Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract of uncertain origin, which includes ulcerative colitis (UC) and Crohn’s disease (CD). The composition of gut microbiota may change in IBD affected individuals, but whether dysbiosis is the cause or the consequence of inflammatory processes in the intestinal tissue is still unclear. Here, the composition of the microbiota and the metabolites in stool of 183 subjects (82 UC, 50 CD, and 51 healthy controls) were determined. The metabolites content and the microbiological profiles were significantly different between IBD and healthy subjects. In the IBD group, Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria were significantly increased, whereas Bacteroidetes and Cyanobacteria were decreased. At genus level Escherichia, Faecalibacterium, Streptococcus, Sutterella and Veillonella were increased, whereas Bacteroides, Flavobacterium, and Oscillospira decreased. Various metabolites including biogenic amines, amino acids, lipids, were significantly increased in IBD, while others, such as two B group vitamins, were decreased in IBD compared to healthy subjects. This study underlines the potential role of an inter-omics approach in understanding the metabolic pathways involved in IBD. The combined evaluation of metabolites and fecal microbiome can be useful to discriminate between healthy subjects and patients with IBD.
Quince (Cydonia oblonga Miller) fruit aqueous acetone extracts were evaluated. High-performance liquid chromatography-diode array detection and electrospray ionization-mass spectrometry were used for the identification and quantification of the phenolic compounds. The total phenolic content of the pulp and peel parts ranged from 37 to 47 and 105 to 157 mg/100 g of fresh weight, respectively. Chlorogenic acid (5-O-caffeoylquinic acid) was the most abundant phenolic compound in the pulp (37%), whereas rutin (quercetin 3-O-rutinoside) was the main one in the peel (36%). The radical scavenging potential of the extracts was determined and compared with that of synthetic antioxidants. The stronger properties corresponded to those obtained from peel material with a 70-80% inhibitory effect on DPPH radicals. The antimicrobial activity of the extracts against different microorganism strains was also investigated. Quince peel extract was the most active for inhibiting bacteria growth with minimum inhibitory and bactericide concentrations in the range of 102-5 x 103 microg polyphenol/mL. It seems that chlorogenic acid acts in synergism with other components of the extracts to exhibit their total antimicrobial activities.
Rotenone and deguelin are the major active ingredients and principal components of cuberesin from Lonchocarpus utilis used as a botanical insecticide and piscicide. They are also potent complex I (NADH:ubiquinone oxidoreductase) inhibitors. Rotenone was known earlier, and deguelin is shown here to induce a Parkinson's disease (PD)-like syndrome after subcutaneous treatment of rats by osmotic minipump. Rotenone at 3 mg/kg/day or deguelin at 6 but not 3 mg/kg/day induces degeneration of the nigrostriatal dopaminergic pathway, as shown by reduced tyrosine hydroxylase immunoreactivity with treatments for 5 or 6 days. The neuropathological lesions are associated with a brain level of parent rotenoid of 0.4-1.3 ppm but not with the much smaller brain level of 12abeta-hydroxyrotenoids or other metabolites analyzed by HPLC and LC/MS. We previously established that the hydroxylated metabolites and derivatives of rotenone and deguelin are all less active (i.e., detoxified) as complex I inhibitors relative to the parent rotenoids. The PD-like syndrome induced in rats by rotenone and deguelin is therefore due to the parent compounds rather than metabolites. Deguelin is about half as active as rotenone in inducing the PD-like syndrome in rats and in acute ip LD50 in mice. Rotenone and deguelin are metabolized by human recombinant 3A4 and 2C19 but not five other P450 enzymes. 2C19 is more selective than 3A4 in forming the 12abeta-hydroxyrotenoids. Identified sites of metabolic attack individually or in combination are as follows: 12abeta hydroxylation and 2-O-demethylation of both compounds, oxidation of the rotenone isopropenyl substituent to mono and diol derivatives, and probable oxidation of the deguelin dimethylchromene double bond. These toxicological features must be considered in using rotenone, deguelin, and their analogues as pesticides, candidate radioimaging and cancer chemopreventive agents, and models of PD.
Despite the uselfuness of nematicidal compounds in agricultural practices, some serious concerns are raised today about their excessive use leading to enhancement of biodegradation mechanisms in soil expressed as lack of efficacy under field conditions and resistance development. Moreover, the phase-out of methyl bromide has led to the need for a valid alternative to organophosporous and carbamate compounds, such us fosthiazate, fenamiphos, oxamyl, and aldicarb. In the past years, intregated pest management strategies have been practised worldwide to maximize crop production while maintaining and contributing to agriculture sustainability. Biopesticides and specifically bionematicides constitute a desirable component of pest management technology and practices. Particularly, in the frame of our ongoing research on natural nematicides of botanical origin, we have reviewed the international bibliography for candidate nematicidal compounds. We report herein the nematicidal activity of plant metabolites on the basis of their chemical characteristics and structure.
Rosiglitazone is a commonly prescribed insulin-sensitizing drug with a selective agonistic activity on the peroxisome proliferator-activated receptor-gamma (PPAR-gamma). PPAR-gamma can modulate inflammatory responses in the brain, and agonists might be beneficial in neurodegenerative diseases. In the present study we used a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine plus probenecid (MPTPp) mouse model of progressive Parkinson's disease (PD) to assess the therapeutic efficacy of rosiglitazone on behavioural impairment, neurodegeneration and inflammation. Mice chronically treated with MPTPp displayed typical features of PD, including impairment of motor and olfactory functions associated with partial loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNc), decrease of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) content and dynorphin (Dyn) mRNA levels in the caudate-putamen (CPu), intense microglial and astroglial response in the SNc and CPu. Chronic rosiglitazone, administered in association with MPTPp, completely prevented motor and olfactory dysfunctions and loss of TH-positive cells in the SNc. In the CPu, loss of striatal DA was partially prevented, whereas decreases in DOPAC content and Dyn were fully counteracted. Moreover, rosiglitazone completely inhibited microglia reactivity in SNc and CPu, as measured by CD11b immunostaining, and partially inhibited astroglial response assessed by glial fibrillary acidic protein immunoreactivity. Measurement of striatal MPP+ levels 2, 4, 6 h and 3 days after chronic treatment indicated that MPTP metabolism was not altered by rosiglitazone. The results support the use of PPAR-gamma agonists as a putative anti-inflammatory therapy aimed at arresting PD progression, and suggest that assessment in PD clinical trials is warranted.
During the liquid chromatographic study of the phenolic fraction of monofloral honeys was detected in the asphodel honey ( Asphodelus microcarpus Salzm. et Viv.) chromatogram a distinctive peak not detected in other monofloral honeys such as Arbutus unedo L., Hedysarum coronarium , Eucalyptus spp., and Galactites tomentosa . After thin layer chromatography (TLC) purification and characterization by NMR and LC-MS/MS, the compound was identified as methyl syringate (MSYR) and confirmed against an original standard. Levels of MSYR were measured in honeys of 2005, 2006, and 2007 by HPLC-DAD analysis. Level determination of MSYR was repeated in 2008 for 2006 and 2007 honeys to evaluate chemical stability of this phenolic compound. Levels of MSYR measured 1 year after the sampling did not show significant statistical differences (p < 0.05). The stability of MSYR was also confirmed by 12 asphodel honey samples collected in 2005 that showed amounts of methyl syringate comparable with those found in fresh honey. For the evaluation of MSYR origin, samples of nectars were collected from flowers and the content of MSYR was measured. Levels of MSYR in honeys are originated from the nectar with an average contribution of the nectar to the honey of 80%. Melissopalinological analysis did not allow the attribution of the honey monofloral origin because levels of asphodel pollen were <6% for all analyzed samples. Previously reported levels of MSYR for robinia, rape, chestnut, clover, linden blossom, dandelion, sunflower, thyme, manuka, and fir honeys were <5 mg/kg. For this reason, a minimum level of 122.6 mg/kg for MSYR in asphodel honeys can be considered as a chemical marker and, unlike the melissopalynological analysis, can be used for the origin attribution and to evaluate the percent of asphodel nectar in the honey.
Strawberry tree honey, due to its characteristic bitter taste, is one of the most typical Mediterranean honeys, with Sardinia being one of the largest producers. According to specific chemical studies, homogentisic acid was identified as a possible marker of this honey. This work, based on HPLC-DAD-MS/MS analysis of strawberry tree (Arbutus unedo L.) honeys, previously selected by sensory evaluation and melissopalynological analysis, showed that, in addition to the above-mentioned acid, there were other high levels of substances useful for the botanical classification of this unifloral honey. Two of these compounds were isolated and identified as (+/-)-2-cis,4-trans-abscisic acid (c,t-ABA) and (+/-)-2-trans,4-trans-abscisic acid (t,t-ABA). A third compound, a new natural product named unedone, was characterized as an epoxidic derivative of the above-mentioned acids. Structures of c,t-ABA, t,t-ABA, and unedone were elucidated on the basis of extensive 1D and 2D NMR experiments, as well as HPLC-MS/MS and Q-TOF analysis. In selected honeys the average amounts of c,t-ABA, t,t-ABA, and unedone were 176.2+/-25.4, 162.3+/-21.1, and 32.9+/-7.1 mg/kg, respectively. Analysis of the A. unedo nectar confirmed the floral origin of these compounds found in the honey. Abscisic acids were found in other unifloral honeys but not in such high amount and with a constant ratio of about 1:1. For this reason, besides homogentisic acid, these compounds could be used as complementary markers of strawberry tree honey.
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