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This study aimed to evaluate the influence of Capsicum baccatum L. Aji Angelo and Bishop crown cultivars to the quality parameters of flavoured olive oils (FOOs) obtained by the addition of both fresh and dried pepper powders (1%) to Dolce di Rossano and Roggianella monovarietal extra virgin olive oils (EVOOs). First, pepper extracts were investigated for their total phenolic, flavonoid, carotenoid content as well as phenolic acids, fatty acid profile, and vitamin C and E content. In order to evaluate the impact of both fresh and dried peppers on the oxidative stability of FOOs, the Rancimat test was applied. 2,2-Azinobis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), ?-carotene bleaching (B-CB) and ferric reducing antioxidant power (FRAP) assays were used to investigate the antioxidant potential. Bishop crown dried extracts showed the highest phenolic, carotenoid and vitamin content, whereas Aji Angelo had the highest amount of capsaicinoids. Among EVOOs, Roggianella EVOO showed the highest antioxidant activity as well as the highest induction time (39.6 h). Remarkably, FOO obtained by the addition of Bishop crown dried pepper extract to Roggianella EVOO showed a higher induction time (44.9 h) with respect to the corresponding EVOO.

In this work, the solubility of vanillic, gallic, syringic, p-coumaric, ferulic and caffeic acids was determined at 37 °C under different conditions, namely pure water and two different ionic media, NaCl(aq) and NaClO4(aq), at different ionic strengths (i.e., 0.16, 0.50, 1.0, 2.0 and 3.0 M). The solubility in water of all the acids was found to be higher than that in both of the ionic media. Moreover, the solubility of hydroxycinnamic acids was lower than that of hydroxybenzoic acids. The activity coefficients of neutral species were calculated from these data, this knowledge is necessary when modeling the dependence of equilibrium constants on the ionic strength. Results obtained in this work can be useful for further studies regarding complex formation equilibria between these ligands and bioavailable metal cations.

Kombucha is a fermented beverage. Its consumption has significantly increased during the last decades due to its perceived beneficial effects. For this reason, it has become a highly commercialized drink that is produced industrially. However, kombucha is still also a homemade beverage, and the parameters which, besides its organoleptic characteristics, define the duration of its potential beneficial properties over time, are poorly known. Therefore, this study aimed to determine the effect of 9-month storage at 4 °C with 30-day sampling on the pH, total phenolic, and flavonoid contents, free radical scavenging properties of kombucha fermented from black tea. Our results highlighted that, after four months, the phenolic content decreased significantly from the initial value of 234.1 ± 1.4 µg GAE mL−1 to 202.9 ± 2.1 µg GAE mL−1, as well its antioxidant capacity tested by two in vitro models, DPPH, and ABTS assays. Concomitantly, the pH value increased from 2.82 to 3.16. The novel findings of this pilot study revealed that kombucha from sugared black tea can be stored at refrigerator temperature for four months. After this period the antioxidant properties of kombucha are no longer retained.

This study was performed to investigate broad bean pods (BBPs), a food waste by-product material, for their glucan and pectin contents, at three different stages of maturation, in order to provide basic support for the functional uses of BBPs and for the development of a potential market for bioactive ingredients from residual sources. In the first instance, the isolation of glucans was performed by carrying out an alkaline extraction on the dry BBP flour, at each stage of maturation. The isolated glucans were dialyzed and the crude and soluble samples were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy analyses. Afterwards, the colorimetric method for the enzymatic measurement of glucans was used. This procedure involved partial acid hydrolysis combined with an enzyme complex for the quantitative determination of α- and β-glucans. The results showed that, regardless of the used method, the glucan content increased with maturation. The maximum total glucan yield was recovered from BBPs at third stage of maturation (45 mg/g). The kit-based procedure revealed the variability of the β-glucan amount with maturation whose percentage, compared to total glucans, increased from 47.6 at the first stage up to 61.9 at the third stage. On the contrary, the pectin content in BBPs decreased with maturation. The yields ranged from 8.7% at the third stage to 17.2% at the first stage of maturation. The degree of esterification was determined by the classical titrimetric method and confirmed by the instrumental FT-IR method. The samples showed an average titrimetric value of 43.4% and the typical fingerprint in IR spectra with an average value of 50.5%. The degree of methoxylation remained almost unchanged during maturation, regardless of the method used.

Lipophenols are an emerging subclass of phenolic compounds characterized by the presence of a lipid moiety. Recently, hydroxytyrosyl oleate (HtyOle), a derivative of hydroxytyrosol, has been identified in olive oil and by-products. Furthermore, HtyOle possesses anti-inflammatory, antioxidant, and tissue regenerating properties. In this work, the potential occurrence of tyrosyl oleate (TyOle) in olive oil was investigated based on the hypothesis that its precursors tyrosol and oleic acid, both present in relatively high amount can be coupled together. Moreover, TyOle effects have been investigated in human keratinocytes to verify its proliferative and antioxidant properties. The quantitative determination of TyOle was carried out by the external standard method in liquid chromatography coupled with mass spectrometry (LC/MS), in negative mode using multiple reaction monitoring (MRM). The proliferative properties of TyOle on immortalized human keratinocytes (HaCat) were evaluated by 3-(4,5-dimethylthiasol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological changes were observed by fluorescent staining with phalloidin (for F-actin) or 4,6-diamidino-2-phenylindole (DAPI, for chromatin) dye. The antioxidant activity was assessed at the level of production of mitochondrial reactive oxygen species (ROS) induced with UV exposure. TyOle was identified in all the oil samples investigated. Interestingly, TyOle concentration was higher in defective or low-quality oils than in extra virgin oils. The formation of TyOle likely occurs during the crushing and kneading processes and its concentration is related to the increase of rancidity and of the concentration of free precursors. Herein we show that TyOle induced an increase in the viability of HaCat cells and cytoskeletal remodeling.

Multiple lines of evidence indicate that activation of the peroxisome proliferator-activated receptor γ (PPARγ) by natural or synthetic ligands exerts tumor suppressive effects in different types of cancer, including breast carcinoma. Over the past decades a new picture of breast cancer as a complex disease consisting of neoplastic epithelial cells and surrounding stroma named the tumor microenvironment (TME) has emerged. Indeed, TME is now recognized as a pivotal element for breast cancer development and progression. Novel strategies targeting both epithelial and stromal components are under development or undergoing clinical trials. In this context, the aim of the present review is to summarize PPARγ activity in breast TME focusing on the role of this receptor on both epithelial/stromal cells and extracellular matrix components of the breast cancer microenvironment. The information provided from the in vitro and in vivo research indicates PPARγ ligands as potential agents with regards to the battle against breast cancer.

Glucans possess a broad spectrum of biological activities. In this context, the present study was performed to isolate glucans from an Italian cultivar of Ziziphus jujuba Mill. at three different harvesting periods, in order to evaluate their effects on wound healing. The dry fruits were subjected to an alkaline extraction and then isolated glucans were purified by dialyzation. The crude and soluble samples were characterized by FT-IR and SEM analyses. Afterwards, total, &alpha, and &beta, glucan content was measured using an enzymatic procedure. The results highlighted that the glucan amount increased as the maturation proceeded as well as the &beta, glucan percentage, which ranged from 48.2 at the first harvesting to 65.4 at the third harvesting. Furthermore, the effects of isolated glucans on the viability and migration of keratinocytes were evaluated using the in vitro MTT and scratch wound assays. The best proliferative effects on keratinocyte migration have been achieved with soluble glucans from third harvesting at 100 &mu, M after 24 and 48 h (*** P &lt, 0.001). The same treated group showed significant narrowing of the scratch area after 24 h and complete closure of the injury after 48 h. The findings highlighted the effectiveness of soluble glucans on regeneration of damaged skin.

Activation of peroxisome proliferator-activated receptor gamma (PPAR&gamma, ) elicits anti-proliferative effects on different tumor cells, including those derived from breast cancer. PPAR&gamma, is also expressed in several cells of the breast tumor microenvironment, among which tumor associated macrophages (TAMs) play a pivotal role in tumor progression and metastasis. We explored the ability of synthetic and natural PPAR&gamma, ligands to modulate TAM polarization. The ligands included rosiglitazone (BRL-49653), and two docosahexaenoic acid (DHA) conjugates, N-docosahexaenoyl ethanolamine (DHEA) and N-docosahexaenoyl serotonin (DHA-5-HT). Human THP-1 monocytic cells were differentiated into M0, M1 and M2 macrophages that were characterized by qRT-PCR, ELISA and western blotting. A TAM-like phenotypic state was generated by adding two different breast cancer cell conditioned media (BCC-CM) to the cultures. Macrophages exposed to BCC-CM concomitantly exhibited M1 and M2 phenotypes. Interestingly, rosiglitazone, DHEA and DHA-5-HT attenuated cytokine secretion by TAMs, and this effect was reversed by the PPAR&gamma, antagonist GW9662. Given the key role played by PPAR&gamma, in the crosstalk between cancer cells and TAMs in tumor progression, its activation via endogenous or synthetic ligands may lead to novel strategies that target both epithelial neoplastic cells and the tumor microenvironment.

In this work complexation of luteolin (H4Lu) with Al(III), Fe(III) and Cu(II) at 37 °C and in 0.16 M NaCl is discussed. To evaluate the competition of the ligand for the metal cations and H+, the protonation constant of luteolin was also determined under the same experimental conditions. Speciation profiles obtained by potentiometric titrations show that in aqueous solution a complexation occurs at 1:1 ligand-to-Al(III) ratio, and at 1:1 and 2:1 ligand-to-cation ratios for Fe(III) and Cu(II). The coordination sites of luteolin to the different metal ions were determined by a computational approach, displaying that copper ion shows no selective preference towards any of the complexation sites of luteolin, while the six-membered chelate ring of the 4–5 site (i.e., the 4-carbonyl-5-hydroxyl site of the A and C rings of the ligand) is the preferred one for aluminum and iron ions. Additionally, we have evaluated the antioxidant and anti-inflammatory properties of free luteolin and of the luteolin-metal ion complexes. The complex with iron was found to have a higher activity than the other complexes (i.e., Fe(III)-Lu > Cu(II)-Lu > Al(III)-Lu), and its DPPH radical scavenging ability was even higher than that of free luteolin. Finally, all luteolin metal complexes were found to significantly reduce lipopolysaccharide (LPS)-induced interleukin (IL)-6 levels in monocyte-derived macrophages with the following order: Fe(III)-Lu > Al(III)-Lu > Cu(II)-Lu > free Lu.

Glycemic control is a mainstay of type 2 diabetes mellitus (T2DM) clinical management. Despite the continuous improvement in knowledge and progress in terms of treatment, the achievement of the physiologic metabolic profile is still an ongoing challenge in diabetic patients. Pancreatic β-cell line INS-1 832/13 was used to assess the insulin secretagogue activity of hydroxytyrosyl oleate (HtyOle) and tyrosyl oleate (TyOle), two naturally occurring lipophenols deriving from the conjugation of oleic acid (OA) and hydroxytyrosol (Hty) or tyrosol (Ty), respectively. The insulin secretion was determined under a glucose-induced insulin secretion (GSIS) condition by the ELISA method. The potential involvement of G-protein-coupled receptor 40 (GPR40), also known as free fatty acid receptor 1 (FFAR1), was investigated by both molecular docking and functional pharmacological approaches. Herein, we demonstrated that HtyOle and TyOle exerted a facilitatory activity on insulin secretion under the GSIS condition. Moreover, we provided evidence that both lipophenols are natural modulators of FFAR1 receptor. From our results, the anti-diabetes properties associated with olive oil consumption can be partly explained by the HtyOle and TyOle effects.

In the present work, a strategy for the synthesis of novel polyacrylates covalently linked to natural antioxidants was accomplished in a two-step process. First, monomers were prepared via lipase-catalyzed transesterification of acrylic acid methyl ester with tyrosol (T) or hydroxytyrosol (HT). Then, tyrosyl acrylate (TA) and hydroxytyrosyl acrylate (HTA) were subjected to radical homopolymerization to give poly(tyrosyl)acrylate (PTA) and poly(hydroxytyrosyl)acrylate (PHTA), respectively. The monomers and the corresponding homopolymers were characterized with FT-IR and NMR techniques and by Folin-Ciocalteu method to give an estimation of the available phenolic groups, as T and HT equivalents, linked to the polymers. The results of DPPH radical scavenging assay indicate that the free radical scavenging activity of tyrosol and hydroxytyrosol was almost completely retained in the corresponding monomers and polymers. In addition, polyacrylate films did not exhibit any cytotoxic activities in vitro on RAT1 normal fibroblast cells, using MTT assay.

A large body of evidence suggests that dietary n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), contribute to a reduced inflammatory tone thereby lowering the risk for several chronic and degenerative diseases. Different mechanisms have been proposed to explain these anti-inflammatory effects, including those involving endocannabinoids and endocannabinoid-like molecules. In this context, fatty acid amides (FAAs), conjugates of fatty acids with amines or amino acids, are an emerging class of compounds. Dopamine conjugates of DHA (N-docosahexaenoyl dopamine, DHDA) and EPA (N-eicosapentaenoyl dopamine, EPDA) have previously been shown to induce autophagy, apoptosis, and cell death in different tumor lines. Additionally, DHDA has displayed anti-inflammatory properties in vitro. Here, we tested the immune-modulatory properties of EPDA in mouse RAW 264.7 and human THP-1 macrophages stimulated with lipopolysaccharide (LPS). EPDA suppressed the production of monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in both cell lines, and nitric oxide (NO), and macrophage-inflammatory protein-3&alpha, (MIP3A) in RAW 264.7 macrophages. At a transcriptional level, EPDA attenuated cyclooxygenase-2 (COX-2) expression in both cell lines and that of MCP-1, IL-6, and interleukin-1&beta, (IL-1&beta, ) in THP-1 macrophages. Although further research is needed to reveal whether EPDA is an endogenous metabolite, our data suggest that this EPA-derived conjugate possesses interesting immune-modulating properties.

Recently, we identified hydroxytyrosyl oleate (HtyOle) in the by-products of olive oil, pomace and olive mill waste water (OMWW). Herein, we report that HtyOle is more accurately quantified by extracting the phenolic fraction from both matrices by using aqueous methanol (80%). By applying this method, HtyOle was also detected in extra virgin olive oil (EVOO). Since olive oil is used in the preparation of many cosmetic formulations, we explored the antioxidant capacity of HtyOle in human keratinocytes. Formation of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as activity of Glutathione-S-transferase (GST) and superoxide dismutase (SOD) were decreased by HtyOle. In addition to that, microRNAs (miRs) involved in both redox status balance and skin regeneration potential were also tested. The following miRs, hsa-miR-21 and hsa-miR-29a, were increased while has-miR-34a was not affected by HtyOle.

Recently, we demonstrated the capability of the ketogenic diet (KD) to influence the microRNA (miR) expression profile. Here, we report that KD is able to normalize miR expression in obese subjects when compared with lean subjects. By applying two different bioinformatics tools, we found that, amongst the miRs returning to comparable levels in lean subjects, four of them are linked to antioxidant biochemical pathways specifically, and the others are linked to both antioxidant and anti-inflammatory biochemical pathways. Of particular interest is the upregulation of hsa-miR-30a-5p, which correlates with the decrease of catalase expression protein in red blood cells.

N-Eicosapentaenoyl vanillylamine (EPVA) and N-docosahexaenoyl vanillylamine (DHVA), derived from n-3 polyunsaturated eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively, were studied for their potential antioxidant and carbohydrate-hydrolysing enzyme inhibitory activities together with capsaicin and the corresponding n-3 polyunsaturated fatty acids (PUFAs). The antioxidant potential was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay, β-carotene bleaching test, and ferric reducing ability power (FRAP). In the ABTS assay the following trend of potency could be observed EPVA > DHVA ≥ capsaicin. In addition, except for the FRAP test, all samples showed a greater activity than the positive controls used as reference compounds in the antioxidant assays. Both EPVA and DHVA showed half maximal inhibitory concentration (IC50) values much lower than acarbose, which was used as the reference drug in the carbohydrate-hydrolysing enzyme inhibitory activity assays. It is interesting to note that structural changes in capsaicin derivatives had higher impacts on α-glucosidase than on α-amylase inhibition. Taken together, our data suggest that both EPVA and DHVA, which are not limited in compliance-related considerations with respect to capsaicin, due to absence of pungency, could be proposed as functional ingredients for the development of products for the management of type II diabetes and border-line hyperglycaemic patients.

In this study, two capsaicin analogues, N-eicosapentaenoyl vanillylamine (EPVA) and N-docosahexaenoyl vanillylamine (DHVA), were enzymatically synthesized from their corresponding n-3 long chain polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both dietary relevant components. The compounds significantly reduced the production of some lipopolysaccharide (LPS)-induced inflammatory mediators, including nitric oxide (NO), macrophage-inflammatory protein-3&alpha, (CCL20) and monocyte chemoattractant protein-1 (MCP-1 or CCL2), by RAW264.7 macrophages. Next to this, only EPVA increased insulin secretion by pancreatic INS-1 832/13 &beta, cells, while raising intracellular Ca2+ and ATP concentrations. This suggests that the stimulation of insulin release occurs through an increase in the intracellular ATP/ADP ratio in the first phase, while is calcium-mediated in the second phase. Although it is not yet known whether EPVA is endogenously produced, its potential therapeutic value for diabetes treatment merits further investigation.

The first example of an additive cyclocarbonylation process leading to 1-thia-4a,9-diazafluoren-4-ones is reported. This process is based on the reaction of readily available 2-(propynylthio)benzimidazoles with carbon monoxide carried out in EtOH at 100 °C under a 5/2 mixture of CO-CO2 at 70 atm in the presence of the PdI2/KI catalytic system. Experimental evidence suggests a mechanistic pathway involving N-palladation of the substrate followed by CO insertion, triple bond insertion, protonolysis, and isomerization.

The synthesis and photophysical characterization of a new family of luminescent water-soluble ionic iridium(III) complexes of the general formula [(ppy)2Ir(bpy)]X are reported. The Ir(III) complexes incorporate a cyclometalated 2-phenylpyridine (ppy), the ancillary ligand 2,2′-bipyridyl (bpy) and different counterions (X− = EtO−, OH−, EtOCH2CO2−, MeOCH2CO2−). These complexes were obtained starting from the cyclometalated Ir(III) chloro-bridged dimer [(ppy)2Ir(μ-Cl)]2, for the first time synthesized through a new microwave assisted synthetic procedure, and subsequently converted into the corresponding hydroxy-bridged dimer [(ppy)2Ir(μ-OH)]2. The latter was eventually used as a sole reagent for the synthesis of all the reported complexes by simply varying the nature of the reaction solvent from water to alcohols and glycol ethers. This study demonstrates the versatility of the [(ppy)2Ir(μ-OH)]2 complex as a precursor to water soluble ionic Ir(III) complexes. Indeed, [(ppy)2Ir(μ-OH)]2 has shown its peculiar chemical reactivity due to both a strong base character and an unexpected oxidative ability towards the alcoholic function of glycol ethers. All the synthesized complexes exhibit, in water solution, an orange emission centred at 606 nm. Moreover, all complexes display the ability to give rise to gel phases in water upon increasing their concentration, and the photophysical study evidenced the various interactions governing the gelification process. The water-solubility of these new luminescent Ir(III) complexes makes them potentially useful in bio-related systems.

Soluble fibers, including pectins from apple and lemon, are commonly used as prebiotic and to prepare functional foods. The present study aimed to investigate the physicochemical and functional properties of pectins extracted from jujubes (Ziziphus jujuba Mill.). Pectins were extracted from jujubes at three stages of harvesting and characterized by FTIR and SEM analyses. Whole milk inoculated with kefir grains was supplemented by 0.25 mg&middot, mL&minus, 1 of pectins. The pH value and vitamin C content were evaluated after 24 and 48 h of fermentation. Pectins from jujubes at the first harvesting stage (PJ1K) showed the lowest methoxylation degree. The addition of pectins enhanced the production of vitamin C during heterolactic process. This result was found to depend on jujube harvesting stage as PJ1K stimulated the growth of yeasts in kefir grains yielding to the highest amount of vitamin C (0.83 &plusmn, 0.01 &micro, g&middot, 1) compared to other samples (0.53&ndash, 0.60 &micro, 1) at 24 h. Lactic acid bacteria diminish pH rapidly with respect to control (4.13 &plusmn, 0.05), according to the stage of maturation, reducing its initial value by 38.3% in PJ1K. Besides being an excellent prebiotic, pectins from jujubes could be used to enrich kefir with vitamin C.

Over the last decades a renewed interest in n−3 very long polyunsaturated fatty acids (PUFAs), derived mainly from fish oils in the human diet, has been observed because of their potential effects against cancer diseases, including breast carcinoma. These n−3 PUFAs mainly consist of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that, alone or in combination with anticancer agents, induce cell cycle arrest, autophagy, apoptosis, and tumor growth inhibition. A large number of molecular targets of n−3 PUFAs have been identified and multiple mechanisms appear to underlie their antineoplastic activities. Evidence exists that EPA and DHA also elicit anticancer effects by the conversion to their corresponding ethanolamide derivatives in cancer cells, by binding and activation of different receptors and distinct signaling pathways. Other conjugates with serotonin or dopamine have been found to exert anti-inflammatory activities in breast tumor microenvironment, indicating the importance of these compounds as modulators of tumor epithelial/stroma interplay. The objective of this review is to provide a general overview and an update of the current n−3 PUFA derivative research and to highlight intriguing aspects of the potential therapeutic benefits of these low-toxicity compounds in breast cancer treatment and care.

Hydroxytyrosyl esters with short, medium and long acyl chains were evaluated for their ability to reduce nitric oxide (NO) production by lipopolysaccharide-stimulated RAW264.7 macrophages. Among the compounds tested, C18 esters, namely hydroxytyrosyl stearate (HtySte) and hydroxytyrosyl oleate (HtyOle), were found to decrease NO production in a concentration-dependent manner, while the other compounds, including the parent hydroxytyrosol, were ineffective in the tested concentration range (0.5–5 μM). Further study of the potential immune-modulating properties of HtyOle revealed a significant and concentration-dependent suppression of prostaglandin E2 production. At a transcriptional level, HtyOle inhibited the expression of inducible NO synthase, cyclooxygenase-2 and interleukin-1β. Moreover, HtyOle was identified for the first time in olive oil by-products by means of high performance liquid chromatography coupled with mass spectrometry. By contrast, HtyOle was not found in intact olives. Our results suggest that HtyOle is formed during oil processing and represents a significant form in which hydroxytyrosol occurs.

Chinotto (Citrus myrtifolia Raf.) is a widely diffused plant native from China and its fruits have a wide-spread use in confectionary and drinks. Remarkably, only little has been reported thus far on its bioactive properties, in contrast to those of the taxonomically related bergamot (Citrus bergamia Risso). The present study aimed to investigate potential in vitro anti-inflammatory and radical scavenging properties of chinotto essential oils (CEOs) and to establish to what extent their composition and bioactivities are dependent on maturation. Essential oil from half ripe chinotto (CEO2) reduced the production of nitric oxide (NO) and the expression of inflammatory genes, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), cytokines, including interleukin-1β (IL-1β) and interleukin-6 (IL-6), and chemokine monocyte chemotactic protein-1 (MCP-1) by lipopolysaccharide (LPS)-stimulated RAW264,7 macrophages. Limonene, linalool, linalyl acetate, and γ-terpinene were found to be the main components in CEO2. Moreover, CEO2 showed high radical scavenging activity measured as Trolox equivalents (TE) against both 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS). These findings show that chinotto essential oil represents a valuable part of this fruit and warrants further in vivo studies to validate its anti-inflammatory potential.

Chinotto (Citrus myrtifolia Raf.) is a widely diffused plant native from China and its fruits have a wide-spread use in confectionary and drinks. Remarkably, only little has been reported thus far on its bioactive properties, in contrast to those of the taxonomically related bergamot (Citrus bergamia Risso). The present study aimed to investigate potential in vitro anti-inflammatory and radical scavenging properties of chinotto essential oils (CEOs) and to establish to what extent their composition and bioactivities are dependent on maturation. Essential oil from half ripe chinotto (CEO2) reduced the production of nitric oxide (NO) and the expression of inflammatory genes, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), cytokines, including interleukin-1&beta, (IL-1&beta, ) and interleukin-6 (IL-6), and chemokine monocyte chemotactic protein-1 (MCP-1) by lipopolysaccharide (LPS)-stimulated RAW264,7 macrophages. Limonene, linalool, linalyl acetate, and &gamma, terpinene were found to be the main components in CEO2. Moreover, CEO2 showed high radical scavenging activity measured as Trolox equivalents (TE) against both 2,2&prime, diphenyl-1-picrylhydrazyl (DPPH) and 2,2&prime, azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS). These findings show that chinotto essential oil represents a valuable part of this fruit and warrants further in vivo studies to validate its anti-inflammatory potential.

Background The omega-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may form conjugates with amines that have potential health benefits against common diseases including cancers. Here we synthesized DHA-dopamine (DHADA) and EPA–dopamine (EPADA) conjugates and studied their biological effects on different breast cancer cell lines. Methods and results MTT assays indicated that increasing concentrations of DHADA and EPADA significantly affected viability in MCF-7, SKBR3 and MDA-MB-231 breast cancer cells, whereas no effect was observed in MCF-10A non-tumorigenic epithelial breast cells. DHADA and EPADA enhanced Beclin-1 expression, as evidenced by immunoblotting, real-time-PCR and functional analyses. Chromatin Immunoprecipitation (ChIP) and Re-ChIP assays revealed that both compounds induced recruitment of Peroxisome-Proliferator-Activated-Receptor gamma (PPARγ) and RNA Polymerase-II at the Retinoic-X-Receptor binding region on Beclin-1 promoter. Moreover, both compounds enhanced autophagosome formation, evaluated by LC-3 and monodansylcadaverine labeling, that was prevented by the PPARγ antagonist GW9662, addressing the direct involvement of PPARγ. Noteworthy, long-term treatment with DHADA and EPADA caused the blockade of autophagic flux followed by apoptotic cell death as evidenced by PARP cleavage and DNA fragmentation in all breast cancer cells. Conclusions We have provided new insights into the molecular mechanism through which PPARγ, as a central molecule in the cross talk between autophagy and apoptosis, mediates DHADA- and EPADA-induced cell death in breast cancer cells. General significance Our findings suggest that omega-3 DHADA- and EPADA activation of PPARγ may assume biological relevance in setting novel adjuvant therapeutic interventions in breast carcinoma.

Several studies indicate that the n-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) contributes to an attenuated inflammatory status in the development of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. To explain these effects, different mechanisms are being proposed, including those involving endocannabinoids and related signaling molecules. Many of these compounds belong to the fatty acid amides, conjugates of fatty acids with biogenic amines. Conjugates of DHA with ethanolamine or serotonin have previously been shown to possess anti-inflammatory and potentially neuroprotective properties. Here, we synthesized another amine conjugate of DHA, N-docosahexaenoyl dopamine (DHDA), and tested its immune-modulatory properties in both RAW 264.7 macrophages and BV-2 microglial cells. N-Docosahexaenoyl dopamine significantly suppressed the production of nitric oxide (NO), the cytokine interleukin-6 (IL-6), and the chemokines macrophage-inflammatory protein-3α (CCL20) and monocyte chemoattractant protein-1 (MCP-1), whereas its parent compounds, dopamine and DHA, were ineffective. Further exploration of potential effects of DHDA on key inflammatory mediators revealed that cyclooxygenase-2 (COX-2) mRNA level and production of prostaglandin E2 (PGE2) were concentration-dependently inhibited in macrophages. In activated BV-2 cells, PGE2 production was also reduced, without changes in COX-2 mRNA levels. In addition, DHDA did not affect NF-kB activity in a reporter cell line. Finally, the immune-modulatory activities of DHDA were compared with those of N-arachidonoyl dopamine (NADA) and similar potencies were found in both cell types. Taken together, our data suggest that DHDA, a potentially endogenous endocannabinoid, may be an additional member of the group of immune-modulating n-3 fatty acid-derived lipid mediators.

Background and Purpose N-docosahexaenoylethanolamine (DHEA) is the ethanolamine conjugate of the long-chain polyunsaturated n-3 fatty acid docosahexaenoic (DHA; 22: 6n-3). Its concentration in animal tissues and human plasma increases when diets rich in fish or krill oil are consumed. DHEA displays anti-inflammatory properties in vitro and was found to be released during an inflammatory response in mice. Here, we further examine possible targets involved in the immune-modulating effects of DHEA. Experimental Approach Antagonists for cannabinoid (CB)1 and CB2 receptors and PPAR? were used to explore effects of DHEA on NO release by LPS-stimulated RAW264.7 cells. The possible involvement of CB2 receptors was studied by comparing effects in LPS-stimulated peritoneal macrophages obtained from CB2-/- and CB2+/+ mice. Effects on NF-?B activation were determined using a reporter cell line. To study DHEA effects on COX-2 and lipoxygenase activity, 21 different eicosanoids produced by LPS-stimulated RAW264.7 cells were quantified by LC-MS/MS. Finally, effects on mRNA expression profiles were analysed using gene arrays followed by Ingenuity® Pathways Analysis. Key Results CB1 and CB2 receptors or PPARs were not involved in the effects of DHEA on NO release. NF-?B and IFN-s, key elements of the myeloid differentiation primary response protein D88 (MyD88)-dependent and MyD88-independent pathways were not decreased. By contrast, DHEA significantly reduced levels of several COX-2-derived eicosanoids. Gene expression analysis provided support for an effect on COX–2-mediated pathways. Conclusions and Implications Our findings suggest that the anti-inflammatory effects of DHEA in macrophages predominantly take place via inhibition of eicosanoids produced through COX-2.

Epidemiologic studies suggest that dietary polyphenol intake is associated with a lower incidence of several non-communicable diseases. Although several foods contain complex mixtures of polyphenols, numerous factors can affect their content. Besides the well-known capability of these molecules to act as antioxidants, they are able to interact with cell-signaling pathways, modulating gene expression, influencing the activity of transcription factors, and modulating microRNAs. Here we deeply describe four polyphenols used as nutritional supplements: quercetin, resveratrol, epigallocatechin gallate (ECGC), and curcumin, summarizing the current knowledge about them, spanning from dietary sources to the epigenetic capabilities of these compounds on microRNA modulation.

Fruit seeds are byproducts from fruit processing. Characterisation of the bioactive compounds present in seeds and evaluation of their potential biological properties is therefore of particular importance in view of a possible valorisation of seeds as a source of health beneficial components. In this work, we have analysed the seeds of Sambucus and Rubus species in order to identify their bioactive components and to determine the antioxidant and anti-inflammatory activities of the extracts. We first analysed their oil content, in order to assess the fatty acid profile and tocopherol content. Moreover, the methanolic extracts of the seeds were analysed for their total phenolic contents and antioxidant capacities. Polyphenols were identified by HPLC-ESI-MS/MS analysis. Furthermore, extracts were evaluated for their inhibitory effects on the production of LPS-induced inflammatory mediators (NO, CCL-20) in RAW 264.7 cells. Our findings show that the methanolic extracts from Rubus seeds have strong antioxidant and anti-inflammatory properties and could therefore represent an attractive source of bioactive compounds for food, cosmetic, or pharmaceutical applications.

The first example of an additive cyclocarbonylation process leading to 1-thia-4a,9-diazafluoren-4-ones is reported. This process is based on the reaction of readily available 2-(propynylthio)benzimidazoles with carbon monoxide carried out in EtOH at 100 °C under a 5/2 mixture of CO–CO2 at 70 atm in the presence of the PdI2/KI catalytic system. Experimental evidence suggests a mechanistic pathway involving N-palladation of the substrate followed by CO insertion, triple bond insertion, protonolysis, and isomerization.

Jujubes are the fruit of Ziziphus jujuba Mill., a plant belonging to Rhamnaceae family widely distributed in the subtropical and tropical regions of Asia, in Australia, and in the Mediterranean region. Jujube is commonly known as Chinese dates, red dates, or tsao. This chapter focuses on the current knowledge on the composition in bioactive compounds and health benefits of jujube. It reviews the studies that have taken into consideration several parameters, including cultivar, origin, pedoclimatic conditions, ripening stage, postharvest processes, and extraction methods, affecting the phytochemical composition of jujube. The chapter discusses the biological effects of jujube extracts obtained from the results of in vitro and in vivo studies. Several studies that have been carried out in order to support the putative health benefits deriving from jujube consumption including antioxidant and neuroprotective, anticancer, anti-inflammatory and immunomodulating, cardioprotective, hepatoprotective, gastrointestinal protective, and antiobesity activities.

The extracts of seven Citrus rootstock seeds have been compared regarding fatty acid profile and antioxidant potential. Sour orange (Citrus aurantium L.) was found to contain the highest oil amount (34%), while the Poncirus trifoliata cultivars contained the highest percentage of unsaturated fatty acids (84-87%). In addition, the antioxidant properties of the extracts from defatted seeds have been evaluated by measuring their radical scavenging activity against 2,2'-diphenyl-1-picrylhydrazyl. The highest antioxidant activities were observed in the case of the acetone extract of sour orange and Citrumelo Swingle (76% and 75%, respectively), at a concentration of 0.17 mg mL(-1). Moreover, the total phenolic content of the extracts, determined using the Folin-Ciocalteau reagent, was found to be correlated with the radical scavenging activity results. The acetone extracts of sour orange and Citrumelo Swingle exhibited the highest phenolic content [112.3 and 103.4 mg gallic acid equivalent g(-1) dry sample weight, respectively].

Four analogues of ochratoxin A (OTA) differing for the aminoacidic moiety were synthesised using ochratoxin α (OTα) as the starting material. The condensation reaction between protected amino acids and OTα, carried out in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC • HCl) and N-hydroxybenzotriazole (HOBt) as coupling agents, followed by deprotection and PTLC purification afforded OTA alanine, leucine, serine and tryptophane analogues in satisfactory yields (33-47%, based on OTα).