on the surface of the implants as well as inside the porous network. Raman spectroscopy results suggested that the identified titanate structures would enhance in vivo apatite formation by promoting ion exchange for the apatite formation process. In vivo results demonstrated that the bioactive titanium achieved over 75 % tissue colonization compared to the 40 % value for the untreated titanium.

  10. Fungal metabolites with anticancer activity.

    PubMed

    Evidente, Antonio; Kornienko, Alexander; Cimmino, Alessio; Andolfi, Anna; Lefranc, Florence; Mathieu, Véronique; Kiss, Robert

    2014-05-01

    Covering: 1964 to 2013. Natural products from bacteria and plants have played a leading role in cancer drug discovery resulting in a large number of clinically useful agents. In contrast, the investigations of fungal metabolites and their derivatives have not led to a clinical cancer drug in spite of significant research efforts revealing a large number of fungi-derived natural products with promising anticancer activity. Many of these natural products have displayed notable in vitro growth-inhibitory properties in human cancer cell lines and select compounds have been demonstrated to provide therapeutic benefits in mouse models of human cancer. Many of these compounds are expected to enter human clinical trials in the near future. The present review discusses the reported sources, structures and biochemical studies aimed at the elucidation of the anticancer potential of these promising fungal metabolites.

  11. Supply chain assessment methodology.

    PubMed

    Topor, E

    2000-08-01

    This article describes an assessment methodology based on the supply chain proficiency model that can be used to set realistic supply chain objectives. The assessment centers on a business model that identifies the logical stages of supply chain proficiency as measured against a comprehensive set of business characteristics. For each characteristic, an enterprise evolves from one stage to the next. The magnitude of change inherent in moving forward usually prohibits skipping stages. Although it is possible to be at different stages for each characteristic, it is usually desirable to maintain balance.

  12. A new sensitive LC/MS/MS analysis of vitamin D metabolites using a click derivatization reagent, 2-nitrosopyridine.

    PubMed

    Wan, Debin; Yang, Jun; Barnych, Bogdan; Hwang, Sung Hee; Lee, Kin Sing Stephen; Cui, Yongliang; Niu, Jun; Watsky, Mitchell A; Hammock, Bruce D

    2017-04-01

    There is an increased demand for comprehensive analysis of vitamin D metabolites. This is a major challenge, especially for 1α,25-dihydroxyvitamin D [1α,25(OH)2VitD], because it is biologically active at picomolar concentrations. 4-Phenyl-1,2,4-triazoline-3,5-dione (PTAD) was a revolutionary reagent in dramatically increasing sensitivity of all diene metabolites and allowing the routine analysis of the bioactive, but minor, vitamin D metabolites. A second generation of reagents used large fixed charge groups that increased sensitivity at the cost of a deterioration in chromatographic separation of the vitamin D derivatives. This precludes a survey of numerous vitamin D metabolites without redesigning the chromatographic system used. 2-Nitrosopyridine (PyrNO) demonstrates that one can improve ionization and gain higher sensitivity over PTAD. The resulting vitamin D derivatives facilitate high-resolution chromatographic separation of the major metabolites. Additionally, a liquid-liquid extraction followed by solid-phase extraction (LLE-SPE) was developed to selectively extract 1α,25(OH)2VitD, while reducing 2- to 4-fold ion suppression compared with SPE alone. LLE-SPE followed by PyrNO derivatization and LC/MS/MS analysis is a promising new method for quantifying vitamin D metabolites in a smaller sample volume (100 µL of serum) than previously reported methods. The PyrNO derivatization method is based on the Diels-Alder reaction and thus is generally applicable to a variety diene analytes.

  13. Tear metabolite changes in keratoconus

    PubMed Central

    Karamichos, D; Zieske, JD; Sejersen, H; Sarker-Nag, A; Asara, John M; Hjortdal, J

    2015-01-01

    While efforts have been made over the years, the exact cause of keratoconus (KC) remains unknown. The aim of this study was to identify alterations in endogenous metabolites in the tears of KC patients compared with age-matched healthy subjects. Three groups were tested: 1) Age-matched controls with no eye disease (N=15), 2) KC – patients wearing Rigid Gas permeable lenses (N=16), and 3) KC – No Correction (N=14). All samples were processed for metabolomics analysis using LC-MS/MS. We identified a total of 296 different metabolites of which >40 were significantly regulated between groups. Glycolysis and gluconeogenesis had significant changes, such as 3-phosphoglycerate and 1,3 diphopshateglycerate. As a result the citric acid cycle (TCA) was also affected with notable changes in Isocitrate, aconitate, malate, and acetylphosphate, up regulated in Group 2 and/or 3. Urea cycle was also affected, especially in Group 3 where ornithine and aspartate were up-regulated by at least 3 fold. The oxidation state was also severely affected. Groups 2 and 3 were under severe oxidative stress causing multiple metabolites to be regulated when compared to Group 1. Group 2 and 3, both showed significant down regulation in GSH-to-GSSG ratio when compared to Group 1. Another indicator of oxidative stress, the ratio of lactate – pyruvate was also affected with Groups 2 and 3 showing at least a 2-fold up regulation. Overall, our data indicate that levels of metabolites related to urea cycle, TCA cycle and oxidative stress are highly altered in KC patients. PMID:25579606

  14. Use of Physiologically Based Biokinetic (PBBK) Modeling to Study Estragole Bioactivation and Detoxification in Humans as Compared with Male Rats

    PubMed Central

    Punt, Ans; Paini, Alicia; Boersma, Marelle G.; Freidig, Andreas P.; Delatour, Thierry; Scholz, Gabriele; Schilter, Benoît; van Bladeren, Peter J.; Rietjens, Ivonne M. C. M.

    2009-01-01

    The extent of bioactivation of the herbal constituent estragole to its ultimate carcinogenic metabolite 1′-sulfooxyestragole depends on the relative levels of bioactivation and detoxification pathways. The present study investigated the kinetics of the metabolic reactions of both estragole and its proximate carcinogenic metabolite 1′-hydroxyestragole in humans in incubations with relevant tissue fractions. Based on the kinetic data obtained a physiologically based biokinetic (PBBK) model for estragole in human was defined to predict the relative extent of bioactivation and detoxification at different dose levels of estragole. The outcomes of the model were subsequently compared with those previously predicted by a PBBK model for estragole in male rat to evaluate the occurrence of species differences in metabolic activation. The results obtained reveal that formation of 1′-oxoestragole, which represents a minor metabolic route for 1′-hydroxyestragole in rat, is the main detoxification pathway of 1′-hydroxyestragole in humans. Due to a high level of this 1′-hydroxyestragole oxidation pathway in human liver, the predicted species differences in formation of 1′-sulfooxyestragole remain relatively low, with the predicted formation of 1′-sulfooxyestragole being twofold higher in human compared with male rat, even though the formation of its precursor 1′-hydroxyestragole was predicted to be fourfold higher in human. Overall, it is concluded that in spite of significant differences in the relative extent of different metabolic pathways between human and male rat there is a minor influence of species differences on the ultimate overall bioactivation of estragole to 1′-sulfooxyestragole. PMID:19447879

  15. An integrated approach for profiling oxidative metabolites and glutathione adducts using liquid chromatography coupled with ultraviolet detection and triple quadrupole-linear ion trap mass spectrometry.

    PubMed

    Chen, Guiying; Cheng, Zhongzhe; Zhang, Kerong; Jiang, Hongliang; Zhu, Mingshe

    2016-09-10

    The use of liquid chromatography (LC) coupled with triple quadrupole linear ion trap (Qtrap) mass spectrometry (MS) for both quantitative and qualitative analysis in drug metabolism and pharmacokinetic studies is of great interest. Here, a new Qtrap-based analytical methodology for simultaneous detection, structural characterization and semi-quantitation of in vitro oxidative metabolites and glutathione trapped reactive metabolites was reported. In the current study, combined multiple ion monitoring and multiple reaction monitoring were served as surveying scans to trigger product ion spectral acquisition of oxidative metabolites and glutathione adduct, respectively. Then, detection of metabolites and recovery of their MS/MS spectra were accomplished using multiple data mining approaches. Additionally, on-line ultraviolet (UV) detection was employed to determine relative concentrations of major metabolites. Analyses of metabolites of clozapine and nomifensine in rat liver microsomes not only revealed multiple oxidative metabolites and glutathione adducts, but also identified their major oxidative metabolism and bioactivation pathways. The results demonstrated that the LC/UV/MS method enabled Qtrap to perform the comprehensive profiling of oxidative metabolites and glutathione adducts in vitro.

  16. Managing Supply Chain Disruptions

    DTIC Science & Technology

    2008-08-09

    functions within and across organizations (CSCMP, 2005). Mentzer et al. (2001) characterize SCM as a philosophy that includes a systems approach with...150 vi LIST OF TABLES Table 2.1. Prominent Supply Chain Related System Theory...process. It is not a matter of a supply chain system encountering a problem, but rather a matter of when a problematic event will occur and how severe

  17. Metabolite and mineral profiling of "Violetto di Niscemi" and "Spinoso di Menfi" globe artichokes by (1)H-NMR and ICP-MS.

    PubMed

    Albergamo, Ambrogina; Rotondo, Archimede; Salvo, Andrea; Pellizzeri, Vito; Bua, Daniel G; Maggio, Antonella; Cicero, Nicola; Dugo, Giacomo

    2017-05-01

    Globe artichoke has been long considered a nutraceutical food for its valuable content of bioactive compounds. However, beside a well-known polyphenol profile, poor information is available about its metabolite and mineral composition. The aim of this study was to investigate edible parts of Sicilian artichokes, 'Spinoso di Menfi' and 'Violetto di Niscemi', by (1)H NMR and ICP-MS for elucidating these compositional aspects. Although bracts and hearts of both artichokes shared a very similar metabolite pattern, 'Spinoso di Menfi' showed a higher number of metabolites, such as amino acids and polyphenols, than 'Violetto di Niscemi'. 'Spinoso di Menfi' was also marked by higher levels of macro- and microelements when compared to 'Violetto di Niscemi'. Also, artichoke heart demonstrated to accumulate higher mineral levels than bracts. (1)H NMR and ICP-MS successfully profiled metabolites and metals in such plant food, partially covering the lack of literature data about 'Spinoso di Menfi' and 'Violetto di Niscemi' artichokes.

  18. Near-Critical Phenomena in Intracellular Metabolite Pools

    PubMed Central

    Elf, Johan; Paulsson, Johan; Berg, Otto G.; Ehrenberg, Måns

    2003-01-01

    The supply and consumption of metabolites in living cells are catalyzed by enzymes. Here we consider two of the simplest schemes where one substrate is eliminated through Michaelis-Menten kinetics, and where two types of substrates are joined together by an enzyme. It is demonstrated how steady-state substrate concentrations can change ultrasensitively in response to changes in their supply rates and how this is coupled to slow relaxation back to steady state after a perturbation. In the one-substrate system, such near-critical behavior occurs when the supply rate approaches the maximal elimination rate, and in the two-substrate system it occurs when the rates of substrate supply are almost balanced. As systems that operate near criticality tend to display large random fluctuations, we also carried out a stochastic analysis using analytical approximations of master equations and compared the results with molecular-level Monte Carlo simulations. It was found that the significance of random fluctuations was directly coupled to the steady-state sensitivity and that the two substrates can fluctuate greatly because they are anticorrelated in such a way that the product formation rate displays only small variation. Basic relations are highlighted and biological implications are discussed. PMID:12524272

  19. Antibacterial metabolites synthesized by psychrotrophic bacteria isolated from cold-freshwater environments.

    PubMed

    Barros, Javier; Becerra, José; González, Carlos; Martínez, Miguel

    2013-03-01

    The ability of three psychrotrophic Gram-negative bacilli isolated from Chilean Patagonian cold freshwater rivers to produce bioactive metabolites was evaluated. The strains were isolated from cold waters rivers and identified by their biochemical properties and 16S rRNA gene analysis. The metabolites fractions showing antibacterial activity were obtained by solvent extraction and partially characterized by gas-mass chromatography (GC-MS). Antibacterial activity of the fractions was evaluated by an agar-well diffusion test upon 14 bacterial strains, both Gram positive and Gram negative. Thermal and proteolytic resistances of the antibacterial metabolites fractions were also evaluated. Molecular analysis allows the identification of the three Patagonian strains as Pseudomonas sp. RG-6 (Pseudomonas brenneri 99.6 % identity), Pseudomonas sp. RG-8 (Pseudomonas trivialis 99.6 % identity) and Yersinia sp. RP-3 (Yersinia aldovae 99.5 % identity). These extracts were able to inhibit both Gram-positive and Gram-negative bacteria but not Listeria monocytogenes. The antibacterial activity of the filtrated supernatants was lost at temperatures ≥60 °C, and was not affected by proteinase K treatment. The chemical structure of the active molecule remains to be elucidated, although the GC-MS analysis of the filtrates suggests that compounds like sesquiterpenes derivatives from β-maaliene or δ-selinene could be responsible of this antibacterial activity. Pristine cold freshwater streams showed to be interesting sources of metabolites-producing microorganisms with antibacterial activity.

  20. A search for antiplasmodial metabolites among fungal endophytes of terrestrial and marine plants of southern India.

    PubMed

    Kaushik, Naveen Kumar; Murali, Thokur Sreepathy; Sahal, Dinkar; Suryanarayanan, T S

    2014-10-01

    Eighty four different fungal endophytes isolated from sea grasses (5), marine algae (36) and leaves or barks of forest trees (43) were grown in vitro and the secondary metabolites secreted by them were harvested by immobilizing them on XAD beads. These metabolites were eluted with methanol and screened using SYBR Green I assay for their antiplasmodial activity against blood stage Plasmodium falciparum in human red blood cell culture. Our results revealed that fungal endophytes belonging to diverse genera elaborate antiplasmodial metabolites. A Fusarium sp. (580, IC50: 1.94 μg ml(-1)) endophytic in a marine alga and a Nigrospora sp. (151, IC50: 2.88 μg ml(-1)) endophytic in a tree species were subjected to antiplasmodial activity-guided reversed phase high performance liquid chromatography separation. Purification led to potentiation as reflected in IC50 values of 0.12 μg ml(-1) and 0.15 μg ml(-1) for two of the fractions obtained from 580. Our study adds further credence to the notion that fungal endophytes are a potential storehouse for a variety of novel secondary metabolites vested with different bioactivities including some that can stall the growth of the malaria parasite.

  1. Metabolite

    MedlinePlus

    Kumar V, Abbas AK, Aster JC. Cellular responses to stress and toxic insults: Adaptation, injury, and death. In: Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease . 9th ed. Philadelphia, PA: ...

  2. Bioactivation mechanism of cytotoxic homocysteine S-conjugates.

    PubMed

    Lash, L H; Elfarra, A A; Rakiewicz-Nemeth, D; Anders, M W

    1990-02-01

    S-(1,2-Dichlorovinyl)-L-homocysteine is a much more potent nephrotoxin than the corresponding cysteine S-conjugate S-(1,2-dichlorovinyl)-L-cysteine (A. A. Elfarra, L. H. Lash, and M. W. Anders (1986) Proc. Natl. Acad. Sci. USA 83, 2667-2671). The objective of the present experiments was to test the hypothesis that the increased toxicity of homocysteine S-conjugates may be associated with the formation of the reactive metabolite 2-oxo-3-butenoic acid, which may arise via a nonenzymatic retro-Michael elimination reaction from the 2-oxo acid metabolites of homocysteine S-conjugates. S-(2-Benzothiazolyl)-L-homocysteine, which was a substrate for purified bovine kidney cysteine conjugate beta-lyase (glutamine transaminase K) and whose metabolism was dependent on the presence of a 2-oxo acid, was cytotoxic in isolated rat kidney cells and was toxic to rat renal mitochondria, whereas the cysteine S-conjugate S-(2-benzothiazolyl)-L-cysteine had little effect. L-Methionine sulfoximine, L-canavanine, and the Michael acceptor methyl vinyl ketone were cytotoxic. The 2-hydroxy acid analogs of S-(1,2-dichlorovinyl)-L-homocysteine and 2-oxo-3-butenoic acid, S-(1,2-dichlorovinyl)-2-hydroxy-4-mercaptobutanoic acid and 2-hydroxy-3-butenoic acid, respectively, which are expected to be metabolized by rat renal L-2-hydroxy (L-amino) acid oxidase to yield 2-oxo-3-butenoic acid, were also cytotoxic. To obtain evidence for the formation of 2-oxo-3-butenoic acid as a product of the metabolism of L-homocysteine S-conjugates and analogs, trapping experiments were conducted. S-(2-Benzothiazolyl)-L-homocysteine, S-(1,2-dichlorovinyl)-L-homocysteine, L-methionine sulfoximine, and L-canavanine were converted by snake venom L-amino acid oxidase to 2-oxo-3-butenoic acid, which was trapped by the nucleophile methanethiol to yield 4-methylthio-2-oxobutanoic acid; the trapped product was derivatized with 2,4-dinitrophenylhydrazine and was identified by its electronic absorption spectrum and by high

  3. Metabolomic-Based Study of the Leafy Gall, the Ecological Niche of the Phytopathogen Rhodococcus Fascians, as a Potential Source of Bioactive Compounds

    PubMed Central

    Nacoulma, Aminata P.; Vandeputte, Olivier M.; De Lorenzi, Manuella; El Jaziri, Mondher; Duez, Pierre

    2013-01-01

    Leafy gall is a plant hyperplasia induced upon Rhodococcus fascians infection. Previously, by genomic and transcriptomic analysis, it has been reported that, at the early stage of symptom development, both primary and secondary metabolisms are modified. The present study is based on the hypothesis that fully developed leafy gall, could represent a potential source of new bioactive compounds. Therefore, non-targeted metabolomic analysis of aqueous and chloroform extracts of leafy gall and non-infected tobacco was carried out by 1H-NMR coupled to principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA). Polar metabolite profiling reflects modifications mainly in the primary metabolites and in some polyphenolics. In contrast, main modifications occurring in non-polar metabolites concern secondary metabolites, and gas chromatography and mass spectrometry (GC-MS) evidenced alterations in diterpenoids family. Analysis of crude extracts of leafy galls and non-infected tobacco leaves exhibited a distinct antiproliferative activity against all four tested human cancer cell lines. A bio-guided fractionation of chloroformic crude extract yield to semi-purified fractions, which inhibited proliferation of glioblastoma U373 cells with IC50 between 14.0 and 2.4 μg/mL. Discussion is focused on the consequence of these metabolic changes, with respect to plant defense mechanisms following infection. Considering the promising role of diterpenoid family as bioactive compounds, leafy gall may rather be a propitious source for drug discovery. PMID:23771021

  4. Metabolomic-based study of the leafy gall, the ecological niche of the phytopathogen Rhodococcus fascians, as a potential source of bioactive compounds.

    PubMed

    Nacoulma, Aminata P; Vandeputte, Olivier M; De Lorenzi, Manuella; Jaziri, Mondher El; Duez, Pierre

    2013-06-14

    Leafy gall is a plant hyperplasia induced upon Rhodococcus fascians infection. Previously, by genomic and transcriptomic analysis, it has been reported that, at the early stage of symptom development, both primary and secondary metabolisms are modified. The present study is based on the hypothesis that fully developed leafy gall, could represent a potential source of new bioactive compounds. Therefore, non-targeted metabolomic analysis of aqueous and chloroform extracts of leafy gall and non-infected tobacco was carried out by 1H-NMR coupled to principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA). Polar metabolite profiling reflects modifications mainly in the primary metabolites and in some polyphenolics. In contrast, main modifications occurring in non-polar metabolites concern secondary metabolites, and gas chromatography and mass spectrometry (GC-MS) evidenced alterations in diterpenoids family. Analysis of crude extracts of leafy galls and non-infected tobacco leaves exhibited a distinct antiproliferative activity against all four tested human cancer cell lines. A bio-guided fractionation of chloroformic crude extract yield to semi-purified fractions, which inhibited proliferation of glioblastoma U373 cells with IC50 between 14.0 and 2.4 µg/mL. Discussion is focused on the consequence of these metabolic changes, with respect to plant defense mechanisms following infection. Considering the promising role of diterpenoid family as bioactive compounds, leafy gall may rather be a propitious source for drug discovery.

  5. Cyclic metabolites: chemical and biological considerations.

    PubMed

    Erve, John C L

    2008-02-01

    Metabolism of xenobiotics can sometimes generate cyclic metabolites. Such metabolites are usually the result of intramolecular reactions occurring within a primary or secondary metabolite and this chemistry may lead to unexpected structures. Intramolecular chemistry is often driven by nucleophilic groups reacting with electrophilic atoms, often carbon, although radical processes also occur. Conjugation of xenobiotics or their metabolites with endogenous thiols, such as glutathione or cysteine, introduce a reactive amino group that can lead to the formation of cyclic structures. Less common than chemically driven cyclizations are enzymatically mediated ring-closures, although this may reflect our incomplete recognition of enzymatic involvement in this step of cyclic metabolite formation. While some cyclic metabolites are biologically inactive, others are biologically active. Thus, a cyclic metabolite may display desirable pharmacology, or, contribute to toxicology. When a cyclic metabolite is identified, it is important to consider the possibility that it is an artifact, i.e. metabonate, that was formed during processing of the sample, for example, through degradation or by chemical reactions with other components present in the matrix. From a medicinal chemistry perspective, a cyclic metabolite with a different chemical scaffold from the parent structure may lead to a new series of structurally novel, biologically active molecules with the same, or different, pharmacology from the parent. This review will cover a selection of cyclic metabolites from a mechanistic point of view, and when possible, discuss their biological relevance.

  6. Microencapsulated Bioactive Agents and Method of Making

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R. (Inventor); Mosier, Benjamin (Inventor)

    2003-01-01

    The invention is directed to microcapsules encapsulating an aqueous solution of a protein, drug or other bioactive substance inside a semi-permeable membrane. The microcapsules are formed by interfacial coacervation where shear forces are limited to 0-100 dynes per square centimeter. The resulting uniform microcapsules can then be subjected to dewatering in order to cause the internal solution to become supersaturated with the dissolved substance. This dewatering allows controlled nucleation and crystallization of the dissolved substance. The crystal-filled microcapsules can be stored, keeping the encapsulated crystals in good condition for further direct use in x-ray crystallography or as injectable formulations of the dissolved drug, protein or other bioactive substance.

  7. Enhancing orthopedic implant bioactivity: refining the nanotopography.

    PubMed

    Wang, Guocheng; Moya, Sergio; Lu, ZuFu; Gregurec, Danijela; Zreiqat, Hala

    2015-01-01

    Advances in nanotechnology open up new possibilities to produce biomimetic surfaces that resemble the cell in vivo growth environment at a nanoscale level. Nanotopographical changes of biomaterials surfaces can positively impact the bioactivity and ossointegration properties of orthopedic and dental implants. This review introduces nanofabrication techniques currently used or those with high potential for use as surface modification of biomedical implants. The interactions of nanotopography with water, proteins and cells are also discussed, as they largely determine the final success of the implants. Due to the well-documented effects of surface chemistry and microtopography on the bioactivity of the implant, we here elaborate on the ability of the nanofabrication techniques to combine the dual (multi) modification of surface chemistry and/or microtopography.

  8. Polyphenols from wolfberry and their bioactivities.

    PubMed

    Zhou, Zheng-Qun; Xiao, Jia; Fan, Hong-Xia; Yu, Yang; He, Rong-Rong; Feng, Xiao-Lin; Kurihara, Hiroshi; So, Kwok-Fai; Yao, Xin-Sheng; Gao, Hao

    2017-01-01

    Nine new phenylpropanoids, one new coumarin, and 43 known polyphenols were isolated from wolfberry. Their structures were determined by spectroscopic analyses, chemical methods, and comparison of NMR data. Polyphenols, an important type of natural products, are notable constituents in wolfberry. 53 polyphenols, including 28 phenylpropanoids, four coumarins, eight lignans, five flavonoids, three isoflavonoids, two chlorogenic acid derivatives, and three other constituents, were identified from wolfberry. Lignans and isoflavonoids were firstly reported from wolfberry. 22 known polyphenols were the first isolates from the genus Lycium. This research presents a systematic study on wolfberry polyphenols, including their bioactivities. All these compounds exhibited oxygen radical absorbance capacity (ORAC), and some compounds displayed DPPH radical scavenging activity. One compound had acetylcholinesterase inhibitory activity. The discovery of new polyphenols and their bioactivities is beneficial for understanding the scientific basis of the effects of wolfberry.

  9. Identifying reference chemicals for thyroid bioactivity screening.

    PubMed

    Wegner, Susanna; Browne, Patience; Dix, David

    2016-10-01

    Reference chemicals were selected based on thyroid bioactivity in 'Tier 1' screening assays used by the U.S. EPA's Endocrine Disruptor Screening Program. Active reference chemicals had significant effects on thyroid-responsive endpoints in the amphibian metamorphosis assay, and the male and female pubertal rat assays. In the absence of thyroid weight or histopathological effects, additional published studies providing mechanistic data on thyroid activity were required for active chemicals. Inactive reference chemicals had no significant effects on thyroid-responsive endpoints in Tier 1 assays, or in amphibian or rodent studies from several online databases. The 34 reference chemicals (29 active and five inactive) will be useful for performance-based validation of alternative, high throughput screening assays for thyroid bioactivity.

  10. Novel bioresorbable and bioactive composites based on bioactive glass and polylactide foams for bone tissue engineering.

    PubMed

    Roether, J A; Gough, J E; Boccaccini, A R; Hench, L L; Maquet, V; Jérôme, R

    2002-12-01

    Bioresorbable and bioactive tissue engineering scaffolds based on bioactive glass (45S5 Bioglass(R)) particles and macroporous poly(DL-lactide) (PDLLA) foams were fabricated. A slurry dipping technique in conjunction with pretreatment in ethanol was used to achieve reproducible and well adhering bioactive glass coatings of uniform thickness on the internal and external surfaces of the foams. In vitro studies in simulated body fluid (SBF) demonstrated rapid hydroxyapatite (HA) formation on the surface of the composites, indicating their bioactivity. For comparison, composite foams containing Bioglass(R) particles as filler for the polymer matrix (in concentration of up to 40 wt %) were prepared by freeze-drying, enabling homogenous glass particle distribution in the polymer matrix. The formation of HA on the composite surfaces after immersion in phosphate buffer saline (PBS) was investigated to confirm the bioactivity of the composites. Human osteoblasts (HOBs) were seeded onto as-fabricated PDLLA foams and onto PDLLA foams coated with Bioglass(R) particles to determine early cell attachment and spreading. Cells were observed to attach and spread on all surfaces after the first 90 min in culture. The results of this study indicate that the fabricated composite materials have potential as scaffolds for guided bone regeneration.

  11. Surface properties of in vitro bioactive and non-bioactive sol-gel derived materials.

    PubMed

    Viitala, R; Jokinen, M; Peltola, T; Gunnelius, K; Rosenholm, J B

    2002-08-01

    The acid-base properties of several in vitro bioactive (able to form bone mineral-like calcium phosphate on their surfaces) and non-bioactive sol-gel processed oxides are studied. The amount of Lewis acid sites was calculated from the pyridine adsorption using the Langmuir adsorption model. The Henry adsorption model was used in cases where no specific affinity between the adsorbent and the probe molecule was observed. The results were used to calculate the specific amounts of acidic and basic sites on SiO2- and TiO2-based materials. The zeta potential was measured for dip-coated TiO2 films, calcium- and phosphate-doped TiO2 films and for a non-bioactive Al2O3 film. Also, the calcium phosphate formation in simulated body fluid on in vitro bioactive TiO2 film was studied with zeta potential measurements. The results showed dependence on the negative surface charge and the important role of calcium adsorption in the beginning of the calcium phosphate formation. Surface topography of the films was investigated with atomic force microscopy, including a detailed analysis of the peak heights and distribution over cross sections. It was observed that in vitro bioactivity was strongly dependent on the nanoscale dimensions. Consequently, the in vitro calcium phosphate formation seems to be due to both the chemical interactions and the surface structure.

  12. Fluoride-containing bioactive glasses: Glass design, structure, bioactivity, cellular interactions, and recent developments.

    PubMed

    Shah, Furqan A

    2016-01-01

    Bioactive glasses (BGs) are known to bond to both hard and soft tissues. Upon exposure to an aqueous environment, BG undergoes ion exchange, hydrolysis, selective dissolution and precipitation of an apatite layer on their surface, which elicits an interfacial biological response resulting in bioactive fixation, inhibiting further dissolution of the glass, and preventing complete resorption of the material. Fluorine is considered one of the most effective in-vivo bone anabolic factors. In low concentrations, fluoride ions (F(-)) increase bone mass and mineral density, improve the resistance of the apatite structure to acid attack, and have well documented antibacterial properties. F(-) ions may be incorporated into the glass in the form of calcium fluoride (CaF2) either by part-substitution of network modifier oxides, or by maintaining the ratios of the other constituents relatively constant. Fluoride-containing bioactive glasses (FBGs) enhance and control osteoblast proliferation, differentiation and mineralisation. And with their ability to release fluoride locally, FBGs make interesting candidates for various clinical applications, dentinal tubule occlusion in the treatment of dentin hypersensitivity. This paper reviews the chemistry of FBGs and the influence of F(-) incorporation on the thermal properties, bioactivity, and cytotoxicity; and novel glass compositions for improved mechanical properties, processing, and bioactive potential.

  13. Bioactive volatile organic compounds from Antarctic (sponges) bacteria.

    PubMed

    Papaleo, Maria Cristiana; Romoli, Riccardo; Bartolucci, Gianluca; Maida, Isabel; Perrin, Elena; Fondi, Marco; Orlandini, Valerio; Mengoni, Alessio; Emiliani, Giovanni; Tutino, Maria Luisa; Parrilli, Ermenegilda; de Pascale, Donatella; Michaud, Luigi; Lo Giudice, Angelina; Fani, Renato

    2013-09-25

    Antarctic bacteria represent a reservoir of unexplored biodiversity, which, in turn, might be correlated to the synthesis of still undescribed bioactive molecules, such as antibiotics. In this work we have further characterized a panel of four marine Antarctic bacteria able to inhibit the growth of human opportunistic multiresistant pathogenic bacteria belonging to the Burkholderia cepacia complex (responsible for the 'cepacia' syndrome in Cystic Fibrosis patients) through the production of a set of microbial Volatile Organic Compounds (mVOCs). A list of 30 different mVOCs synthesized under aerobic conditions by Antarctic bacteria was identified by GC-SPME analysis. Cross-streaking experiments suggested that Antarctic bacteria might also synthesize non-volatile molecules able to enhance the anti-Burkholderia activity. The biosynthesis of such a mixture of mVOCs was very probably influenced by both the presence/absence of oxygen and the composition of media used to grow the Antarctic strains. The antimicrobial activity exhibited by Antarctic strains also appeared to be more related to their taxonomical position rather than to the sampling site. Different Bcc bacteria were differently sensitive to the 'Antarctic' mVOCs and this was apparently related neither to the taxonomical position of the different strains nor to their source. The genome sequence of three new Antarctic strains was determined revealing that only P. atlantica TB41 possesses some genes belonging to the nrps-pks cluster. The comparative genomic analysis performed on the genome of the four strains also revealed the presence of a few genes belonging to the core genome and involved in the secondary metabolites biosynthesis. Data obtained suggest that the antimicrobial activity exhibited by Antarctic bacteria might rely on a (complex) mixture of mVOCs whose relative concentration may vary depending on the growth conditions. Besides, it is also possible that the biosynthesis of these compounds might occur

  14. Green tea catechins and their metabolites in human skin before and after exposure to ultraviolet radiation☆☆☆★

    PubMed Central

    Clarke, Kayleigh A.; Dew, Tristan P.; Watson, Rachel E.B.; Farrar, Mark D.; Osman, Joanne E.; Nicolaou, Anna; Rhodes, Lesley E.; Williamson, Gary

    2016-01-01

    Dietary flavonoids may protect against sunburn inflammation in skin. Preliminary reports using less complete analysis suggest that certain catechins and their metabolites are found in skin biopsies and blister fluid after consumption of green tea; however, it is not known if they are affected by solar-simulated ultraviolet radiation (UVR) or whether conjugated forms, with consequently altered bioactivity, are present. The present study tested the hypothesis that UVR affects the catechin levels in the skin of healthy volunteers after consumption of green tea and how catechins in the plasma are related to their presence in skin tissue samples. In an open oral intervention study, 11 subjects consumed green tea and vitamin C supplements daily for 3 months. Presupplementation and postsupplementation plasma samples, suction blister fluid and skin biopsies were collected; the latter two samples were collected both before and after UVR. A sensitive high-performance liquid chromatography/mass spectrometric assay was used to measure the intact catechin metabolites, conjugates and free forms. Seven green tea catechins and their corresponding metabolites were identified postsupplementation in skin biopsies, 20 in blister fluid and 26 in plasma, with 15 green tea catechin metabolites present in both blister fluid and plasma. The valerolactone, O-methyl-M4-O-sulfate, a gut microbiota metabolite of catechins, was significantly increased 1.6-fold by UVR in blister fluid samples. In conclusion, there were some common catechin metabolites in the plasma and blister fluid, and the concentration was always higher in plasma. The results suggest that green tea catechins and metabolites are bioavailable in skin and provide a novel link between catechin metabolites derived from the skin and gut microbiota. PMID:26454512

  15. Petroleum Supply Monthly

    SciTech Connect

    1996-02-01

    The Petroleum Supply Monthly (PSM) is one of a family of four publications produced by the Petroleum Supply Division within the Energy Information Administration (EIA) reflecting different levels of data timeliness and completeness. The other publications are the Weekly Petroleum Status Report (WPSR), the Winter Fuels Report, and the Petroleum Supply Annual (PSA). Data presented in the PSM describe the supply and disposition of petroleum products in the United States and major U.S. geographic regions. The data series describe production, imports and exports, inter-Petroleum Administration for Defense (PAD) District movements, and inventories by the primary suppliers of petroleum products in the United States (50 States and the District of Columbia). The reporting universe includes those petroleum sectors in primary supply. Included are: petroleum refiners, motor gasoline blenders, operators of natural gas processing plants and fractionators, inter-PAD transporters, importers, and major inventory holders of petroleum products and crude oil. When aggregated, the data reported by these sectors approximately represent the consumption of petroleum products in the United States. Data presented in the PSM are divided into two sections: Summary Statistics and Detailed Statistics.

  16. Petroleum supply monthly

    SciTech Connect

    1995-10-01

    The Petroleum Supply Monthly (PSM) is one of a family of four publications produced by the Petroleum Supply Division within the Energy Information Administration (EIA) reflecting different levels of data timeliness and completeness. The other publications are the Weekly Petroleum Status Report (WPSR), the Winter Fuels Report, and the Petroleum Supply Annual (PSA). Data presented in the PSM describe the supply and disposition of petroleum products in the United States and major US geographic regions. The data series describe production, imports and exports, inter-Petroleum Administration for Defense (PAD) District movements, and inventories by the primary suppliers of petroleum products in the United States (50 States and the District of Columbia). The reporting universe includes those petroleum sectors in primary supply. Included are: petroleum refiners, motor gasoline blends, operators of natural gas processing plants and fractionators, inter-PAD transporters, importers, and major inventory holders of petroleum products and crude oil. When aggregated, the data reported by these sectors approximately represent the consumption of petroleum products in the United States.

  17. Cameroonian medicinal plants: a bioactivity versus ethnobotanical survey and chemotaxonomic classification

    PubMed Central

    2013-01-01

    Background In Cameroon herbs are traditionally used to meet health care needs and plans are on the way to integrate traditional medicine in the health care system, even though the plans have not been put into action yet. The country however has a rich biodiversity, with ~8,620 plant species, some of which are commonly used in the treatment of several microbial infections and a range of diseases (malaria, trypanosomiasis, leishmaniasis, diabetes and tuberculosis). Methods Our survey consisted in collecting published data from the literature sources, mainly from PhD theses in Cameroonian university libraries and also using the author queries in major natural product and medicinal chemistry journals. The collected data includes plant sources, uses of plant material in traditional medicine, plant families, region of collection of plant material, isolated metabolites and type (e.g. flavonoid, terpenoid, etc.), measured biological activities of isolated compounds, and any comments on significance of isolated metabolites on the chemotaxonomic classification of the plant species. This data was compiled on a excel sheet and analysed. Results In this study, a literature survey led to the collection of data on 2,700 secondary metabolites, which have been previously isolated or derived from Cameroonian medicinal plants. This represents distinct phytochemicals derived from 312 plant species belonging to 67 plant families. The plant species are investigated in terms of chemical composition with respect to the various plant families. A correlation between the known biological activities of isolated compounds and the ethnobotanical uses of the plants is also attempted. Insight into future direction for natural product search within the Cameroonian forest and Savanna is provided. Conclusions It can be verified that a phytochemical search of active secondary metabolites, which is inspired by knowledge from the ethnobotanical uses of medicinal plants could be very vital in a drug

  18. The genus Nonomuraea: A review of a rare actinomycete taxon for novel metabolites.

    PubMed

    Sungthong, Rungroch; Nakaew, Nareeluk

    2015-05-01

    The genus Nonomuraea is a rare actinomycete taxon with a long taxonomic history, while its generic description was recently emended. The genus is less known among the rare actinomycete genera as its taxonomic position was revised several times. It can be found in diverse ecological niches, while most of its member species were isolated from soil samples. However, new trends to discover the genus in other habitats are increasing. Generic abundance of the genus was found to be dependent on geographical changes. Novel sources together with selective and invented isolation techniques might increase a chance to explore the genus and its novel candidates. Interestingly, some of its members have been revealed as a valuable source of novel metabolites for medical and industrial purposes. Broad-range of potent bioactive compounds including antimicrobial, anticancer, and antipsychotic substances, broad-spectrum antibiotics and biocatalysts can be synthesized by the genus. In order to investigate biosynthetic pathways of the bioactive compounds and self-resistant mechanisms to these compounds, the links from genes to metabolites have yet been needed for further discovery and biotechnological development of the genus Nonomuraea.

  19. Defensive Metabolites from Antarctic Invertebrates: Does Energetic Content Interfere with Feeding Repellence?

    PubMed Central

    Núñez-Pons, Laura; Avila, Conxita

    2014-01-01

    Many bioactive products from benthic invertebrates mediating ecological interactions have proved to reduce predation, but their mechanisms of action, and their molecular identities, are usually unknown. It was suggested, yet scarcely investigated, that nutritional quality interferes with defensive metabolites. This means that antifeedants would be less effective when combined with energetically rich prey, and that higher amounts of defensive compounds would be needed for predator avoidance. We evaluated the effects of five types of repellents obtained from Antarctic invertebrates, in combination with diets of different energetic values. The compounds came from soft corals, ascidians and hexactinellid sponges; they included wax esters, alkaloids, a meroterpenoid, a steroid, and the recently described organic acid, glassponsine. Feeding repellency was tested through preference assays by preparing diets (alginate pearls) combining different energetic content and inorganic material. Experimental diets contained various concentrations of each repellent product, and were offered along with control compound-free pearls, to the Antarctic omnivore amphipod Cheirimedon femoratus. Meridianin alkaloids were the most active repellents, and wax esters were the least active when combined with foods of distinct energetic content. Our data show that levels of repellency vary for each compound, and that they perform differently when mixed with distinct assay foods. The natural products that interacted the most with energetic content were those occurring in nature at higher concentrations. The bioactivity of the remaining metabolites tested was found to depend on a threshold concentration, enough to elicit feeding repellence, independently from nutritional quality. PMID:24962273

  20. Continuing hunt for endophytic actinomycetes as a source of novel biologically active metabolites.

    PubMed

    Masand, Meeta; Jose, Polpass Arul; Menghani, Ekta; Jebakumar, Solomon Robinson David

    2015-12-01

    Drug-resistant pathogens and persistent agrochemicals mount the detrimental threats against human health and welfare. Exploitation of beneficial microorganisms and their metabolic inventions is most promising way to tackle these two problems. Since the successive discoveries of penicillin and streptomycin in 1940s, numerous biologically active metabolites have been discovered from different microorganisms, especially actinomycetes. In recent years, actinomycetes that inhabit unexplored environments have received significant attention due to their broad diversity and distinctive metabolic potential with medical, agricultural and industrial importance. In this scenario, endophytic actinomycetes that inhabit living tissues of plants are emerging as a potential source of novel bioactive compounds for the discovery of drug leads. Also, endophytic actinomycetes are considered as bio-inoculants to improve crop performance through organic farming practices. Further efforts on exploring the endophytic actinomycetes associated with the plants warrant the likelihood of discovering new taxa and their metabolites with novel chemical structures and biotechnological importance. This mini-review highlights the recent achievements in isolation of endophytic actinomycetes and an assortment of bioactive compounds.

  1. Nanotech: propensity in foods and bioactives.

    PubMed

    Kuan, Chiu-Yin; Yee-Fung, Wai; Yuen, Kah-Hay; Liong, Min-Tze

    2012-01-01

    Nanotechnology is seeing higher propensity in various industries, including food and bioactives. New nanomaterials are constantly being developed from both natural biodegradable polymers of plant and animal origins such as polysaccharides and derivatives, peptides and proteins, lipids and fats, and biocompatible synthetic biopolyester polymers such as polylactic acid (PLA), polyhydroxyalkonoates (PHA), and polycaprolactone (PCL). Applications in food industries include molecular synthesis of new functional food compounds, innovative food packaging, food safety, and security monitoring. The relevance of bioactives includes targeted delivery systems with improved bioavailability using nanostructure vehicles such as association colloids, lipid based nanoencapsulator, nanoemulsions, biopolymeric nanoparticles, nanolaminates, and nanofibers. The extensive use of nanotechnology has led to the need for parallel safety assessment and regulations to protect public health and adverse effects to the environment. This review covers the use of biopolymers in the production of nanomaterials and the propensity of nanotechnology in food and bioactives. The exposure routes of nanoparticles, safety challenges, and measures undertaken to ensure optimal benefits that outweigh detriments are also discussed.

  2. Transfersomes: self-optimizing carriers for bioactives.

    PubMed

    Rai, Kavita; Gupta, Yashwant; Jain, Anekant; Jain, Sanjay K

    2008-01-01

    The transdermal route of drug delivery has gained great interest of pharmaceutical research, as it circumvents number of problems associated with oral route of drug administration. The major barrier in transdermal delivery of drug is the skin intrinsic barrier, the stratum corneum, the outermost envelop of the skin that offers the principal hurdle for diffusion of hydrophilic ionizable bioactives. Recently, various strategies have been used to augment the transdermal delivery of bioactives. Mainly, they include iontophoresis, electrophoresis, sonophoresis, chemical permeation enhancers, microneedles, and vesicular system (liposomes, niosomes, elastic liposomes such as ethosomes and transfersomes). Among these strategies transferosomes appear promising. Transport of this vesicular system through skin and epithelial hurdle depends upon the flexibility of their membrane, which can be attained using appropriate ratio of surfactant. Transfersomes have shown immense potential in drug delivery across the skin. Recent success also demonstrates the potential of transfersome in vaccine, steroid, protein, and peptide delivery across the skin. It is also used for transporting genetic material and achieving transfection. This review highlights the various aspects of the transferosomes in the effective delivery of drug/bioactives across the skin.

  3. [Multiple emulsions; bioactive compounds and functional foods].

    PubMed

    Jiménez-Colmenero, Francisco

    2013-01-01

    The continued appearance of scientific evidence about the role of diet and/or its components in health and wellness, has favored the emergence of functional foods which currently constitute one of the chief factors driving the development of new products. The application of multiple emulsions opens new possibilities in the design and development of functional foods. Multiple emulsions can be used as an intermediate product (food ingredient) into technological strategies normally used in the optimization of the presence of bioactive compounds in healthy and functional foods. This paper presents a summary of the types, characteristics and formation of multiple emulsions, possible location of bioactive compounds and their potential application in the design and preparation of healthy and functional foods. Such applications are manifested particularly relevant in relation to quantitative and qualitative aspects of lipid material (reduced fat/calories and optimization of fatty acid profile), encapsulation of bioactive compounds mainly hydrophilic and sodium reduction. This strategy offers interesting possibilities regarding masking flavours and improving sensory characteristics of foods.

  4. Bioactive peptides of animal origin: a review.

    PubMed

    Bhat, Z F; Kumar, Sunil; Bhat, Hina Fayaz

    2015-09-01

    Bioactive peptides are specific protein fragments which, above and beyond their nutritional capabilities, have a positive impact on the body's function or condition which may ultimately influence health. Although, inactive within the sequence of the parent proteins, these peptides can be released during proteolysis or fermentation and play an important role in human health by affecting the digestive, endocrine, cardiovascular, immune and nervous systems. Several peptides that are released in vitro or in vivo from animal proteins have been attributed to different health effects, including antimicrobial properties, blood pressure-lowering (ACE inhibitory) effects, cholesterol-lowering ability, antithrombotic and antioxidant activities, opioid activities, enhancement of mineral absorption and/or bioavailability, cytomodulatory and immunomodulatory effects, antiobesity, and anti-genotoxic activity. Several functional foods based on the bioactivities of these peptides with scientifically evidenced health claims are already on the market or under development by food companies. Consumer's increasing interest in these products has given an impetus to the food industry and scientific sector who are continuously exploring the possibilities for the development of new functional products based on these peptides. In this review, we describe above stated properties of bioactive peptides of animal origin.

  5. Minimum information about a bioactive entity (MIABE).

    PubMed

    Orchard, Sandra; Al-Lazikani, Bissan; Bryant, Steve; Clark, Dominic; Calder, Elizabeth; Dix, Ian; Engkvist, Ola; Forster, Mark; Gaulton, Anna; Gilson, Michael; Glen, Robert; Grigorov, Martin; Hammond-Kosack, Kim; Harland, Lee; Hopkins, Andrew; Larminie, Christopher; Lynch, Nick; Mann, Romeena K; Murray-Rust, Peter; Lo Piparo, Elena; Southan, Christopher; Steinbeck, Christoph; Wishart, David; Hermjakob, Henning; Overington, John; Thornton, Janet

    2011-08-31

    Bioactive molecules such as drugs, pesticides and food additives are produced in large numbers by many commercial and academic groups around the world. Enormous quantities of data are generated on the biological properties and quality of these molecules. Access to such data - both on licensed and commercially available compounds, and also on those that fail during development - is crucial for understanding how improved molecules could be developed. For example, computational analysis of aggregated data on molecules that are investigated in drug discovery programmes has led to a greater understanding of the properties of successful drugs. However, the information required to perform these analyses is rarely published, and when it is made available it is often missing crucial data or is in a format that is inappropriate for efficient data-mining. Here, we propose a solution: the definition of reporting guidelines for bioactive entities - the Minimum Information About a Bioactive Entity (MIABE) - which has been developed by representatives of pharmaceutical companies, data resource providers and academic groups.

  6. Nutrients and bioactive compounds content of Baillonella toxisperma, Trichoscypha abut and Pentaclethra macrophylla from Cameroon

    PubMed Central

    Fungo, Robert; Muyonga, John; Kaaya, Archileo; Okia, Clement; Tieguhong, Juius C; Baidu-Forson, Jojo J

    2015-01-01

    Baillonella toxisperma, Pentaclethra macrophylla and Trichoscypha abut are important foods for communities living around forests in Cameroon. Information on the nutritional value and bioactive content of these foods is required to establish their contribution to the nutrition and health of the communities. Samples of the three foods were obtained from four villages in east and three villages in south Cameroon. The foods were analyzed for proximate composition, minerals and bioactive content using standard chemical analysis methods. T. abut was found to be an excellent source of bioactive compounds; flavonoids (306 mg/100 g), polyphenols (947 mg/100 g), proanthocyanins (61.2 mg/100 g), vitamin C (80.05 mg/100 g), and total oxalates (0.6 mg/100 g). P. macrophylla was found to be a rich source of total fat (38.71%), protein (15.82%) and total fiber (17.10%) and some bioactive compounds; vitamin E (19.4 mg/100 g) and proanthocyanins (65.0 mg/100 g). B. toxisperma, was found to have high content of carbohydrates (89.6%), potassium (27.5 mg/100 g) and calcium (37.5 mg/100 g). Flavonoids, polyphenols, vitamins C and E are the main bioactive compounds in these forest foods. The daily consumption of some of these fruits may coffer protection against some ailments and oxidative stress. Approximately 200 g of either B. toxisperma or P. macrophylla, can supply 100% iron and zinc RDAs for children aged 1–3 years, while 300 g of the two forest foods can supply about 85% iron and zinc RDAs for non-pregnant non-lactating women. The three foods provide 100% daily vitamins C and E requirements for both adults and children. The results of this study show that Baillonella toxisperma, Pentaclethra macrophylla and Trichoscypha abut can considerably contribute towards the human nutrient requirements. These forest foods also contain substantial levels of health promoting phytochemicals notably flavonoids, polyphenols, vitamins C and E. These foods therefore have

  7. Perioperative supply chain management.

    PubMed

    Feistritzer, N R; Keck, B R

    2000-09-01

    Faced with declining revenues and increasing operating expenses, hospitals are evaluating numerous mechanisms designed to reduce costs while simultaneously maintaining quality care. Many facilities have targeted initial cost reduction efforts in the reduction of labor expenses. Once labor expenses have been "right sized," facilities have continued to focus on service delivery improvements by the optimization of the "supply chain" process. This report presents a case study of the efforts of Vanderbilt University Medical Center in the redesign of its supply chain management process in the department of Perioperative Services. Utilizing a multidisciplinary project management structure, 3 work teams were established to complete the redesign process. To date, the project has reduced costs by $2.3 million and enhanced quality patient care by enhancing the delivery of appropriate clinical supplies during the perioperative experience.

  8. Interfacial design for a bioactive composite

    NASA Astrophysics Data System (ADS)

    MacDonald, Jeanne Marie

    2001-07-01

    The objective for this project is to develop a bioactive dental composite showing enhanced mechanical properties through the development of a designed interface and to experimentally evaluate and model these interfaces. The efficiency of the surface modifications is analyzed as it relates to the bioactivity of the filler, a sol-gel derived bioglass (60 mol% SiO2, 36 mol% CaO, 4 mol% P2O5), and to the enhancement of mechanical properties. Among the filler surfaces studied are a methacryloxypropyl triethoxysilane (MAMTES) coupling agent combined with a methyl triethoxysilane (MTES) coupling agent, and a grafted sulfonated polysulfone (SPSF) with different degrees of sulfonation. The resin system chosen is based on 2,2'-bis-(4-methacryloylethoxyphenyl) propane using triethylene glycol dimethacrylate as a diluent to improve processability. To help offset the polymerization shrinkage, nadic methyl anhydride is added Hydrolysis of this anhydride provides a mechanism for offsetting shrinkage. A dependence on the ratio of methacrylate functionalized coupling agent on the reinforcing capabilities of the filler was discovered. This dependence also translates into the stabilization of the interface after a solution soak. Enhanced properties at mid-level ratios of MAMTES to MTES show the importance of the coupling system and not just the presence of a coupling agent to the enhancement of a composite. Evidence of the bioactivity of the composites is seen in a comparison of composite samples after submersion in either pure water or a salt solution. Additional weight gain could be the result of the sorption of HCA forming ions (calcium and phosphate) from the salt solution. The lower weight gain rate for the silanated composite supports a shielding effect of the coupling agent to the bioactivity of the filler. Sulfonated polysulfones were successfully prepared and grafted onto the BioglassRTM filler. A dependence on the level of sulfonation on the reinforcing capabilities of the

  9. Putting microbes to work: dairy fermentation, cell factories and bioactive peptides. Part II: bioactive peptide functions.

    PubMed

    Hayes, Maria; Stanton, Catherine; Fitzgerald, Gerald F; Ross, R Paul

    2007-04-01

    A variety of milk-derived biologically active peptides have been shown to exert both functional and physiological roles in vitro and in vivo, and because of this are of particular interest for food science and nutrition applications. Biological activities associated with such peptides include immunomodulatory, antibacterial, anti-hypertensive and opioid-like properties. Milk proteins are recognized as a primary source of bioactive peptides, which can be encrypted within the amino acid sequence of dairy proteins, requiring proteolysis for release and activation. Fermentation of milk proteins using the proteolytic systems of lactic acid bacteria is an attractive approach for generation of functional foods enriched in bioactive peptides given the low cost and positive nutritional image associated with fermented milk drinks and yoghurt. In Part II of this review, we focus on examples of milk-derived bioactive peptides and their associated health benefits, to illustrate the potential of this area for the design and improvement of future functional foods.

  10. Coal supply for California

    NASA Technical Reports Server (NTRS)

    Yancik, J. J.

    1978-01-01

    The potential sources and qualities of coals available for major utility and industrial consumers in California are examined and analyzed with respect to those factors that would affect the reliability of supplies. Other considerations, such as the requirements and assurances needed by the coal producers to enter into long-term contracts and dedicate large reserves of coal to these contracts are also discussed. Present and potential future mining contraints on coal mine operators are identified and analyzed with respect to their effect on availability of supply.

  11. Isolation of Bioactive Compounds from Sunflower Leaves (Helianthus annuus L.) Extracted with Supercritical Carbon Dioxide.

    PubMed

    El Marsni, Zouhir; Torres, Ascension; Varela, Rosa M; Molinillo, José M G; Casas, Lourdes; Mantell, Casimiro; Martinez de la Ossa, Enrique J; Macias, Francisco A

    2015-07-22

    The work described herein is a continuation of our initial studies on the supercritical fluid extraction (SFE) with CO2 of bioactive substances from Helianthus annuus L. var. Arianna. The selected SFE extract showed high activity in the wheat coleoptile bioassay, in Petri dish phytotoxicity bioassays, and in the hydroponic culture of tomato seeds. Chromatographic fractionations of the extracts and a spectroscopic analysis of the isolated compounds showed 52 substances belonging to 10 different chemical classes, which were mainly sesquiterpene lactones, diterpenes, and flavonoids. Heliannuol M (31), helivypolides K and L (36, 37), and helieudesmanolide B (38) are described for the first time in the literature. Metabolites have been tested in the etiolated wheat coleoptile bioassay with good results in a noteworthy effect on germination. The most active compounds were also tested on tomato seeds, heliannuol A (30) and leptocarpin (45) being the most active, with values similar to those of the commercial herbicide.

  12. Biodiversity, bioactive natural products and biotechnological potential of plant-associated endophytic actinobacteria.

    PubMed

    Qin, Sheng; Xing, Ke; Jiang, Ji-Hong; Xu, Li-Hua; Li, Wen-Jun

    2011-02-01

    Endophytic actinobacteria, which exist in the inner tissues of living plants, have attracted increasing attention among taxonomists, ecologists, agronomists, chemists and evolutionary biologists. Numerous studies have indicated that these prolific actinobacteria appear to have a capacity to produce an impressive array of secondary metabolites exhibiting a wide variety of biological activity, such as antibiotics, antitumor and anti-infection agents, plant growth promoters and enzymes, and may contribute to their host plants by promoting growth and enhancing their ability of withstanding the environmental stresses. These microorganisms may represent an underexplored reservoir of novel species of potential interest in the discovery of novel lead compounds and for exploitation in pharmaceutical, agriculture and industry. This review focuses on new findings in the isolation methods, bio- and chemical diversity of endophytic actinobacteria and reveals the potential biotechnological application. The facing problems and strategies for biodiversity research and bioactive natural products producing are also discussed.

  13. The Use of Endophytes to Obtain Bioactive Compounds and Their Application in Biotransformation Process

    PubMed Central

    Pimentel, Mariana Recco; Molina, Gustavo; Dionísio, Ana Paula; Maróstica Junior, Mário Roberto; Pastore, Gláucia Maria

    2011-01-01

    Endophytes are microorganisms that reside asymptomatically in the tissues of higher plants and are a promising source of novel organic natural metabolites exhibiting a variety of biological activities. The laboratory of Bioaromas (Unicamp, Brazil) develops research in biotransformation processes and functional evaluation of natural products. With the intent to provide subsidies for studies on endophytic microbes related to areas cited before, this paper focuses particularly on the role of endophytes on the production of anticancer, antimicrobial, and antioxidant compounds and includes examples that illustrate their potential for human use. It also describes biotransformation as an auspicious method to obtain novel bioactive compounds from microbes. Biotransformation allows the production of regio- and stereoselective compounds under mild conditions that can be labeled as “natural,” as discussed in this paper. PMID:21350663

  14. Humudifucol and Bioactive Prenylated Polyphenols from Hops (Humulus lupulus cv. "Cascade").

    PubMed

    Forino, Martino; Pace, Simona; Chianese, Giuseppina; Santagostini, Laura; Werner, Markus; Weinigel, Christina; Rummler, Silke; Fico, Gelsomina; Werz, Oliver; Taglialatela-Scafati, Orazio

    2016-03-25

    Humulus lupulus (hop plant) has long been used in traditional medicine as a sedative and antimicrobial agent. More recently, attention has been devoted to the phytoestrogenic activity of the plant extracts as well as to the anti-inflammatory and chemopreventive properties of the prenylated chalcones present. In this study, an Italian sample of H. lupulus cv. "Cascade" has been investigated and three new compounds [4-hydroxycolupulone (6), humudifucol (7) and cascadone (8)] have been purified and identified by means of NMR spectroscopy along with four known metabolites. Notably, humudifucol (7) is the first prenylated dimeric phlorotannin discovered in nature. Because structurally related phloroglucinols from natural sources were found previously to inhibit microsomal prostaglandin E2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO), the isolated compounds were evaluated for their bioactivity against these pro-inflammatory target proteins. The prenylated chalcone xanthohumol inhibited both enzymes at low μM concentrations.

  15. Bioactive Compounds Produced by Strains of Penicillium and Talaromyces of Marine Origin

    PubMed Central

    Nicoletti, Rosario; Trincone, Antonio

    2016-01-01

    In recent years, the search for novel natural compounds with bioactive properties has received a remarkable boost in view of their possible pharmaceutical exploitation. In this respect the sea is entitled to hold a prominent place, considering the potential of the manifold animals and plants interacting in this ecological context, which becomes even greater when their associated microbes are considered for bioprospecting. This is the case particularly of fungi, which have only recently started to be considered for their fundamental contribution to the biosynthetic potential of other more valued marine organisms. Also in this regard, strains of species which were previously considered typical terrestrial fungi, such as Penicillium and Talaromyces, disclose foreground relevance. This paper offers an overview of data published over the past 25 years concerning the production and biological activities of secondary metabolites of marine strains belonging to these genera, and their relevance as prospective drugs. PMID:26901206

  16. Isolation, Identification, and Bioactivity of Monoterpenoids and Sesquiterpenoids from the Mycelia of Edible Mushroom Pleurotus cornucopiae.

    PubMed

    Wang, Shaojuan; Bao, Li; Zhao, Feng; Wang, Quanxin; Li, Shaojie; Ren, Jinwei; Li, Li; Wen, Huaan; Guo, Liangdong; Liu, Hongwei

    2013-05-29

    Edible mushroom is a profilic source of bioactive metabolites for the development of drugs and nutraceuticals. In this work, four new monoterpenoids (1-4) and one new sesquiterpenoid (6) were isolated from the mycelia of edible mushroom Pleurotus cornucopiae fermented on rice. Their structures were established by nuclear magnetic resonance, mass spectrometry, and circular dichroism (CD) data analysis. Compound 1 possesses an unusual spiro[benzofuran-3,2'-oxiran] skeleton. The absolute configuration of the 6,7-diol moieties in compounds 1, 2, and 6 was assigned using the in situ dimolybdenum CD method. Compounds 1-5, 7, and 8 showed moderate inhibitory activity against nitric oxide production in lipopolysaccaride-activated macrophages, with IC50 values in the range of 60-90 μM. Compounds 6 and 7 also exhibited slight cytotoxicity against HeLa and HepG2 cells.

  17. Choline Metabolites: Gene by Diet Interactions

    PubMed Central

    Smallwood, Tangi; Allayee, Hooman; Bennett, Brian J.

    2015-01-01

    Purpose of review This review highlights recent advances in our understanding of the interactions between genetic polymorphisms in genes that metabolize choline and the dietary requirements of choline and how these interactions relate to human health and disease. Recent findings The importance of choline as an essential nutrient has been well established but our appreciation of the interaction between our underlying genetic architecture and dietary choline requirements is only beginning. It has been shown in both human and animal studies that choline deficiencies contribute to diseases such as non-alcoholic fatty liver disease and various neurodegenerative diseases. An adequate supply of dietary choline is important for optimum development, highlighted by the increased maternal requirements during fetal development and in breast-fed infants. We discuss recent studies investigating variants in PEMT and MTHFR1 that are associated with a variety of birth defects. In addition to genetic interactions, we discuss several recent studies that uncover changes in fetal global methylation patterns in response to maternal dietary choline intake that result in changes in gene expression in the offspring. In contrast to the developmental role of adequate choline, there is now an appreciation of the role choline has in cardiovascular disease through the gut microbiota-mediated metabolite trimethylamine N-oxide. This pathway highlights some of our understanding of how the microbiome affects nutrient processing and bioavailability. Finally, in order to better characterize the genetic architecture regulating choline requirements, we discuss recent results focused on identifying polymorphisms that regulate choline and its derivative products. Summary Here we discuss recent studies that have advanced our understanding of how specific alleles in key choline metabolism genes are related to dietary choline requirements and human disease. PMID:26655287

  18. Characterization of proflavine metabolites in rainbow trout.

    PubMed

    Yu, Z; Hayton, W L; Chan, K K

    1997-04-01

    Proflavine (3,6-diaminoacridine) has potential for use as an antiinfective in fish, and its metabolism by rainbow trout was therefore studied. Fourteen hours after intraarterial bolus administration of 10 mg/kg of proflavine, three metabolites were found in liver and bile, and one metabolite was found in plasma using reversed-phase HPLC with UV detection at 262 nm. Treatment with hydrochloric acid converted the three metabolites to proflavine, which suggested that the metabolites were proflavine conjugates. Treatment with beta-glucuronidase and saccharic acid 1,4-lactone, a specific beta-glucuronidase inhibitor, revealed that two metabolites were proflavine glucuronides. For determination of UV-VIS absorption and mass spectra, HPLC-purified metabolites were isolated from liver. Data from these experiments suggested that the proflavine metabolites were 3-N-glucuronosyl proflavine (PG), 3-N-glucuronosyl,6-N-acetyl proflavine (APG), and 3-N-acetylproflavine (AP). The identities of the metabolites were verified by chemical synthesis. When synthetic PG and AP were compared with the two metabolites isolated from trout, they had the same molecular weight as determined by matrix-assisted, laser desorption ionization, time-of-flight MS. In addition, they coeluted on HPLC under different mobile phase conditions. Finally, the in vitro incubation with liver subcellular preparations confirmed this characterization and provided the evidence that APG can be formed by glucuronidation of AP or acetylation of PG.

  19. Supply-Chain Optimization Template

    NASA Technical Reports Server (NTRS)

    Quiett, William F.; Sealing, Scott L.

    2009-01-01

    The Supply-Chain Optimization Template (SCOT) is an instructional guide for identifying, evaluating, and optimizing (including re-engineering) aerospace- oriented supply chains. The SCOT was derived from the Supply Chain Council s Supply-Chain Operations Reference (SCC SCOR) Model, which is more generic and more oriented toward achieving a competitive advantage in business.

  20. Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer.

    PubMed

    Miller, Jessica A; Lang, Julie E; Ley, Michele; Nagle, Ray; Hsu, Chiu-Hsieh; Thompson, Patricia A; Cordova, Catherine; Waer, Amy; Chow, H-H Sherry

    2013-06-01

    Limonene is a bioactive food component found in citrus peel oil that has shown chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open-label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited 43 women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for two to six weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean = 41.3 μg/g tissue), whereas the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P = 0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase-3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, insulin-like growth factor binding protein-3 (IGFBP-3), and interleukin-6 (IL-6) levels were observed following limonene intervention. There was a small but statistically significant postintervention increase in insulin-like growth factor I (IGF-I) levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell-cycle arrest and reduced cell proliferation. Furthermore, placebo-controlled clinical trials and translational research are warranted to establish limonene's role for breast cancer prevention or treatment.

  1. Metabolite induction via microorganism co-culture: a potential way to enhance chemical diversity for drug discovery.

    PubMed

    Bertrand, Samuel; Bohni, Nadine; Schnee, Sylvain; Schumpp, Olivier; Gindro, Katia; Wolfender, Jean-Luc

    2014-11-01

    Microorganisms have a long track record as important sources of novel bioactive natural products, particularly in the field of drug discovery. While microbes have been shown to biosynthesize a wide array of molecules, recent advances in genome sequencing have revealed that such organisms have the potential to yield even more structurally diverse secondary metabolites. Thus, many microbial gene clusters may be silent under standard laboratory growth conditions. In the last ten years, several methods have been developed to aid in the activation of these cryptic biosynthetic pathways. In addition to the techniques that demand prior knowledge of the genome sequences of the studied microorganisms, several genome sequence-independent tools have been developed. One of these approaches is microorganism co-culture, involving the cultivation of two or more microorganisms in the same confined environment. Microorganism co-culture is inspired by the natural microbe communities that are omnipresent in nature. Within these communities, microbes interact through signaling or defense molecules. Such compounds, produced dynamically, are of potential interest as new leads for drug discovery. Microorganism co-culture can be achieved in either solid or liquid media and has recently been used increasingly extensively to study natural interactions and discover new bioactive metabolites. Because of the complexity of microbial extracts, advanced analytical methods (e.g., mass spectrometry methods and metabolomics) are key for the successful detection and identification of co-culture-induced metabolites. This review focuses on co-culture studies that aim to increase the diversity of metabolites obtained from microbes. The various strategies are summarized with a special emphasis on the multiple methods of performing co-culture experiments. The analytical approaches for studying these interaction phenomena are discussed, and the chemical diversity and biological activity observed among the

  2. Lightweight Regulated Power Supply

    NASA Technical Reports Server (NTRS)

    Mclyman, C. W.

    1985-01-01

    Power-supply circuit regulates output voltage by adjusting frequency of chopper circuit according to variations. Currently installed in battery charger for electric wheelchair, circuit is well suited to other uses in which light weight is important - for example, in portable computers, radios, and test instruments.

  3. Teleconnected food supply shocks

    NASA Astrophysics Data System (ADS)

    Bren d'Amour, Christopher; Wenz, Leonie; Kalkuhl, Matthias; Steckel, Jan Christoph; Creutzig, Felix

    2016-03-01

    The 2008-2010 food crisis might have been a harbinger of fundamental climate-induced food crises with geopolitical implications. Heat-wave-induced yield losses in Russia and resulting export restrictions led to increases in market prices for wheat across the Middle East, likely contributing to the Arab Spring. With ongoing climate change, temperatures and temperature variability will rise, leading to higher uncertainty in yields for major nutritional crops. Here we investigate which countries are most vulnerable to teleconnected supply-shocks, i.e. where diets strongly rely on the import of wheat, maize, or rice, and where a large share of the population is living in poverty. We find that the Middle East is most sensitive to teleconnected supply shocks in wheat, Central America to supply shocks in maize, and Western Africa to supply shocks in rice. Weighing with poverty levels, Sub-Saharan Africa is most affected. Altogether, a simultaneous 10% reduction in exports of wheat, rice, and maize would reduce caloric intake of 55 million people living in poverty by about 5%. Export bans in major producing regions would put up to 200 million people below the poverty line at risk, 90% of which live in Sub-Saharan Africa. Our results suggest that a region-specific combination of national increases in agricultural productivity and diversification of trade partners and diets can effectively decrease future food security risks.

  4. Exploration Supply Chain Simulation

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Exploration Supply Chain Simulation project was chartered by the NASA Exploration Systems Mission Directorate to develop a software tool, with proper data, to quantitatively analyze supply chains for future program planning. This tool is a discrete-event simulation that uses the basic supply chain concepts of planning, sourcing, making, delivering, and returning. This supply chain perspective is combined with other discrete or continuous simulation factors. Discrete resource events (such as launch or delivery reviews) are represented as organizational functional units. Continuous resources (such as civil service or contractor program functions) are defined as enabling functional units. Concepts of fixed and variable costs are included in the model to allow the discrete events to interact with cost calculations. The definition file is intrinsic to the model, but a blank start can be initiated at any time. The current definition file is an Orion Ares I crew launch vehicle. Parameters stretch from Kennedy Space Center across and into other program entities (Michaud Assembly Facility, Aliant Techsystems, Stennis Space Center, Johnson Space Center, etc.) though these will only gain detail as the file continues to evolve. The Orion Ares I file definition in the tool continues to evolve, and analysis from this tool is expected in 2008. This is the first application of such business-driven modeling to a NASA/government-- aerospace contractor endeavor.

  5. Supply chain management.

    PubMed

    Palevich, R F

    1999-02-01

    This article describes how Do It Best Corp. has used technology to improve its supply chain management. Among other topics it discusses the company's use of electronic data interchange, the Internet, electronic forecasting, and warehouse management systems to gain substantial savings and increase its competitiveness.

  6. Maintenance and supply options

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The object of the Maintenance and Supply Option was to develop a high level operational philosophy related to maintenance and supply operations and incorporate these concepts into the Lunar Base Study. Specific products to be generated during this task were three trade studies and a conceptual design of the Logistic Supply Module. The crew size study was performed to evaluate crew sizes from the baseline size of four to a crew size of eight and determine the preferred crew size. The second trade study was to determine the impact of extending surface stay times and recommend a preferred duration of stay time as a function of crew, consumables, and equipment support capabilities. The third trade study was an evaluation of packaging and storage methods to determine the preferred logistics approach to support the lunar base. A modified scenario was developed and served as the basis of the individual trade studies. Assumptions and guidelines were also developed from experience with Apollo programs, Space Shuttle operations, and Space Station studies. With this information, the trade studies were performed and a conceptual design for the Logistic Supply Module was developed.

  7. Supply and Demand

    MedlinePlus

    ... breast to continue producing an adequate supply of milk. In fact, the protein contained in the residual milk remaining in the ... or fluid) content, and the composition of your milk will change. Over the next week or so, the protein content will decline and the fat and lactose ...

  8. Baby supplies you need

    MedlinePlus

    ... Newborn care - baby supplies References Carlo WA. The newborn infant. In: Kliegman RM, Stanton BF, St Geme JW, ... A.M. Editorial team. Related MedlinePlus Health Topics Infant and Newborn Care Browse the Encyclopedia A.D.A.M., ...

  9. Supply chain quality.

    PubMed

    Feary, Simon

    2009-01-01

    As the development of complex manufacturing models and virtual companies become more prevalent in today's growing global markets, it is increasingly important to support the relationships between manufacturer and supplier. Utilising these relationships will ensure that supply chains operate more effectively and reduce costs, risks and time-to-market time frames, whilst maintaining product quality.

  10. Liquid Chromatography-Mass Spectrometry-Based Rapid Secondary-Metabolite Profiling of Marine Pseudoalteromonas sp. M2.

    PubMed

    Kim, Woo Jung; Kim, Young Ok; Kim, Jin Hee; Nam, Bo-Hye; Kim, Dong-Gyun; An, Cheul Min; Lee, Jun Sik; Kim, Pan Soo; Lee, Hye Min; Oh, Joa-Sup; Lee, Jong Suk

    2016-01-20

    The ocean is a rich resource of flora, fauna, and food. A wild-type bacterial strain showing confluent growth on marine agar with antibacterial activity was isolated from marine water, identified using 16S rDNA sequence analysis as Pseudoalteromonas sp., and designated as strain M2. This strain was found to produce various secondary metabolites including quinolone alkaloids. Using high-resolution mass spectrometry (MS) and nuclear magnetic resonance (NMR) analysis, we identified nine secondary metabolites of 4-hydroxy-2-alkylquinoline (pseudane-III, IV, V, VI, VII, VIII, IX, X, and XI). Additionally, this strain produced two novel, closely related compounds, 2-isopentylqunoline-4-one and 2-(2,3-dimetylbutyl)qunoline-4-(1H)-one, which have not been previously reported from marine bacteria. From the metabolites produced by Pseudoalteromonas sp. M2, 2-(2,3-dimethylbutyl)quinolin-4-one, pseudane-VI, and pseudane-VII inhibited melanin synthesis in Melan-A cells by 23.0%, 28.2%, and 42.7%, respectively, wherein pseudane-VII showed the highest inhibition at 8 µg/mL. The results of this study suggest that liquid chromatography (LC)-MS/MS-based metabolite screening effectively improves the efficiency of novel metabolite discovery. Additionally, these compounds are promising candidates for further bioactivity development.

  11. Liquid Chromatography-Mass Spectrometry-Based Rapid Secondary-Metabolite Profiling of Marine Pseudoalteromonas sp. M2

    PubMed Central

    Kim, Woo Jung; Kim, Young Ok; Kim, Jin Hee; Nam, Bo-Hye; Kim, Dong-Gyun; An, Cheul Min; Lee, Jun Sik; Kim, Pan Soo; Lee, Hye Min; Oh, Joa-Sup; Lee, Jong Suk

    2016-01-01

    The ocean is a rich resource of flora, fauna, and food. A wild-type bacterial strain showing confluent growth on marine agar with antibacterial activity was isolated from marine water, identified using 16S rDNA sequence analysis as Pseudoalteromonas sp., and designated as strain M2. This strain was found to produce various secondary metabolites including quinolone alkaloids. Using high-resolution mass spectrometry (MS) and nuclear magnetic resonance (NMR) analysis, we identified nine secondary metabolites of 4-hydroxy-2-alkylquinoline (pseudane-III, IV, V, VI, VII, VIII, IX, X, and XI). Additionally, this strain produced two novel, closely related compounds, 2-isopentylqunoline-4-one and 2-(2,3-dimetylbutyl)qunoline-4-(1H)-one, which have not been previously reported from marine bacteria. From the metabolites produced by Pseudoalteromonas sp. M2, 2-(2,3-dimethylbutyl)quinolin-4-one, pseudane-VI, and pseudane-VII inhibited melanin synthesis in Melan-A cells by 23.0%, 28.2%, and 42.7%, respectively, wherein pseudane-VII showed the highest inhibition at 8 µg/mL. The results of this study suggest that liquid chromatography (LC)-MS/MS-based metabolite screening effectively improves the efficiency of novel metabolite discovery. Additionally, these compounds are promising candidates for further bioactivity development. PMID:26805856

  12. Free and total urinary phthalate metabolite concentrations among pregnant women from the Healthy Baby Cohort (HBC), China.

    PubMed

    Zhu, Yingshuang; Wan, Yanjian; Li, Yuanyuan; Zhang, Bin; Zhou, Aifen; Cai, Zongwei; Qian, Zhengmin; Zhang, Chuncao; Huo, Wenqian; Huang, Kai; Hu, Jie; Cheng, Lu; Chang, Huailong; Huang, Zheng; Xu, Bing; Xia, Wei; Xu, Shunqing

    2016-03-01

    Total urinary phthalate metabolites (the free plus glucuronidated forms) have been frequently measured in the general population. However, data are limited on the free forms which may be more bioactive, especially for sensitive population such as pregnant women. Here the data gap was addressed by measuring concentrations of free and total forms of six phthalate metabolites in 293 urine samples from pregnant women at delivery, who were randomly selected from the prospective Healthy Baby Cohort (HBC), China. We observed detectable concentrations of the total amount of phthalate metabolites in all urine samples. The geometric mean (GM) urinary concentrations of free and total mono-butyl phthalate (MBP) (5.20, 54.49ng/mL) were the highest, followed by mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) (4.52, 7.27ng/mL). For most of phthalate metabolites, urinary concentrations were significantly higher in women who were nulliparous. Significantly higher concentrations of mono-ethyl phthalate (MEP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) were found in women who had higher educational level. To our knowledge, this is the first study to report the free and total forms of phthalate metabolites among pregnant women in China. The results suggest that exposure characteristics may be related to parity and education.

  13. Secondary metabolite profiling of Curcuma species grown at different locations using GC/TOF and UPLC/Q-TOF MS.

    PubMed

    Lee, Jueun; Jung, Youngae; Shin, Jeoung-Hwa; Kim, Ho Kyoung; Moon, Byeong Cheol; Ryu, Do Hyun; Hwang, Geum-Sook

    2014-07-04

    Curcuma, a genus of rhizomatous herbaceous species, has been used as a spice, traditional medicine, and natural dye. In this study, the metabolite profile of Curcuma extracts was determined using gas chromatography-time of flight mass spectrometry (GC/TOF MS) and ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) to characterize differences between Curcuma aromatica and Curcuma longa grown on the Jeju-do or Jin-do islands, South Korea. Previous studies have performed primary metabolite profiling of Curcuma species grown in different regions using NMR-based metabolomics. This study focused on profiling of secondary metabolites from the hexane extract of Curcuma species. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) plots showed significant differences between the C. aromatica and C. longa metabolite profiles, whereas geographical location had little effect. A t-test was performed to identify statistically significant metabolites, such as terpenoids. Additionally, targeted profiling using UPLC/Q-TOF MS showed that the concentration of curcuminoids differed depending on the plant origin. Based on these results, a combination of GC- and LC-MS allowed us to analyze curcuminoids and terpenoids, the typical bioactive compounds of Curcuma, which can be used to discriminate Curcuma samples according to species or geographical origin.

  14. Microbial production of isoquinoline alkaloids as plant secondary metabolites based on metabolic engineering research

    PubMed Central

    SATO, Fumihiko; KUMAGAI, Hidehiko

    2013-01-01

    Plants produce a variety of secondary metabolites that possess strong physiological activities. Unfortunately, however, their production can suffer from a variety of serious problems, including low levels of productivity and heterogeneous quality, as well as difficulty in raw material supply. In contrast, microorganisms can be used to produce their primary and some of their secondary metabolites in a controlled environment, thus assuring high levels of efficiency and uniform quality. In an attempt to overcome the problems associated with secondary metabolite production in plants, we developed a microbial platform for the production of plant isoquinoline alkaloids involving the unification of the microbial and plant metabolic pathways into a single system. The potential applications of this system have also been discussed. PMID:23666088

  15. Chemical characterization of bioactive compounds from the endophytic fungus Diaporthe helianthi isolated from Luehea divaricata

    PubMed Central

    Specian, Vânia; Sarragiotto, Maria Helena; Pamphile, João Alencar; Clemente, Edmar

    2012-01-01

    Endophytic microorganisms, defined as fungi or bacteria that colonize the interior of plants without causing any immediate negative effects or damages, have reciprocal relationships with host plants. In some cases their presence is beneficial to the host due to the synthesis of bioactive compounds, among which several alcohols, esters, ketones and others that may react with other compounds and may be lethal to pathogenic microorganisms. Diaporthe helianthi (Phomopsis helianthi in its anamorphic phase) is available worldwide, especially in Europe, Asia and America. Isolated in Europe as an agent of the sunflower stem cancer, it has also been endophytically isolated from tropical and temperate plants. A D. helianthi strain isolated from Luehea divaricata has been employed in current research. An investigation of the secondary metabolite from D. helianthi by CC and NMR of 1H and 13C yielded the separation of 10 fractions and the identification of the phenolic compound 2(-4 hydroxyphenyl)-ethanol (Tyrosol). Its antimicrobial reaction was tested and the ensuing antagonistic effects on the human pathogenic bacteria Enterococcus hirae, Escherichia coli, Micrococcus luteus, Salmonella typhi, Staphylococcus aureus, phytopathogenic Xanthomonas asc. phaseoli and phytopathogenic fungi were demonstrated. Results show that bioactive compounds and Tyrosol produced by D. helianthi have a biotechnological potential. PMID:24031942

  16. Bioactive compounds from marine mussels and their effects on human health.

    PubMed

    Grienke, Ulrike; Silke, Joe; Tasdemir, Deniz

    2014-01-01

    The consumption of marine mussels as popular seafood has increased steadily over the past decades. Awareness of mussel derived molecules, that promote health, has contributed to extensive research efforts in that field. This review highlights the bioactive potential of mussel components from species of the genus Mytilus (e.g. M. edulis) and Perna (e.g. P. canaliculus). In particular, the bioactivity related to three major chemical classes of mussel primary metabolites, i.e. proteins, lipids, and carbohydrates, is evaluated. Within the group of proteins the focus is mainly on mussel peptides e.g. those obtained by bio-transformation processes, such as fermentation. In addition, mussel lipids, comprising polyunsaturated fatty acids (PUFAs), are discussed as compounds that are well known for prevention and treatment of rheumatoid arthritis (RA). Within the third group of carbohydrates, mussel polysaccharides are investigated. Furthermore, the importance of monitoring the mussel as food material in respect to contaminations with natural toxins produced by microalgae is discussed.

  17. Picocyanobacteria from a clade of marine Cyanobium revealed bioactive potential against microalgae, bacteria, and marine invertebrates.

    PubMed

    Costa, Maria Sofia; Costa, Margarida; Ramos, Vítor; Leão, Pedro N; Barreiro, Aldo; Vasconcelos, Vítor; Martins, Rosário

    2015-01-01

    The production of bioactive compounds either toxic or with pharmacological applications by cyanobacteria is well established. However, picoplanktonic forms within this group of organisms have rarely been studied in this context. In this study, the toxicological potential of picocyanobacteria from a clade of marine Cyanobium strains isolated from the Portuguese coast was examined using different biological models. First, strains were identified by applying morphological and molecular approaches and cultured under lab conditions. A crude extract and three fractions reflecting a preliminary segregation of lipophilic metabolites were tested for toxicity with the marine microalga Nannochloropsis sp., the bacteria Pseudomonas sp., the brine shrimp Artemia salina, and fertilized eggs of the sea urchin Paracentrotus lividus. No significant apparent adverse effects were noted against Artemia salina. However, significant adverse effects were found in all other assays, with an inhibition of Nannochloropsis sp. and Pseudomonas sp. growth and marked reduction in Paracentrotus lividus larvae length. The results obtained indicated that Cyanobium genus may serve as a potential source of interesting bioactive compounds and emphasize the importance of also studying smaller picoplanktonic fractions of marine cyanobacteria.

  18. High expression level of antioxidants and pharmaceutical bioactivities of endophytic fungus Chaetomium globosum JN711454.

    PubMed

    Selim, Khaled A; El-Beih, Ahmed A; Abdel-Rahman, Tahany M; El-Diwany, Ahmed I

    2016-01-01

    In order to maximize antioxidant activity of pharmaceutical bioactive endophytic fungus Chaetomium globosum JN711454 during fermentation process, designed fermentation experiments of culture media for three levels of eight culture factors were performed using a Taguchi orthogonal array (OA) design with layout L18 (2(1) × 3(7)). The agitation and the potato extract were the most significant affecting factors, and their interaction contributed significantly to fungus activity. The production of antioxidants was more favorable for static condition with 25 g potato extract/100 m. The remaining factors had no strong impact when considered individually. The validation of statistically optimized medium indicated the improvement of antioxidant activity to a level of twofold with approximately overall 40% enhancement in activity. The extract of optimized medium was investigated for various pharmaceutical bioactivities; it revealed a moderate antimicrobial activity, strong anticancer activity against HepG-2, UACC62 cell lines, an antiviral activity against HSV-2 virus, and strong inhibitory activity to butyrylcholinesterase enzyme, one of the neurohydrolase enzymes that play a major role in development of Alzheimer's disease. As a result of applying statistical fermentation designs, the optimized conditions of endophytic fungus C. globosum JN711454 developed a cost-effective production medium by using inexpensive commercial potato extracts statically, which can lower the energy requirement and could become an efficient, economic, and viable fermentation process for production of pharmaceutical secondary metabolites.

  19. Red Raspberries and Their Bioactive Polyphenols: Cardiometabolic and Neuronal Health Links12

    PubMed Central

    Burton-Freeman, Britt M; Sandhu, Amandeep K; Edirisinghe, Indika

    2016-01-01

    Diet is an essential factor that affects the risk of modern-day metabolic diseases, including cardiovascular disease, diabetes mellitus, obesity, and Alzheimer disease. The potential ability of certain foods and their bioactive compounds to reverse or prevent the progression of the pathogenic processes that underlie these diseases has attracted research attention. Red raspberries (Rubus idaeus L.) are unique berries with a rich history and nutrient and bioactive composition. They possess several essential micronutrients, dietary fibers, and polyphenolic components, especially ellagitannins and anthocyanins, the latter of which give them their distinctive red coloring. In vitro and in vivo studies have revealed various mechanisms through which anthocyanins and ellagitannins (via ellagic acid or their urolithin metabolites) and red raspberry extracts (or the entire fruit) could reduce the risk of or reverse metabolically associated pathophysiologies. To our knowledge, few studies in humans are available for evaluation. We review and summarize the available literature that assesses the health-promoting potential of red raspberries and select components in modulating metabolic disease risk, especially cardiovascular disease, diabetes mellitus, obesity, and Alzheimer disease—all of which share critical metabolic, oxidative, and inflammatory links. The body of research is growing and supports a potential role for red raspberries in reducing the risk of metabolically based chronic diseases. PMID:26773014

  20. Red Raspberries and Their Bioactive Polyphenols: Cardiometabolic and Neuronal Health Links.

    PubMed

    Burton-Freeman, Britt M; Sandhu, Amandeep K; Edirisinghe, Indika

    2016-01-01

    Diet is an essential factor that affects the risk of modern-day metabolic diseases, including cardiovascular disease, diabetes mellitus, obesity, and Alzheimer disease. The potential ability of certain foods and their bioactive compounds to reverse or prevent the progression of the pathogenic processes that underlie these diseases has attracted research attention. Red raspberries (Rubus idaeus L.) are unique berries with a rich history and nutrient and bioactive composition. They possess several essential micronutrients, dietary fibers, and polyphenolic components, especially ellagitannins and anthocyanins, the latter of which give them their distinctive red coloring. In vitro and in vivo studies have revealed various mechanisms through which anthocyanins and ellagitannins (via ellagic acid or their urolithin metabolites) and red raspberry extracts (or the entire fruit) could reduce the risk of or reverse metabolically associated pathophysiologies. To our knowledge, few studies in humans are available for evaluation. We review and summarize the available literature that assesses the health-promoting potential of red raspberries and select components in modulating metabolic disease risk, especially cardiovascular disease, diabetes mellitus, obesity, and Alzheimer disease-all of which share critical metabolic, oxidative, and inflammatory links. The body of research is growing and supports a potential role for red raspberries in reducing the risk of metabolically based chronic diseases.

  1. Bioactivation and toxicity of acetaminophen in a rat hepatocyte micropatterned coculture system.

    PubMed

    Ukairo, Okechukwu; McVay, Michael; Krzyzewski, Stacy; Aoyama, Simon; Rose, Kelly; Andersen, Melvin E; Khetani, Salman R; Lecluyse, Edward L

    2013-10-01

    We have recently shown that primary rat hepatocytes organized in micropatterned cocultures with murine embryonic fibroblasts (HepatoPac™) maintain high levels of liver functions for at least 4 weeks. In this study, rat HepatoPac was assessed for its utility to study chemical bioactivation and associated hepatocellular toxicity. Treatment of HepatoPac cultures with acetaminophen (APAP) over a range of concentrations (0-15 mM) was initiated at 1, 2, 3, or 4 weeks followed by the assessment of morphological and functional endpoints. Consistent and reproducible concentration-dependent effects on hepatocyte structure, viability, and basic functions were observed over the 4-week period, and were exacerbated by depleting glutathione using buthionine sulfoximine or inducing CYP3A using dexamethasone, presumably due to increased reactive metabolite-induced stress and adduct formation. In conclusion, the results from this study demonstrate that rat HepatoPac represents a structurally and functionally stable hepatic model system to assess the long-term effects of bioactivated compounds.

  2. Chemical diversity of biologically active metabolites in the sclerotia of Inonotus obliquus and submerged culture strategies for up-regulating their production.

    PubMed

    Zheng, Weifa; Miao, Kangjie; Liu, Yubing; Zhao, Yanxia; Zhang, Meimei; Pan, Shenyuan; Dai, Yucheng

    2010-07-01

    Inonotus obliquus (Fr.) Pilat is a white rot fungus belonging to the family Hymenochaetaceae in the Basidiomycota. In nature, this fungus rarely forms a fruiting body but usually an irregular shape of sclerotial conk called 'Chaga'. Characteristically, I. obliquus produces massive melanins released to the surface of Chaga. As early as in the sixteenth century, Chaga was used as an effective folk medicine in Russia and Northern Europe to treat several human malicious tumors and other diseases in the absence of any unacceptable toxic side effects. Chemical investigations show that I. obliquus produces a diverse range of secondary metabolites including phenolic compounds, melanins, and lanostane-type triterpenoids. Among these are the active components for antioxidant, antitumoral, and antiviral activities and for improving human immunity against infection of pathogenic microbes. Geographically, however, this fungus is restricted to very cold habitats and grows very slowly, suggesting that Chaga is not a reliable source of these bioactive compounds. Attempts for culturing this fungus axenically all resulted in a reduced production of bioactive metabolites. This review examines the current progress in the discovery of chemical diversity of Chaga and their biological activities and the strategies to modulate the expression of desired pathways to diversify and up-regulate the production of bioactive metabolites by the fungus grown in submerged cultures for possible drug discovery.

  3. Microencapsulation for the improved delivery of bioactive compounds into foods.

    PubMed

    Champagne, Claude P; Fustier, Patrick

    2007-04-01

    The development of functional foods through the addition of bioactive compounds holds many technological challenges. Microencapsulation is a useful tool to improve the delivery of bioactive compounds into foods, particularly probiotics, minerals, vitamins, phytosterols, lutein, fatty acids, lycopene and antioxidants. Several microencapsulation technologies have been developed for use in the food industry and show promise for the production of functional foods. Moreover, these technologies could promote the successful delivery of bioactive ingredients to the gastrointestinal tract. Future research is likely to focus on aspects of delivery and the potential use of co-encapsulation methodologies, where two or more bioactive ingredients can be combined to have a synergistic effect.

  4. History and trends of bioactive glass-ceramics.

    PubMed

    Montazerian, Maziar; Dutra Zanotto, Edgar

    2016-05-01

    The interest around bioactive glass-ceramics (GCs) has grown significantly over the last two decades due to their appropriate biochemical and mechanical properties. The intense research effort in this field has led to some new commercial products for biomedical applications. This review article begins with the basic concepts of GC processing and development via controlled heat treatments of monolithic pieces or sinter-crystallization of powdered glasses. We then go on to describe the processing, properties, and applications of some commercial bioactive GCs and discuss selected valuable reported researches on several promising types of bioactive GCs. The article finishes with a section on open relevant research directions for bioactive GC development.

  5. Metabolic engineering for the microbial production of marine bioactive compounds.

    PubMed

    Mao, Xiangzhao; Liu, Zhen; Sun, Jianan; Lee, Sang Yup

    2017-03-06

    Many marine bioactive compounds have medicinal and nutritional values. These bioactive compounds have been prepared using solvent-based extraction from marine bio-resources or chemical synthesis, which are costly, inefficient with low yields, and environmentally unfriendly. Recent advances in metabolic engineering allowed to some extent more efficient production of these compounds, showing promises to meet the increasing demand of marine natural bioactive compounds. In this paper, we review the strategies and statuses of metabolic engineering applied to microbial production of marine natural bioactive compounds including terpenoids and their derivatives, omega-3 polyunsaturated fatty acids, and marine natural drugs, and provide perspectives.

  6. Bioactive Peptides from Muscle Sources: Meat and Fish

    PubMed Central

    Ryan, Joseph Thomas; Ross, Reynolds Paul; Bolton, Declan; Fitzgerald, Gerald F.; Stanton, Catherine

    2011-01-01

    Bioactive peptides have been identified in a range of foods, including plant, milk and muscle, e.g., beef, chicken, pork and fish muscle proteins. Bioactive peptides from food proteins offer major potential for incorporation into functional foods and nutraceuticals. The aim of this paper is to present an outline of the bioactive peptides identified in the muscle protein of meat to date, with a focus on muscle protein from domestic animals and fish. The majority of research on bioactives from meat sources has focused on angiotensin-1-converting enzyme (ACE) inhibitory and antioxidant peptides. PMID:22254123

  7. Characterization of bioactive peptides obtained from marine invertebrates.

    PubMed

    Lee, Jung Kwon; Jeon, Joong-Kyun; Kim, Se-Kwon; Byun, Hee-Guk

    2012-01-01

    Bioactive peptides as products of hydrolysis of diverse marine invertebrate (shellfish, crustacean, rotifer, etc.) proteins are the focus of current research. After much research on these muscles and by-products, some biologically active peptides were identified and applied to useful compounds for human utilization. This chapter reviews bioactive peptides from marine invertebrates in regarding to their bioactivities. Additionally, specific characteristics of antihypertensive, anti-Alzheimer, antioxidant, antimicrobial peptide enzymatic production, methods to evaluate bioactivity capacity, bioavailability, and safety concerns of peptides are reviewed.

  8. Characterization of the bioactive and mechanical behavior of dental ceramic/sol-gel derived bioactive glass mixtures.

    PubMed

    Abbasi, Zahra; Bahrololoum, Mohammad E; Bagheri, Rafat; Shariat, Mohammad H

    2016-02-01

    Dental ceramics can be modified by bioactive glasses in order to develop apatite layer on their surface. One of the benefits of such modification is to prolong the lifetime of the fixed dental prosthesis by preventing the formation of secondary caries. Dental ceramic/sol-gel derived bioactive glass mixture is one of the options for this modification. In the current study, mixtures of dental ceramic/bioactive glass with different compositions were successfully produced. To evaluate their bioactive behavior, prepared samples were immersed in a simulated body fluid at various time intervals. The prepared and soaked specimens were characterized using Fourier transform infrared spectroscopy, X-ray diffractometry and scanning electron microscopy. Since bioactive glasses have deleterious effects on the mechanical properties of dental ceramics, 3-point bending tests were used to evaluate the flexural strength, flexural strain, tangent modulus of elasticity and Weibull modulus of the specimens in order to find the optimal relationship between mechanical and bioactive properties.

  9. Accumulation of a bioactive triterpene saponin fraction of Quillaja brasiliensis leaves is associated with abiotic and biotic stresses.

    PubMed

    de Costa, Fernanda; Yendo, Anna Carolina Alves; Fleck, Juliane Deise; Gosmann, Grace; Fett-Neto, Arthur Germano

    2013-05-01

    The saponins from leaves of Quillaja brasiliensis, a native species from Southern Brazil, show structural and functional similarities to those of Quillaja saponaria barks, which are currently used as adjuvants in vaccine formulations. The accumulation patterns of an immunoadjuvant fraction of leaf triterpene saponins (QB-90) in response to stress factors were examined, aiming at understanding the regulation of accumulation of these metabolites. The content of QB-90 in leaf disks was significantly increased by application of different osmotic stress agents, such as sorbitol, sodium chloride and polyethylene glycol in isosmotic concentrations. Higher yields of bioactive saponins were also observed upon exposure to salicylic acid, jasmonic acid, ultrasound and UV-C light. Experiments with shoots indicated a significant increase in QB-90 yields with moderate increases in white light irradiance and by mechanical damage applied to leaves. The increased accumulation of these terpenes may be part of a defense response. The results herein described may contribute to further advance knowledge on the regulation of accumulation of bioactive saponins, and at defining strategies to improve yields of these useful metabolites.

  10. Effects of different culture conditions on biological potential and metabolites production in three Penicillium isolates.

    PubMed

    Reis, Filipa S; Ćirić, Ana; Stojković, Dejan; Barros, Lillian; Ljaljević-Grbić, Milica; Soković, Marina; Ferreira, Isabel C F R

    2015-02-01

    The genus Penicillium is well known for its importance in drug and food production. Certain species are produced on an industrial scale for the production of antibiotics (e.g. penicillin) or for insertion in food (e.g. cheese). In the present work, three Penicillium species, part of the natural mycobiota growing on various food products were selected - P. ochrochloron, P. funiculosum and P. verrucosum var. cyclopium. The objective of our study was to value these species from the point of view of production of bioactive metabolites. The species were obtained after inoculation and growth in Czapek and Malt media. Both mycelia and culture media were analyzed to monitor the production of different metabolites by each fungus and their release to the culture medium. The concentrations of sugars, organic acids, phenolic acids and tocopherols were determined. Antioxidant activity of the phenolic extracts was evaluated, as also the antimicrobial activity of phenolic acids, organic acids and tocopherols extracts. Rhamnose, xylose, fructose and trehalose were found in all the mycelia and culture media; the prevailing organic acids were oxalic and fumaric acids, and protocatechuic and p-hydroxybenzoic acids were the most common phenolic acids; γ-tocopherol was the most abundant vitamin E isoform. Generally, the phenolic extracts corresponding to the mycelia samples revealed higher antioxidant activity. Concerning the antimicrobial activity there were some fluctuations, however all the studied species revealed activity against the tested strains. Therefore, the in-vitro bioprocesses can be an alternative for the production of bioactive metabolites that can be used by pharmaceutical industry.

  11. Cyanobacterial Metabolite Calothrixins: Recent Advances in Synthesis and Biological Evaluation

    PubMed Central

    Xu, Su; Nijampatnam, Bhavitavya; Dutta, Shilpa; Velu, Sadanandan E.

    2016-01-01

    The marine environment is host to unparalleled biological and chemical diversity, making it an attractive resource for the discovery of new therapeutics for a plethora of diseases. Compounds that are extracted from cyanobacteria are of special interest due to their unique structural scaffolds and capacity to produce potent pharmaceutical and biotechnological traits. Calothrixins A and B are two cyanobacterial metabolites with a structural assembly of quinoline, quinone, and indole pharmacophores. This review surveys recent advances in the synthesis and evaluation of the biological activities of calothrixins. Due to the low isolation yields from the marine source and the promise this scaffold holds for anticancer and antimicrobial drugs, organic and medicinal chemists around the world have embarked on developing efficient synthetic routes to produce calothrixins. Since the first review appeared in 2009, 11 novel syntheses of calothrixins have been published in the efforts to develop methods that contain fewer steps and higher-yielding reactions. Calothrixins have shown their potential as topoisomerase I poisons for their cytotoxicity in cancer. They have also been observed to target various aspects of RNA synthesis in bacteria. Further investigation into the exact mechanism for their bioactivity is still required for many of its analogs. PMID:26771620

  12. Synthetic cannabinoids: analysis and metabolites.

    PubMed

    Elsohly, Mahmoud A; Gul, Waseem; Wanas, Amira S; Radwan, Mohamed M

    2014-02-27

    Cannabimimetics (commonly referred to as synthetic cannabinoids), a group of compounds encompassing a wide range of chemical structures, have been developed by scientists with the hope of achieving selectivity toward one or the other of the cannabinoid receptors CB1 and CB2. The goal was to have compounds that could possess high therapeutic activity without many side effects. However, underground laboratories have used the information generated by the scientific community to develop these compounds for illicit use as marijuana substitutes. This chapter reviews the different classes of these "synthetic cannabinoids" with particular emphasis on the methods used for their identification in the herbal products with which they are mixed and identification of their metabolites in biological specimens.

  13. Bioactive and inert dental glass-ceramics.

    PubMed

    Montazerian, Maziar; Zanotto, Edgar Dutra

    2017-02-01

    The global market for dental materials is predicted to exceed 10 billion dollars by 2020. The main drivers for this growth are easing the workflow of dentists and increasing the comfort of patients. Therefore, remarkable research projects have been conducted and are currently underway to develop improved or new dental materials with enhanced properties or that can be processed using advanced technologies, such as CAD/CAM or 3D printing. Among these materials, zirconia, glass or polymer-infiltrated ceramics, and glass-ceramics (GCs) are of great importance. Dental glass-ceramics are highly attractive because they are easy to process and have outstanding esthetics, translucency, low thermal conductivity, high strength, chemical durability, biocompatibility, wear resistance, and hardness similar to that of natural teeth, and, in certain cases, these materials are bioactive. In this review article, we divide dental GCs into the following two groups: restorative and bioactive. Most restorative dental glass-ceramics (RDGCs) are inert and biocompatible and are used in the restoration and reconstruction of teeth. Bioactive dental glass-ceramics (BDGCs) display bone-bonding ability and stimulate positive biological reactions at the material/tissue interface. BDGCs are suggested for dentin hypersensitivity treatment, implant coating, bone regeneration and periodontal therapy. Throughout this paper, we elaborate on the history, processing, properties and applications of RDGCs and BDGCs. We also report on selected papers that address promising types of dental glass-ceramics. Finally, we include trends and guidance on relevant open issues and research possibilities. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 619-639, 2017.

  14. Levels of compounds and metabolites in wheat ears and grains in organic and conventional agriculture.

    PubMed

    Zörb, Christian; Niehaus, Karsten; Barsch, Aiko; Betsche, Thomas; Langenkämper, Georg

    2009-10-28

    In this work, wheat from two farming systems, organic and conventional, was analyzed. Organic agriculture is one of the fastest growing sectors in the food industry of Europe and the United States. It is an open question, whether organic or conventional agricultural management influences variables such as metabolism, nutrient supply, seed loading and metabolite composition of wheat. Our aim was to detect if organic or conventional farming systems would affect concentrations of metabolites and substances in developing ears and in corresponding matured grain. Therefore, broadband metabolite profiles together with lipids, cations, starch and protein concentrations of wheat ears in the last phase of grain development and of matured grain from organic and conventional agriculture of a rigorously controlled field trial with two organic and two conventional systems were examined. It appears that seed metabolism and supply of developing ears differ in organic and conventional agriculture. However, the differences in 62 metabolite concentrations become marginal or disappear in the matured grains, indicating an adjustment of nutrients in the matured grain from organic agriculture. This result suggests a high degree of homeostasis in the final seed set independent of the growing regime.

  15. Active Metabolites of Isoxazolylpenicillins in Humans

    PubMed Central

    Thijssen, H. H. W.; Mattie, H.

    1976-01-01

    Metabolites of the isoxazolylpenicillins that still possessed antibacterial activity were shown to be present in urine and serum. In healthy subjects, the amounts excreted in urine were low; 10 to 23% of the excreted penicillin activities represented the metabolites. The highest amount of metabolite in urine was found for oxacillin, and the lowest was found for flucloxacillin. No extreme differences in the amounts of metabolite excreted were observed when the compounds were administered orally or intravenously. In one healthy subject metabolite levels were estimated for cloxacillin in serum. Very low levels were found, i.e., about 9% of the activity. In subjects with highly impaired renal function, the metabolite may represent up to 50% of the total level of penicillin in serum. The antibacterial activities of the different metabolites were of the same order of magnitude as those of the respective parent compounds. Also, the activity against benzylpenicillin-resistant staphylococci was retained. It is not likely that the formation of the active metabolites should influence therapeutic results. PMID:825029

  16. Processing, properties, and in vitro bioactivity of polysulfone-bioactive glass composites.

    PubMed

    Oréfice, Rodrigo; Clark, Arthur; West, Jon; Brennan, Anthony; Hench, Larry

    2007-03-01

    The mismatch between the mechanical properties of bioceramics and natural tissue has restricted in several cases a wider application of ceramics in medical and dental fields. To overcome this problem, polymer matrix composites can be designed to combine bioactive properties of some bioceramics with the superior mechanical properties of some engineering plastics. In this work, polymer particulate composites composed of a high mechanical-property polymer and bioactive glass particles were produced and both the in vitro bioactivity and properties of the system were investigated. Composites with different volume fraction and particle size were prepared. In vitro tests showed that hydroxy-carbonate-apatite can be deposited on the surface of a composite as early as 20 h in a simulated body fluid. Ionic evolution from a composite with 40% volume fraction of particles was demonstrated to be similar to bulk bioactive glasses. The mechanical properties of some of the obtained composites had values comparable with the ones reported for bone. Moreover, a physical model based on dynamical mechanical tests showed evidences that the interface of the composite was aiding in the stress transfer process.

  17. Bioactive glass coupling with natural polyphenols: Surface modification, bioactivity and anti-oxidant ability

    NASA Astrophysics Data System (ADS)

    Cazzola, Martina; Corazzari, Ingrid; Prenesti, Enrico; Bertone, Elisa; Vernè, Enrica; Ferraris, Sara

    2016-03-01

    Polyphenols are actually achieving an increasing interest due to their potential health benefits, such as antioxidant, anticancer, antibacterial and bone stimulation abilities. However their poor bioavailability and stability hamper an effective clinical application as therapeutic principles. The opportunity to couple these biomolecules with synthetic biomaterials, in order to obtain local delivery at the site of interest, improve their bioavailability and stability and combine their properties with the ones of the substrate, is a challenging opportunity for the biomedical research. A silica based bioactive glass, CEL2, has been successfully coupled with gallic acid and natural polyphenols extracted from red grape skins and green tea leaves. The effectiveness of grafting has been verified by means of XPS analyses and the Folin&Ciocalteu tests. In vitro bioactivity has been investigated by soaking in simulated body fluid (SBF). Surface modification after functionalization and early stage reactivity in SBF have been studied by means of zeta potential electrokinetic measurements in KCl and SBF. Finally the antioxidant properties of bare and modified bioactive glasses has been investigated by means of the evaluation of free radical scavenging activity by Electron Paramagnetic Resonance (EPR)/spin trapping technique after UV photolysis of H2O2 highlighting scavenging activity of the bioactive glass.

  18. In vitro bioactivity and mechanical properties of bioactive glass nanoparticles/polycaprolactone composites.

    PubMed

    Ji, Lijun; Wang, Wenjun; Jin, Duo; Zhou, Songtao; Song, Xiaoli

    2015-01-01

    Nanoparticles of bioactive glass (NBG) with a diameter of 50-90 nm were synthesized using the Stöber method. NBG/PCL composites with different NBG contents (0 wt.%, 10 wt.%, 20 wt.%, 30 wt.% and 40 wt.%) were prepared by a melt blending and thermal injection moulding technique, and characterized with XRD, FTIR, and SEM to study the effect of NBG on the mechanical properties and in vitro bioactivity of the NBG/PCL composites. In spite of the high addition up to 40 wt.%, the NBG could be dispersed homogeneously in the PCL matrix. The elastic modulus of the NBG/PCL composites was improved remarkably from 198±13 MPa to 851±43 MPa, meanwhile the tensile strength was retained in the range of 19-21.5 MPa. The hydrophilic property and degradation behavior of the NBG/PCL composites were also improved with the addition of the NBG. Moreover, the composites with high NBG content showed outstanding in vitro bioactivity after being immersed in simulated body fluid, which could be attributed to the excellent bioactivity of the synthesized NBG.

  19. Physicochemical properties and bioactivity of freeze-cast chitosan nanocomposite scaffolds reinforced with bioactive glass.

    PubMed

    Pourhaghgouy, Masoud; Zamanian, Ali; Shahrezaee, Mostafa; Masouleh, Milad Pourbaghi

    2016-01-01

    Chitosan based nanocomposite scaffolds were prepared by freeze casting method through blending constant chitosan concentration with different portions of synthesized bioactive glass nanoparticles (BGNPs). Transmission Electron Microscopy (TEM) image showed that the particles size of bioactive glass (64SiO2.28CaO.8P2O5) prepared by sol-gel method was approximately less than 20 nm. Fourier Transform Infrared Spectroscopy (FT-IR) and X-ray Diffraction (XRD) analysis showed proper interfacial bonding between BGNPs and chitosan polymers. Scanning Electron Microscopy (SEM) images depicted a unidirectional structure with homogenous distribution of BGNPs among chitosan matrix associated with the absence of pure chitosan scaffold's wall pores after addition of only 10 wt.% BGNPs. As the BGNP content increased from 0 to 50 wt.%, the compressive strength and compressive module values increased from 0.034 to 0.419 MPa and 0.41 to 10.77 MPa, respectively. Biodegradation study showed that increase in BGNP content leads to growth of weight loss amount. The in vitro biomineralization studies confirmed the bioactive nature of all nanocomposites. Amount of 30 wt.% BGNPs represented the best concentration for absorption capacity and bioactivity behaviors.

  20. Influence of barium substitution on bioactivity, thermal and physico-mechanical properties of bioactive glass.

    PubMed

    Arepalli, Sampath Kumar; Tripathi, Himanshu; Vyas, Vikash Kumar; Jain, Shubham; Suman, Shyam Kumar; Pyare, Ram; Singh, S P

    2015-04-01

    Barium with low concentration in the glasses acts as a muscle stimulant and is found in human teeth. We have made a primary study by substituting barium in the bioactive glass. The chemical composition containing (46.1-X) SiO2--24.3 Na2O-26.9 CaO-2.6 P2O5, where X=0, 0.4, 0.8, 1.2 and 1.6mol% of BaO was chosen and melted in an electric furnace at 1400±5°C. The glasses were characterized to determine their use in biomedical applications. The nucleation and crystallization regimes were determined by DTA and the controlled crystallization was carried out by suitable heat treatment. The crystalline phase formed was identified by using XRD technique. Bioactivity of these glasses was assessed by immersion in simulated body fluid (SBF) for various time periods. The formation of hydroxy carbonate apatite (HCA) layer was identified by FTIR spectrometry, scanning electron microscope (SEM) and XRD which showed the presence of HCA as the main phase in all tested bioactive glass samples. Flexural strength and densities of bioactive glasses have been measured and found to increase with increasing the barium content. The human blood compatibility of the samples was evaluated and found to be pertinent.

  1. The Influence of Phase Separation on Bioactivity of Spray Pyrolyzed Bioactive Glass.

    PubMed

    Shih, Shao-ju; Tzeng, Wei-lung; Chou, Yu-jen; Chen, Chin-yi; Chen, Yu-ju

    2015-06-01

    In this study, bioactive glass (BG) particles were synthesized directly using spray pyrolysis (SP). Since the bioactivity of glass particles is well correlated with their chemical composition, how to obtain homogenous bioactive glass becomes an important issue. For SP, the main reason for chemical inhomogeneity was considered to be caused by the difference in the precipitation speed of each precursor. So, two Si-containing precursors of BG, namely tetraethyl orthosilicate (TEOS) and silicon acetate (SiA), have been applied to prepare BG particles. The bioglasses were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy and energy dispersive spectroscopy to examine their phase composition, and surface structures, inner morphologies and chemical compositions. It was observed that, under the calcination temperature of 700 degrees C, TEOS-derived powder contained Si-rich nanoparticles and Si-deficit submicron particles as inhomogeneity, whereas the SiA-derived powder was homogenous. The reason of inhomogeneity is that TEOS dissolves in "volatile" ethanol more readily than in water via the SP mechanism of "gas-to-particle-conversion" to form Si-rich nanoparticles. The presence of Si-rich nanoparticles causes Si-deficit "wollastonite submicron particles" to form, which impairs the bioactivity. Finally, BG particle formation mechanisms from different precursors have been proposed.

  2. Human milk composition: nutrients and bioactive factors.

    PubMed

    Ballard, Olivia; Morrow, Ardythe L

    2013-02-01

    This article provides an overview of the composition of human milk, its variation, and its clinical relevance. The composition of human milk is the biological norm for infant nutrition. Human milk also contains many hundreds to thousands of distinct bioactive molecules that protect against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. Some of these molecules (eg, lactoferrin) are being investigated as novel therapeutic agents. Human milk changes in composition from colostrum to late lactation, within feeds, by gestational age, diurnally, and between mothers. Feeding infants with expressed human milk is increasing.

  3. Marine Nucleosides: Structure, Bioactivity, Synthesis and Biosynthesis

    PubMed Central

    Huang, Ri-Ming; Chen, Yin-Ning; Zeng, Ziyu; Gao, Cheng-Hai; Su, Xiangdong; Peng, Yan

    2014-01-01

    Nucleosides are glycosylamines that structurally form part of nucleotide molecules, the building block of DNA and RNA. Both nucleosides and nucleotides are vital components of all living cells and involved in several key biological processes. Some of these nucleosides have been obtained from a variety of marine resources. Because of the biological importance of these compounds, this review covers 68 marine originated nucleosides and their synthetic analogs published up to June 2014. The review will focus on the structures, bioactivities, synthesis and biosynthetic processes of these compounds. PMID:25474189

  4. Marine nucleosides: structure, bioactivity, synthesis and biosynthesis.

    PubMed

    Huang, Ri-Ming; Chen, Yin-Ning; Zeng, Ziyu; Gao, Cheng-Hai; Su, Xiangdong; Peng, Yan

    2014-12-02

    Nucleosides are glycosylamines that structurally form part of nucleotide molecules, the building block of DNA and RNA. Both nucleosides and nucleotides are vital components of all living cells and involved in several key biological processes. Some of these nucleosides have been obtained from a variety of marine resources. Because of the biological importance of these compounds, this review covers 68 marine originated nucleosides and their synthetic analogs published up to June 2014. The review will focus on the structures, bioactivities, synthesis and biosynthetic processes of these compounds.

  5. Effect of nitrogen and fluorine on mechanical properties and bioactivity in two series of bioactive glasses.

    PubMed

    Bachar, Ahmed; Mercier, Cyrille; Tricoteaux, Arnaud; Hampshire, Stuart; Leriche, Anne; Follet, Claudine

    2013-07-01

    Bioactive glasses are able to bond to bone through formation of carbonated hydroxyapatite in body fluids, and fluoride-releasing bioactive glasses are of interest for both orthopaedic and, in particular, dental applications for caries inhibition. However, because of their poor strength their use is restricted to non-load-bearing applications. In order to increase their mechanical properties, doping with nitrogen has been performed on two series of bioactive glasses: series (I) was a "bioglass" composition (without P2O5) within the quaternary system SiO2-Na2O-CaO-Si3N4 and series (II) was a simple substitution of CaF2 for CaO in series (I) glasses keeping the Na:Ca ratio constant. The objective of this work was to evaluate the effect of the variation in nitrogen and fluorine content on the properties of these glasses. The density, glass transition temperature, hardness and elastic modulus all increased linearly with nitrogen content which indicates that the incorporation of nitrogen stiffens the glass network because N is mainly in 3-fold coordination with Si atoms. Fluorine addition significantly decreases the thermal property values but the mechanical properties of these glasses remain unchanged with fluorine. The combination of both nitrogen and fluorine in oxyfluoronitride glasses gives better mechanical properties at much lower melting temperatures since fluorine reduces the melting point, allows higher solubility of nitrogen and does not affect the higher mechanical properties arising from incorporation of nitrogen. The characterization of these N and F substituted bioactive glasses using (29)Si MAS NMR has shown that the increase in rigidity of the glass network can be explained by the formation of SiO3N, SiO2N2 tetrahedra and Q(4) units with extra bridging anions at the expense of Q(3) units. Bioactivity of the glasses was investigated in vitro by examining apatite formation on the surface of glasses treated in acellular simulated body fluid (SBF) with ion

  6. [Pharmacological research on bonnecor and its metabolites].

    PubMed

    Poppe, H; Heer, S; Barch, R

    1990-01-01

    The antiarrhythmic and local anesthetic effects of 4 metabolites (G 491, ABD 19-200, ABD 19-199, ABD 19-205) of a new antiarrhythmic drug bonnecor (GS-015) were studied on the models of arrhythmias induced by aconitine (rats), barium chloride (rabbits), electrical fibrillation (cats), ouabain (dogs) as well as surface anesthesia (rabbit cornea). The side effects on the cardiovascular system were investigated on anesthetized cats. As compared with the original compound (bonnecor) metabolites G 491 and ABD 19-200 on different test models exhibited the action which on the antiarrhythmic terms was 2-14 times less weak than that of bonnecor but the metabolites were less toxic. Metabolites ABD 19-199 and ABD 19-205 reach the degree of effectiveness of bonnecor but their toxicity is higher. It follows from the above that the beneficial effect of bonnecor is not achieved by its metabolites.

  7. Biological control of toxigenic citrus and papaya-rotting fungi by Streptomyces violascens MT7 and its extracellular metabolites.

    PubMed

    Choudhary, Bharti; Nagpure, Anand; Gupta, Rajinder K

    2015-12-01

    An Indian indigenous, Loktak Lake soil isolate Streptomyces violascens MT7 was assessed for its biocontrol potential both in vitro and in vivo against toxigenic fruit-rotting fungi. Strain MT7 exhibited broad-spectrum antifungal activity against various pathogenic postharvest fungi of citrus and papaya. In shake-flask fermentation, antagonist S. violascens MT7 highly produced extracellular antifungal metabolites in early stationary growth phase in glucose-yeast extract-malt extract (M93) broth. Both extracellular culture fluid (ECF) and its n-butanol extract showed significant broad-spectrum fungal mycelial inhibition of several tested fruit-rotting fungi. Antifungal metabolite was found to be heat stable, nonpeptidic, and polyene type antibiotic. The lowest minimum inhibitory concentration (MIC) of n-butanol extract against Colletotrichum gloeosporioides MTCC 9664 and Aspergillus niger MTCC 281 was 0.0312 and 0.0625 mg/ml, respectively. Purification of n-butanol extract through silica gel chromatography resulted in partial purification of bioactive metabolite and the TLC autobiography revealed the presence of single antifungal metabolite with Rf value of 0.755. In vivo bioassays demonstrated the biocontrol potential of tested biocontrol agents on fruit-rotting fungi. Use of cell suspension of S. violascens MT7, extracellular metabolite(s), and n-butanol extract significantly (p < 0.05) reduced sour-rot development on Citrus reticulata Blanco (oranges) and soft-rot development on papaya fruits. Therefore, these results strongly suggest a high potential for application of S. violascens MT7 and its extracellular metabolites as an effective eco-friendly alternative to synthetic fungicides for controlling toxigenic citrus and papaya-rotting fungi.

  8. Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

    SciTech Connect

    Prueksaritanont, Thomayant . E-mail: thomayant_prueksaritanont@merck.com; Lin, Jiunn H.; Baillie, Thomas A.

    2006-12-01

    This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models.

  9. High voltage power supply

    NASA Technical Reports Server (NTRS)

    Ruitberg, A. P.; Young, K. M. (Inventor)

    1985-01-01

    A high voltage power supply is formed by three discrete circuits energized by a battery to provide a plurality of concurrent output signals floating at a high output voltage on the order of several tens of kilovolts. In the first two circuits, the regulator stages are pulse width modulated and include adjustable ressistances for varying the duty cycles of pulse trains provided to corresponding oscillator stages while the third regulator stage includes an adjustable resistance for varying the amplitude of a steady signal provided to a third oscillator stage. In the first circuit, the oscillator, formed by a constant current drive network and a tuned resonant network included a step up transformer, is coupled to a second step up transformer which, in turn, supplies an amplified sinusoidal signal to a parallel pair of complementary poled rectifying, voltage multiplier stages to generate the high output voltage.

  10. Discontinuous Mode Power Supply

    NASA Technical Reports Server (NTRS)

    Lagadinos, John; Poulos, Ethel

    2012-01-01

    A document discusses the changes made to a standard push-pull inverter circuit to avoid saturation effects in the main inverter power supply. Typically, in a standard push-pull arrangement, the unsymmetrical primary excitation causes variations in the volt second integral of each half of the excitation cycle that could lead to the establishment of DC flux density in the magnetic core, which could eventually cause saturation of the main inverter transformer. The relocation of the filter reactor normally placed across the output of the power supply solves this problem. The filter reactor was placed in series with the primary circuit of the main inverter transformer, and is presented as impedance against the sudden changes on the input current. The reactor averaged the input current in the primary circuit, avoiding saturation of the main inverter transformer. Since the implementation of the described change, the above problem has not reoccurred, and failures in the main power transistors have been avoided.

  11. Composite bone cements loaded with a bioactive and ferrimagnetic glass-ceramic: Leaching, bioactivity and cytocompatibility.

    PubMed

    Verné, Enrica; Bruno, Matteo; Miola, Marta; Maina, Giovanni; Bianco, Carlotta; Cochis, Andrea; Rimondini, Lia

    2015-08-01

    In this work, composite bone cements, based on a commercial polymethylmethacrylate matrix (Palamed®) loaded with ferrimagnetic bioactive glass-ceramic particles (SC45), were produced and characterized in vitro. The ferrimagnetic bioactive glass-ceramic belongs to the system SiO2-Na2O-CaO-P2O5-FeO-Fe2O3 and contains magnetite (Fe3O4) crystals into a residual amorphous bioactive phase. Three different formulations (containing 10, 15 and 20 wt.% of glass-ceramic particles respectively) have been investigated. These materials are intended to be applied as bone fillers for the hyperthermic treatment of bone tumors. The morphological, compositional, calorimetric and mechanical properties of each formulation have been already discussed in a previous paper. The in vitro properties of the composite bone cements described in the present paper are related to iron ion leaching test (by graphite furnace atomic absorption spectrometer), bioactivity (i.e. the ability to stimulate the formation of a hydroxyapatite - HAp - layer on their surface after soaking in simulated body fluid SBF) and cytocompatibility toward human osteosarcoma cells (ATCC CRL-1427, Mg63). Morphological and chemical characterizations by scanning electron microscopy and energy dispersion spectrometry have been performed on the composite samples after each test. The iron release was negligible and all the tested samples showed the growth of HAp on their surface after 28 days of immersion in a simulated body fluid (SBF). Cells showed good viability, morphology, adhesion, density and the ability to develop bridge-like structures on all investigated samples. A synergistic effect between bioactivity and cell mineralization was also evidenced.

  12. Discovery Strategies of Bioactive Compounds Synthesized by Nonribosomal Peptide Synthetases and Type-I Polyketide Synthases Derived from Marine Microbiomes.

    PubMed

    Amoutzias, Grigoris D; Chaliotis, Anargyros; Mossialos, Dimitris

    2016-04-16

    Considering that 70% of our planet's surface is covered by oceans, it is likely that undiscovered biodiversity is still enormous. A large portion of marine biodiversity consists of microbiomes. They are very attractive targets of bioprospecting because they are able to produce a vast repertoire of secondary metabolites in order to adapt in diverse environments. In many cases secondary metabolites of pharmaceutical and biotechnological interest such as nonribosomal peptides (NRPs) and polyketides (PKs) are synthesized by multimodular enzymes named nonribosomal peptide synthetases (NRPSes) and type-I polyketide synthases (PKSes-I), respectively. Novel findings regarding the mechanisms underlying NRPS and PKS evolution demonstrate how microorganisms could leverage their metabolic potential. Moreover, these findings could facilitate synthetic biology approaches leading to novel bioactive compounds. Ongoing advances in bioinformatics and next-generation sequencing (NGS) technologies are driving the discovery of NRPs and PKs derived from marine microbiomes mainly through two strategies: genome-mining and metagenomics. Microbial genomes are now sequenced at an unprecedented rate and this vast quantity of biological information can be analyzed through genome mining in order to identify gene clusters encoding NRPSes and PKSes of interest. On the other hand, metagenomics is a fast-growing research field which directly studies microbial genomes and their products present in marine environments using culture-independent approaches. The aim of this review is to examine recent developments regarding discovery strategies of bioactive compounds synthesized by NRPS and type-I PKS derived from marine microbiomes and to highlight the vast diversity of NRPSes and PKSes present in marine environments by giving examples of recently discovered bioactive compounds.

  13. Discovery Strategies of Bioactive Compounds Synthesized by Nonribosomal Peptide Synthetases and Type-I Polyketide Synthases Derived from Marine Microbiomes

    PubMed Central

    Amoutzias, Grigoris D.; Chaliotis, Anargyros; Mossialos, Dimitris

    2016-01-01

    Considering that 70% of our planet’s surface is covered by oceans, it is likely that undiscovered biodiversity is still enormous. A large portion of marine biodiversity consists of microbiomes. They are very attractive targets of bioprospecting because they are able to produce a vast repertoire of secondary metabolites in order to adapt in diverse environments. In many cases secondary metabolites of pharmaceutical and biotechnological interest such as nonribosomal peptides (NRPs) and polyketides (PKs) are synthesized by multimodular enzymes named nonribosomal peptide synthetases (NRPSes) and type-I polyketide synthases (PKSes-I), respectively. Novel findings regarding the mechanisms underlying NRPS and PKS evolution demonstrate how microorganisms could leverage their metabolic potential. Moreover, these findings could facilitate synthetic biology approaches leading to novel bioactive compounds. Ongoing advances in bioinformatics and next-generation sequencing (NGS) technologies are driving the discovery of NRPs and PKs derived from marine microbiomes mainly through two strategies: genome-mining and metagenomics. Microbial genomes are now sequenced at an unprecedented rate and this vast quantity of biological information can be analyzed through genome mining in order to identify gene clusters encoding NRPSes and PKSes of interest. On the other hand, metagenomics is a fast-growing research field which directly studies microbial genomes and their products present in marine environments using culture-independent approaches. The aim of this review is to examine recent developments regarding discovery strategies of bioactive compounds synthesized by NRPS and type-I PKS derived from marine microbiomes and to highlight the vast diversity of NRPSes and PKSes present in marine environments by giving examples of recently discovered bioactive compounds. PMID:27092515

  14. A new paradigm for known metabolite identification in metabonomics/metabolomics: metabolite identification efficiency.

    PubMed

    Everett, Jeremy R

    2015-01-01

    A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE) and metabolite identification carbon efficiency (MICE), both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field.

  15. Supply Chain Interoperability Measurement

    DTIC Science & Technology

    2015-06-19

    Supply Chain Interoperability Measurement DISSERTATION June 2015 Christos E. Chalyvidis, Major, Hellenic Air ...Force AFIT-ENS-DS-15-J-001 DEPARTMENT OF THE AIR FORCE AIR UNIVERSITY AIR FORCE INSTITUTE OF TECHNOLOGY Wright-Patterson Air Force...are those of the author and do not reflect the official policy or position of the United States Air Force, Department of Defense, or the United

  16. Streamlining the supply chain.

    PubMed

    Neumann, Lydon

    2003-07-01

    Effective management of the supply chain requires attention to: Product management--formulary development and maintenance, compliance, clinical involvement, standardization, and demand-matching. Sourcing and contracting--vendor consolidation, GPO portfolio management, price leveling, content management, and direct contracting Purchasing and payment-cycle--automatic placement, web enablement, centralization, evaluated receipts settlement, and invoice matching Inventory and distribution management--"unofficial" and "official" locations, vendor-managed inventory, automatic replenishment, and freight management.

  17. Bioprospecting Chemical Diversity and Bioactivity in a Marine Derived Aspergillus terreus.

    PubMed

    Adpressa, Donovon A; Loesgen, Sandra

    2016-02-01

    A comparative metabolomic study of a marine derived fungus (Aspergillus terreus) grown under various culture conditions is presented. The fungus was grown in eleven different culture conditions using solid agar, broth cultures, or grain based media (OSMAC). Multivariate analysis of LC/MS data from the organic extracts revealed drastic differences in the metabolic profiles and guided our subsequent isolation efforts. The compound 7-desmethylcitreoviridin was isolated and identified, and is fully described for the first time. In addition, 16 known fungal metabolites were also isolated and identified. All compounds were elucidated by detailed spectroscopic analysis and tested for antibacterial activities against five human pathogens and tested for cytotoxicity. This study demonstrates that LC/MS based multivariate analysis provides a simple yet powerful tool to analyze the metabolome of a single fungal strain grown under various conditions. This approach allows environmentally-induced changes in metabolite expression to be rapidly visualized, and uses these differences to guide the discovery of new bioactive molecules.

  18. Bioactive compounds produced by gut microbial tannase: implications for colorectal cancer development.

    PubMed

    López de Felipe, Félix; de Las Rivas, Blanca; Muñoz, Rosario

    2014-01-01

    The microorganisms in the human gastrointestinal tract have a profound influence on the transformation of food into metabolites which can impact human health. Gallic acid (GA) and pyrogallol (PG) are bioactive compounds displaying diverse biological properties, including carcinogenic inhibiting activities. However, its concentration in fruits and vegetables is generally low. These metabolites can be also generated as final products of tannin metabolism by microbes endowed with tannase, which opens up the possibility of their anti-cancer potential being increased. Patients with colorectal cancer (CRC) display an imbalanced gut microbiota respect to healthy population. The recent use of next generation sequencing technologies has greatly improved knowledge of the identity of bacterial species that colonize non-tumorous and tumorous tissues of CRC patients. This information provides a unique opportunity to shed light on the role played by gut microorganisms in the different stages of this disease. We here review the recently published gut microbiome associated to CRC patients and highlight tannase as an underlying gene function of bacterial species that selectively colonize tumorous tissues, but not adjacent non-malignant tissues. Given the anti-carcinogenic roles of GA and PG produced by gut tannin-degrading bacteria, we provide an overview of the possible consequences of this intriguing coincidence for CRC development.

  19. Penicillium arizonense, a new, genome sequenced fungal species, reveals a high chemical diversity in secreted metabolites

    PubMed Central

    Grijseels, Sietske; Nielsen, Jens Christian; Randelovic, Milica; Nielsen, Jens; Nielsen, Kristian Fog; Workman, Mhairi; Frisvad, Jens Christian

    2016-01-01

    A new soil-borne species belonging to the Penicillium section Canescentia is described, Penicillium arizonense sp. nov. (type strain CBS 141311T = IBT 12289T). The genome was sequenced and assembled into 33.7 Mb containing 12,502 predicted genes. A phylogenetic assessment based on marker genes confirmed the grouping of P. arizonense within section Canescentia. Compared to related species, P. arizonense proved to encode a high number of proteins involved in carbohydrate metabolism, in particular hemicellulases. Mining the genome for genes involved in secondary metabolite biosynthesis resulted in the identification of 62 putative biosynthetic gene clusters. Extracts of P. arizonense were analysed for secondary metabolites and austalides, pyripyropenes, tryptoquivalines, fumagillin, pseurotin A, curvulinic acid and xanthoepocin were detected. A comparative analysis against known pathways enabled the proposal of biosynthetic gene clusters in P. arizonense responsible for the synthesis of all detected compounds except curvulinic acid. The capacity to produce biomass degrading enzymes and the identification of a high chemical diversity in secreted bioactive secondary metabolites, offers a broad range of potential industrial applications for the new species P. arizonense. The description and availability of the genome sequence of P. arizonense, further provides the basis for biotechnological exploitation of this species. PMID:27739446