Pharmacological evaluation of antinociceptive and anti-inflammatory activities of LQFM202: a new piperazine derivative.

Advances have been made in the search for new multi-target modulators to control pain and inflammation. Therefore, compound 3,5-di-tert-butyl-4-hydroxyphenyl)(4-methylpiperazin-1-yl)methanone (LQFM202) was synthesised and evaluated. First, in vitro assays were performed for COX-1, COX-2, and 5-LOX enzymes. Subsequently, adult female Swiss albino mice treated orally with LQFM202 at doses of 25-200 mg/kg were subjected to acetic acid-induced writhing, formalin-induced pain, carrageenan-induced hyperalgesia, carrageenan- or zymosan-induced paw oedema, or pleurisy. LQFM202 inhibited COX-1, COX-2, and LOX-5 (IC50 = 3499 µM, 1565 µM, and 1343 µM, respectively). In acute animal models, LQFM202 (50, 100, or 200 mg/kg) decreased the amount of abdominal writhing (29%, 52% and 48%, respectively). Pain in the second phase of the formalin test was reduced by 46% with intermediate dose. LQFM202 (100 mg/kg) reduced the difference in nociceptive threshold in all 4 h evaluated (46%, 37%, 30%, and 26%, respectively). LQFM202 (50 mg/kg) decreased the carrageenan-oedema from the second hour (27%, 31% and 25%, respectively); however, LQFM202 (100 mg/kg) decreased the carrageenan-oedema in all hours evaluated (35%, 42%, 48% and 50%, respectively). When using zymosan, LQFM202 (50 mg/kg) decreased the oedema in all hours evaluated (33%, 32%, 31% and 20%, respectively). In the carrageenan-pleurisy test, LQFM202 (50 mg/kg) reduced significantly the number of polymorphonuclear cells (34%), the myeloperoxidase activity (53%), TNF-α levels (47%), and IL-1ß levels (58.8%). When using zymosan, LQFM202 (50 mg/kg) reduced the number of polymorphonuclear and mononuclear cells (54% and 79%, respectively); and the myeloperoxidase activity (46%). These results suggest antinociceptive and anti-inflammatory effects of LQFM202.

Phytochemical Analysis and Antimicrobial Activity of Myrcia tomentosa (Aubl.) DC. Leaves.

This work describes the isolation and structural elucidation of compounds from the leaves of Myrcia tomentosa (Aubl.) DC. (goiaba-brava) and evaluates the antimicrobial activity of the crude extract, fractions and isolated compounds against bacteria and fungi. Column chromatography was used to fractionate and purify the extract of the M. tomentosa leaves and the chemical structures of the compounds were determined using spectroscopic techniques. The antibacterial and antifungal activities were assessed using the broth microdilution method. The phytochemical investigation isolated 11 compounds: α-bisabolol, α-bisabolol oxide B, α-cadinol, ß-sitosterol, n-pentacosane, n-tetracosane, quercetin, kaempferol, avicularin, juglanin and guaijaverin. The crude ethanolic extract and its fractions were tested against 15 bacteria and 9 yeasts. The crude extract inhibited the in vitro growth of yeasts at concentration of 4 to 32 µg/mL. The hexane, dichloromethane, ethyl acetate and aqueous fractions inhibited Candida sp. at concentrations of 4 to 256 µg/mL, whereas the Cryptococcus sp. isolates were inhibited only by the hexane and dichloromethane fractions in minimal inhibitory concentrations (MICs) at 16 to 64 µg/mL. The flavonoid quercetin-3-O-α-arabinofuranose (avicularin) was the most active compound, inhibiting Candida species in concentrations of 2 to 32 µg/mL. The MIC values suggest potential activity of this plant species against yeast.

Chrysin bonded to ß-d-glucose tetraacetate enhances its protective effects against the neurotoxicity induced by aluminum in Swiss mice.

OBJECTIVES: To evaluate whether the glycosylation of chrysin (CHR) enhances its protective effects against aluminum-induced neurotoxicity. METHODS: To compare the antioxidant, anticholinesterase, and behavioral effects of CHR with its glycosylated form (CHR bonded to ß-d-glucose tetraacetate, denoted as LQFM280), we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (aluminum-induced neurotoxicity in Swiss mice) models. KEY FINDINGS: LQFM280 demonstrated higher antioxidant activity than CHR in both models. Specifically, LQFM280 exhibited the ability to exert antioxidant effects in the cytoplasm of SH-SY5Y cells, indicating its competence in traversing neuronal membranes. Remarkably, LQFM280 proved more effective than CHR in recovering memory loss and counteracting neuronal death in the aluminum chloride mice model, suggesting its increased bioavailability at the brain level. CONCLUSIONS: The glycosylation of CHR with ß-d-glucose tetraacetate amplifies its neuroprotective effects, positioning LQFM280 as a promising lead compound for safeguarding against neurodegenerative processes involving oxidative stress.

A t-test ranking-based discriminant analysis for classification of free-range and barn-raised broiler chickens by 1H NMR spectroscopy.

Intensive systems of raising chickens in barns prevail worldwide for financial reasons. In contrast, free-range chickens are raised in better welfare conditions, and preferred by consumers due to their distinctive taste/flavor, having higher market prices. Thus, free-range chickens have been the target of frauds. In this study, 1H NMR metabolic profiles of breasts of free-range and barn-raised broilers (108 individuals) were compared by two discriminant models, based on t-test ranking and partial least squares (PLS-DA). Both models provided 100 % of correct classification in both training and test sets, being the univariate model based on t-test screening simpler and more robust. Among other differences, barn-raised broilers presented lower carnosine and anserine concentrations, and higher free amino acids contents. Univariate discrimination was based on the ratio of two NMR signals assigned to ß-alanine and carnosine + anserine, respectively. As an additional advantage, this profiling method could be adapted to other measurement platforms.

1H NMR as a simple methodology for differentiating barn and free-range chicken eggs.

The conventional intensive system produces cheap and safe chicken eggs, but exposes the animals to stress due to overcrowding on farms. This work compared the 1HNMR lipidic profile of chicken eggs produced in conventional and free-range systems. Sample preparation consisted of a single-step extraction and centrifugation, and the 1H NMR experimental time was just 3 min per sample. Eggs from free-range chickens had higher concentrations of ω-3 and ω-6 polyunsaturated fatty acids. The ratio between the signals at δ2.85 and 4.14 from bis-allylic polyunsaturated fatty acids and glycerol moiety, respectively, was able to correctly classify 93.8 % of the samples. These results were similar to those of PLS-DA, used for comparative purposes. Therefore, the proposed method could be easily used to assist quality control and fraud prevention in the egg industry. Free-range eggs had higher concentrations of cholesterol but, as they are smaller, similar amounts to conventional ones.

Nose-to-brain drug delivery mediated by polymeric nanoparticles: influence of PEG surface coating.

Intranasal administration of mucus-penetrating nanoparticles is an emerging trend to increase drug delivery to the brain. In order to overcome rapid nasal mucociliary clearance, low epithelial permeation, and local enzymatic degradation, we investigated the influence of PEGylation on nose-to-brain delivery of polycaprolactone (PCL) nanoparticles (PCL-NPs) encapsulating bexarotene, a potential neuroprotective compound. PEGylation with 1, 3, 5, and 10% PCL-PEG did not affect particle diameter or morphology. Upon incubation with artificial nasal mucus, only 5 and 10% of PCL-PEG coating were able to ensure NP stability and homogeneity in mucus. Rapid mucus-penetrating ability was observed for 98.8% of PCL-PEG5% NPs and for 99.5% of PCL-PEG10% NPs. Conversely, the motion of non-modified PCL-NPs was markedly slower. Fluorescence microscopy showed that the presence of PEG on NP surface did not reduce their uptake by RMPI 2650 cells. Fluorescence tomography images evidenced higher translocation into the brain for PCL-PEG5% NPs. Bexarotene loaded into PCL-PEG5% NPs resulted in area under the curve in the brain (AUCbrain) 3 and 2-fold higher than that for the drug dispersion and for non-PEGylated NPs (p < 0.05), indicating that approximately 4% of the dose was directly delivered to the brain. Combined, these results indicate that PEGylation of PCL-NPs with PCL-PEG5% is able to reduce NP interactions with the mucus, leading to a more efficient drug delivery to the brain following intranasal administration. Graphical abstract.