Phytochemical, In Vitro, In Vivo, and In Silico Research on the Extract of Ajuga chamaepitys (L.) Schreb.

The present study focuses on the chemical characterization of a dry extract obtained from the species Ajuga chamaepitys (L.) Schreb, evaluating its antioxidant properties, toxicity, and in silico profile. Quantitative analysis of the dry extract revealed a notable amount of phytochemical compounds: 59.932 ± 21.167 mg rutin equivalents (mg REs)/g dry weight, 45.864 ± 4.434 mg chlorogenic acid equivalents (mg ChAEs)/g dry weight and, respectively, 83.307 ± 3.989 mg tannic acid equivalents (TAEs)/g dry weight. By UHPLC-HRMS/MS, the following were quantified as major compounds: caffeic acid (3253.8 µg/g extract) and kaempherol (3041.5 µg/g extract); more than 11 types of polyphenolic compounds were quantified (genistin 730.2 µg/g extract, naringenin 395 µg/g extract, apigenin 325.7 µg/g extract, galangin 283.3 µg/g extract, ferulic acid 254.3 µg/g extract, p-coumaric acid 198.2 µg/g extract, rutin 110.6 µg/g extract, chrysin 90.22 µg/g extract, syringic acid 84.2 µg/g extract, pinocembrin 32.7 µg/g extract, ellagic acid 18.2 µg/g extract). The antioxidant activity was in accordance with the amount of phytochemical compounds: IC50DPPH = 483.6 ± 41.4 µg/mL, IC50ABTS•+ = 127.4 ± 20.2 µg/mL, and EC50FRAP = 491.6 ± 2 µg/mL. On the larvae of Artemia sp., it was found that the extract has a low cytotoxic action. In silico studies have highlighted the possibility of inhibiting the activity of protein kinases CDK5 and GSK-3b for apigenin, galangin, and kaempferol, with possible utility for treating neurodegenerative pathologies and neuropathic pain. Further studies are warranted to confirm the predicted molecular mechanisms of action and to further investigate the therapeutic potential in animal models of neurological disorders.

Incidence of Urinary Infections and Behavioral Risk Factors.

This evaluation of the impact of behavioral risk factors on the incidence of urinary infections was based on a questionnaire in which 1103 respondents, predominantly women (883), participated. From the statistical processing of the data, it was observed that 598 of the respondents were of normal weight; the rest, more than half, were underweight or overweight (χ2 = 32.46, p < 0.001), with male respondents being predominantly overweight or obese (169 out of a total of 220). Most of the respondents were young (χ2 = 15.45, p < 0.001), under the age of 45 (840). According to the processed data, it was found that respondents in the age group of 26-35 years showed the greatest vulnerability to recurrent urinary infections, while the age group of 18-25 years recorded the highest number of responses related to the rare presence or even absence of episodes of urinary infections. A body weight-related vulnerability was also noted among the respondents; the majority of obese people declared that they face frequent episodes of urinary infections. Regarding diet quality, 210 respondents reported an adherence to an unhealthy diet, 620 to a moderately healthy diet, and 273 to a healthy diet. Of the respondents who adhered to a healthy diet, 223 were women (χ2 = 2.55, p = 0.279). There was a close connection between diet quality and the frequency of urinary infections: from the statistical processing of the data, it was observed that the highest percentage of respondents who rarely (57.14%) or never got urinary infections (29.30%) were among those who adhered to a healthy diet, and the highest percentage of those who declared that they often got urinary infections were among those with increased adherence to an unhealthy diet (χ2 = 13.46, p = 0.036). The results of this study highlight a strong impact of obesity, reduced consumption of fruit and vegetables, and sedentary lifestyle on the risk of recurring urinary infections.

Semperivium Ruthenicum Koch Extract-Loaded Bio-Adhesive Formulation: A Novel Oral Antioxidant Delivery System for Oxidative Stress Reduction.

Periodontitis is a chronic inflammatory disease that affects the oral cavity and can ultimately lead to tooth loss. Oxidative stress has been identified as a key factor in the development of periodontitis. In recent years, natural polyphenols have gained attention for their anti-inflammatory and antioxidant effects. This study aims to evaluate the potential of a bio-adhesive patch loaded with Semperivium ruthenicum Koch extract, rich in polyphenols, as a novel oral antioxidant delivery system for reducing oxidative stress in periodontitis. The plant extracts were prepared by maceration and were subjected to HPLC analysis for the identification and quantification of polyphenols. The bio-adhesive patches were prepared using a solvent-casting technique and characterized for their technical characteristics and release kinetics. The patches demonstrated satisfactory technical characteristics and followed Korsmeyer-Peppas release kinetics, with the active ingredients diffusing non-Fickian from the polymer matrix as it eroded over time. The bio-adhesive strength of the patches was comparable to other similar formulations, suggesting that the obtained patches can be tested in vivo conditions. The results suggest that treating oral periodontitis with natural polyphenols may effectively scavenge free radicals and regulate cytokine activity, leading to a reduction in oxidative stress. The non-smoking group had a mean saliva antioxidant activity of 7.86 ± 0.66% while the smoking group had a mean value of 4.53 ± 0.15%. Furthermore, treating oral oxidative stress may also contribute to overall gut health, as studies have shown a correlation between oral and gut microbiomes. Therefore, the use of bio-adhesive patches containing polyphenols may provide a promising approach for the treatment of periodontitis and its associated complications.

Therapeutic Benefits and Dietary Restrictions of Fiber Intake: A State of the Art Review.

Throughout history, malnutrition and deficiency diseases have been a problem for our planet's population. A balanced diet significantly influences everyone's health, and fiber intake appears to play a more important role than previously thought. The natural dietary fibers are a category of carbohydrates in the constitution of plants that are not completely digested in the human intestine. High-fiber foods, such as fruits, vegetables and whole grains, have consistently been highly beneficial to health and effectively reduced the risk of disease. Although the mode of action of dietary fiber in the consumer body is not fully understood, nutritionists and health professionals unanimously recognize the therapeutic benefits. This paper presents the fiber consumption in different countries, the metabolism of fiber and the range of health benefits associated with fiber intake. In addition, the influence of fiber intake on the intestinal microbiome, metabolic diseases (obesity and diabetes), neurological aspects, cardiovascular diseases, autoimmune diseases and cancer prevention are discussed. Finally, dietary restrictions and excess fiber are addressed, which can cause episodes of diarrhea and dehydration and increase the likelihood of bloating and flatulence or even bowel obstruction. However, extensive studies are needed regarding the composition and required amount of fiber in relation to the metabolism of saprotrophic microorganisms from the enteral level and the benefits of the various pathologies with which they can be correlated.

In Silico and Experimental Investigation of the Biological Potential of Some Recently Developed Carprofen Derivatives.

The efficient regioselective bromination and iodination of the nonsteroidal anti-inflammatory drug (NSAID) carprofen were achieved by using bromine and iodine monochloride in glacial acetic acid. The novel halogenated carprofen derivatives were functionalized at the carboxylic group by esterification. The regioselectivity of the halogenation reaction was evidenced by NMR spectroscopy and confirmed by X-ray analysis. The compounds were screened for their in vitro antibacterial activity against planktonic cells and also for their anti-biofilm effect, using Gram-positive bacteria (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212) and Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). The cytotoxic activity of the novel compounds was tested against HeLa cells. The pharmacokinetic and pharmacodynamic profiles of carprofen derivatives, as well as their toxicity, were established by in silico analyses.

Black Sea Mussels Qualitative and Quantitative Chemical Analysis: Nutritional Benefits and Possible Risks through Consumption.

Mussels have a particular nutritional value, representing a highly valued food source and thus sought after worldwide. Their meat is a real culinary delicacy, rich in proteins, lipids, carbohydrates, trace elements, enzymes, and vitamins. The seasonal variation of mussels' biochemical composition has been studied to determine the best harvesting period to capitalize on various biologically active fractions. In this work biochemical determinations have been performed on fresh flesh samples of Mytilus galloprovincialis specimens from the Black Sea coast to study seasonal variations in mussels' biochemical compounds. An analysis of significant lipid classes and the fatty acid composition of lipid extracts obtained from mussel flesh has also been performed. Since mussels retain pollutants from the marine environment, in parallel, the concentration of heavy metals in the meat of mussels collected for the analysis of the chemical composition was investigated. The impact and risk of heavy metal poisoning due to food consumption of mussels contaminated due to pollution of the marine harvesting area was evaluated by the bio-concentration factor of metals and estimated daily intakes of heavy metals through mussel consumption.

Green solvents for the formation of amide linkages.

The formation of the amide bond is among the most commonly performed transformations in the pharmaceutical industry and the wider chemical industry. The current methods for its installation in organic compounds frequently rely on the use of large amounts of organic solvents, mainly N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), and dichloromethane (DCM), which have been associated with adverse environmental and health concerns over the last decades. This fact led academia and industry to make significant efforts toward the development of synthetic routes with the aim to avoid, reduce or replace the use of hazardous solvents. The present review fits into this framework and discusses the literature existing over the past ten years on strategies for reducing and replacing hazardous solvents, focusing on the use of biobased and neoteric solvents, such as ionic liquids and deep eutectic solvents (ILs and DESs, respectively), and on the reaction media that proved to be greener alternatives for amide bond formation.

Synthesis and Toxicity Evaluation of New Pyrroles Obtained by the Reaction of Activated Alkynes with 1-Methyl-3-(cyanomethyl)benzimidazolium Bromide.

A series of new pyrrole derivatives were designed as chemical analogs of the 1,4-dihydropyridines drugs in order to develop future new calcium channel blockers. The new tri- and tetra-substituted N-arylpyrroles were synthesized by the one-pot reaction of 1-methyl-3-cyanomethyl benzimidazolium bromide with substituted alkynes having at least one electron-withdrawing substituent, in 1,2-epoxybutane, acting both as the solvent and reagent to generate the corresponding benzimidazolium N3-ylide. The structural characterization of the new substituted pyrroles was based on IR, NMR spectroscopy as well as on single crystal X-ray analysis. The toxicity of the new compounds was assessed on the plant cell using Triticum aestivum L. species and on the animal cell using Artemia franciscana Kellogg and Daphnia magna Straus crustaceans. The compounds showed minimal phytotoxicity on Triticum rootlets and virtually no acute toxicity on Artemia nauplii, while on Daphnia magna, it induced moderate to high toxicity, similar to nifedipine. Our research indicates that the newly synthetized pyrrole derivatives are promising molecules with biological activity and low acute toxicity.

Synthesis of 1-(2-Fluorophenyl)pyrazoles by 1,3-Dipolar Cycloaddition of the Corresponding Sydnones.

3-Arylsydnones bearing fluorine and bromine atoms on the benzene ring were synthesized from N-nitroso-2-fluorophenylglycines and characterized by NMR spectroscopy. These were employed further in synthesis of the corresponding 1-(2-fluorophenyl)pyrazoles by 1,3-dipolar cycloaddition reaction with dimethyl acetylenedicarboxylate (DMAD) as activated dipolarophile. The sydnones as reaction intermediates were characterized by single crystal X-ray diffraction analysis showing interesting features such as halogen bonding as an important interaction in modeling the crystal structure.

Introducing chirality in halogenated 3-arylsydnones and their corresponding 1-arylpyrazoles obtained by 1,3-dipolar cycloaddition.

New 1-arylpyrazoles substituted with halogen atoms (Br, I) were synthesized from the corresponding sydnones by 1,3-dipolar cycloaddition. By introduction of a prochiral group such as isopropyl, in the ortho position of the benzene ring, in the starting phenylglycine 1 the rotamers caused by the hindered rotation between the phenyl and the heterocyclic ring were detected by NMR spectroscopy for 1-arylpyrazoles and for the first time for 3-arylsydnones. The N-nitrosophenylglycines present E-Z stereoisomerism due to the partial C-N double bond character. All the new compounds were structurally characterized by NMR spectroscopy and confirmed by X-ray crystallography. The crystal structures of N-nitrosophenylglycine 2c and of the sydnone 3c present similar Br⋯Br type II halogen contacts.

Sydnone C-4 heteroarylation with an indolizine ring via Chichibabin indolizine synthesis.

The synthesis of sydnones heteroarylated at C-4 with an indolizine was achieved by Chichibabin (Tschitschibabin) indolizine synthesis starting from the corresponding sydnone-N-pyridinium bromides. The latter compounds were also transformed to sydnone-indolizines connected through a keto group at the C-4 position by refluxing them in 1,2-epoxybutane with an activated alkyne. The structures of the new compounds were assigned by FTIR, NMR spectroscopy and X-ray analysis.

Synthesis of pyrrolo[2,1-a]isoquinolines by multicomponent 1,3-dipolar cycloaddition.

Pyrrolo[2,1-a]isoquinoline derivatives were synthesized by one-pot three-component reactions starting from isoquinoline, 2-bromoacetophenones and different non-symmetrical acetylenic dipolarophiles using 1,2-epoxypropane as solvent. The structure of the compounds was assigned by IR and NMR spectroscopy.

Synthesis and X-ray structure of a new pyrrolo[1,2-b]-pyridazine derivative.

The synthesis, characterization and X-ray crystal structure of 2-(4-chloro-phenyl)-7-methylpyrrolo[1,2-b]pyridazine are reported. The compound crystallizes in the space group P2(1)/c (No.14) with a =3.8568(1), b = 11.0690(3), c = 26.4243(7) A, beta =92.777(1) degrees and Z = 4. Accurate molecular parameters for the novel heterocyclic system were obtained from intensity data collected at 113K. The molecule assumes a planar conformation in the crystal and the packing is based on pi-pi stacking with interplanar spacing 3.400 å, typical of aromatic molecules with potential for displaying useful optical properties.