Walking around the Autonomous Province of Trento (Italy): An Ethnobotanical Investigation.

The Trentino-South Tyrol region is a special statute region of northeastern Italy. This territory is of particular interest for its morphology, flourishing vegetation, and history, having been a meeting area among different civilizations. Hence, Trentino is characterized by an ethnic plurality and a rich ethnobotanical knowledge, even if the available information is fragmentary, widely dispersed, and often guarded in oral popular culture. To fill this gap, in the present work 200 subjects were interviewed using an ethnobotanical survey. The resulting 817 citations referred to 64 native species, used either for human or animal health or for domestic purposes. As a second step, for each plant exploited for medicinal purposes, local importance was evaluated by calculating their relative frequency of citation. Moreover, the main traditional preparations were discussed. Among them, the most cited and exploited ones are Achillea millefolium, Arnica montana, Hypericum perforatum, Malva sylvestris, Pinus mugo, and Satureja montana, for which a deeper analysis has been performed. Lastly, the ethnobotanical knowledge of the plants growing in this territory will add a piece to the mosaic of traditional medicine in Italy and may lay the foundation for a nature-aided drug discovery process.

Microwave-Assisted and Conventional Extractions of Volatile Compounds from Rosa x damascena Mill. Fresh Petals for Cosmetic Applications.

Rosa x damascena Mill. essential oil is mainly used in the cosmetics and perfumery industry, but it also finds application in the food industry as a flavoring agent. The chemical composition of essential oils is affected by environment, soil, harvesting technique, storage condition, and extraction methods. Nowadays, the study and design of greener, more efficient, and sustainable extractive procedures is the main and strategic focus in the chemical research and development of botanical derivatives, especially as regards fragrances and essential oils. Several technologies are available, and the best method to use depends on the desired chemicals, but conventional extractive processes are often laborious and time-consuming, involve large amounts of solvents, and may cause the partial loss of volatiles, affecting the quality of the final product. In the last decade, microwave irradiation has been successfully applied to classical techniques, often improving the general extractive efficiency and extract quality. In the present paper, as a preliminary analytical screening approach, two microwave-mediated techniques, Solvent-Free Microwave Extraction (SFME) and Microwave Hydrodiffusion and Gravity (MHG), and two conventional procedures, Hydrodistillation (HD) and Steam Distillation (SD), were applied and compared for the extraction of volatile compounds from R. x damascena fresh petals to highlight differences and advantages of the selected procedure and of the obtained extracts useful in a cosmetic context as fragrances or active ingredients. The chemical composition of the extracts was investigated by GC-MS and GC-FID. Sixty-one components, distributed in the four techniques, were identified. SD and HD are dominated by oxygenated terpenes (59.01% and 50.06%, respectively), while MHG and SFME extracts are dominated by alcohols (61.67% and 46.81%, respectively). A relevant variability in the composition of the extracts relating to the extraction techniques used was observed. To point out the correlation between the process and composition of the obtained natural products, principal component analysis (PCA) of the data extracted from GC-FID was used. Taking into account a cosmetic application, SFME shows several advantages when compared with the other procedures. The extract (obtained in a significantly higher amount) contains a meaningful lower level of potential fragrance allergenic compounds and quite a double amount of benzyl alcohol and 2-phenyl ethanol that can also enhance the preservative action in personal care products.

Chemical Composition of Essential Oil from Flowers of Five Fragrant Dendrobium (Orchidaceae).

A detailed chemical composition of Dendrobium essential oil has been only reported for a few main species. This article is the first to evaluate the essential oil composition, obtained by steam distillation, of five Indian Dendrobium species: Dendrobium chrysotoxum Lindl., Dendrobium harveyanum Rchb.f., and Dendrobium wardianum R.Warner (section Dendrobium), Dendrobium amabile (Lour.) O'Brien, and Dendrobium chrysanthum Wall. ex Lindl. (section Densiflora). We investigate fresh flower essential oil obtained by steam distillation, by GC/FID and GC/MS. Several compounds are identified, with a peculiar distribution in the species: Saturated hydrocarbons (range 2.19-80.20%), organic acids (range 0.45-46.80%), esters (range 1.03-49.33%), and alcohols (range 0.12-22.81%). Organic acids are detected in higher concentrations in D. chrysantum, D. wardianum, and D. harveyanum (46.80%, 26.89%, and 7.84%, respectively). This class is represented by palmitic acid (13.52%, 5.76, and 7.52%) linoleic acid (D. wardianum 17.54%), and (Z)-11-hexadecenoic acid (D. chrysantum 29.22%). Esters are detected especially in species from section Dendrobium, with ethyl linolenate, methyl linoleate, ethyl oleate, and ethyl palmitate as the most abundant compounds. Alcohols are present in higher concentrations in D. chrysantum (2.4-di-tert-butylphenol, 22.81%), D. chrysotoxum (1-octanol, and 2-phenylethanol, 2.80% and 2.36%), and D. wardianum (2-phenylethanol, 4.65%). Coumarin (95.59%) is the dominant compound in D. amabile (section Densiflora) and detected in lower concentrations (range 0.19-0.54%) in other samples. These volatile compounds may represent a particular feature of these plant species, playing a critical role in interacting with pollinators.

Beta-amyloid short- and long-term synaptic entanglement.

Beta-amyloid (Aß) is a peptide that derives from the proteolytic cleavage of the amyloid precursor protein (APP) by several secretases. Since its isolation and sequencing from Alzheimer's disease (AD) brains, Aß has been intensively investigated in the context of AD as the main pathogenic marker responsible for neurodegenerative processes. During the last three decades, results from several independent studies have converged to form the so-called amyloid cascade hypothesis of AD and several therapeutic strategies designed to modulate the APP amyloidogenic pathway have been developed. However, none of the clinical trials targeting Aß culminated in a significant clinical outcome, thus challenging the concept that targeting Aß, at least within the time window so far explored in clinical trials, may have a therapeutic effect. However, besides its presence in AD brains, brain cells produce Aß, thus suggesting that, under normal conditions, the peptide may have a role in the regulation of brain functions, which is consistent with its ubiquitous presence and normal synthesis. Taking into account that Aß has been found to exhibit a dual role strictly correlated with its concentration (neuromodulatory/neuroprotective vs neurotoxic), we discuss emerging evidence indicating that physiological concentrations of Aß peptide modulate synaptic activity. The review examines the physiological effects of Aß on acute synaptic activities and the functional interplay existing between Aß and different neurotransmitter systems, i.e. cholinergic, glutamatergic, GABAergic, catecholaminergic, serotoninergic, and peptidergic. The review also provides an insight into the different mechanisms through which Aß affects synaptic activity, focusing in particular on Aß interaction with the key synaptic proteins that regulate the neurotransmitter release machinery. These interactions may help to identify or recognize alterations in neurotransmitter activity and correlated behaviors as predictive signs for the development of AD and to understand the limitations of current interventions and the failure so far of amyloid targeted therapies.

Stromal Vascular Fraction Loaded Silk Fibroin Mats Effectively Support the Survival of Diabetic Mice after Pancreatic Islet Transplantation.

The aim of this study is to assess whether stromal vascular fraction (SVF)-soaked silk fibroin nonwoven mats (silk-SVF) can preserve the functionality of encapsulated pancreatic endocrine cells (alginate-PECs) after transplantation in the subcutaneous tissue of diabetic mice. Silk scaffolds are selected to create an effective 3D microenvironment for SVF delivery in the subcutaneous tissue before diabetes induction: silk-SVF is subcutaneously implanted in the dorsal area of five healthy animals; after 15 d, mice are treated with streptozotocin to induce diabetes and then alginate-PECs are implanted on the silk-SVF. All animals appear in good health, increasing weight during time, and among them, one presents euglycemia until the end of experiments. On the contrary, when PECs are simultaneously implanted with SVF after diabetes induction, mice are euthanized due to suffering. This work clearly demonstrates that silk-SVF creates a functional niche in subcutaneous tissue and preserves endocrine cell survival and engraftment.

Multidimensional Effects of Soy Isoflavone by Food or Supplements in Menopause Women: a Systematic Review and Bibliometric Analysis.

Isoflavones can exert their action on various levels: on cardiovascular system, bone and muscle health, on cancer, on menopausal symptoms, on obesity, on thyroid and on cognitive function. The aim of this systematic review is to evaluate the multidimensional effects of phytoestrogens in postmenopausal woman, and specifically to explore the impact on scientific literature. A research strategy was planned on PubMed and Scopus by defining the following key words:: menopause, climacteric, soy, isoflavone, phytoestrogens, cardiovascular system, bone mineral density, muscle mass, cancer, thyroid, obesity, cognitive. A total of 43 studies (in humans) were retrieved. The majority (12) describe the applications of soy isoflavones on cardiovascular disease, followed by effects on bone and muscle health (9), and studies concerning their action on menopausal symptoms (7), on cancer (6), on obesity (4), on cognitive function (3) and on thyroid function (2). The citation analysis revealed a growing interest for this topic and the papers on thyroid function are the most cited. Citation trends ofthe articles regarding the action on cardiovascular disease and on obesity are growing in the last years. Concerning the research areas, this review has assessed the effectiveness of various activities of isoflavones on welfare of menopausal women. In particular, literature show that a specific dosage of isoflavdnes reduces cardiovascular disease (from 20 to 100 mg/die), may be protective in osteoporosis and muscular fatigue (from 20 to 80 mg/die), may be useful for cancer prevention on endometrium, mammary glands and liver (from 50 to 100 mg/die), might improve menopausal symptoms, particularly in reducing the frequency of hot flashes (from 50 to 120 mg/die), can reduce abdominal fat and circulating inflammatory markers (from 80 to 160 mg/die), may ameliorate the pdssible interaction between endogenous estrogen and thyroid function (75 mg/die) and improve visual memory (from 50 to 100 mg/die).

Effects of soluble ß-amyloid on the release of neurotransmitters from rat brain synaptosomes.

Contradictory results have been reported on the interaction of beta-amyloid (Aß) with cholinergic receptors. The present paper investigates the modulatory effect of Aß1-40 on the neurotransmitter release evoked by nicotinic (nAChRs) and muscarinic (mAChRs) receptors. Aß1-40 inhibits both nicotinic and muscarinic-evoked [(3)H]DA overflow from rat nerve endings. Added to perfusion medium, Aß1-40 is able to enter into synaptosomes; it exerts its inhibitory effect at extracellular sites when release is stimulated by nAChRs and intracellularly when release is evoked by mAChRs. Moreover, our data show that Aß1-40 acts as non competitive antagonist of heteromeric α4ß2* but not of α3ß4* nAChRs which modulate [(3)H]NA overflow. Positive allosteric modulators of nAChRs counteract its inhibitory effect. It might be that compounds of this type could be useful to prevent, slow down the appearance or reverse the cognitive decline typical of the normal processes of brain aging.

Dangerous liaisons between beta-amyloid and cholinergic neurotransmission.

The review examines the multifaceted interactions between cholinergic transmission and beta-amyloid suggesting a continuum in the action of the peptide that at low concentrations (picomolar-low nanomolar) may directly stimulate nicotinic cholinergic receptor while desensitizing them at increasing concentrations (high nanomolar-low micromolar). In addition high beta-amyloid concentrations may reduce the synaptic release of several neurotransmitters, including glutamate, aspartate, GABA, glycine and dopamine, when the release is elicited through cholinergic stimulation but not following depolarization. The effect of beta-amyloid has been observed both in vitro and in vivo in at least three different brain areas (nucleus accumbens, striatum, hippocampus) suggesting that the peptide may exert some general effects even if not all the brain areas have been evaluated. In turn the activation of cholinergic receptors may affect the amyloid precursor protein processing diverting the metabolism toward non-amyloidogenic products. These actions, dissociated from those described in the case of high beta-amyloid concentrations leading to neurotoxic oligomers, may participate to cause dysfunctions in the neurotransmitter activity, in turn leading, at least from a theoretical point of view, to early neuropsychiatric disturbances in the disease. Complexively these observations underscore novel relationships between two main players in Alzheimer's disease pathogenesis that are beta-amyloid and cholinergic transmission. Also emerges the inherent difficulty of targeting beta-amyloid in a context in which the peptide exerts several actions beyond neurotoxicity.

Inhibitory effects of beta-amyloid on the nicotinic receptors which stimulate glutamate release in rat hippocampus: the glial contribution.

We investigated on the neuronal nicotinic acetylcholine receptor subtypes involved in the cholinergic control of in vivo hippocampal glutamate (GLU), aspartate (ASP) and inhibitory γ-aminobutyric acid (GABA) overflow. We also investigated on the possible contribution of nicotinic acetylcholine receptors subtypes present on astrocytes in the regulation of the three neurotransmitter amino acids overflow using hippocampal gliosomes and on the effects of beta-amyloid (Aß) 1-40 on the nicotinic control of amino acid neurotransmitter release. Nicotine was able to enhance the in vivo overflow of the three amino acids being more potent in stimulating GLU overflow. The α7 selective agonist PHA543613 induced an overflow very similar to that of nicotine. The α4ß2 selective agonist 5IA85380 was significantly less potent in inducing GLU overflow while the overflow of ASP and GABA were almost inconsistent. Aß1-40 inhibited the neurotransmitter overflow stimulated by PHA543613 but not the one evoked by 5IA85380. In hippocampal gliosomes nicotine elicited selectively GLU overflow which was also evoked by 5IA85380 and by the α7 selective agonist choline. Nicotine- and choline-induced glutamate overflow in gliosomes was inhibited by Aα1-40. In conclusion nicotine administration in vivo elicits hippocampal GLU release mostly through α7 nicotinic acetylcholine receptors likely present both on neurons and astrocytes. Aß inhibitory effect on the nicotinic-control of GLU release seems to depend primarily to the inhibition of α7 nicotinic acetylcholine receptors functional responses.

Beta Amyloid Differently Modulate Nicotinic and Muscarinic Receptor Subtypes which Stimulate in vitro and in vivo the Release of Glycine in the Rat Hippocampus.

Using both in vitro (hippocampal synaptosomes in superfusion) and in vivo (microdialysis) approaches we investigated whether and to what extent ß amyloid peptide 1-40 (Aß 1-40) interferes with the cholinergic modulation of the release of glycine (GLY) in the rat hippocampus. The nicotine-evoked overflow of endogenous GLY in hippocampal synaptosomes in superfusion was significantly inhibited by Aß 1-40 (10 nM) while increasing the concentration to 100 nM the inhibitory effect did not further increase. Both the Choline (Ch; α7 agonist; 1 mM) and the 5-Iodo-A-85380 dihydrochloride (5IA85380, α4ß2 agonist; 10 nM)-evoked GLY overflow were inhibited by Aß 1-40 at 100 nM but not at 10 nM concentrations. The KCl evoked [(3)H]GLY and [(3)H]Acetylcholine (ACh) overflow were strongly inhibited in presence of oxotremorine; however this inhibitory muscarinic effect was not affected by Aß 1-40. The effects of Aß 1-40 on the administration of nicotine, veratridine, 5IA85380, and PHA543613 hydrochloride (PHA543613; a selective agonist of α7 subtypes) on hippocampal endogenous GLY release in vivo were also studied. Aß 1-40 significantly reduced (at 10 µM but not at 1 µM) the nicotine-evoked in vivo release of GLY. Aß 1-40 (at 10 µM but not at 1 µM) significantly inhibited the PHA543613 (1 mM)-elicited GLY overflow while was ineffective on the GLY overflow evoked by 5IA85380 (1 mM). Aß 40-1 (10 µM) did not produce any inhibitory effect on nicotine-evoked GLY overflow both in the in vitro and in vivo experiments. Our results indicate that (a) the cholinergic modulation of the release of GLY occurs by the activation of both α7 and α4ß2 nicotinic ACh receptors (nAChRs) as well as by the activation of inhibitory muscarinic ACh receptors (mAChRs) and (b) Aß 1-40 can modulate cholinergic evoked GLY release exclusively through the interaction with α7 and the α4ß2 nAChR nicotinic receptors but not through mAChR subtypes.

Dual effect of beta-amyloid on α7 and α4ß2 nicotinic receptors controlling the release of glutamate, aspartate and GABA in rat hippocampus.

BACKGROUND: We previously showed that beta-amyloid (Aß), a peptide considered as relevant to Alzheimer's Disease, is able to act as a neuromodulator affecting neurotransmitter release in absence of evident sign of neurotoxicity in two different rat brain areas. In this paper we focused on the hippocampus, a brain area which is sensitive to Alzheimer's Disease pathology, evaluating the effect of Aß (at different concentrations) on the neurotransmitter release stimulated by the activation of pre-synaptic cholinergic nicotinic receptors (nAChRs, α4ß2 and α7 subtypes). Particularly, we focused on some neurotransmitters that are usually involved in learning and memory: glutamate, aspartate and GABA. METHODOLOGY/FINDINGS: WE USED A DUAL APPROACH: in vivo experiments (microdialysis technique on freely moving rats) in parallel to in vitro experiments (isolated nerve endings derived from rat hippocampus). Both in vivo and in vitro the administration of nicotine stimulated an overflow of aspartate, glutamate and GABA. This effect was greatly inhibited by the highest concentrations of Aß considered (10 µM in vivo and 100 nM in vitro). In vivo administration of 100 nM Aß (the lowest concentration considered) potentiated the GABA overflow evoked by nicotine. All these effects were specific for Aß and for nicotinic secretory stimuli. The in vitro administration of either choline or 5-Iodo-A-85380 dihydrochloride (α7 and α4ß2 nAChRs selective agonists, respectively) elicited the hippocampal release of aspartate, glutamate, and GABA. High Aß concentrations (100 nM) inhibited the overflow of all three neurotransmitters evoked by both choline and 5-Iodo-A-85380 dihydrochloride. On the contrary, low Aß concentrations (1 nM and 100 pM) selectively acted on α7 subtypes potentiating the choline-induced release of both aspartate and glutamate, but not the one of GABA. CONCLUSIONS/SIGNIFICANCE: The results reinforce the concept that Aß has relevant neuromodulatory effects, which may span from facilitation to inhibition of stimulated release depending upon the concentration used.

Different presynaptic nicotinic receptor subtypes modulate in vivo and in vitro the release of glycine in the rat hippocampus.

In the present study, using an in vivo approach (a microdialysis technique associated to HPLC with fluorimetric detection) and in vitro purified hippocampal synaptosomes in superfusion, we investigated the glycinergic transmission in the hippocampus, focusing on the nicotinic control of glycine (GLY) release. The acute administration of nicotine in vivo was able to evoke endogenous GLY release in the rat hippocampus. The specific nicotinic agonists PHA-543613 hydrochloride (PHA543613) selective for the α7 nicotinic receptor subtype administered in vivo also elicited GLY release in a similar extent, while the α4ß2 agonist 5-IA85380 dihydrochloride (5IA85380) was less effective. Nicotine elicited GLY overflow also from hippocampal synaptosomes in vitro. This overflow was Ca(2+)-dependent and inhibited by methyllycaconitine (MLA), but was not modified by dihydro-beta-erythroidine (DHßE, 1 µM). Choline(Ch)-evoked GLY overflow was Ca(2+) dependent, unaltered in presence of DHßE and blocked by methyllycaconitine (MLA). Additionally, 5IA85380 elicited a GLY overflow, which in turn was Ca(2+) dependent, was significantly inhibited by DHßE but was unaffected by MLA. The GLY overflow produced by these nicotinic agonists quantitatively resembles that evoked by 9 mM KCl. The effects of a high concentration of 5IA85380 (1mM), in the presence of 2 µM DHßE, on the release of GLY was also studied comparatively to that on glutamate and aspartate release. The nicotinic agonist 5IA85380 tested at high concentration (1mM) was able to produce a stimulatory effect of endogenous release of the three amino acids, even in the presence of 2 µM DHßE, indicating the existence of a DHßE resistant, α4ß2 nAChR subtype with a functional role in the modulation of GLY, ASP, and GLU release. Our results show that in the rat hippocampus the release of GLY is, at least in part, of neuronal origin and is modulated by the activation of both α7 and α4ß2 (low and high affinity) nAChR subtypes.

Specific neuromodulatory actions of amyloid-beta on dopamine release in rat nucleus accumbens and caudate putamen.

We previously demonstrated that amyloid-beta (Abeta) has a neuromodulatory action in the nucleus accumbens (NAc). In this area of the brain, the peptide disrupts the cholinergic control of dopamine (DA) release both in vivo and in vitro. The aim of the present work was to extend the research on the neuromodulatory effect of Abeta (1-40) on DA transmission to different release stimuli and to another dopaminergic brain area, the caudate putamen (CPu), in order to clarify whether the effect of the peptide is stimulus- or brain area-selective. We performed both in vivo (microdialysis associated to HPLC) and in vitro studies (synaptosomes in superfusion). Both in NAc and in CPu and both in vivo and in vitro, Abeta did not affect either basal or potassium-stimulated DA release. In CPu, the Abeta ability to impair the DA release evoked by the cholinergic agonist carbachol, observed in NAc, was confirmed only in vitro. Moreover, in vitro Abeta affected a specific component of the DA overflow evoked by the non-selective metabotropic glutamate receptors agonist t-ACPD. Altogether, these results show that Abeta may have different neuromodulatory actions depending upon the secretory stimulus and, in vivo, the brain area investigated.

Acute beta-amyloid administration disrupts the cholinergic control of dopamine release in the nucleus accumbens.

The clinical presentation of Alzheimer's disease is characterized by memory deficits but it also involves the impairment of several cognitive functions. Some of these cognitive and executive functions are mediated by limbic areas and are regulated by dopaminergic neurotransmission. Furthermore, literature data suggest that beta-amyloid (Abeta) can influence synaptic activity in absence of neurotoxicity and in particular can impair cholinergic modulation of other neurotransmitter actions. In the present study, we evaluated whether small concentrations of Abeta could disrupt cholinergic control of dopamine (DA) release in nucleus accumbens using in vivo (brain dialysis) and in vitro (isolated synaptosomes) models. The cholinergic agonist carbachol (CCh) greatly enhanced DA release from dopaminergic nerve endings in nucleus accumbens both in vivo and in vitro. This effect was mainly exerted on muscarinic receptors because it was inhibited by the muscarinic antagonist atropine and it was unaffected by the nicotinic antagonist mecamylamine. Also the nicotinic agonists epibatidine and nicotine evoked a dopaminergic outflow in nucleus accumbens, which, however, was lower. Abeta 1-40 in absence of neurotoxicity fully inhibited the DA release evoked by CCh and only marginally affected the DA release evoked by epibatidine. The PKC inhibitor GF109203X mimicked the effect of Abeta on DA release and, in turn, Abeta impaired PKC activation by CCh. We can suggest that, in nucleus accumbens, Abeta disrupted in vivo and in vitro cholinergic control of DA release by acting on muscarinic transduction machinery.

Catecholamines increase in the urine of non-segmental vitiligo especially during its active phase.

Neural factors appear to play a major role in the pathogenesis of vitiligo. To investigate the possible correlation between vitiligo and peripheral monoaminergic system activity, we used high-pressure liquid chromatography and electrochemical detector methods to evaluate the basal urine excretion values of catecholamines [norepinephrine (NE), epinephrine and dopamine (DA)], their relative metabolites [3-methoxy-4-hydroxyphenylglycol (MHPG), normetanephrine (NMN), metanephrine (MN), vanilmandelic acid (VMA) and homovanillic acid], as well as 5-hydroxyindoleacetic acid (5-HIAA), in 35 healthy subjects and in 70 patients, suffering from non-segmental vitiligo at different stages of the disease. Levels of NE, DA, NMN, MN, MHPG, VMA and 5-HIAA were found to be significantly higher in patients than in controls. The patients with progressive vitiligo (n = 56) presented increased urinary excretion values for all parameters (in particular, NE levels) than other patients. Interestingly, in patients at its more recent vitiligo onset (<1 yr), NE values were different to those of subjects affected from 1 to 5 yr and from 6 to 10 yr. This result was confirmed by the significant negative relationship detected between NE excretion values and disease duration. In both vitiligo and control groups, significant correlations were found between monoamines as well as between these monoamines and their metabolites. The increase in catecholamine turnover, mainly occurring at the onset of the disease, is probably due to the stress associated with the appearance of lesions. Moreover, considering that these compounds readily produce toxic free-radicals and that vitiliginous subjects have a defective free radical defence mechanism, they may also contribute to the disappearance of melanocytes in the early phases of vitiligo.