A reverse translational approach reveals the protective roles of Mangifera indica in inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) are chronic intestinal disorders often characterized by a dysregulation of T cells, specifically T helper (Th) 1, 17 and T regulatory (Treg) repertoire. Increasing evidence demonstrates that dietary polyphenols from Mangifera indica L. extract (MIE, commonly known as mango) mitigate intestinal inflammation and splenic Th17/Treg ratio. In this study, we aimed to dissect the immunomodulatory and anti-inflammatory properties of MIE using a reverse translational approach, by initially using blood from an adult IBD inception cohort and then investigating the mechanism of action in a preclinical model of T cell-driven colitis. Of clinical relevance, MIE modulates TNF-α and IL-17 levels in LPS spiked sera from IBD patients as an ex vivo model of intestinal barrier breakdown. Preclinically, therapeutic administration of MIE significantly reduced colitis severity, pathogenic T-cell intestinal infiltrate and intestinal pro-inflammatory mediators (IL-6, IL-17A, TNF-α, IL-2, IL-22). Moreover, MIE reversed colitis-induced gut permeability and restored tight junction functionality and intestinal metabolites. Mechanistic insights revealed MIE had direct effects on blood vascular endothelial cells, blocking TNF-α/IFN-γ-induced up-regulation of COX-2 and the DP2 receptors. Collectively, we demonstrate the therapeutic potential of MIE to reverse the immunological perturbance during the onset of colitis and dampen the systemic inflammatory response, paving the way for its clinical use as nutraceutical and/or functional food.

Food-inspired peptides from spinach Rubisco endowed with antioxidant, antinociceptive and anti-inflammatory properties.

Rubiscolin-6 (amino acid sequence: YPLDLF) is a selective δ-opioid receptor peptide isolated from spinach Rubisco. Its synthetic analogue, peptide YPMDIV is the most potent described so far for its increased opioid activity, thus in this work it was considered as lead compound for the design of twelve new analogues e.g. LMAS1-12. Firstly all the novel compounds have been tested for their antinociceptive and anti-inflammatory capacity in vitro and in vivo in order to evaluate their ability to maintain or loss the original activity. Among them peptides LMAS5-8 gave the best results, thus their antioxidant properties have been investigated along with their enzymatic inhibitory ability. Peptide LMAS6 shows a strong antioxidant (154.25 mg TE/g CUPRAC) and inhibitor activity on tyrosinase (84.49 mg KAE/g), indicating a potential role in food industry as anti-browning agent, while peptides LMAS5 and LMAS7 possess a modest cholinesterase inhibitory activity suggesting a conceivable use for nutraceuticals production.

Synthesis, Biological Activity and Molecular Docking of Chimeric Peptides Targeting Opioid and NOP Receptors.

Recently, mixed opioid/NOP agonists came to the spotlight for their favorable functional profiles and promising outcomes in clinical trials as novel analgesics. This study reports on two novel chimeric peptides incorporating the fragment Tyr-c[D-Lys-Phe-Phe]Asp-NH2 (RP-170), a cyclic peptide with high affinity for µ and κ opioid receptors (or MOP and KOP, respectively), conjugated with the peptide Ac-RYYRIK-NH2, a known ligand of the nociceptin/orphanin FQ receptor (NOP), yielding RP-170-RYYRIK-NH2 (KW-495) and RP-170-Gly3-RYYRIK-NH2 (KW-496). In vitro, the chimeric KW-496 gained affinity for KOP, hence becoming a dual KOP/MOP agonist, while KW-495 behaved as a mixed MOP/NOP agonist with low nM affinity. Hence, KW-495 was selected for further in vivo experiments. Intrathecal administration of this peptide in mice elicited antinociceptive effects in the hot-plate test; this action was sensitive to both the universal opioid receptor antagonist naloxone and the selective NOP antagonist SB-612111. The rotarod test revealed that KW-495 administration did not alter the mice motor coordination performance. Computational studies have been conducted on the two chimeras to investigate the structural determinants at the basis of the experimental activities, including any role of the Gly3 spacer.

Phenolic Analysis and In Vitro Biological Activity of Red Wine, Pomace and Grape Seeds Oil Derived from Vitis vinifera L. cv. Montepulciano d'Abruzzo.

Grape pomace is commonly considered a waste product of monovarietal red wine production. Methods: HPLC-DAD analysis was performed to determine the polyphenol and flavonoid contents of all the extracts obtained from Montepulciano d'Abruzzo red wine and grape skins whereas, GC-MS was applied to the determination of fatty acid composition in grape seeds oil. Biological characterization involves antioxidant and antimicrobial assays for all the extracts and seeds oil; Their ability to inhibit α-glucosidase, α-amylase, α-tyrosinase, and ChE enzymes was also detected, together with anti-inflammatory activity on wine, grape skin extracts, and seeds oil by lipoxygenase (5-LOX) and LPS-stimulated macrophage release assays. Data indicate significative polyphenols content (199.31 ± 7.21 mgGAE/g), antioxidant (CUPRAC assay (1036.98 mgTE/g)), enzymatic inhibition (α-tyrosinase: 151.30 ± 1.20 mgKAE/g) and anti-inflammatory activities for wine-organic extract 2, while the antimicrobial activity of grape skin decoction is higher than those reported by wine extracts on three bacterial strains. Interestingly only dealcoholized wine and wine-aqueous extract exerts inhibitory effects on α-glucosidase (20.62 ± 0.23 mmolACAE/g and 19.81 ± 0.03 mmolACAE/g, respectively), while seeds oil is rich in oleic and linoleic acids. These results confirm the strong antioxidant properties of Montepulciano d'Abruzzo grape pomace, suggesting the potential use of this waste product as functional food supplements in the human diet and in cosmeceutics.

Ammonium Glycyrrhizinate Prevents Apoptosis and Mitochondrial Dysfunction Induced by High Glucose in SH-SY5Y Cell Line and Counteracts Neuropathic Pain in Streptozotocin-Induced Diabetic Mice.

Glycyrrhiza glabra, commonly known as liquorice, contains several bioactive compounds such as flavonoids, sterols, triterpene, and saponins; among which, glycyrrhizic acid, an oleanane-type saponin, is the most abundant component in liquorice root. Diabetic peripheral neuropathy is one of the major complications of diabetes mellitus, leading to painful condition as neuropathic pain. The pathogenetic mechanism of diabetic peripheral neuropathy is very complex, and its understanding could lead to a more suitable therapeutic strategy. In this work, we analyzed the effects of ammonium glycyrrhizinate, a derivate salt of glycyrrhizic acid, on an in vitro system, neuroblastoma cells line SH-SY5Y, and we observed that ammonium glycyrrhizinate was able to prevent cytotoxic effect and mitochondrial fragmentation after high-glucose administration. In an in vivo experiment, we found that a short-repeated treatment with ammonium glycyrrhizinate was able to attenuate neuropathic hyperalgesia in streptozotocin-induced diabetic mice. In conclusion, our results showed that ammonium glycyrrhizinate could ameliorate diabetic peripheral neuropathy, counteracting both in vitro and in vivo effects induced by high glucose, and might represent a complementary medicine for the clinical management of diabetic peripheral neuropathy.

Viscum album L. homogenizer-assisted and ultrasound-assisted extracts as potential sources of bioactive compounds.

Viscum album L. (Mistletoe) is one of the most famous plants in many countries utilized for several purposes. The current study aimed to describe chemical profiles and biological activities of homogenizer-assisted extract (HAE) and ultrasound-assisted extract (UAE)) of V. album parts (leaf, fruits, and seeds). Antioxidant (radical scavenging, reducing power, metal chelation, and phosphomolybdenum assays) and enzyme inhibitory properties (cholinesterases, amylase, glucosidase, and tyrosinase) were selected for biological evaluation. Chemical profiles were studied by HPLC-MS/MS and 32 compounds were identified in the extracts; caffeoylquinic acids and its derivatives, dimethylated flavonoids were the most significant compounds. Generally, the leaf extracts exhibited the best antioxidant and enzyme inhibitory effects in our tests. Multivariate analysis was performed to obtain more information for these data, then strong correlations between total bioactive compounds and tested parameters were observed. The present findings encourage us to further investigate V. album as a potential candidate for pharmaceutical and nutraceutical applications. PRACTICAL APPLICATIONS: Viscum album L. commonly called European mistletoe is a woody perennial shrub growing on coniferous trees with lathery leaves, small flowers, and white berries. It belongs to the Santalaceae R. Br. family from Europe and western/southern Asia. Traditional medicine recognizes mistletoe as a folk remedy to manage inflammation, hypertension, ulcers, and other diseases due to the presence of different bioactive compounds, among them mistletoe lectins and viscotoxins. Recent studies documented the possible therapeutic applications of Viscum extracts in association with cancer's therapy leading to improvements in health and patient's quality of life. Thus, this work gives novel data regarding the phytochemical characterizations and antioxidant/enzymatic inhibitor activities of different types of extracts from seeds, leaves, and fruits of Viscum L. obtained by homogenizer-assisted and ultrasound-assisted techniques, in order to increase the data set of potential applications in medicine.

Beneficial Role of Phytochemicals on Oxidative Stress and Age-Related Diseases.

Aging is related to a number of functional and morphological changes leading to progressive decline of the biological functions of an organism. Reactive Oxygen Species (ROS), released by several endogenous and exogenous processes, may cause important oxidative damage to DNA, proteins, and lipids, leading to important cellular dysfunctions. The imbalance between ROS production and antioxidant defenses brings to oxidative stress conditions and, related to accumulation of ROS, aging-associated diseases. The purpose of this review is to provide an overview of the most relevant data reported in literature on the natural compounds, mainly phytochemicals, with antioxidant activity and their potential protective effects on age-related diseases such as metabolic syndrome, diabetes, cardiovascular disease, cancer, neurodegenerative disease, and chronic inflammation, and possibly lower side effects, when compared to other drugs.

An animal tracking system for behavior analysis using radio frequency identification.

Evaluating the behavior of mice and rats has substantially contributed to the progress of research in many scientific fields. Researchers commonly observe recorded video of animal behavior and manually record their observations for later analysis, but this approach has several limitations. The authors developed an automated system for tracking and analyzing the behavior of rodents that is based on radio frequency identification (RFID) in an ultra-high-frequency bandwidth. They provide an overview of the system's hardware and software components as well as describe their technique for surgically implanting passive RFID tags in mice. Finally, the authors present the findings of two validation studies to compare the accuracy of the RFID system versus commonly used approaches for evaluating the locomotor activity and object exploration of mice.

Brain nerve growth factor unbalance induced by anabolic androgenic steroids in rats.

PURPOSE: Anabolic androgenic steroids (AAS) are synthetic androgen-like compounds that are abused in sport communities despite their adverse effects. Nerve growth factor (NGF) influences neuronal differentiation and survival, and it also mediates higher brain functions such as learning and memory. Changes in NGF expression have been implicated in neurodegenerative disorders, including Alzheimer disease. Hence, we decided to study the effect of chronic AAS exposure on brain NGF profile, NGF-dependent cholinergic function, and related behavioral performance. METHODS: Male Wistar rats were injected for 4 wk with either nandrolone or stanozolol at daily doses (5.0 mg·kg(-1), s.c.) that are considered equivalent to those abused by humans. NGF levels and NGF receptor (TrkA and p75NTR) expression were measured in the hippocampus and in the basal forebrain. Choline acetyltransferase expression was evaluated in basal forebrain. Spatial learning and memory were assessed using the Morris water maze. RESULTS: AAS treatment caused region-specific changes in the expression of NGF and its receptors. Both nandrolone and stanozolol increased NGF levels in the hippocampus and reduced NGF levels in the basal forebrain, reduced p75NTR expression in the hippocampus, and failed to affect TrkA expression in the basal forebrain. Finally, AAS treatment reduced the expression of choline acetyltransferase in the basal forebrain and impaired the behavioral performance in the Morris water maze. CONCLUSION: The evidence that supraphysiological doses of AAS cause neurotrophic unbalance and related behavioral disturbances raises the concern that AAS abuse in humans may affect mechanisms that lie at the core of neuronal plasticity.

Stimulus-dependent specificity for annexin 1 inhibition of the inflammatory nociceptive response: the involvement of the receptor for formylated peptides.

In this study we investigated how the peptides derived from the glucocorticoid-inducible protein annexin 1 are able to alter the nociceptive threshold of mice. The effects of the annexin1 fragment 2-26 (Anxa1(2-26)) on nociceptive threshold were studied using both chemical (formalin test) and thermal (hot plate and tail flick test) nociceptive stimuli on mice. Subcutaneous administration of Anxa1(2-26) into the dorsal surface of the mouse's hind paw was able to selectively reduce formalin-induced nociceptive behavior in the last phase of the test. The same effect was observed after intracerebroventricular administration, however, this was not the case when performing the hot plate or tail flick tests. Of the shortest Anxa1(2-26)-derived peptides, Anxa1(2-12) reduced the nociceptive response to formalin, however, the Anxa1(2-6) did not. The possible involvement of the receptors for formylated peptide in the anti-nociceptive action of Anxa1(-26) and Anxa1(2-12) was studied, choosing the formalin test. We found that the formyl peptide receptor agonist formyl-MLF (fMLF) induced anti-nociceptive effects in the formalin test both after the peripheral and central administration. The formyl peptide receptor antagonist N-t-butoxycarbonyl-MLP did not alter the response to formalin, but it was able to block the anti-nociceptive effects of Anxa1(2-26,) Anxa1(2-12) and fMLF after peripheral or central administration. These results indicate that exogenously administered Anxa1 can peripherally and centrally inhibit the nociceptive transmission associated with inflammatory processes through a mechanism that involves formyl peptide receptors.