Unique Bioactive Compounds Research Articles

Characterization of the antioxidant activity of Portuguese lavanders: Lavandula stoechas ssp. luisieri and Lavandula pedunculata

The interest in natural products chemistry is closely related with the urgent need of new drugs. The genus Lavandula (Lamiaceae) is known for its richness and unique bioactive compounds. It is established in Iberia and in Portugal some of its species are part of the “montado” flora, namely L. stoechas ssp. luisieri and L. pedunculata [1]. The antioxidant compounds play an important role in the organisms protection against oxidative stress, which could be related with the development of several pathologies as cancer, diabetes, atherosclerosis, Parkinson, Alzheimer and others aging related diseases [2, 3]. Moreover, the use of natural antioxidant compounds is preferred than the synthetic ones due to toxicity issues, already restricted by FDA and EMA [4]. In order to evaluate the antioxidant activity of five different polarity extracts of L. stoechas ssp. luisieri and L. pedunculata, several assays were performed namely, the free radical scavenge qualitative and quantitative and the lipid peroxidation inhibition, as well as the total phenols and the total flavonoids determination. The antioxidant activity of dichloromethane and methanol extract from L. stoechas ssp. luisieri and of all the five extracts from L. pedunculata was quite meaningful, corresponding to a 70% average of free radical DPPH scavenge. Methanol and water extracts of both species are rich in phenols and flavonoids which are related with the great antioxidant activity of those extracts. The lipid peroxidation inhibition assay applied to the dichloromethane, methanol and water extracts revealed an inhibition percentage of about 10 to 25% superior than BHT (positive control). In conclusion, our results let us to assume that methanol extract from these Portuguese lavenders gathers a great potential to be an alternative for new developments of food preservative, anti-aging and in skin protective cosmetic formulations and as protectors against aging related diseases, cancer and diabetes.

Canadian buckwheat: A unique, useful and under-utilized crop

Izydorczyk, M. S., McMillan, T., Bazin, S., Kletke, J., Dushnicky, L. and Dexter, J. 2014. Canadian buckwheat: A unique, useful and under-utilized crop. Can. J. Plant Sci. 94: 509–524. Buckwheat is a broad-leafed herbaceous annual plant, belonging to the genus Fagopyrum of the family Polygonaceae, the “smartweed” family, also called the buckwheat, rhubarb, or sorrel family. Although not a cereal, buckwheat on the whole resembles cereal grains; it is handled and processed like other cereals and officially listed among the 20 grains inspected and graded by the Canadian Grain Commission. In addition to starch (65–75% dwb) and proteins (13–14% dwb), buckwheat is a source of flavonoids (with rutin being the most distinctive), a group of polyphenolic compounds with a potential to inhibit lipoprotein oxidation and to reduce risk of cardiovascular diseases, and fagopyritols, another group of unique bioactive compounds first identified in buckwheat and associated with reduction of symptoms on non-insulin-dependent diabetes. Buckwheat proteins do not contain gluten, and buckwheat is regarded as an excellent alternative source of protein for individuals with celiac disease. Buckwheat is a particularly good dietary source of Zn, Cu, Mn and Mg. Buckwheat starch and dietary fibre constituents exhibit some distinctive physicochemical and functional properties. Despite the availability of several high-yielding, high-quality Canadian buckwheat cultivars and the well-established production of buckwheat on the Canadian prairies, buckwheat is found in relatively few food products manufactured in North America, and Canada remains largely an exporter of buckwheat rather than its processor. Buckwheat can be roller milled into various types of flours with variable composition and properties. Buckwheat milling fractions can be relatively easily incorporated in a variety of food products to improve their nutritional qualities and potential health benefits, but much more attention should be paid to the development and improvement of modern food processing techniques to improve the palatability and acceptability of buckwheat products.

Canadian buckwheat: A unique, useful and under-utilized crop

Izydorczyk, M. S., McMillan, T., Bazin, S., Kletke, J., Dushnicky, L. and Dexter, J. 2014. Canadian buckwheat: A unique, useful and under-utilized crop. Can. J. Plant Sci. 94: 509-524. Buckwheat is a broad-leafed herbaceous annual plant, belonging to the genus Fagopyrum of the family Polygonaceae, the “smartweed” family, also called the buckwheat, rhubarb, or sorrel family. Although not a cereal, buckwheat on the whole resembles cereal grains; it is handled and processed like other cereals and officially listed among the 20 grains inspected and graded by the Canadian Grain Commission. In addition to starch (65-75% dwb) and proteins (13-14% dwb), buckwheat is a source of flavonoids (with rutin being the most distinctive), a group of polyphenolic compounds with a potential to inhibit lipoprotein oxidation and to reduce risk of cardiovascular diseases, and fagopyritols, another group of unique bioactive compounds first identified in buckwheat and associated with reduction of symptoms on non-insulin-dependent diabetes. Buckwheat proteins do not contain gluten, and buckwheat is regarded as an excellent alternative source of protein for individuals with celiac disease. Buckwheat is a particularly good dietary source of Zn, Cu, Mn and Mg. Buckwheat starch and dietary fibre constituents exhibit some distinctive physicochemical and functional properties. Despite the availability of several high-yielding, high-quality Canadian buckwheat cultivars and the well-established production of buckwheat on the Canadian prairies, buckwheat is found in relatively few food products manufactured in North America, and Canada remains largely an exporter of buckwheat rather than its processor. Buckwheat can be roller milled into various types of flours with variable composition and properties. Buckwheat milling fractions can be relatively easily incorporated in a variety of food products to improve their nutritional qualities and potential health benefits, but much more attention should be paid to the development and improvement of modern food processing techniques to improve the palatability and acceptability of buckwheat products.

Seaweed and human health

Seaweeds may have an important role in modulating chronic disease. Rich in unique bioactive compounds not present in terrestrial food sources, including different proteins (lectins, phycobiliproteins, peptides, and amino acids), polyphenols, and polysaccharides, seaweeds are a novel source of compounds with potential to be exploited in human health applications. Purported benefits include antiviral, anticancer, and anticoagulant properties as well as the ability to modulate gut health and risk factors for obesity and diabetes. Though the majority of studies have been performed in cell and animal models, there is evidence of the beneficial effect of seaweed and seaweed components on markers of human health and disease status. This review is the first to critically evaluate these human studies, aiming to draw attention to gaps in current knowledge, which will aid the planning and implementation of future studies.

Estimation of Total Bioactive Compounds in Pigmented and Non Pigmented Genotypes of Sorghum (Sorghum bicolor (L.) Moench)

Sorghum seed contains unique bioactive compounds on par with other cereals. Bioactive compounds in plants can be defined as secondary plant metabolites. The secondary bioactive compounds in plants appear to be randomly synthesized but they are not useless junk. They can be used as anantimicrobial, antioxidant, and anti-inflammatory activity. Hence, In the present study, we have investigated to estimate the total bioactive compounds in selected genotypes by using spectrophotometer to quantitative and qualitative assay on six different genotypes including non pigmented (IS 3477, IS 33095, IS 7005) pigmented (IS 2898, IS 7155, IS 1202). The range of bioactive compounds between the pigmented and non pigmented genotypes detected high amount of total Polyphenols, Tannins, Flavonoids, Carotenoids and Anthocyaninsi.e.,40.33 ± 0.98-96.24 ± 1.97 mg GAE/100 gm, 26.61 ± 1.00-88.42 ± 1.89 mg TAE/100 gm, 2.16 ± 0.15- 8.48 ± 0.16mg QUE/100 gm, 2.35 ± 0.10-21.20 ± 0.38 β-CAE/100 gm, 2.31 ± 0.22-8.49 ± 0.52C-3-G mg/100 gm respectively. Among the genotypes, pigmented genotypes showed high levels of bioactive compounds than non pigmented genotypes.

Dual potential of microalgae as a sustainable biofuel feedstock and animal feed.

The rise in global population has led to explorations of alternative sources of energy and food. Because corn and soybean are staple food crops for humans, their common use as the main source of dietary energy and protein for food-producing animals directly competes with their allocation for human consumption. Alternatively, de-fatted marine microalgal biomass generated from the potential biofuel production may be a viable replacement of corn and soybean meal due to their high levels of protein, relatively well-balanced amino acid profiles, and rich contents of minerals and vitamins, along with unique bioactive compounds. Although the full-fatted (intact) microalgae represent the main source of omega-3 (n-3) polyunsaturated fatty acids including docohexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the de-fatted microalgal biomass may still contain good amounts of these components for enriching DHA/EPA in eggs, meats, and milk. This review is written to highlight the necessity and potential of using the de-fatted microalgal biomass as a new generation of animal feed in helping address the global energy, food, and environmental issues. Nutritional feasibility and limitation of the biomass as the new feed ingredient for simple-stomached species are elaborated. Potential applications of the biomass for generating value-added animal products are also explored.

Abstract C105: Development and utilization of a cell morphology database, MorphoBase, for drug target identification.

Abstract Background: Tumor cells often dynamically and specifically change shape depending on the mode of action of a drug. It prompted us to accumulate information on morphological changes induced by various compounds with known mechanisms and construct a database linking morphology to drug function, termed “MorphoBase,” which may be helpful in the target identification of a drug and the discovery of unique bioactive compounds. Material and Methods: We designed a high-content imaging algorithm to segment the cells and quantify the effects of various authentic compounds on morphological changes in 2 cancer cell lines, srcts-NRK and HeLa cells, against 12 morphological parameters. We also developed a data analysis program that incorporated multivariate statistical tools to analyze the similarities in morphological changes; principal component analysis (PCA) was applied to visualize phenotypic responses, and the similarities in morphological changes were ranked by 2 statistical computations: “Similarity ranking” determined by Euclidean distances and “Probability scores.” Results: A test set of 208 authentic compounds was created and their multiparametric phenotype responses were analyzed. As a result, inhibitors with a common mode of action formed clusters in PCA and were mutually ranked in their top 20 nearest neighbors, suggesting that MorphoBase can be used to successfully profile phenotypes by drug function. The importance of this database was verified by establishing the molecular targets of three antimitotic drugs and a new cytotoxic fungal metabolite pyrrolizilactone. When compared the similarity in induction of each morphologic feature with those in the dataset, their molecular targets were predicted to be tubulin and proteasome, respectively. We thus demonstrated that these compounds actually inhibit plausible targets in vitro and in a cell-based system. Conclusions: As an alternative to current high-content approaches, we developed a phenotype profiling system, based on MorphoBase. Our new system classifies the compounds by mode of action and predicts the molecular target of compounds with unknown mechanisms. This sensitive and convenient profiling tool has the potential to significantly cut the time it takes to establish on- and off-target effects of novel anticancer drugs, and will facilitate the discovery of bioactive compounds with unique mechanisms of action as well. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C105. Citation Format: Yushi Futamura, Makoto Kawatani, Makoto Muroi, Harumi Aono, Hiroyuki Osada. Development and utilization of a cell morphology database, MorphoBase, for drug target identification. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C105.

Antioxidant and antimicrobial properties of marine actinomycetes from sipadan Island, Sabah

Marine actinomycetes have great potential as producers of unique bioactive compounds due to its special adaptation in the harsh environment in the ocean. In this study, 100 strains of actinomycetes were isolated from marine sponges collected from sea area close to Sipadan Island in Sabah. Each strain was fermented in mannitol-peptone broth and the secondary metabolites were extracted by using acetone. The secondary metabolites were tested for their antimicrobial and antioxidant activity. The data showed that 22 strains exhibited potent antioxidant activity (IC50 between 56.3 and 99.1 μg/ml) in DPPH assay and 31 strains have strong inhibition activity (8 mm to 19 mm) on test pathogens (Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Klebsiella spp., Streptococcus pneumonia and Pseudomonas aeruginosa) in antimicrobial assay . These results give evidence that it is essential to scrutinize these under explored marine microbes in search of new drugs which have great potential to be used in the pharmaceutical fields. Keywords : Sipadan island, sponges, marine actinomycetes, antioxidant, antimicrobial.

Whole-Grain Cereal Bioactive Compounds and Their Health Benefits: A Review

Whole-grain cereals have received considerable attention in the last several decades due to the presence of unique blend of bioactive components like phytochemicals and antioxidants. However phytochemicals and antioxidants in whole-grains have not received as much attention as the phytochemicals in fruits and vegetables, although the increased consumption of whole-grains and whole-grain products has been associated with reduced risk of developing chronic diseases such as cardiovascular diseases, type 2 diabetes, some cancers and allcause mortality. These unique bioactive compounds in whole-grains are proposed to be responsible for the health benefits of whole-grain consumption. In this paper, various whole-grain bioactive compounds and the health benefits associated with their consumption are reviewed.

An Integrated In Vitro and In Vivo High-Throughput Screen Identifies Treatment Leads for Ependymoma

Using a mouse model of ependymoma-a chemoresistant brain tumor-we combined multicell high-throughput screening (HTS), kinome-wide binding assays, and invivo efficacy studies, to identify potential treatments with predicted toxicity against neural stem cells (NSC). We identified kinases within the insulin signaling pathway and centrosome cycle as regulators of ependymoma cell proliferation, and their corresponding inhibitors as potential therapies. FDA approved drugs not currently used to treat ependymoma were also identified that posses selective toxicity against ependymoma cells relative to normal NSCs both invitro and invivo, e.g., 5-fluorouracil. Our comprehensive approach advances understanding of the biology and treatment of ependymoma including the discovery of several treatment leads for immediate clinical translation.

Stem cells of marine invertebrates: Regulation of proliferation and induction of differentiation in vitro

The review surveys own and the literature data on the plasticity of marine invertebrate stem cells. Stem and embryonic cell cultures of marine invertebrates are a novel model system characterized by a high level of physiological and synthetic processes. The production of biologically active substances in vitro may be an alternative to chemical synthesis and aquaculture. The factors involved in determination and maintenance of the pluripotency of marine invertebrate stem cells have been analyzed. The technology of the directed differentiation of marine invertebrate stem cells into certain functionally active cells in vitro embraces the use of different growth factors, various natural and artificial substrates, and unique bioactive compounds from marine invertebrate tissues. To increase the expression levels of regulatory genes, we applied genetically engineered constructions with foreign genes. The regulation of growth and differentiation of marine invertebrate stem cells opens new prospective uses for their application in marine biotechnology and is helpful for research in developmental biology.

PP‐05 Pharmacology/pharmacotherapy

Pedalium murex is a fruit-bearing annual herb, native to South India, Mexico and tropical Africa. The plant is widely used to treat numerous diseases including gastric ulcer, asthma, heart problems, anti inflammatory activity and particularly urinary disorders. Traditional medicine has become a skilled approach by means of rational values in handling a variety of diseases and developing an affordable phytotherapy. It is proclaimed that P.murex is an expensive source of unique bioactive compounds for the development of natural medicines against various diseases.This review provides the details of ethno pharmacological importance of P. murex, as well as its composition of phytochemicals, biological activities and traditional usage. Also provides a source for future studies such as isolation of bioactive components and mechanism of action of this plant extract.

Biology of the Porifera: cell culture

The discovery that dissociated sponge cells will reaggregate to form a functional organism was the basis for the establishment of sponge cell cultures that have been used as a model for the study of fundamental processes in developmental biology and immunology. More recent is the discovery of unique bioactive compounds in marine sponges, and the feasibility of in vitro production of these chemicals is being evaluated. Techniques are well established for cell dissociation; development of several nutrient media formulations has resulted in improvements in viability and cell division; and molecular approaches to identification of genes responsible for regulation of cell cycling may provide unique perspectives in culture optimization. The use of novel substrates for immobilization of cells offers alternatives for proliferation and scale-up. All of these results support the potential for development of a model system for the study of basic metabolic processes involved in cell differentiation, as well as an in vitro production system for sponge-derived bioactive compounds. Perhaps more important, however, is the development of cell lines of these "simple" metazoans to facilitate basic cell physiology and molecular biology research that may be applied to understanding more complex metazoan systems, including humans.

Sponges

What are sponges? Called Porifera because they are porous or ‘pore bearing’, sponges are animals designed around a unique body plan of canals and chambers through which they pump water to extract food. There is no centralized gut, no front or back. They lack conventional nerves and muscle, which means movement is only at the pace of the individual cell crawling. There are an estimated 15,000 sponge species living today, but only about half of them have been described and named. Their ecology and survival is often reliant upon the ability to produce unique bioactive compounds; as a result, many species are targets of natural product chemists and bioprospectors. Are all sponges alike? Three classes of sponges have been defined, each with unique body plan features. Demosponges are cellular and most are supported by a siliceous skeleton of two- and four-rayed spicules. Hexactinellid or glass sponges have a six-rayed glass skeleton and are syncytial rather than cellular. This construction allows them to propagate action potentials over great distances. Calcareous sponges comprise less than 5% of living sponges and are characterized by a calcium carbonate skeleton and cellular organization. This is the only group in which the three grades of sponge body design – asconoid, syconoid and leuconoid – are apparent. Although systematists still use this three-class taxonomy, current phylogenetic analysis suggests that sponges could be paraphyletic, with the calcareous sponges grouping with other metazoans. How do sponges reproduce? Sponges have a great array of reproductive patterns. There are no reproductive organs as such, so gametes are derived from stem cells in the adult. Some groups are oviparous and release gametes into the sea, but far more sponges brood their eggs and embryos so that development occurs in the adult. In the latter group, embryogenesis generally gives rise to differentiated cell types that are organized by gastrulation-like processes to form a bi-layered – and in some a tri-layered – larva that is free-swimming for one to several days. Some sponges can also reproduce asexually by budding off portions of the adult body, or by sequestering cells into an overwintering cyst or gemmule. What can sponges tell us about the evolutionary origins of multicellularity? Similarity between the feeding cell of sponges (the choanocyte) and cells of a group of unicellular and colonial protists (choanoflagellates) suggested to early workers that sponges were examples of some of the earliest evolutionary experiments with multicellularity. Recent molecular phylogenies have confirmed that sponges are metazoans and that choanoflagellates are their nearest sister group. Because of their ancient origins, sponges have long been used as models for exploring the origin of key metazoan characteristics such as neurons, muscle and tissues. Haeckel (1872) and Metschnikoff (1874) studied sponges to determine whether germ layers are homologous in all animals, and Haeckel coined the term ‘gastrula’ for the ciliated larva. Wilson (1910) discovered that cells from dissociated pieces of sponge could recognize each other and reaggregate to form a new individual. If cells from two species are mixed they will sort into species-specific clumps before reforming. Evidence of self-recognition in sponges suggests this is an ancient animal trait. Today, sponges are considered the most basal extant evolutionary lineage in the animal kingdom. While the adult sponge lacks an easily recognizable metazoan body plan, the embryo and larva have great affinities with other animals. Sponge cells move during embryogenesis in a manner akin to gastrulation, resulting in different larval cell types being patterned along an anterior–posterior axis. Recent evidence suggests that many metazoan transcription factor families are expressed during sponge embryogenesis. Is there a sponge model system? Few sponges live well in aquaria so it has been difficult developing sponge model systems. European and Japanese groups have pioneered use of adult formation from gemmules of the demosponges Ephydatia and Spongilla, showing the expression of homeobox and other developmental genes during formation of canals and chambers. Aggregate cultures of demosponge cells – the ‘primorph’ system of Geodia and Suberites – also allow for analysis of formation of the adult body plan, and many genes have been identified that are expressed during this process. Recently a tropical marine demosponge, Reniera, with year-round embryos and larvae has been identified and studied. Because of the clearer relationship of sponge embryos to other animals, this last model has the potential to draw sponges tighter into the metazoan fold. Is there a sponge genome project? Yes:the US Department of Energy Joint Genome Institute will sequence the genome of Reniera (http://www.jgi.doe.gov/sequencing/why/CSP2005/reniera.html). DNA for the project is derived from Reniera larvae, which lack the diversity of prokaryotic and eukaryotic contaminants found in adult sponges. There is also a number of developmental and adult EST projects.

Synthesis and phenotypic screening of a Guanine-mimetic library.

Going for guanine. We have synthesized a split-pool library of guanine-mimetics. Phenotypic screening of this library in mammalian tissue culture cells by fluorescence microscopy revealed several unique bioactive compounds, see scheme.

Products of the isoprostane pathway: unique bioactive compounds and markers of lipid peroxidation.

We previously reported the discovery of prostaglandin F2-like compounds (F2-isoprostanes) formed by nonenzymatic free-radical-induced peroxidation of arachidonic acid. Quantification of F2-isoprostanes has proven to be a major advance in assessing oxidative stress status in vivo. Central in the pathway of formation of isoprostanes are prostaglandin H2-like endoperoxides, which also undergo rearrangement in vivo to form E-ring, D-ring, and thromboxane-ring compounds. E2- and D2-isoprostanes also undergo dehydration in vivo to form reactive cyclopentenone A2- and J2-isoprostanes, which are susceptible to Michael addition reactions with thiols. Recently, we described the formation of highly reactive gamma-ketoaldehydes (now termed isoketals) as products of isoprostane endoperoxide rearrangement which readily adduct to lysine residues on proteins and induce cross-links at rates that far exceed other aldehyde products of lipid peroxidation. Isoprostane-like compounds (neuroprostanes) and isoketal-like compounds (neuroketals) are formed from oxidation of docosahexaenoic acid, which is enriched in the brain, and measurement of neuroprostanes may provide a unique marker of oxidative neuronal injury.