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New bioactive compounds of plant origin.

Crude extracts of Withania somnifera (WS) and Polygonum equisetiforme (PE) as well as the pure compounds isolated therefrom were screened for antibacterial and antifungal activity against 20 bacterial and 17 fungal cultures. The crude extract of PE and WS inhibited the growth of T. mentagrophyte, M. canis and A. boydii at an MIC of 450-500 microg/ml whereas the pure compounds inhibited the growth at MIC of 300-350 micro/ml. Species of Corynebacterium, Bacillus, Streptococcus and Staphylococcus were found to be highly susceptible to both the crude sad the pure compounds. MIC values of both crude extracts for different organisms tested were found to be higher (200-350 microg/ml) than the pure compounds (150-170 microg/ml). The crude extract of PE did not inhibit the growth of Ps. aeruginosa, however, the pure compound was found to be bacteriostatic. Brine shrimp and BALB/c mice lethality test indicated that these extracts maybe toxic at high concentration.

Journal Article↗

Echinoderms: their culture and bioactive compounds.

Of the five extant classes of echinoderms, it is the sea urchins (Echinoidea) and the sea cucumbers (Holothuroidea) that are both commercially fished and heavily overexploited. In sea urchins, it is the gonad of both males and females, normally referred to as'roe', that is a sought-after food. In the sea cucumber, the principal product is the boiled and dried body-wall or 'bêche-de-mer' for which there is an increasing demand. Many sea urchin and sea cucumber fisheries still have no management system or restrictions in place, and for those that do, the prognosis for catches to continue even at a reduced level is poor. Cultivation of these species increasingly becomes a necessity, both for stock enhancement programs and as a means to meet market demand. Sea urchin culture has been practised on a large scale in Japan for many decades, and effective methods for the culture and reseeding of species in these waters have been long established. Juvenile urchins are produced in their millions in state-sponsored hatcheries, for release to managed areas of seafloor. Outside of Japan, sea urchin cultivation is still a fairly recent practice, less than 10 years old, and largely still at a research level, although a range of species are now being produced in a variety of different culture systems. It is essential that the culture systems are adapted to be species-specific and meet with local environmental constraints. Sea cucumber cultivation originated in Japan in the 1930s and is now well established there and in China. Methods for mass cultivation of the tropical Holothuria scabra are now well established and practised in India, Australia, Indonesia, the Maldives and the Solomon Islands, with the focus of the research effort for both temperate and tropical species being centred on the production of juveniles in hatcheries for the restoration and enhancement of wild stocks. Like many other marine organisms, echinoderms have been, and continue to be, examined as a source of biologically active compounds with biomedical applications. Sea cucumber has been valued in Chinese medicine for hundreds of years as a cure for a wide variety of ailments. Some more recently isolated compounds, mainly from sea cucumbers and starfish, and including those with antitumour, antiviral, anticoagulant and antimicrobial activity are summarised below. When wild stocks decline, the demand created in the market place raises to the price of the product and, consequently, culturing is more likely to become viable economically. As this review shows, there have been dramatic advances in the culture methods of sea urchins and sea cucumbers in the last 10-15 years, to the extent that one can conclude that currently the major obstacles to successful cultivation are indeed economic rather than biological. Hence the future of the echinoculture industry is closely linked to that of the fisheries, whose fate will ultimately determine the market forces that will shape this growing industry.

Animals↗

Comparative ethnopharmacology: a rational method for the search of bioactive compounds in plants.

In the present preliminary communication on comparative ethnopharmacology a limited universe of data extracted from the Journal of Ethnopharmacology (vols. 1-25) was used for the construction of ethnopharmacological profiles of ten families of dicotyledons. Intraprofile analysis suggested the main uses of plant species (indicated by the maximal citation frequencies), as opposed to the spurious ones (represented by base line fluctuations), to possess a solid chemotaxonomic basis. Interprofile analysis via correlation of ethnopharmacological distances and morphological (evolutionary) distances among the same plant families suggested comparative ethnopharmacology to possess also a phylogenetic (chemosystematic) basis. This result establishes comparative ethnopharmacology as a novel and potentially useful scientific discipline.

Plants, Medicinal↗

Biorhythms, system organization and bioactive compounds. I. Theoretical background.

Theoretical considerations are presented for the analysis of nonautonomous, nonlinear, and nonconservative systems. It was suggested that stability and the kind of oscillations are different expressions of the same thing, the response to external signals. A necessary condition of oscillatory systems is that the system consists of coupled units and that the system be influenced by external starting signals. Periodicities can only be observed when the energy dissipation of the system is compensated by maintaining signals. The internal description of biosystems is essentially structural, and the system behavior should be described in terms of system variables, their interrelationships, and the input-output relations in a single equation system.

Feedback↗

Structural studies on bioactive compounds. Part 26. Hydrogen bonding in the crystal structure of the N-methylformamide solvate of the immunomodulatory agent 2-amino-5-bromo-6-phenylpyrimidin-4-one (bropirimine): implications for the design of novel anti-tumour strategies.

The immunomodulatory agent bropirimine crystallizes from N-methylformamide (NMF) as a triply hydrogen-bonded duplex in the manner of a Watson-Crick guanine:cytosine base pair. The stoichiometry of the solvate is bropirimine:NMF (2:1) and all NMF molecules are in the Z-rotomeric form. The intermolecular hydrogen bonding is disrupted when the solvate is dissolved in deuteriated dimethyl sulphoxide at 37 degrees C. Bropirimine and other molecules which possess the 2-aminopyrimidin-4-one fragment are potentially capable of recognizing guanine or cytosine residues in single-stranded RNA or DNA by Watson-Crick bonding or double-stranded DNA by Hoogsteen bonds. The immunomodulatory properties of these compounds might be triggered by these encounters.

Adjuvants, Immunologic↗

Structural studies on bioactive compounds. Part 27. Chemistry of the immunomodulatory agent bropirimine.

The 2-amino-6-phenylpyrimidin-4(3H)-ones bropirimine (1) and the debrominated analogue (4) undergo electrophilic nitration and sulphonation in the meta-position of the 6-phenyl group in strongly acidic conditions. Subsequent electrophilic substitutions take place in the 5-position of the pyrimidine ring, if vacant. Rearrangement of the 2-nitramino-6-phenyl-pyrimidines (22) and (23) furnishes the 2-amino-6-(3-nitrophenyl)pyrimidines (9) and (18), respectively. Nucleophilic substitutions, in contrast, occur readily in the pyrimidine 2-, 4- and 6-positions. Debromination of bropirimine by hydrazine hydrate can be rationalized by invoking an initial attack by the nucleophile at the electron-deficient pyrimidine 6-position. The reactive 4-chloro group in 5-bromo-4-chloro-2-formylamino-6-phenylpyrimidine (25) can be displaced with a range of nucleophiles (azide ion, ethanol, hydrazine, and primary and secondary aliphatic amines), without loss of the bromo substituent.

Adjuvants, Immunologic↗

Flavonoid-mediated inhibition of intestinal ABC transporters may affect the oral bioavailability of drugs, food-borne toxic compounds and bioactive ingredients.

The transcellular transport of ingested food ingredients across the intestinal epithelial barrier is an important factor determining bioavailability upon oral intake. This transcellular transport of many chemicals, food ingredients, drugs or toxic compounds over the intestinal epithelium can be highly dependent on the activity of membrane bound ATP binding cassette (ABC) transport proteins, able to export the compounds from the intestinal cells. The present review describes the ABC transporters involved in the efflux of bioactive compounds from the intestinal cells, either to the basolateral blood side, facilitating absorption, or back into the intestinal lumen, reducing bioavailability. The role of the ABC transporters in intestinal transcellular uptake also implies a role for inhibitors of these transporters in modulation of the bioavailability upon oral uptake. The present paper focuses on the role of flavonoids as important modulators or substrates of intestinal ABC transport proteins. Several examples of such an effect of flavonoids are presented. It can be concluded that flavonoid-mediated inhibition of ABC transporters may affect the bioavailability of drugs, bioactive food ingredients and/or food-borne toxic compounds upon oral uptake. All together it appears that the flavonoid-mediated interactions at the level of the intestinal ABC transport proteins may be an important mechanism for unexpected food-drug, food-toxin or food-food interactions. The overview also indicates that future studies should focus on i) in vivo validation of the flavonoid-mediated effects on bioavailability of drugs, toxins and beneficial bioactive food ingredients detected in in vitro models, and on ii) the role of flavonoid phase II metabolism in modulating the activity of the flavonoids to act as ABC transporter inhibitors and/or substrates.

ATP-Binding Cassette Transporters↗

Initiation of an Aquaculture of Sponges for the Sustainable Production of Bioactive Metabolites in Open Systems: Example, Geodia cydonium.

Among Metazoa, sponges (phylum Porifera) are the richest source for different bioactive compounds. The availability of the raw material is, however, restricted. To obtain enough of the bioactive compounds for application in human therapy, sponges have to be cultured in in vitro systems. One technique for the establishment of a long-term cell culture from sponges has recently been elaborated. Here, we present a procedure to cultivate tissue samples from sponges in an open system. The species Geodia cydonium, which produces bioactive compounds, has been selected. Tissue samples of approximately 10 g were attached to the bottoms of cultivation trays. After 2 to 3 days, the tissue samples formed a robust contact with the metal support. Subsequently, sets of trays, called tray batteries, either remained in huge aquaria at the Center for Marine Research or were transferred to the vicinity of a fish and mussel farm. The growth rates of the samples remained unchanged within the first month; however, after 3 and 6 months, they increased to 147% and 189%, respectively. In parallel, extracts were prepared from the tissue samples and tested for cytotoxicity in a mouse lymphoma cell assay system. Extracts from cultured tissue initially had a low inhibitory potency; however, after cultivation for 3 or 6 months, values comparable to those of extracts from sponges taken from the biotope were found. In addition, a molecular marker was applied to document the response (health state) of the tissue and the identity of the material in culture. The CD63 molecule was chosen because the expression of this molecule in mammalian systems changes with the age of the animals. The corresponding complementary DNA was isolated from Geodia cydonium. With this probe, the level of expression in cultured tissue samples decreased immediately after starting cultivation; after a cultivation period of 6 months, however, values were similar to those found in controls. These data show that sponge species that produce bioactive compounds can be cultivated in open systems, in which they retain their potency to produce bioactive compounds as well as their health state.

Journal Article↗

Liquid chromatography-tandem mass spectrometry of bioactive pharmaceutical compounds in the aquatic environment--a decade's activities.

The occurrence of bioactive pharmaceutical compounds in the aquatic environment is an emerging concern. Liquid chromatography, coupled with mass spectrometry (LC-MS) or tandem mass spectrometry (LC-MS-MS) using an electrospray ionization interface, is a crucial tool for addressing this issue. We review in this manuscript LC-MS and LC-MS-MS studies on waterborne PhACs in the last decade, including research activity in different geographical areas and the current status of the technology used for sample preparation, chromatographic separation, and mass spectrometric detection. A detailed overview on quality-control and quality-assurance (QC/QA) procedures is also presented, with emphasis on the need for a concerted approach to determine the numerical values associated with detection limits, and the use of low-level data qualifiers.

Animals↗

Skin bioavailability of dietary vitamin E, carotenoids, polyphenols, vitamin C, zinc and selenium.

Dietary bioactive compounds (vitamin E, carotenoids, polyphenols, vitamin C, Se and Zn) have beneficial effects on skin health. The classical route of administration of active compounds is by topical application direct to the skin, and manufacturers have substantial experience of formulating ingredients in this field. However, the use of functional foods and oral supplements for improving skin condition is increasing. For oral consumption, some dietary components could have an indirect effect on the skin via, for example, secondary messengers. However, in the case of the dietary bioactive compounds considered here, we assume that they must pass down the gastrointestinal tract, cross the intestinal barrier, reach the blood circulation, and then be distributed to the different tissues of the body including the skin. The advantages of this route of administration are that the dietary bioactive compounds are metabolized and then presented to the entire tissue, potentially in an active form. Also, the blood continuously replenishes the skin with these bioactive compounds, which can then be distributed to all skin compartments (i.e. epidermis, dermis, subcutaneous fat and also to sebum). Where known, the distribution and mechanisms of transport of dietary bioactive compounds in skin are presented. Even for compounds that have been studied well in other organs, information on skin is relatively sparse. Gaps in knowledge are identified and suggestions made for future research.

Administration, Oral↗