Orodispersible Film Based on Maltodextrin: A Convenient and Suitable Method for Iron Supplementation.

Orodispersible film (ODF) is an innovative dosage form used to administer drugs and nutrients, designed to disintegrate or dissolve in the oral cavity without needing water. One of the advantages of ODF is that it is suitable for administration in older people and children who have difficulty swallowing because of psychological or physiological deficiencies. This article describes the development of an ODF based on maltodextrin, which is easy to administer, has a pleasant taste, and is suitable for iron supplementation. An ODF containing 30 mg of iron as pyrophosphate and 400 µg of folic acid (iron ODF) was developed and manufactured on an industrial scale. The kinetic profile for serum iron and folic acid upon consumption of ODF compared with a Sucrosomial® iron capsule (known for its high bioavailability) was evaluated in a crossover clinical trial. The study was conducted in nine healthy women, and the serum iron profile (AUC0-8, Tmax, and Cmax) of both formulations was defined. Results showed that the rate and extent of elemental iron absorption with iron ODF was comparable to that obtained using the Sucrosomial® iron capsule. These data represent the first evidence of iron and folic acid absorption concerning the newly developed ODF. Iron ODF was proven to be a suitable product for oral iron supplementation.

Rhus Coriaria L. Extract: Antioxidant Effect and Modulation of Bioenergetic Capacity in Fibroblasts from Parkinson's Disease Patients and THP-1 Macrophages.

Sumac, Rhus coriaria L., is a Mediterranean plant showing several useful properties, such as antioxidant and neuroprotective effects. Currently, there is no evidence about its possible neuroprotective action in Parkinson's disease (PD). We hypothesized that sumac could modulate mitochondrial functionality in fibroblasts of familial early-onset PD patients showing PARK2 mutations. Sumac extract volatile profile, polyphenolic content and antioxidant activity have been previously characterized. We evaluated ROS and ATP levels on sumac-treated patients' and healthy control fibroblasts. In PD fibroblasts, all treatments were effective in reducing H2O2 levels, while patients' ATP content was modulated differently, probably due to the varying mutations in the PARK2 gene found in individual patients which are also involved in different mitochondrial phenotypes. We also investigated the effect of sumac extract on THP-1-differentiated macrophages, which show different embryogenic origin with respect to fibroblasts. In THP-1 macrophages, sumac treatment determined a reduction in H2O2 levels and an increase in the mitochondrial ATP content in M1, assuming that sumac could polarize the M1 to M2 phenotype, as demonstrated with other food-derived compounds rich in polyphenols. In conclusion, Rhus coriaria L. extracts could represent a potential nutraceutical approach to PD.

Development and Box-Behnken design optimization of a green extraction method natural deep eutectic solvent-based for phenolic compounds from barley malt rootlets.

In recent years, attention has been turned finding new sources of phenolic compounds, antioxidant molecules, main by-products from the agri-food chain like barley malt rootlets (BMRs). Traditionally, phenolic compounds are extracted from food matrices using different procedures, for example, solid-liquid, liquid-liquid, or solid-phase extraction techniques employing organic solvents. With the advent of green chemistry, attention has been paid to the search for green, nontoxic, inexpensive, and nonflammable solvents and the natural deep eutectic solvents (NADESs) respect these characteristics. The aim of this project was to develop and optimize an environmentally friendly, inexpensive, and rapid extraction method for phenolic compounds from BMRs using natural DESs as extractive solvents. Several natural DESs were tested as extractive solvents and, among them, the best results in terms of total phenolic content were obtained using a choline chloride-malic acid (1:2 molar ratio)-based mixture. Box-Behnken experimental design guaranteed the extraction of 9.51 ± 0.83 gallic acid equivalent/g of BMRs, under the following optimal extraction conditions: 1:21 solid-to-liquid ratio, 80°C as extraction temperature, 43 min as the time of extraction, and 29% as a percentage of added water in the NADESs. Phenolic acids and flavonoids were detected in the BMRs extract through HPLC-PDA/MS analysis.

Bovine Colostrum Applications in Sick and Healthy People: A Systematic Review.

Colostrum is the first secretion of mammalian glands during the early period after birth giving. Its components are biologically active and have beneficial effects on new-born growth and well-being. Bovine colostrum has the highest concentration of these substances and its supplementation or application may provide health benefits. This systematic review was conducted to update current knowledge on bovine colostrum effects including all administration routes on healthy and sick subjects. Full texts or abstracts of twenty-eight papers as reports of systematic reviews, randomized controlled trials, observational studies and case series were included after searches in Medline, Embase, Cochrane Library and Cinahl databases. The full texts of selected studies were assessed for quality using validated tools and their results were summarized in different categories. Studies were highly heterogeneous as regards to population, intervention, outcome and risk of bias. Bovine colostrum topical application was shown effective on vaginal dryness related symptoms limitation. Its use as food supplement showed interesting effects preventing upper respiratory illness in sportsmen, modulating immune system response and reducing intestinal permeability in healthy and sick subjects. Conflicting results were provided in pediatric population and little evidence is available on its use with older adults. Further studies are mandatory to better understand all factors influencing its activity.

Distribution of bioactives in entire mill chain from the drupe to the oil and wastes.

Industrial olive oil production generates large amounts of by-products, mainly pomaces and wastewaters. The latter, in particular, represents serious environmental problems requiring special treatments prior to disposal. While olive pomace finds use as alternative energy source, wastewaters still remain a task since it is not reusable, representing an additional cost on olive oil for its treatments. This study is a "comprehensive" overview on the distribution of bioactives in entire mill chain from the drupe to the oil and wastes. Identification was achieved through liquid chromatography coupled with mass spectrometry, spectrofotometric and fluorimetric detection. Phenols resulted the most abundant class of substances, with the highest hydroxytyrosol amounts in wastewater (214 mg/kg). Pomace contained a total of 304 mg/kg in terms of bioactives, thus representing a potential food supplement ingredient for functional foods with high nutritional values.

Chemical Characterization of Three Accessions of Brassica juncea L. Extracts from Different Plant Tissues.

Indian mustard or Brassica juncea (B. juncea) is an oilseed plant used in many types of food (as mustard or IV range salad). It also has non-food uses (e.g., as green manure), and is a good model for phytoremediation of metals and pesticides. In recent years, it gained special attention due to its biological compounds and potential beneficial effects on human health. In this study, different tissues, namely leaves, stems, roots, and flowers of three accessions of B. juncea: ISCI 99 (Sample A), ISCI Top (Sample B), and "Broad-leaf" (Sample C) were analyzed by HPLC-PDA/ESI-MS/MS. Most polyphenols identified were bound to sugars and phenolic acids. Among the three cultivars, Sample A flowers turned were the richest ones, and the most abundant bioactive identified was represented by Isorhamnetin 3,7-diglucoside (683.62 µg/100 mg dry weight (DW) in Sample A, 433.65 µg/100 mg DW in Sample B, and 644.43 µg/100 mg DW in Sample C). In addition, the most complex samples, viz. leaves were analyzed by GC-FID/MS. The major volatile constituents of B. juncea L. leaves extract in the three cultivars were benzenepropanenitrile (34.94% in Sample B, 8.16% in Sample A, 6.24% in Sample C), followed by benzofuranone (8.54% in Sample A, 6.32% in Sample C, 3.64% in Sample B), and phytone (3.77% in Sample B, 2.85% in Sample A, 1.01% in Sample C). The overall evaluation of different tissues from three B. juncea accessions, through chemical analysis of the volatile and non-volatile compounds, can be advantageously taken into consideration for future use as dietary supplements and nutraceuticals in food matrices.

Choline-chloride and betaine-based deep eutectic solvents for green extraction of nutraceutical compounds from spent coffee ground.

Coffee beans contain several compounds which have shown nutraceutial properties; among them chlorogenic acids (CGAs) are the most studied, have shown nutraceutical properties. These molecules are also present in the waste by-product known as spent coffee grounds (SCG). SCG are generated during the production of coffee drink, whereby roasted, ground coffee beans are heat or steam treated. A HPLC-PDA/ESI-MS method has been developed for the analysis of the most representative CGAs in SCG samples using a green extraction approach based on deep eutectic solvents (DESs). We examined fifteen different DESs based on choline chloride and betaine as hydrogen bond acceptor in combination with different hydrogen bond donors being seven alcohols, two organic acids, one sugar and urea. Fifteen CGAs were detected, identified and quantified for the evaluation of extraction efficiency. A betaine-based DES with triethylene glycol (molar ratio 1:2) was the most effective one at extracting CGAs from SCG also compared to a conventional organic solvent. Thirty percent of water added to DES and sample to solvent ratio 1:15 (g/mL) were selected as the best extraction conditions. The chromatographic method was validated studying LOD, LOQ, retention time and peak area precision, and linearity range. Retention time and peak area repeatability were determined obtaining RSDs values below 0.63 % and 8.51 %, respectively. Inter-day precision was determined obtaining RSDs value below 0.58 % and 8.80 % for retention time and peak area, respectively.

Brassica incana Ten. (Brassicaceae): Phenolic Constituents, Antioxidant and Cytotoxic Properties of the Leaf and Flowering Top Extracts.

Brassica incana Ten. is an edible plant belonging to the Brassicaceae family. In this work, the phenolic composition and the antioxidant and cytotoxic properties of the hydroalcoholic extracts obtained from the leaves and the flowering tops of B. incana grown wild in Sicily (Italy) were studied for the first time. A total of 17 and 20 polyphenolic compounds were identified in the leaf and in the flowering top extracts, respectively, by HPLC-PDA-ESI-MS analysis. Brassica incana extracts showed in vitro antioxidant properties; the leaf extract displayed greater radical scavenging activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test than the flowering top extract (IC50 = 1.306 ± 0.049 mg/mL and 2.077 ± 0.011 mg/mL), which in turn had a stronger ferrous ion chelating ability than the other (IC50 = 0.232 ± 0.002 mg/mL and 1.147 ± 0.016 mg/mL). The cytotoxicity of the extracts against human colorectal adenocarcinoma (CaCo-2) and breast cancer (MCF-7) cell lines was evaluated through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the lactic dehydrogenase (LDH) release determination. The extracts showed cytotoxic efficacy against Caco-2 cells, with the flowering top extract being the most effective (about 90% activity at the highest concentration tested). In the brine shrimp lethality bioassay, the extracts exhibited no toxicity, indicating their potential safety.

Determination of the Metabolite Content of Brassica juncea Cultivars Using Comprehensive Two-Dimensional Liquid Chromatography Coupled with a Photodiode Array and Mass Spectrometry Detection.

Plant-based foods are characterized by significant amounts of bioactive molecules with desirable health benefits beyond basic nutrition. The Brassicaceae (Cruciferae) family consists of 350 genera; among them, Brassica is the most important one, which includes some crops and species of great worldwide economic importance. In this work, the metabolite content of three different cultivars of Brassica juncea, namely ISCI Top, "Broad-leaf," and ISCI 99, was determined using comprehensive two-dimensional liquid chromatography coupled with a photodiode array and mass spectrometry detection. The analyses were carried out under reversed-phase conditions in both dimensions, using a combination of a 250-mm microbore cyano column and a 50-mm RP-Amide column in the first and second dimension (2D), respectively. A multi (three-step) segmented-in-fraction gradient for the 2D separation was advantageously investigated here for the first time, leading to the identification of 37 metabolites. In terms of resolving power, orthogonality values ranged from 62% to 69%, whereas the corrected peak capacity values were the highest for B. juncea ISCI Top (639), followed by B. juncea "Broad-leaf" (502). Regarding quantification, B. juncea cv. "Broad-leaf" presented the highest flavonoid content (1962.61 mg/kg) followed by B. juncea cv. ISCI Top (1002.03 mg/kg) and B. juncea cv. ISCI 99 (211.37 mg/kg).

Application of deep eutectic solvents for the extraction of phenolic compounds from extra-virgin olive oil.

A HPLC-DAD/ESI-MS method has been developed and validated for the analysis of the most representative phenolic compounds in extra-virgin olive oil (EVOO) samples using a green extraction approach based on deep eutectic solvents (DESs) at room temperature. We examined ten DESs based on choline chloride and betaine in combination with different hydrogen bond donors comprising six alcohols, two organic acids, and one urea. Five phenolic compounds, belonging to the classes of secoiridoids and phenolic alcohols, were selected for the evaluation of extraction efficiency. A betaine-based DES with glycerol (molar ratio 1:2) was found to be the most effective for extracting phenolic compounds as compared to a conventional solvent. The optimization of the extraction method involved the study of the quantity of water to be added to the DES and evaluation of the sample-to-solvent ratio optimal condition. Thirty percent of water added to DES and sample to solvent ratio 1:1 (w/v) were selected as the best conditions. The chromatographic method was validated by studying LOD, LOQ, intraday and interday retention time precision, and linearity range. Recovery values obtained spiking seed oil sample aliquots with standard compounds at 5 and 100 µg/g concentration were in the range between 75.2% and 98.7%.

Extraction, Analysis, and Antioxidant Activity Evaluation of Phenolic Compounds in Different Italian Extra-Virgin Olive Oils.

The analysis of phenolic compounds in extra virgin olive oils was carried out by high-performance liquid chromatography utilizing photodiode array and mass spectrometry detectors. The chromatographic profile of thirty samples from four Italian Regions highlighted the presence of secoiridoids, phenolic alcohols, flavonoids, and phenolic acid classes. A similar qualitative profile was observed with some differences in peak area and fifteen compounds were tentatively identified. Quantitative analysis was performed by UV detection considering eight standard phenolic compounds. The chromatographic method, after optimization, was validated studying some parameters, e.g., intra-day and inter-day retention time precision, limit of detection, limit of quantification, and linearity. Recovery of the method was performed achieving good results (10 and 50 g·g-1 with recovery of 72.9⁻92.1% (w/w) and 79.1⁻102.8% (w/w), respectively). In all samples secoiridoids were the main compounds ranging from 85 to more than 99% (w/w) of the total concentration of detected phenolic compounds while phenolic acids accounted for the lowest percentage (0.1⁻0.6%, w/w). Finally, total concentration of phenolic compounds and antioxidant activity were determined with different chemical assays. A good and significant correlation among total phenolic compound concentration and antioxidant activity was observed. A significant different phenolic compound concentration and antioxidant activity was determined between samples from Puglia and Sicily. This was studied performing statistical analysis by one-way analysis of variance (ANOVA) followed by Bonferroni post-hoc test.

Determination of key flavonoid aglycones by means of nano-LC for the analysis of dietary supplements and food matrices.

A method for the analysis of flavonoids (myricetin, quercetin, naringenin, hesperitin, and kaempferol), with interesting bioactivity, has been developed and validated utilizing nano-LC technique. In order to find optimal conditions, capillary columns (75 µm id × 10 cm) packed with different types of stationary phases, Kinetex® C18 core-shell (2.6 µm particle size), Hydride-based RP-C18 (sub-2 µm particle size), and LiChrospher® 100 RP-18 endcapped (5 µm particle size) were evaluated. The method was validated using Hydride-based RP-C18 stationary phase, with sub-2 µm particle size. A good chromatographic performance, expressed in terms of repeatability (RSD, in the range 1.63-4.68% for peak area), column-to-column reproducibility (RSD not higher than 8.01% for peak area), good linearity and sensitivity was obtained. In particular limit of detection values between 0.07 and 0.31 µg/mL were achieved with on column focusing technique. The method was applied to the determination of studied flavonoids in dietary supplements as well as in food matrices. The amount of quercetin found in the first analyzed dietary supplement, was in agreement to the labeled content. In the other samples, where the content of flavonoids was not labeled, most of the studied flavonoids were determined in amounts somewhere comparable to those reported in literature.

Nano-liquid chromatography in nutraceutical analysis: determination of polyphenols in bee pollen.

In this study, a nano-liquid chromatography based method for the simultaneous separation of 16 polyphenols employing UV-vis detection has been developed. A 100 µm I.D. capillary column packed with C18 core-shell particles (2.6 µm particle size, 100 Å) for 10 cm was employed. The separation of analytes was performed with a step gradient in less than 20 min, using 0.5% formic acid aqueous solution and acetonitrile as eluents. The optimized analytical method was validated and the resulting RSD% for intra-day and inter-day repeatability, related to retention time, retention factor and peak area, were below 4.68 and 5.57%, respectively. LOD and LOQ values were as low as 0.78 and 3.12 µg/mL, while linearity, assessed in the concentration range of interest for all analytes, gave R(2)≥0.990. The method was finally applied to the analysis of polyphenols extracted from a collected bee pollen. Nine polyphenols, namely o-, p-coumaric acid, ferulic acid, myricetin, cinnamic acid, quercetin, naringenin, hesperitin and kaempferol, were identified. All analytes, with the exception of p-coumaric acid and myricetin, which partially co-eluted with other pollen components, were also quantified in the sample.

Determination of petitgrain oils landmark parameters by using gas chromatography-combustion-isotope ratio mass spectrometry and enantioselective multidimensional gas chromatography.

Gas chromatography-combustion-isotope mass spectrometry was employed for the assessment of the Carbon isotope ratios of volatiles in Italian mandarin and lemon petitgrain oils. In addition, the composition of the whole oil and the enantiomeric distribution of selected chiral compounds were determined for all the samples by using gas chromatography and by multidimensional and conventional enantioselective gas chromatography. The composition of the oils was compared with previous studies. The enantiomeric distribution of lemon petitgrain oils is here reported for the first time. On the composition of mandarin petitgrain oil, the information available in literature, to date, is relative only to one sample from Egypt. Carbon isotope ratio of several terpene hydrocarbons and of their oxygenated derivatives contained in petitgrains was compared with the δ (13)C(VPDB) values of the same compounds present in the corresponding genuine Italian Citrus peel oil. The results prove that the isotopic values obtained for lemon and mandarin petitgrain oils are very close to those relative to the corresponding peel oils determined in previous studies.

Chemical characterization of Sacha Inchi (Plukenetia volubilis L.) oil.

A chemical characterization of the major components, namely, triacylglycerols (TAGs), polyphenols, and tocopherols in a Sacha inchi oil derived from cold pressing of the seed, is hereby reported. To tackle such a task, high-performance liquid chromatography in combination with photodiode array (PDA), fluorescence (RF), and mass spectrometry (MS) detection was employed. The latter was interfaced with atmospheric pressure chemical ionization and with electrospray ionization for the analysis of TAGs and polyphenols, respectively, whereas RF detection was tested for the determination of tocopherol content. Furthermore, fatty acid methyl esters (FAMEs) were evaluated by gas chromatography-flame ionization detector. A 93% amount of total fatty acids was represented by unsaturated FAMEs with the greatest percentage represented by linoleic (L) and linolenic (Ln) accounting for approximately 50 and 36%, respectively. The main TAGs (>10%) were represented by LLnL, LnLnLn, and LnLLn; the latter was present in the oil sample at the highest percentage (22.2%). Among tocopherols, γ-tocopherol was detected to be the most abundant component (over 50%). The polyphenolic composition was also investigated, and a total of 15 compounds were positively identified, through the complementary analytical information coming from PDA and MS data. To the best of our knowledge, this is the first report providing a thorough chemical characterization of a Plukenetia volubilis L. oil.

Glycogen synthase kinase-3beta inhibition attenuates the degree of arthritis caused by type II collagen in the mouse.

Recently, glycogen synthase kinase-3 (GSK-3) has being identified as an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and plays an important role in the pathophysiology of a number of diseases. The aim of this study was to investigate the effects of GSK-3beta inhibition on the degree of arthritis caused by type II collagen (CII) in the mouse (collagen-induced arthritis; CIA). Mice developed erosive hind paw arthritis when immunized with CII in an emulsion in complete Freund's adjuvant (CFA). The incidence of CIA was 100% by day 28 in the CII-challenged mice and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint margins. Treatment of mice with the GSK-3beta inhibitor TDZD-8 (1 mg/kg/day i.p.) starting at the onset of arthritis (day 25) ameliorated the clinical signs at days 26-35 and improved histological status in the joint and paw. Immunohistochemical analysis for nitrotyrosine, poly(ADP-ribose) (PAR), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) revealed a positive staining in inflamed joints from mice subjected to CIA. The degree of staining for nitrotyrosine, PAR, iNOS, and COX-2 was significantly reduced in CII-challenged mice treated with the GSK-3beta inhibitor. Plasma levels of tumor necrosis factor (TNF)-alpha and the joint tissue levels of macrophage inflammatory protein (MIP)-1alpha and MIP-2 were also significantly reduced by GSK-3beta inhibition. These data demonstrate that GSK-3beta inhibition exerts an anti-inflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.

Reduction in the evolution of murine type II collagen-induced arthritis by treatment with rosiglitazone, a ligand of the peroxisome proliferator-activated receptor gamma.

OBJECTIVE: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid, and thyroid hormone receptors. The thiazolidinedione rosiglitazone is a PPARgamma ligand that modulates the transcription of target genes. The aim of this study was to investigate the effects of rosiglitazone on the inflammatory response in mice with collagen-induced arthritis (CIA). METHODS: CIA was induced in DBA/1J mice by an intradermal injection of 100 microl of an emulsion of bovine type II collagen (CII; 100 microg) in Freund's complete adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Rosiglitazone (10 mg/kg/day) or vehicle (10% DMSO) was administered beginning on day 25 (arthritis onset) until day 35. Clinical, radiographic, histopathologic, and laboratory assessments were performed. RESULTS: Mice immunized with CII in CFA developed erosive arthritis of the hind paws. Macroscopic evidence of CIA first appeared as periarticular erythema and edema of the hind paws. The incidence of CIA was 100% by day 27 in the CII-challenged mice, and the severity progressed over the 35-day study period. Radiographic evaluation revealed focal resorption of bone. Histopathologic features of CIA included erosion of cartilage at the joint margins. Rosiglitazone treatment ameliorated the clinical signs on days 26-35 and improved the histologic findings in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in rosiglitazone-treated mice, as indicated by elevation of malondialdehyde levels, formation of nitrotyrosine, and activation of poly(ADP-ribose) polymerase. Plasma levels of the proinflammatory cytokines tumor necrosis factor, interleukin-1beta, and interleukin-6 were also significantly reduced by rosiglitazone treatment. CONCLUSION: These data demonstrate that rosiglitazone exerts an antiinflammatory effect on chronic inflammation and is able to ameliorate the tissue damage associated with CIA.

Protective effects of cyanidin-3-O-glucoside from blackberry extract against peroxynitrite-induced endothelial dysfunction and vascular failure.

Anthocyanins are a group of naturally occurring phenolic compounds as colorants in several plants, flowers and fruits. These pigments have a great importance as quality indicators, as chemotaxonomic markers and antioxidants. The content of blackberry (Rubus species) juice was investigated by HPLC/ESI/MS using narrow bore HPLC columns. Using this method we demonstrated that cyanidin-3-O-glucoside represents about 80% of the total anthocyanin contents in blackberry extract. Here we investigated antioxidant activity of the blackberry juice and cyanidin-3-O-glucoside on the endothelial dysfunction in cells and in vascular rings exposed to peroxynitrite. In human umbilical vein endothelial cells (HUVEC) in vitro, peroxynitrite caused a significant suppression of mitochondrial respiration (38 +/- 2.1% of control cells), as measured by the mitochondrial-dependent conversion of the dye MTT to formazan. Peroxynitrite caused DNA strand breakage (63 +/- 1.9% single strand vs 3 +/- 0.9% single strand in control cells), as measured by the alkaline unwinding assay, and caused an activation of PARS, as measured by the incorporation of radiolabeled NAD(+) to nuclear proteins. Blackberry juice (different dilutions that contained 80 ppm;40 ppm;14.5 ppm of cyanidin-3-O-glucoside) and cyanidin-3-O-glucoside (as chloride) (0.085 microM; 0.028 microM; 0.0085 microM) reduced the peroxynitrite-induced suppression of mitochondrial respiration, DNA damage and PARS activation in HUVECs. Vascular rings exposed to peroxynitrite exhibited reduced endothelium-dependent relaxant responses in response to acetylcholine as well as a vascular contractility dysfunction in response to norepinephrine. The development of this peroxynitrite-induced vascular dysfunction was ameliorated by the blackberry juice (different dilutions that contained 80 ppm;40 ppm;14.5 ppm of cyanidin-3-O-glucoside) and cyanidin-3-O-glucoside (as chloride) (0.085 microM;0.028 microM;0.0085 microM). In conclusion our findings clearly demonstrate that blackberry juice containing cyanidin-3-O-glucoside is a scavenger of peroxynitrite and that exert a protective effect against endothelial dysfunction and vascular failure induced by peroxynitrite.

The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) attenuates the development of acute and chronic inflammation.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid, and thyroid hormone receptors. The PPAR-gamma receptor subtype seems to play a pivotal role in the regulation of cellular proliferation and inflammation. Recent evidence also suggests that the cyclopentenone prostaglandin (PG) 15-deoxyDelta(12,14)-PGJ(2) (15d-PGJ(2)), which is a metabolite of prostaglandin D(2), functions as an endogenous ligand for PPAR-gamma. We postulated that 15d-PGJ(2) would attenuate inflammation. In the present study, we have investigated the effects of 15d-PGJ(2) of acute and chronic inflammation (carrageenan-induced pleurisy and collagen-induced arthritis, respectively) in animal models. We report for the first time, to our knowledge, that 15d-PGJ(2) (given at 10, 30, or 100 microg/kg i.p. in the pleurisy model or at 30 microg/kg i.p every 48 h in the arthritis model) exerts potent anti-inflammatory effects (e.g., inhibition of pleural exudate formation, mononuclear cell infiltration, delayed development of clinical indicators, and histological injury) in vivo. Furthermore, 15d-PGJ(2) reduced the increase in the staining (immunohistochemistry) for nitrotyrosine and poly (ADP-ribose) polymerase and the expression of inducible nitric-oxide synthase and cyclooxygenase-2 in the lungs of carrageenan-treated mice and in the joints from collagen-treated mice. Thus, 15d-PGJ(2) reduces the development of acute and chronic inflammation. Therefore, the cyclopentenone prostaglandin 15d-PGJ(2) may be useful in the therapy of acute and chronic inflammation.