Current Bioactive Compounds - Volume 10, Issue 1, 2014

Diet and lifestyle are considered essential to promote and maintain the well-being as well as to prevent the onset of diseases linked to wrong lifestyle and dietary habits that can both determine pathological conditions. Many of these require pharmacological therapy; nevertheless, some can be prevented and taken care of with the use of nutraceuticals in the daily diet. Nutraceuticals are pharmacologically active substances that can be extracted from vegetal or animal food, concentrated and administered in a suitable pharmaceutical form. A nutraceutical hence is a food or part of a food that produces health beneficial effects, including the prevention and/or treatment of a disease. The proper use of these food-drugs can help to reduce and/or to slow the onset of diseases, and, in particular, all the lifestyle related health conditions, e.g. the metabolic syndrome, which is strongly depending on the improper lifestyle and incorrect dietary habit. The effectiveness of nutraceuticals can be seen with their inclusion in the daily diet as a preventive agent against the onset of disease and, therefore, beyond the diet but before the need to use a drug to treat the symptoms arising from the onset of a pathologic condition. Hypercholesterolemia, hypertension, obesity are some relevant and current examples of lifestyle related diseases for which a proper education and prevention that includes nutraceuticals in the diet is needed.

Amino terminal peptides of the general form Gly-Gly-His have been used to introduce single sites of metal binding and redox activity into a wide range of biomolecules to create bioactive compounds and conjugates capable of substrate oxidation. We report here that Gly-Gly-His-like peptides linked in a tandem fashion can also be generated leading to multi-metal binding arrays. While metal binding by the native Gly-Gly-His motif (typically to Cu2+, Ni2+, or Co2+) requires a terminal peptide amine ligand, previous work has demonstrated that an ornithine (Orn) residue can be substituted for the terminal Gly residue to allow solid-phase peptide synthesis to continue via the side chain N-δ. This strategy thus frees the Orn residue N-α for metal binding and permits placement of a Gly-Gly-His-like metal binding domain at any location within a linear, synthetic peptide chain. As we show here, this strategy also permits the assembly of tandem arrays of metal binding units in linear peptides of the form: NH2-Gly-Gly-His-[( δ)-Orn-Gly-His]n-(δ)-Orn-Gly-His- CONH2 (where n = 0, 1, and 2). Metal binding titrations of these tandem arrays monitored by UV-vis and ESI-MS indicated that they bind Cu2+, Ni2+, or Co2+ at each available metal binding site. Further, it was found that these systems retained their ability to modify DNA oxidatively and to an extent greater than their parent M(II)•Gly-Gly-His. These findings suggest that the tandem array metallopeptides described here may function with increased efficiency as “next generation” appendages in the design of bioactive compounds and conjugates.

Aims: To investigate the in vitro and in vivo anti-inflammatory effects of Bacopa monnieri extracts in HL-60 cells and in OVA-induced airway inflammation in BALB/C mice. Materials and Methods: Bacopa monnieri (Brahmi) leaves and stems were collected in Vidisha (M.P.), India, identified and air-dried. The dried plant materials were pulverized to a powder, extracted in methanol to exhaustion, dried and fractionated. The extracts and fractions were tested for their effects on leukotriene C4 synthase, leukotriene A4hydrolase and cyclooxygenase-2 in HL-60 cells. The active dried methanol extract of B. monnieri was then tested in vivo in an OVAinduced asthma mouse model and inflammation was assessed using 2-D imaging. Results: Bacopa monnieri extracts and partitions inhibited leukotriene-C4-synthase, leukotriene-A4-hydrolase and/or cyclooxygenase- 2 (COX-2) activities in cultured HL-60 cells. The EtOAc partition of the extracts inhibited the activity of leukotriene-C4-synthase by 69%, and down-regulated the expression of the mRNA of this enzyme in HL-60 cells. The results demonstrated significant inhibition of leukotriene-C4-synthase, leukotriene-A4-hydrolase and cyclooxygenase-2 (COX-2) activities by the EtOAc fraction of B. monnieri, suggesting a plausible mechanism of action for the management of asthma. Intragastric administration of the B. monnieri extract led to a reduction of OVA-induced lung inflammation as determined by 2-D in vivo imaging using a Xenogen IVIS imaging system. Two compounds were isolated from the active fraction, namely quercetin and isochlorogenic acid A. Conclusions: Extracts of B. monnieri exhibited significant anti-inflammatory effects both in vitro and in vivo, which supported its traditional use for the treatment of inflammatory lung disease and asthma.

Tyrosinase is a copper-containing enzyme that catalyzes melanin synthesis in skin melanocytes by oxidation. Eighteen compounds of different classes, i.e., pentacyclic triterpenes, flavonoids, steroids, aromatics, mono and triglycerides and straight chain hydrocarbons were isolated from the fruit pulp and seeds of Madhuca latifolia and were identified as betulinic acid 3-β-caprylate (1), stigmasterol (2), ursolic acid (3), p-hydroxyacetophenone (4), hydroquinone (5), 4-hydroxymethylbenzoate (6), quercetin (7), taxifolin (8), hexadecenoic acid (9), β-amyrin acetate (10), triglyceride of stearo-oleo-palmitin (11), erythrodiol 3-β-caprylate (12), oleanolic acid 3-β-caprylate (13), monoglyceride of oleic acid (14), nonacosane (15), madhushazone (16), madhusalmone (17), madhucic acid (18). Structural characterizations of these were made by comparison of 1H and 13C NMR spectra with those reported in the literatures. The tyrosinase inhibitory potency of these compounds has been evaluated and attempts to justify their structure-acitivity relationships have been made in the present work. The compounds 3, 4, 5, 6a (acetyle derivative of 6), 7, 8a (acetyl derivative of 8), 16, 17, and 18 exhibited much better potency than the reference inhibitor kojic acid, whereas compound 3 was the most active among them.

The effect of triterpene glycosides - monoammonium salt of glycyrrhizinic acid (monoammonium glycyrrhizinate) and of alpha-hederin and hederacoside C from ivy (Hedera L.) on chromatin condensation in human buccal epithelium cells was investigated. Heterochromatin granules in cell nuclei were stained with 2% orcein. The state of chromatin was assessed by heterochromatin granules quantity - HGQ at magnification x 600. The number of granules was assessed in 30 nuclei and the mean HGQ value was calculated. Each experiment was done in triplex. In experiments were used cells of 4 donors. Cells were placed in solutions of glycosides in concentrations of 5, 25, and 50 mg/l for 2 hours. Statistical analysis was performed by the Student’s method. The monoammonium glycyrrhizinate was tested in cells of one donor and induced HGQ increase in a concentration of 50 mg/l. The alpha-hederin in a concentration of 25 mg/l caused a significant increase of HGQ in cells of all four donors. Hederacoside C in concentrations 5 and 25 mg/l induced increase of HGQ in cells of three donors of four. Cells of one donor were resistant to hederacoside C. By computation analysis it was shown that triterpene glycosides have low genotoxic activity. The HGQ determination enables to register individual peculiarities in cell response to biologically active compounds which may be used in personalized medicine.

Lectins are a heterogeneous group of proteins that specifically and reversibly bind to carbohydrates without altering their covalent structure. Advances in the plant lectin research have provided many insights into the role of carbohydrate- protein interactions, which have contributed to the development of various others (for example: oncology, immunology, microbiology, molecular biology and diagnostic). Isolectins isolated from Cratylia mollis, a native plant of Brazilian Caatinga biome, have demonstrated a remarkable biotechnological aptitude, especially the isoform called Cramoll 1,4 (pCramoll). This work aims to present a comprehensive review of the biomedical applications of pCramoll, which has been used as immunomodulatory, antitumoral, mitogenic, antiparasitic, and healing agent. Other biotechnological applications also involve the characterization of human cancerous tissues, and the development of af nity matrices and biosensors. The present review comprises of four main themes: (1) an overview of plant lectins and their biological effects; (2) general characteristics of the pCramoll; (3) biotechnological applications of this lectin; and (4) recent progress in production of pCramoll in heterologous system. The process of isolation, structural characterization and biotechnological applications of pCramoll is one of the greatest success stories among Brazilian lectins. Recently, the expression of functional recombinant Cramoll 1 (rCramoll) in Escherichia coli was reported by our group. This review will be a valuable resource for more studies in the lectin field, which has a great potential to reveal new targets for therapeutic strategies, molecular diagnosis and biotechnology process.

The Genus Garcinia is one of the tropical underutilized medicinal fruit crops. It contains around 200 species, out of which 35 species are available in India. In India it is present in two different ecosystems, the Western Ghats and the Himalayan foot hills. G. indica, G. gummi-gutta, G. xanthochymus, G. subelliptica and G. mangostana are the common species of Western Ghats while G. lanceaefolia, G.pedunculata, and G. kydia are common species in North eastern Himalayan foot hills. The medicinal importance of Garcinia is due to the presence of HCA (hydroxycitric acid) an anti-obesity compound. Among the primary metabolites, carbohydrates are present in good percentage. The mineral composition showed a great variation in the percentages of potassium, calcium and magnesium (SD being 17.2, 3.5 and 12.15 respectively). The study of vitamin content, organic acids, xanthones and anti-oxidant activity reveals that Garcinia is an important medicinal crop with ample nutraceutical properties.

Breast cancer and prostate cancer are the most common invasive types of cancers in women and men. Many of the recent advances in understanding the pathophysiology of breast and prostate cancers have paved the way for new treatment strategies. The alarming increase in the global cancer death toll has fueled the quest for new effective anti-tumor drugs through biological screening of both terrestrial and marine organisms. Recently, marine-derived natural bioactive products, isolated from aquatic fungi, cyanobacteria, sponges, algae, and tunicates, have been found to exhibit various anti-cancer activities including anti-angiogenic, anti-proliferative, inhibition of topoisomerase activities and induction of apoptosis. Thus, marine derived chemical derivatives such as alkaloids, macrolides, terpenes and other miscellaneous compounds possess anticancer properties. Hence, this review discusses the role of marine compounds on breast and prostate cancer.