Anti-Inflammatory Potential of 1-Nitro-2-Phenylethylene.

Inflammation is a reaction of the host to infectious or sterile stimuli and has the physiological purpose of restoring tissue homeostasis. However, uncontrolled or unresolved inflammation can lead to tissue damage, giving rise to a plethora of chronic inflammatory diseases, including metabolic syndrome and autoimmunity pathologies with eventual loss of organ function. Beta-nitrostyrene and its derivatives are known to have several biological activities, including anti-edema, vasorelaxant, antiplatelet, anti-inflammatory, and anticancer. However, few studies have been carried out regarding the anti-inflammatory effects of this class of compounds. Thereby, the aim of this study was to evaluate the anti-inflammatory activity of 1-nitro-2-phenylethene (NPe) using in vitro and in vivo assays. Firstly, the potential anti-inflammatory activity of NPe was evaluated by measuring TNF-α produced by human macrophages stimulated with lipopolysaccharide (LPS). NPe at non-toxic doses opposed the inflammatory effects induced by LPS stimulation, namely production of the inflammatory cytokine TNF-α and activation of NF-κB and ERK pathways (evaluated by phosphorylation of inhibitor of kappa B-alpha [IκB-α] and extracellular signal-regulated kinase 1/2 [ERK1/2], respectively). In a well-established model of acute pleurisy, pretreatment of LPS-challenged mice with NPe reduced neutrophil accumulation in the pleural cavity. This anti-inflammatory effect was associated with reduced activation of NF-κB and ERK1/2 pathways in NPe treated mice as compared to untreated animals. Notably, NPe was as effective as dexamethasone in both, reducing neutrophil accumulation and inhibiting ERK1/2 and IκB-α phosphorylation. Taken together, the results suggest a potential anti-inflammatory activity for NPe via inhibition of ERK1/2 and NF-κB pathways on leukocytes.

Evaluating the Antimicrobial Efficacy of a Designed Synthetic Peptide against Pathogenic Bacteria.

Recent research has focused on discovering peptides that effectively target multi-resistant bacteria while leaving healthy cells unharmed. In this work, we describe the antimicrobial properties of RK8, a peptide composed of eight amino acid residues. Its activity was tested against multidrug-resistant Gram-negative and Gram-positive bacteria. RK8's efficacy in eradicating mature biofilm and increasing membrane permeability was assessed using Sytox Green. Cytotoxicity assays were conducted both in vitro and in vivo models. Circular dichroism analysis revealed that RK8 adopted an extended structure in water and sodium dodecyl sulfate (SDS). RK8 exhibited MICs of 8-64 µM and MBCs of 4-64 µM against various bacteria, with higher effectiveness observed in Staphylococcus aureus (MRSA) and E. coli KPC+ strains than others. Ciprofloxacin and Vancomycin showed varying MIC and MBC values lower than RK8 for Gram-positive bacteria, but competitive for Gram-negative bacteria. The combination of RK8 and ciprofloxacin showed a synergistic effect. The RK8 peptides could reduce 38% of the mature A. baumannii biofilm. Sytox Green reagent achieved 100% membrane permeation of Gram-positive and Gram-negative bacteria. The RK8 peptide did not show cytotoxic effects against murine macrophages (64 µM), erythrocytes (100 µM) or Galleria mellanella larvae (960 µM). In the stability test against peptidases, the RK8 peptide was stable, maintaining around 60% of the molecule intact after 120 min of incubation. These results highlight the potential of RK8 to be a promising strategy for developing a new antimicrobial and antibiofilm agent, inspiring and motivating further research in antimicrobial peptides.

Neuroinflammation: An overview of neurodegenerative and metabolic diseases and of biotechnological studies.

Neuroinflammation is an important factor contributing to cognitive impairment and neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), ischemic injury, and multiple sclerosis (MS). These diseases are characterized by inexorable progressive injury of neuron cells, and loss of motor or cognitive functions. Microglia, which are the resident macrophages in the brain, play an important role in both physiological and pathological conditions. In this review, we provide an updated discussion on the role of ROS and metabolic disease in the pathological mechanisms of activation of the microglial cells and release of cytotoxins, leading to the neurodegenerative process. In addition, we also discuss in vivo models, such as zebrafish and Caenorhabditis elegans, and provide new insights into therapeutics bioinspired by neuropeptides from venomous animals, supporting high throughput drug screening in the near future, searching for a complementary approach to elucidating crucial mechanisms associated with neurodegenerative disorders.

Microbiological quality, chemical profile as well as antioxidant and antidiabetic activities of Schinus terebinthifolius Raddi.

Schinus terebinthifolius Raddi, commonly known as Brazilian peppertree, is a plant species widely used in Brazilian traditional medicine for various purposes. The objective of this study was to assess the microbiological quality, safety, chemical profile as well as antioxidant and antidiabetic potentials of different parts of S. terebinthifolius. Microbiological analysis of the methanolic extracts of the roots (MESR), stem bark (MESB) and leaves (MESL) of S. terebinthifolius showed no microbial growth. The concentrations of phenolic compounds, phenolic acids and flavonoids were determined by spectrophotometry. The phenolic compounds of the MESL were identified by liquid chromatography coupled to a diode array detector and mass spectrometer (LC-DAD-MS). The antioxidant activities of the extracts were analyzed by 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl radical (DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical (ABTS+), fluorescence recovery after photobleaching (FRAP), reducing power, ß-carotene bleaching and malondialdehyde (MDA) assays in human erythrocytes. The antidiabetic properties of the extracts were demonstrated in vitro by their inhibition of the α-glucosidase enzyme and their anti-glycation activity via fructose and glyoxal. After showing no acute toxicity in vivo, MESL was able to lower postprandial glycemia after glucose overload in normoglycemic mice as well as the water and feed intake, liver weight, glycemia and serum levels of glycated hemoglobin, aspartate transaminase (AST) and alanine transaminase (ALT) in diabetic mice. Overall, S. terebinthifolius extracts showed microbiological safety along with antioxidant and antidiabetic activities, likely mediated by its chemical constituents, such as gallic acid, gallotannins and glycosylated flavonols.

Antioxidant, anti-inflammatory, and hypoglycemic effects of the leaf extract from Passiflora nitida Kunth.

Diabetes mellitus is a metabolic disease characterized by abnormally high plasma glucose levels, leading to major complications, such as insulin resistance, obesity, hyperlipidemia, and hypertension, also with alterations in the immune and neuronal systems. Brazilian plants have been studied as important sources for new molecules with medicinal properties. The genus Passiflora known as "Maracujá" has been used as a traditional folk medicine for a long time, so an investigation was performed regarding an endemic kind of passion fruit (Passiflora nitida Kunth) from Amazonas, Brazil. Here, we aimed to determine its potential biological activity against metabolic syndrome, oxidative stress, pain, and inflammation. The hydroethanol leaf extract revealed an in vitro α-glucosidase inhibitory activity of 50 % inhibitory concentration (IC50) = 6.78 ± 0.31 µg/mL and an α-amylase inhibition of IC50= 93.36 ± 4.37. In vivo, experiments of different saccharide tolerance resulted in significant glycemia control and, with alloxan-diabetic mice, resulted in a decrease of total cholesterol, a hypoglycemic effect, and an antioxidant activity by thiobarbituric acid-reactive substances measurement. Also, it decreased the carrageenan-induced edema volume and the rate of writhing as a nociceptive response. These results indicate positive effects of P. nitida extract and its potential to inhibit metabolic syndrome.