Structural elucidation of a new triquinane sesquiterpenoid, presilphiperfolane-7α,8α-diol, 1a, isolated from Pulicaria vulgaris, was accomplished by combining solvent-induced removal of chemical ...shift degeneracy and computational (DFT-GIAO) prediction of NMR spectra with the analysis of 1H NMR splitting patterns. In addition to extensive NMR experiments (in 10 different solvents), MS, and FTIR, the identity of 1a was also confirmed by chemical transformations. The applied approach can facilitate structural elucidation of organic molecules and decrease the probability of an erroneous identification, permitting an unambiguous stereochemical elucidation and full NMR assignment. The pharmacological/toxicological profile of 1a was evaluated in several different models.
Among the fewest drugs discovered are those belonging to the class of anxiolytics. Although some drug targets for anxiety disorders are established, it is hard to modify and selectively choose the ...active principle for those targets. Thus, the ethnomedical approach to treating anxiety disorders remains one of the most prevalent ways for (self)managing the symptoms. Melissa officinalis L. (lemon balm) has been extensively used as an ethnomedicinal remedy for the treatment of different psyche-related symptoms, especially dose related to restlessness.
This work aimed to evaluate the anxiolytic activity, in several in vivo models, of the essential oil extracted from Melissa officinalis (MO) and its main constituent citronellal, a widespread plant utilized for managing anxiety.
In the present study several animal models were used to assess MO anxiolytic potential in mice. The effect of the MO essential oil applied in doses ranging from 12.5 to 100 mg/kg was estimated in light/dark, hole board, and marble burying tests. In parallel doses of citronellal corresponding to the ones in the MO essential oil were applied to animals to determine if this is the activity carrier.
The results indicate that the MO essential oil exerts anxiolytic potential in all three experimental settings by significantly altering the traced parameters. The effects of citronellal are somewhat inconclusive and should not be interpreted only as anxiolytic but rather as a combination of anti-anxiety and motor-inhibiting effects.
In conclusion, we could say that the results of the present study provide a base for future mechanistic studies that would evaluate the activity of M. officinalis essential oil on various neurotransmitter systems involved in the generation, propagation, and maintenance of anxiety.
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•Melissa officinalis essential oil might possess promising anxiolytic effects.•Citronellal and M. officinalis exert in vivo anxiolytic-like activity.•In a dose of 12.5 mg/kg M. officinalis essential oil acts as anxiolytic.•The anxiolytic activity of citronellal might be due to motor inhibition.
Herein, upgraded chloroquine (CQ) derivatives capable of overcoming Plasmodium resistance and, at the same time, suppressing excessive immune response and risk of concurrent bacteremia were ...developed. Twelve new ferrocene–CQ hybrids tethered with a small azathia heterocycle (1,3-thiazolidin-4-one, 1,3-thiazinan-4-one, or 5-methyl-1,3-thiazolidin-4-one) were synthesized and fully characterized. All hybrids were evaluated for their in vitro antiplasmodial, antimicrobial, and immunomodulatory activities. Additional assays were performed on selected hybrids to gain insights into their mode of action. Although only hybrid 4a was more potent than the parent drug toward CQ-resistant Dd2 Plasmodium falciparum strain, several other hybrids (such as 6b, 6c, and 6d) manifested substantially improved antimicrobial and immunomodulatory properties. Interesting structure–activity relationship data were obtained, hinting at future research for the development of new multitarget chemotherapies for malaria and other infectious diseases complicated by drug resistance, bacterial co-infection, and immune-driven pathology issues.
This study aimed to evaluate the protective action of oregano (
) essential oil and its monoterpene constituents (thymol and carvacrol) in L-arginine-induced kidney damage by studying inflammatory ...and tissue damage parameters. The determination of biochemical markers that reflect kidney function, i.e., serum levels of urea and creatinine, tissue levels of neutrophil-gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1), as well as a panel of oxidative-stress-related and inflammatory biomarkers, was performed. Furthermore, histopathological and immunohistochemical analyses of kidneys obtained from different experimental groups were conducted. Pre-treatment with the investigated compounds prevented an L-arginine-induced increase in serum and tissue kidney damage markers and, additionally, decreased the levels of inflammation-related parameters (TNF-α and nitric oxide concentrations and myeloperoxidase activity). Micromorphological kidney tissue changes correlate with the alterations observed in the biochemical parameters, as well as the expression of CD95 in tubule cells and CD68 in inflammatory infiltrate cells. The present results revealed that oregano essential oil, thymol, and carvacrol exert nephroprotective activity, which could be, to a great extent, associated with their anti-inflammatory, antiradical scavenging, and antiapoptotic action and, above all, due to their ability to lessen the disturbances arising from acute pancreatic damage. Further in-depth studies are needed in order to provide more detailed explanations of the observed activities.
This study aimed to examine the effects of post-activation performance enhancement (PAPE) on swim start performance and lower body power performance after different warm-up protocols. Ten male ...national-level swimmers performed three different warm-ups: (i) a swim-specific warm-up (SW, control protocol); (ii) PAPE (an experimental protocol); and (iii) SW followed by PAPE (SW + PAPE, an experimental protocol). PAPE consisted of performing three series of 5 drop jumps. A repeated-measures ANOVA showed significant differences between the protocols in the swim start performance (F = 8.89; P < 0.001) and countermovement jump (F = 2.22; P = 0.047). SW + PAPE induced greater improvements in swim start time to 15 m (ES = - 0.47, P = 0.017) and entry time (ES = - 1.83, P < 0.001), the countermovement jump reactive strength index modified (ES = - 1.83, P < 0.001), eccentric rate of force development (ES = 0.69, P = 0.047), and index of explosive strength (ES = 0.94, P = 0.005) compared to SW. The current findings of this study indicate that the drop jump PAPE protocol, in addition to SW, is an effective tool because it could improve athletes' capacity for a more efficient swim start and their countermovement jump performance. Furthermore, the results of this study indicate that PAPE induced by drop jumps could be time-efficient and practically applicable in facilities with limited resources.
Marrubiin is a diterpene with a long history of a wide range of biological activities. In this study, the anti-inflammatory effects of marrubiin were investigated using several in vitro and in vivo ...assays. Marrubiin inhibited carrageenan-induced peritoneal inflammation by preventing inflammatory cell infiltration and peritoneal mast cell degranulation. The anti-inflammatory activity was further demonstrated by monitoring a set of biochemical parameters, showing that the peritoneal fluid of animals treated with marrubiin had lower levels of proteins and lower myeloperoxidase activity compared with the fluid of animals that were not treated. Marrubiin exerted the most pronounced cytotoxic activity towards peripheral mononuclear cells, being the main contributors to peritoneal inflammation. Additionally, a moderate lipoxygenase inhibition activity of marrubiin was observed.
L-Glutamic acid decarboxylase (GAD) is an enzyme that ensures the balance between the levels of two neurotransmitters, γ-aminobutyric acid (GABA) and L-glutamic acid (L-Glu), necessary for proper ...brain functioning. A reduction in the concentrations of GABA and/or GAD activity has been implicated in the symptoms associated with epilepsy, which could be plausibly alleviated by the application of GAD activators. As any unnecessary interference in GAD catalytic activity could be detrimental, it is important to study whether CNS (or other) drug candidates act on GAD or not. The ability to identify and reduce this risk early could significantly improve the process of drug development. Although many methods for measuring GAD activity in various biological samples have been described, only few (such as manometric and radiometric) were adopted as in vitro assays for the screening of potential GAD inhibitors/activators. However, these methods require specialized equipment and/or an expensive radiolabeled substrate, and may have sensitivity and/or reliability issues. Therefore, this study aimed to develop an HPLC-DAD-based assay that would allow a simple and more accurate measurement of GAD inhibition or activation using unpurified mice or rat brain homogenates. This assay is based on the quantification of GABA, formed during the enzymatic reaction, after its derivatization with dansyl chloride. Various parameters were evaluated to optimize the assay procedure (e.g. homogenate volume, incubation time, DMSO content, GAD, GABA, and dansyl-GABA stabilities). This assay was validated for pharmacological screenings using 3-mercaptopropionic acid and gallic acid and GAD obtained from different experimental animals.
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•Glutamate decarboxylase (GAD) regulates the interconversion of L-Glu to GABA.•Only 2 methods with serious issues are in use for in vitro measurements of GAD.•An improved simple HPLC-based assay for GAD activity was developed.•No need for specialized equipment, expensive reagents, and pure enzyme use.•Possibility of sample storage and different enzyme sources utilization.
The exposure of humans to artificial light at night (ALAN) with predominant blue part of the visible spectrum is strongly influencing circadian rhythm and sleep through melanopsin-containing retinal ...ganglion cells (RGC). We hypothesized that reducing the amount of emitted blue light from screens of mobile phones during the night will increase sleep quality in our student population. The aim of the work was to investigate the effect of reducing blue light from smartphone screen during the night on subjective quality of sleep among students of medicine. The target population was students of medicine aged 20 to 22 years old of both sexes. The primary outcome of the study was subjective sleep quality, assessed by the Serbian version of the Pittsburgh Sleep Quality Index (PSQI). The mean total PSQI score before intervention was 6.83 ± 2.73 (bad), while after the intervention the same score was statistically significant reduced to 3.93 ± 1.68 (good) with large effect size. The study has shown that a reduction of blue light emission from LED backlight screens of mobile phones during the night leads to improved subjective quality of sleep in students, as well as improvement in daytime functioning and going to sleep.
The currently used immunohistochemical approach in determining the estrogen receptor (ER) positivity of breast cancers (BCs) is inherently subjective and additionally limited by its semi-quantitative ...nature. The application of software in the analysis of digitized slide images may overcome some of these limitations. However, the utilization of such an approach requires that the entire staining procedure is standardized.
We aimed to establish a procedure for the photometric and morphometric analysis of BC immunohistochemical parameters that can possibly be used for a diagnostic purpose that is in line with the current semi-quantitative scoring system.
Semi-quantitative analysis of ER-stained tissue sections was performed following the Allred scoring system guidelines. The quantitative analysis was performed in ImageJ software after color deconvolution. The quantitative analysis of 66 cases of invasive lobular BC included: Percent of ER-positive cells, average nuclear coloration intensity, and the quantitative ER score. The percent of ER-positive tumor cells was counted using a standard grid overlay, while optical density (0.0-1.0) was measured within each nucleus at the grid points.
A statistical analysis revealed a significant positive correlation (
= 0.886,
< 0.001) between the subjective semi-quantitative and quantitative ER scores, with a large effect size (
= 3.8215). We observed strong statistically significant correlations between individual parameters of the total ER score, percentage of ER-positive nuclei, and color intensity, obtained by the two independent methods.
Additionally, besides excluding subjectivity, the up to now unreported cases of 3 + 0, 4 + 0, and 5 + 0 Allred scores were detected only by the application of the proposed quantitative approach.
Objectives
As there are no previous studies of the European wild‐garlic (Allium ursinum) effects on the gastrointestinal system, despite its traditional applications in gastrointestinal disorders' ...treatment and regular use in the human diet, we have quantified and compared spasmolytic, antimicrobial and antioxidant activities of its different leaf extracts.
Methods
Wild‐garlic extracts were tested for spasmolytic activity on isolated rat ileum, antimicrobial activity on selected Gram‐positive and Gram‐negative bacteria and fungi by microdilution method and antioxidant capacity by DPPH radical‐scavenging assay.
Key findings
Wild‐garlic extracts were found to decrease ileal basal tone. As the relaxation of K+‐induced contractions was similar to one caused by papaverin, the observed spasmolytic effect was most likely mediated through Ca2+‐channel inhibition. Ethanolic extract (with the highest phenolic and high alk(en)yl cysteine sulphoxides’ levels) produced the strongest spasmolytic activity. In case of acetylcholine‐induced contractions, only hydromethanolic extract showed no statistical difference in comparison with positive control. All samples exhibited certain antioxidant potential and strong antimicrobial activity against tested enteropathogenic strains (Salmonella enteritidis was the most sensitive, followed by Escherichia coli, Proteus mirabilis and Enterococcus faecalis).
Conclusion
Besides other already established health‐promoting effects, wild garlic could be useful in treatment of mild gastrointestinal disturbances.
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