Globe artichoke (Cynara scolymus L.) is a well-known medicinal plant belonging to Asteraceae family, widely cultivated also as food in the Mediterranean region. The immature inflorescence (head) is the edible part of the plant. Every year, the globe artichoke processing industry generates around 60-80% of waste and by-products (WBPs) that are still rich in metabolites. The recovery of value-added biomass creates an opportunity for recycling resources to the circular economy. The aim of this study is to valorize WBP from C. scolymus cv “Romanesco” harvested in the central regions of Italy. In particular, we focused our attention on inulin, a fructo-oligosaccharide that works as a prebiotic, due to the regulation of intestinal microbiota via stimulating the growth of beneficial bacteria. Moreover, inulin has other useful effects on human health. Indeed, it improves lipid metabolism, promotes weight loss, lowers blood sugar, etc. WBPs were extracted by using green extraction technologies obtaining a rich-inulin solid analyzed by Fourier-transform infrared spectroscopy (FTIR), thin-layer chromatography (TLC) and nuclear magnetic resonance (NMR).

In the pathogenesis of inflammatory processes caused by viral and bacterial infections, there are various disorders of many systems of the organism, including pathology of hemostasis system characterized by prethrombotic state. According to clinical recommendations, the use of new oral anticoagulants is aimed at reducing the risk of hypercoagulation disorders, that’s why the search and study of new direct anticoagulant compounds is relevant. Pyrimidine derivatives have been shown to exhibit various types of pharmacological activity, including anticoagulant activity. To study the effect of a new condensed triazolopyrimidine derivative in vitro and in vivo on coagulogram parameters (without and in conditions of hypercytokinemia). Dabigatran etexilate was studied as a comparison drug. For in vitro studies, the test samples were studied in a dose-dependent manner. In the in vivo test, the triazolopyrimidine derivative and the comparison drug were administered to rats once intragastrically at doses of 5.5 mg/kg and 12 mg/kg, respectively, 2 h before the study. Hypercytokinemia was created by lipopolysaccharide by intravenous injection at a dose of 2 mg/kg into the tail vein of the rat. The effect of the tested compound and the comparison drug on rat blood coagulogram parameters (APTT, TT, PT) was determined chronometrically on a SOLAR hemocoagulometer (Belorussia). It was shown that the tested sample and the comparison drug manifested antithrombin activity comparable in terms of IC₅₀ in in vitro test. Triazolopyrimidine derivative in in vivo experiments at a single intragastric administration to rats prolonged thrombin time 5.6 times relative to control values, but was 2 times inferior to the comparison drug dabigatran etexilate. However, under conditions of hypercytokinemia the tested compound was 1.3 times superior to the comparison drug in antithrombin activity. The new triazolopyrimidine derivative in in vitro and in vivo experiments showed high antithrombin activity in sepsis-mediated conditions causing a systemic inflammatory response, which may make a significant contribution to reducing the risk of thrombosis in viral and bacterial infections.

Chronic pruritus has been associated with the neurokinin 1 receptor (NK1R) and its agonist substance P (SP). With the recent disclosure of the receptor’s crystallographic structure, the design of new NK1R antagonists was facilitated. In the marine environment, several SP antagonists were isolated inspiring the synthesis of novel compounds. Since pruritus and inflammation often go together, developing compounds with antipruritic and anti-inflammatory activities is a promising strategy. Therefore, we aim for the structure-based drug design of new SP antagonists based on marine natural products (MNP) to obtain innovative compounds for topical treatment of pruritus-associated inflammatory skin diseases and to evaluate their activity in silico and in vitro. In silico, eighteen marine-inspired compounds were found to bind to NK1R with better or equal docking scores than the natural MNP and demonstrated positive pharmacokinetic properties for skin permeation. In vitro, no relevant cytotoxicity and a 50% reduction in the release of the pro-inflammatory mediator nitric oxide (NO) was detected. The significant decrease in inducible nitric oxide synthase (iNOS) protein levels and NO release, together with the absence of NO-scavenging potential, suggests the blockage of pro-inflammatory signaling pathways upstream of iNOS synthesis. A structure-activity relationship was established, and two new compounds have already been synthesized by two different pathways and structurally characterized. Marine-inspired products are promising sources of anti-inflammatory compounds and NK1R antagonists for the treatment of skin conditions characterized by pruritus and inflammation.

Background and Purpose: The temporal lobe epilepsy (TLE) is the most common type of partial complex seizure in adulthood. High doses of pilocarpine to rats induce status epilepticus (SE) and reproduce the main characteristics of TLE. This model appears to be highly isomorphic with the human disease, so it has been used to elucidate the main mechanisms involved with epileptogenesis. Methods: Here, we employed a two-dimensional gel electrophoresis (2-DE) to study differential expression of proteins in the hippocampus of rats exhibiting SRS induced by pilocarpine (360mg/kg, N=6) compared to a control group (saline, N=6). Both groups were analyzed 90 days after SE onset. Hippocampi were homogenized in a lysis buffer and used to perform 2-DE. Protein spots analyzed by PDQuest software and identified by LC-ESI-MS/MS and MASCOT MS/MS ions search. Results: forty proteins were found differentially expressed in the hippocampus of epileptic rats compared to control animals from which thirty-seven were successfully identified. Twenty-nine of the identified proteins were up-regulated in epileptic rats while six proteins were down-regulated and two proteins were expressed only in the control animals. Conclusion: Some of the proteins differentially expressed in the hippocampus of rats with SRS were also observed altered in the hippocampus of patients with TLE. Such proteins are part of metabolic pathways responsible for the maintenance of vital functions for the cell. Besides, proteins potentially involved in neuronal development and plasticity, neuroprotection mechanisms and neuronal excitability were also found up-regulated in epileptic rats.

The multi-drug resistant pathogen Pseudomonas aeruginosa has been designated by the WHO as a high-priority for the development of new anti-infective treatments. Among Gram-negative bacteria, this species secretes a characteristic cytotoxic pigment called pyocyanin and is able to form biofilms that act as protective barriers against the immune system and antibiotics. Such pathogenicity is mainly regulated by the quorum sensing (QS) pathways that orchestrate the bacterial communication according to the population density. P. aeruginosa possesses a specific QS system : pqs. In this circuit, the transcription factor PqsR stimulates the expression of virulence-related genes via recognition of its auto-inducer PQS (Pseudomonas Quinolone Signal). This notably controls the secretion of pyocyanin and the establishment of biofilms. Therefore, the development of QS inhibitors as anti-virulence agents (AVA) able to tackle P. aeruginosa without affecting bacterial growth appears as a promising strategy to circumvent the selection pressure mediated by conventional antibiotherapy. Ultimately, they could restore the efficacy of antibiotics in dual therapy or potentiate the immune system response in monotherapy. In particular, the design of PqsR inhibitors seems like a sustainable approach to combat P. aeruginosa specifically. In the literature, benzamide-benzimidazole, indole-naphtalene and benzofurane-aminoquinoline hybrids have been reported as such quenchers. Meanwhile, our team discovered a hit 2-heteroaryl-4-quinolone that displays interesting anti-biofilm and anti-pyocyanin activities. By structural analogy with these bi-aromatic molecules, we have recently developed a new family of 2-heteroaryl-4-aminoquinolines with promising anti-virulence properties. The presentation describes the synthesis of our new AVA as well as their physicochemical and biological evaluation.

It is well known that thiosalicylic acid and its S-alkyl derivatives have found applications in medicinal inorganic chemistry. Here are the study results on the interactions between the isobutyl derivatives of thiosalicylic acid (ligand, L) and human serum albumin (HSA). In particular, serum albumin is the primary soluble protein found in the human circulatory system. The metabolism of drugs, their distribution, and effectiveness strongly depend on the drug-albumin interaction. This interaction also affects the concentration of free drugs in the body. The interactions of the isobutyl derivatives of thiosalicylic acid (L) with HSA under physiological conditions was investigate by spectroscopy measurements and molecular docking. The results suggest that ligand could interact with HSA and influenced a slight change in the conformation of HSA through the static quenching mechanism. The analysis revealed that the HSA molecule has a moderate reaction to the ligand, as there is only one binding site for the ligand on the protein.

Herein we present the results obtained in the in silico ADME screening and drug-likeness evaluation of three Schiff bases based on vanillin aldehyde. As an amine counterpart, the selenourea, urea and thiourea were used. According to the obtained results, all three compounds have demonstrated optimal lipophilicity and moderate solubility necessary for the achievement of good bioavailability when administrated orally. Ii was also observed that all compounds have potential to be well absorbed into systematic circulation in GIT (gastrointestinal tract), without possibility to cross blood-brain barrier. The urea-based compound has showed no potential to inhibit any of five P450 isoform. The target screening has indicated that the family of cytosolic proteins and enzymes were the most probable physiological targets for the screened compounds.

Postprandial hyperlipidemia is an important risk factor for atherosclerosis and cardiovascular disease. Silicon (Si) intake has been shown to reduce postprandial hyperlipidemia. Diatomaceous earth (DE) is a highly concentrated source of silicon dioxide. Its use as a dietary Si supplement could have beneficial lipid-lowering effects. The objectives of this study were to investigate the antihyperlipidemic effect of DE on postprandial triglyceridemia and fat digestibility. Rats were daily administered for a week 1 ml of olive oil by oral gavage (C, control group) plus 4 mg Si/kg b.w./day of DE (DE group) (Vitality Gesf S.L). The area under the curve (AUC) of the oral triglyceride tolerance test (OTTT) was calculated. Gastric and intestinal fat content were extracted and composition were determined by HPSEC. A decrease in postprandial triglyceridemia was observed in DE group vs. C group, showing a lower plasma triglyceride AUC within the firsts 2.5 hours. DE rats showed higher amount of remaining fat in the stomach (P<0.05), without changes in its composition. DE increased the amount of fat remaining in the intestinal lumen (P<0.05), that presented higher levels of undigested triglycerides, leading to a decrease in lipid absorption. This study suggests that dietary DE supplementation could be a powerful tool in the treatment of postprandial hypertriglyceridemia by reducing fat digestion and absorption.