Search

Knowledge of drug pharmacokinetics and tissue distribution is precious for ensuring patient safety and optimizing treatments. The varied use of local anesthetics, as well as the fact that anesthetics can sometimes have low therapeutic indices and numerous adverse drug reactions, makes any novel pharmacokinetics information valuable. The present manuscript describes a pharmacokinetic study of ropivacaine carried out after plane block anesthesia on an animal model, using high sensitivity, accurate, and precise LC-MS/MS bioanalysis. Both plasmatic concentrations and tissue distribution of ropivacaine and its primary active metabolite were determined. The results showed a tissue affinity of the anesthetics, a clearance of ropivacaine mainly by hepatic metabolism, and the final, mainly renal excretion of the hydroxylated metabolite. While the results cannot simply and directly be transposed to human pharmacokinetics, they offer a valuable basis for future studies and can contribute to a better understanding of the bioavailability and toxicology of the widely used modern anesthetic.

Abstract Background Cancer stem-like cells (CSCs) have been extensively researched as the primary drivers of therapy resistance and tumor relapse in patients with breast cancer. However, due to lack of specific molecular markers, increased phenotypic plasticity and no clear clinicopathological features, the assessment of CSCs presence and functionality in solid tumors is challenging. While several potential markers, such as CD24/CD44, have been proposed, the extent to which they truly represent the stem cell potential of tumors or merely provide static snapshots is still a subject of controversy. Recent studies have highlighted the crucial role of the tumor microenvironment (TME) in influencing the CSC phenotype in breast cancer. The interplay between the tumor and TME induces significant changes in the cancer cell phenotype, leading to the acquisition of CSC characteristics, therapeutic resistance, and metastatic spread. Simultaneously, CSCs actively shape their microenvironment by evading immune surveillance and attracting stromal cells that support tumor progression. Methods In this study, we associated in vitro mammosphere formation assays with bulk tumor microarray profiling and deconvolution algorithms to map CSC functionality and the microenvironmental landscape in a large cohort of 125 breast tumors. Results We found that the TME score was a significant factor associated with CSC functionality. CSC-rich tumors were characterized by an immune-suppressed TME, while tumors devoid of CSC potential exhibited high immune infiltration and activation of pathways involved in the immune response. Gene expression analysis revealed IFNG, CXCR5, CD40LG, TBX21 and IL2RG to be associated with the CSC phenotype and also displayed prognostic value for patients with breast cancer. Conclusion These results suggest that the characterization of CSCs content and functionality in tumors can be used as an attractive strategy to fine-tune treatments and guide clinical decisions to improve patients therapy response.

Background/Objectives: Angiogenesis plays a crucial role in tumor development and is a driving force for the aggressiveness of several types of cancer. Our team developed a novel series of thiosemicarbazone-containing quinazoline derivatives, TSC1-TSC10, as potential VEGFR2 inhibitors with proven anti-angiogenic and antiproliferative potential. Methods: The TSC1-TSC10 series was synthesized and characterized by spectral data. Extensive methodology was applied both in vitro (Alamar Blue assay, Scratch assay, CAM assay, and VEGFR2 kinase assay) and in silico (docking studies, MDs, and MM-PBSA) for the confirmation of the biological potential. Results: TSC10 emerged as the most promising compound, with a favorable cytotoxic potential across the cell panel (Ea.Hy296, HaCaT, and A375) in agreement with the in vitro VEGFR2 kinase assay (IC50 = 119 nM). A comparable motility reduction in the vascular endothelial cells to that of the reference drug sorafenib was provided by TSC10, with a similar anti-angiogenic potential in the more complex in ovo model of the CAM assay. The in silico experiments confirmed the successful accommodation of the active site of the kinase domain similar to sorafenib for the entire TSC1-TSC10 series, providing valuable key insight into the complex stability driving force for the evaluated compounds. Conclusions: The in vitro evaluations of the biological potential correlated with the in silico predictions by computer-aided complex simulations provided a solid confirmation of the initial hypothesis for the TSC1-TSC10 series.

Background: Blackcurrant (Ribes nigrum L.) leaves are valuable sources of bioactive compounds, including phenolic acids, flavonoids, and tannins, which contribute to their potent antioxidant, anti-inflammatory, and antimicrobial properties. Objectives: The overall aim of this study was to investigate the antimicrobial potential of extracts rich in bioactive compounds from blackcurrant leaves prepared in natural deep eutectic solvents (NaDESs). The objectives included the optimization of polyphenols extraction in NaDESs, characterization of the phytochemical composition by liquid chromatography–mass spectrometry (LC-MS), explanation of the chemical interactions between solvent systems and the main bioactive compound (chlorogenic acid) by molecular dynamics simulations, and evaluation of biological efficacy through antimicrobial tests. Methods: Two hydrogen-bond acceptors (HBAs) and three hydrogen-bond donors (HBDs) were tested. The experimental design included variables such as the HBA:HBD molar ratio, water percentage, extraction time, and extraction techniques used, specifically ultrasound-assisted extraction (UAE) and ultra-turrax extraction (UTE). The evaluated responses included the total polyphenol content, total flavonoid content, and total antioxidant activity. Antimicrobial assays were performed on four Gram-positive and three Gram-negative bacterial species, as well as one fungus, Candida albicans. Results: The extracts obtained by UAE showed higher concentrations of polyphenols and increased antioxidant potential. LC-MS analysis revealed the predominant presence of chlorogenic acid. The extracts showed significant activities against Gram-positive bacteria and Candida albicans. Conclusions: This study highlights the antioxidant and antimicrobial potentials of blackcurrant leaves extracts prepared in NaDESs, confirming that this type of solvent enhances polyphenols extraction and offers perspectives for new therapeutic formulations.

Background/Objectives: In psychiatric disorders, antipsychotics and antidepressant medication are often administered together. Aripiprazole, a third-generation antipsychotic drug, is extensively metabolized by CYP2D6 and CYP3A4 isoenzymes, while bupropion, used in depressive disorders, is known as a moderate or strong CYP2D6 enzyme inhibitor. This in vivo experiment aimed to assess the presence of a pharmacokinetic drug interaction between aripiprazole and bupropion and its magnitude on the systemic exposure of aripiprazole. Methods: 24 healthy Wistar albino male rats were included in two study groups. A single dose of 8 mg/kg aripiprazole was given to rats in the reference group, while the test group received repeated doses of bupropion for 6 days, followed by a single dose of aripiprazole. An LC-MS/MS method was developed for the concomitant quantification of aripiprazole and its active metabolite, dehydroaripiprazole, and non-compartmental analysis was employed to assess their pharmacokinetic parameters. Results: The mean AUC0-∞ of aripiprazole increased 5.65-fold (1117.34 ± 931.41 vs. 6311.66 ± 2978.71 hr·ng/mL), the mean Cmax increased by 96.76% and the apparent systemic clearance decreased over 9-fold after bupropion repeated doses. The exposure to aripiprazole’s active metabolite increased as well, having a 4-fold increase in the mean AUC0–∞ (from 461.13 ± 339.82 to 1878.66 ± 1446.91 hr·ng/mL) and a 2-fold increase in the mean Cmax. Conclusions: The total exposure to the aripiprazole parent compound and active moiety significantly increased after bupropion pretreatment in this preclinical in vivo experiment. Clinical studies should further establish the significance of this interaction in humans.

Background: Linezolid has been found to have considerable interindividual variability, especially in critically ill patients, which can lead to suboptimal plasma concentration. To overcome this shortcoming, several solutions have been proposed. These include using loading dose, higher maintenance doses, and dose stratification according to the patient’s particularities, therapeutic drug monitoring, and drug administration via continuous infusion (CI) instead of intermittent infusion (II). In the present study, we aim to compare the pharmacokinetic (PK) parameters of linezolid after administration as II versus CI to critically ill patients. Methods: In a prospective study conducted in an intensive care unit, we compared the same two daily doses of linezolid administered via II versus CI. The serum concentration was measured, and pharmacokinetic parameters were calculated. The pharmacokinetic/pharmacodynamic (PK/PD) indices for efficacy chosen were area under the concentration–time curve at steady state divided by the minimum inhibitory concentration over 80 (AUC24–48/MIC > 80). Results: Greater serum concentration variability was observed in the II group than in the CI group. The %T > MIC > 80% was achieved for MICs of 1 and 2 µg/mL 100% of the time, whereas for the II group, this was 93% and 73%, respectively. AUC24–48/MIC > 80 was reached in 100% of cases in the CI group compared with 87% in the II group for a MIC of 1 µg/mL. Conclusions: The two infusion methods may be used comparably, but utilizing CI as an alternative to II may have potential benefits, including avoiding periods of suboptimal concentrations, which may enhance safety profiles and clinical outcomes. Considering the relatively few studies performed on linezolid to date, which are increasing in number, the results of the present study may be of interest.

Bee products and natural oils are appreciated due to their beneficial effects on health, which are strongly related to several pharmacological and biological activities. The present study aimed to assess the bioactive potential of two bee products with the addition of natural oils, the first product consisting of honeydew honey, soft propolis extract and Thymus sp. (thyme) essential oil, whereas the second product comprises honeydew honey and Hippophae rhamnoides L. (sea buckthorn) oil. In order to reach the proposed goal, the following analyses were carried out: determination of the physico-chemical parameters of the honeydew honey sample, used as a common basis for the two products; compositional analysis of sea buckthorn oil (total carotenoids, fatty acids, tocopherols, sterols) and thyme essential oil (organic compounds); evaluation of the total polyphenols and flavones/flavonols content; evaluation of the antioxidant capacity (DPPH and FRAP methods). The results highlighted the superior quality and compliance with the legal framework of the honeydew honey sample and natural oils. Moreover, the two investigated products exhibited a rich content of bioactive compounds as well as good antioxidant activity.

A series of thiazolyl–catechol compounds with antioxidant and cytotoxic activities were synthesized by a Hantzsch heterocyclization, using diverse thioamides as the thiocarbonyl component and 4-chloroacetyl-catechol as haloketone. These compounds were characterized by MS, IR spectroscopy, and NMR. Their antioxidant potential was evaluated by antiradical, electron transfer, and ferrous ion chelation assays using ascorbic acid, Trolox, and EDTA-Na2 as references. The cytotoxicity of the synthesized compounds was evaluated on two different cell types, normal human foreskin fibroblasts (BJ) and human pulmonary malignant cells (A549), using gefitinib as a reference anticancer drug. The results obtained from the tests highlighted compounds 3g and 3h with significant antioxidant activities. The highest cytotoxic potency against A549 cells was exhibited by compounds 3i and 3j, while compound 3g demonstrated exceptional selectivity on malignant cells compared to gefitinib. These promising results encourage further investigation into targeted modifications on position 2 of the thiazole ring, in order to develop novel therapeutic agents.

Melatonin is commonly found in various fruits, juices, and some fermented beverages. Its concentration in wine is influenced by soil properties, climatic factors, and yeast activity. Even if it is found in fermented beverages in relatively low proportions, melatonin still holds significant nutritional value, giving anti-aging properties, anti-inflammatory actions, and antidepressant effects. In this context, this article focuses on evaluating the impact of different Saccharomyces and non-Saccharomyces yeast species on the formation of melatonin and its contribution to wines’ total antioxidant capacity. Considering that the antioxidant activity of wine is usually related to the content of phenolic compounds, ten such compounds were analyzed. The evaluation of bioactive compounds was performed using high-performance liquid chromatography (HPLC) coupled with mass spectrometry. The total antioxidant capacity of wine samples was evaluated by the ABTS+ method. The administration of bâtonnage products increased the efficiency of non-Saccharomyces yeasts. The mixtures of Saccharomyces and non-Saccharomyces yeasts generated higher values for melatonin. The results confirm a significant impact from the grape variety and the specific yeast strains on the melatonin concentration. Also, a strong dependence between antioxidant activity and melatonin levels was observed. Given the limited existing studies on the presence of melatonin in wines, new perspectives are needed for future exploration and understanding.

The species of the genus Euphrasia present important medicinal potential according to their traditional uses. However, few studies aim to sustain this fact by scientific evidence. The present study aimed to explore the phytochemical profile and investigate the antioxidant, antimicrobial and antiproliferative potential of E. officinalis subsp. pratensis Fr. (EO) and E. stricta J.P.Wolff ex J.F.Lehm (ES). The tested samples consisted of ethanolic extracts. The identification and quantification of phenolic compounds were performed using spectrophotometric and LC–MS/MS methods. The antioxidant capacity was evaluated using the DPPH, FRAP and xanthine oxidase methods. Antimicrobial properties were screened using disk diffusion, broth microdilution and anti-biofilm assays, while antiproliferative potential was assessed on a colorectal adenocarcinoma human cancer cell line (DLD-1). The LC–MS/MS analysis showed chlorogenic acid and rutin as the dominant constituents in the tested extracts. The antioxidant activity assays showed important capacity for both samples; in vitro antimicrobial and anti-biofilm properties were exhibited, especially against Gram-positive bacteria, and an important inhibitory potential was observed on the proliferation of the DLD-1 cell line. The findings in the present study contribute to the recommendation of EO and ES for the prevention and treatment of oxidative stress-related pathologies, cancer and microbial infections.

Two series, “a” and “b”, each consisting of nine chemical compounds, with 2,3-disubstituted quinazolin-4(3H)-one scaffold, were synthesized and evaluated for their anticonvulsant activity. They were investigated as dual potential positive allosteric modulators of the GABAA receptor at the benzodiazepine binding site and inhibitors of carbonic anhydrase II. Quinazolin-4(3H)-one derivatives were evaluated in vivo (D1–3 = 50, 100, 150 mg/kg, administered intraperitoneally) using the pentylenetetrazole (PTZ)-induced seizure model in mice, with phenobarbital and diazepam, as reference anticonvulsant agents. The in silico studies suggested the compounds act as anticonvulsants by binding on the allosteric site of GABAA receptor and not by inhibiting the carbonic anhydrase II, because the ligands-carbonic anhydrase II predicted complexes were unstable in the molecular dynamics simulations. The mechanism targeting GABAA receptor was confirmed through the in vivo flumazenil antagonism assay. The pentylenetetrazole experimental anticonvulsant model indicated that the tested compounds, 1a–9a and 1b–9b, present a potential anticonvulsant activity. The evaluation, considering the percentage of protection against PTZ, latency until the onset of the first seizure, and reduction in the number of seizures, revealed more favorable results for the “b” series, particularly for compound 8b.

Considering the pivotal role of angiogenesis in solid tumor progression, we developed a novel series of quinazoline–thiazole hybrids (SA01–SA07) as antiproliferative and anti-angiogenic agents. Four out of the seven compounds displayed superior antiproliferative activity (IC50 =1.83-4.24 µM) on HepG2 cells compared to sorafenib (IC50 = 6.28 µM). The affinity towards the VEGFR2 kinase domain was assessed through in silico prediction by molecular docking, molecular dynamics studies, and MM-PBSA. The series displayed a high degree of similarity to sorafenib regarding the binding pose within the active site of VEGFR2, with a different orientation of the 4-substituted-thiazole moieties in the allosteric pocket. Molecular dynamics and MM-PBSA evaluations identified SA05 as the hybrid forming the most stable complex with VEGFR2 compared to sorafenib. The impact of the compounds on vascular cell proliferation was assessed on EA.hy926 cells. Six compounds (SA01–SA05, SA07) displayed superior anti-proliferative activity (IC50 = 0.79–5.85 µM) compared to sorafenib (IC50 = 6.62 µM). The toxicity was evaluated on BJ cells. Further studies of the anti-angiogenic effect of the most promising compounds, SA04 and SA05, through the assessment of impact on EA.hy296 motility using a wound healing assay and in ovo potential in a CAM assay compared to sorafenib, led to the confirmation of the anti-angiogenic potential.

This study aimed to investigate the biotransformation capabilities of a hydroquinone-tolerant Digitalis purpurea cell line (DpHQ) for bioconverting hydroquinone (HQ) into arbutin, a compound with significant therapeutic and cosmetic applications. The research evaluated the influence of various HQ concentrations, feeding protocols, and carbon sources on arbutin bioconversion yield. By using HPLC-MS for the quantification of arbutin in biomass and medium, the study revealed that higher precursor (HQ) concentration led to a more pronounced growth inhibition under single dosing than sequential dosing. At lower sugar (3%) and precursor (4 mM HQ) levels, arbutin predominantly remained within the cells, whereas higher sugar (6%) and HQ (5–6 mM) levels promoted its release into the medium. Arbutin production ranged from 591 mg/L under single dosing to 3049 mg/L with sequential dosing, with the highest yield being achieved with 5 mM HQ in divided doses and 6% glucose. This study holds novelty for being the first to demonstrate the DpHQ’s tolerance to high concentrations of HQ and its efficient capabilities to bioconvert HQ to arbutin, indicating that D. purpurea is equipped with the enzymes required for this process. These aspects highlight its potential as a biotechnological source for arbutin synthesis.

The biological activity of Galium verum herba was exerted on various tumor cell lines with incredible results, but their potential effect on malignant melanoma has not been established yet. Therefore, the current study was structured in two directions: (i) the investigation of the phytochemical profile of diethyl ether (GvDEE) and butanol (GvBuOH) extracts of G. verum L. and (ii) the evaluation of their biological profile on A375 human malignant melanoma cell line. The GvDEE extract showed an FT-IR profile different from the butanol one, with high antioxidant capacity (EC50 of GvDEE = 0.12 ± 0.03 mg/mL > EC50 of GvBuOH = 0.18 ± 0.05 mg/mL). The GvDEE extract also showed antimicrobial potential, especially against Gram-positive bacteria strains, compared to the butanol extract, which has no antimicrobial activity against any bacterial strain tested. The results regarding the antitumor potential showed that both extracts decreased A375 cell viability largely (69% at a dose of 55 µg/mL of the GvDEE extract). Moreover, both extracts induce nuclear fragmentation by forming apoptotic bodies and slight chromatin condensation, which is more intense for GvDEE. Considering the results, one can state that the Galium verum herba possesses antitumor effects on the A375 human malignant melanoma cell line, a promising phytocompound for the antitumor approach to skin cancer.

Epilobium hirsutum L., commonly known as hairy willowherb, is a perennial herbaceous plant native to Europe and Asia. In Romania, the Epilobium genus includes 17 species that are used in folk medicine for various purposes. This study aimed to investigate the anti-inflammatory and antitumor potential of the optimized extract of Epilobium hirsutum (EH) in animal models. The first study investigated the anti-inflammatory properties of EH optimized extract and the model used was carrageenan-induced paw inflammation. Wistar rats were divided into three groups: negative control, positive control treated with indomethacin, and a group treated with the extract. Oxidative stress markers, cytokine levels, and protein expressions were assessed. The extract demonstrated anti-inflammatory properties comparable to those of the control group. In the second study, the antitumor effects of the extract were assessed using the tumor model of Ehrlich ascites carcinoma. Swiss albino mice with Ehrlich ascites were divided into four groups: negative, positive treated with cyclophosphamide (Cph), Group 3 treated with Cph and EH optimized extract, and Group 4 treated with extract alone. Samples from the ascites fluid, liver, and heart were analyzed to evaluate oxidative stress, inflammation, and cancer markers. The extract showed a reduction in tumor-associated inflammation and oxidative stress. Overall, the EH optimized extract exhibited promising anti-inflammatory and antitumor effects in the animal models studied. These findings suggest its potential as a natural adjuvant therapeutic agent for addressing inflammation and oxidative stress induced by different pathologies.

This study aimed to investigate the polyphenolic composition and antioxidant and antimicrobial potential of six Romanian Stachys species: S. officinalis, S. germanica, S. byzantina, S. sylvatica, S. palustris, and S. recta. The LC-MS/MS method was used to analyze the polyphenolic profile, while the phenolic contents were spectrophotometrically determined. The antioxidant activity was evaluated using the following methods: DPPH, FRAP, nitrite-induced autooxidation of hemoglobin, inhibition of cytochrome c-catalyzed lipid peroxidation, and electron paramagnetic resonance spectroscopy. The in vitro antimicrobial properties were assessed using agar-well diffusion, broth microdilution, and antibiofilm assays. Fifteen polyphenols were identified using LC-MS and chlorogenic acid was the major component in all the samples (1131.8–6761.4 μg/g). S. germanica, S. palustris, and S. byzantina extracts each displayed an intense antiradical action in relation to high contents of TPC (6.40 mg GAE/mL), flavonoids (3.90 mg RE/mL), and caffeic acid derivatives (0.89 mg CAE/mL). In vitro antimicrobial and antibiofilm properties were exhibited towards Candida albicans, Gram-positive and Gram-negative strains, with the most intense efficacy recorded for S. germanica and S. byzantina when tested against S. aureus. These results highlighted Stachys extracts as rich sources of bioactive compounds with promising antioxidant and antimicrobial efficacies and important perspectives for developing phytopharmaceuticals.

Galium species are used worldwide for their antioxidant, antibacterial, antifungal, and antiparasitic properties. Although this plant has demonstrated its antitumor properties on various types of cancer, its biological activity on cutaneous melanoma has not been established so far. Therefore, the present study was designed to investigate the phytochemical profile of two extracts of G. verum L. herba (ethanolic and ethyl acetate) as well as the biological profile (antioxidant, antimicrobial, and antitumor effects) on human skin cancer. The extracts showed similar FT-IR phenolic profiles (high chlorogenic acid, isoquercitrin, quercitrin, and rutin), with high antioxidant capacity (EC50 of ethyl acetate phase (0.074 ± 0.01 mg/mL) > ethanol phase (0.136 ± 0.03 mg/mL)). Both extracts showed antimicrobial activity, especially against Gram-positive Streptococcus pyogenes and Staphylococcus aureus bacilli strains, the ethyl acetate phase being more active. Regarding the in vitro antitumor test, the results revealed a dose-dependent cytotoxic effect against A375 melanoma cell lines, more pronounced in the case of the ethyl acetate phase. In addition, the ethyl acetate phase stimulated the proliferation of human keratinocytes (HaCaT), while this effect was not evident in the case of the ethanolic phase at 24 h post-stimulation. Consequently, G. verum l. could be considered a promising phytocompound for the antitumor approach of cutaneous melanoma.

This study explores the bioactive potential of young shoots from blackcurrant, European blueberry, and mountain cranberry, widely employed in gemmotherapy and phytotherapy, as rich sources of antioxidants, antimicrobial agents, and anti-inflammatory components. The primary aims of this study were to enhance the extraction conditions for bioactive compounds from blackcurrant young shoots using Modde software for experimental design, to conduct a comprehensive phytochemical analysis of blackcurrant, European blueberry, and mountain cranberry young shoot extracts through LC–MS analysis, and to evaluate the in vitro biological activities of these optimized extracts. The experimental design comprised multiple variables: extraction techniques, solvent type, extraction time, apparent pH, and the solvent-to-vegetal product ratio. The responses included total phenolic content, total flavonoid content, condensed tannin content, and total antioxidant activity determined through the DPPH assay. Furthermore, the antioxidant potential of the extracts was validated through in vitro cell culture experiments, in addition to the cytotoxicity assessments conducted on both normal and cancer cell lines. Extracts obtained through Ultra-Turrax extraction using 70% acetone displayed high levels of polyphenolic compounds and enhanced antioxidant potential, regardless of young shoots origin. LC–MS analysis revealed the predominant occurrence of chlorogenic acid, hyperoside, and isoquercitrin in all examined samples. The optimized extracts also displayed significant biological potential when evaluated in vitro on cell lines. These results provide valuable insights into the potent bioactive components present in these young shoot extracts, paving the way for further exploration in therapeutic applications.

The objective of this study was to develop microspheres (Ms) from natural materials, chitosan (Ch) and sodium alginate (Na-Alg), that protect Ruta graveolens L. (RG) extract against temperature, pH, and the oxidative impact of degradation. The microspheres also masked the unpleasant taste by enclosing them in a biodegradable polymeric matrix. First, the total polyphenols, total flavonoid content, and antioxidant activity were quantified spectrophotometrically. Individual polyphenol contents were identified and quantified by high-performance liquid chromatography (HPLC) with UV detection. The RG extract was encapsulated in microspheres of chitosan–sodium alginate–Ruta graveolens L. extract (CARG-Ms) using two distinct procedures (method 1, in which the RG extract was added to the Ch solution and the Na-Alg solution was dripped into this mixture, and method 2, in which the RG extract was added to the Na-Alg solution and then dripped into the Ch solution) to determine which method was more advantageous. All microspheres were evaluated and characterized by confocal laser-scanning microscopy (CLSM), scanning electron microscopy (SEM), optical scanning, entrapping efficiency (EE%), swelling index (SWL%), and in vitro release (RGrel%), and all results underwent univariate and multivariate analysis using a regression model. Following these tests, it was observed that the extract had an appreciable flavonoid content of 37.98%, with antioxidant properties evidenced by the 54.25% inhibition of DPPH. Of the polyphenolic compounds identified in the extract by using the HPLC method, rutin was present in the highest amount, at 745.17 μg/mL. The microspheres prepared by method 2, which contained the highest concentration of chitosan, had several desirable properties, including a high degree of roughness, high entrapping efficiency (75%), a wrinkled appearance, a better in vitro release capacity, and a lower SWL%. On the other hand, CARG-Ms prepared by method 1, which contained a smaller concentration of Ch, had faster swelling and slower release of the extract due to the lower entrapping efficiency (35%). These results suggest that the concentration of wall material and the preparation method play important roles in the encapsulation process and final particle characteristics. According to the obtained results, after the multivariate statistical analysis, it can be observed that the microspheres prepared via method 2 of the complex coacervation process were the most efficient for encapsulating rue extract in microspheres, because the extract was protected against degradation from the gastrointestinal tract.

Taraxaci folium and Matricariae flos plant extracts contain a wide range of bioactive compounds with antioxidant and anti-inflammatory effects. The aim of the study was to evaluate the phytochemical and antioxidant profile of the two plant extracts to obtain a mucoadhesive polymeric film with beneficial properties in acute gingivitis. The chemical composition of the two plant extracts was determined by high-performance liquid chromatography coupled with mass spectrometry. To establish a favourable ratio in the combination of the two extracts, the antioxidant capacity was determined by the method of reduction of copper ions Cu2+ from neocuprein and by reduction of the compound 1.1-diphenyl-2-2picril-hydrazyl. Following preliminary analysis, we selected the plant mixture Taraxaci folium/matricariae flos in the ratio of 1:2 (m/m), having an antioxidant capacity of 83.92% ± 0.02 reduction of free nitrogen radical of 1.1-diphenyl-2-2picril-hydrazyl reagent. Subsequently, bioadhesive films of 0.2 mm thickness were obtained using various concentrations of polymer and plant extract. The mucoadhesive films obtained were homogeneous and flexible, with pH ranging from 6.634 to 7.016 and active ingredient release capacity ranging from 85.94–89.52%. Based on in vitro analysis, the film containing 5% polymer and 10% plant extract was selected for in vivo study. The study involved 50 patients undergoing professional oral hygiene followed by a 7-day treatment with the chosen mucoadhesive polymeric film. The study showed that the film used helped accelerate the healing of acute gingivitis after treatment, with anti-inflammatory and protective action.

One of the objectives of this study consists of the assessment of the antitumor activity of several extracts from three selected plant species: Xanthium spinosum L., Trifolium pratense L., and Coffea arabica L. and also a comparative study of this biological activity, with the aim of establishing a superior herbal extract for antitumor benefits. The phytochemical profile of the extracts was established by HPLC-MS analysis. Further, the selected extracts were screened in vitro for their antitumor activity and antioxidant potential on two cancer cell lines: A549—human lung adenocarcinoma and T47D-KBluc—human breast carcinoma and on normal cells. One extract per plant was selected for in vivo assessment of antitumor activity in an Ehrlich ascites mouse model. The extracts presented high content of antitumor compounds such as caffeoylquinic acids in the case of X. spinosum L. (7.22 µg/mL—xanthatin, 4.611 µg/mL—4-O-caffeoylquinic acid) and green coffee beans (10.008 µg/mL—cafestol, 265.507 µg/mL—4-O-caffeoylquinic acid), as well as isoflavones in the case of T. pratense L. (6806.60 ng/mL—ononin, 102.78 µg/mL—biochanin A). Concerning the in vitro results, the X. spinosum L. extracts presented the strongest anticancerous and antioxidant effects. In vivo, ascites cell viability decreased after T. pratense L. and green coffee bean extracts administration, whereas the oxidative stress reduction potential was important in tumor samples after T. pratense L. Cell viability was also decreased after administration of cyclophosphamide associated with X. spinosum L. and T. pratense L. extracts, respectively. These results suggested that T. pratense L. or X. spinosum L. extracts in combination with chemotherapy can induce lipid peroxidation in tumor cells and decrease the tumor viability especially, T. pratense L. extract.

Coccidiosis in pigs seldom results in important economic losses. However, it can influence growth rates in weaners and it is an important hygiene indicator in swine farms. Certain herbs, along with their extracts, have been used over the course of history in traditional medicine. The aim of this study was to evaluate the in vitro anticoccidial effects of Allium sativum L. (garlic), Artemisia absinthium L. (wormwood), Coriandrum sativum L. (coriander), Cucurbita pepo L. (pumpkin), Satureja hortensis L. (summer savory), and Calendula officinalis L. (marigold) against Eimeria suis and Eimeria debliecki oocysts. The stock solution of oocysts (58% E. suis + 42% E. debliecki) was incubated for three days, before adding the tested solutions. The unsporulated Eimeria spp. oocysts were then placed in a 3 mL well plate and incubated for 96 h at 27 °C, in a suspension containing serial dilutions of alcoholic plant extracts (5%, 2.5%, 1.25%, 0.625%, and 0.312%). The percentage of sporulated and destroyed oocysts was recorded every 24 h for 96 h. All extracts had a good in vitro anticoccidial effect against oocysts of Eimeria spp. compared with the control groups. Oocyst sporulation was significantly (p = 0.05) inhibited by the 5% marigold extract (3.6% sporulated oocysts). The same extract had the highest lytic effect on oocysts (65.2% destroyed oocysts). Our results prove that the most effective alcoholic plant extract is the marigold extract, followed, in order of efficiency, by the wormwood, coriander, garlic, pumpkin, and summer savory extracts. This study represents a preliminary contribution for establishing a new generation of natural disinfectants aimed at destroying Eimeria oocysts in the context of swine contamination.

The objectives of the present study consisted of identifying the impact of extraction methods and parameters held over the phytochemistry and biological activities of green coffee beans. Extraction processes belonging to two categories were performed: classical methods—maceration, Soxhlet extraction, and such innovative methods as turboextraction, ultrasound-assisted extraction, and a combination of the latter two. Total polyphenolic and flavonoid content, as well as in vitro antioxidant activity of the resulted extracts were spectrophotometrically determined. Extracts displaying the highest yields of bioactive compounds were subjected to High Performance Liquid Chromatography-Mass Spectrometry analysis. The extracts with the best phytochemical profiles were selected for biological activity assessment. In vivo, a model of plantar inflammation in Wistar rats was used to determine antioxidant activity, by evaluating the oxidative stress reduction potential, and anti-inflammatory activity. In vitro antimicrobial activity was also determined. The Soxhlet extraction and ultrasound-assisted extraction gave the highest bioactive compound yields. The highest total polyphenolic content was 2.691 mg/mL gallic acid equivalents and total flavonoid content was 0.487 mM quercetin equivalents for the Soxhlet extract subjected to 60 min extraction time. Regarding the antioxidant activity, ultrasound-assisted extraction reached the highest levels, i.e., 9.160 mg/mL Trolox equivalents in the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay and 26.676 mM Trolox equivalents in the FRAP (Ferric Reducing Antioxidant Power) assay, at a 30 min extraction time and 50 °C extraction temperature. The 60 min Soxhlet extract reached the highest level for the ABTS+ (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, 16.136 mM Trolox equivalents, respectively. Chlorogenic acid was present in the highest concentration in the same Soxhlet extract, 1657.179 µg/mL extract, respectively. Sterolic compounds were found in high concentrations throughout all the analyzed extracts. A proportional increase between yields and extraction parameter values was observed. Increased inhibition of Gram-negative bacteria was observed. The finally selected Soxhlet extract, that of 60 min extraction time, presented a significant in vivo antioxidant activity, with a slight anti-inflammatory activity. Antioxidant levels were elevated after 2 h of extract administration. Pro-inflammatory cytokine secretion was not influenced by the administration of the extract.

The present research investigated the in vivo anti-inflammatory and cardioprotective activities, as well as the antioxidant potential of Taraxacum officinale tincture (TOT), in relation to the polyphenolic composition. Chromatographic and spectrophotometric techniques were used to determine the polyphenolic profile of TOT and the antioxidant activity was preliminarily assessed in vitro by DPPH• and FRAP spectrophotometric methods. The in vivo anti-inflammatory and cardioprotective activities were studied in rat turpentine-induced inflammation and in rat isoprenaline-induced myocardial infarction (MI) models. The main polyphenolic compound identified in TOT was cichoric acid. The oxidative stress determinations showed the capacity of the dandelion tincture not only to decrease the total oxidative stress (TOS), the oxidative stress index (OSI), and the total antioxidant capacity (TAC), but also the malondialdehide (MDA), thiols (SH), and nitrites/nitrates (NOx) levels both in inflammation and MI models. In addition, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatin kinase-MB (CK-MB), and nuclear factor kappa B (NF-κB) parameters were decreased by the administration of the tincture. The results show that T. officinale could be considered a valuable source of natural compounds with important benefits in pathologies linked to oxidative stress.

The present study focuses on the chemical and biological analysis of the ethanolic 70% v/v extracts obtained from Amorpha fruticosa leaves, branches and fruits. The total phenolic content determined by Folin-Ciocalteu method was the highest in leaves extract (159.5 mg/g). The HPLC-MS analysis indicated the presence of ferulic acid, luteolin and rutoside in all three extracts. The antioxidant activity was tested by the DPPH method and the results indicated a good scavenging activity (EC50 = 18.8 ± 0.2 µg/mL) for the fruit extract, followed by leaf extract (EC50 = 38.03 ± 0.75 µg/mL) and branch extract (EC50 = 221.16 ± 1.7 µg/mL). The antimicrobial activity evaluated by agar disc diffusion method indicated the inhibition of growth for Staphylococcus aureus and Sarcina lutea for all samples.

Epilobium species are used in Romanian folk medicine as tinctures, tea, or tablets for ameliorating the symptoms of benign prostate hyperplasia (BPH), but scientific-based evidence is scarce for this species or other endemic plants of the same genus. Therefore, the aims of this research were to evaluate the phytochemical profile of five endemic Epilobium species (E. hirsutum L., E. parviflorum Schreb., E. palustre L. E. dodonaei Vill., and E. angustifolium L.) and to assess their in vitro biological activity. For enhanced recovery of polyphenols, a D-optimal experimental plan was developed using Modde software and the optimal working conditions were ultra-turrax-assisted extraction, for 8 min, with 30% ethanol in water. The optimized extracts were obtained from various plant parts and were further characterized by LC-MS analysis, with the major compound being oenothein B. All extracts demonstrated good antioxidant activity, evaluated by DPPH and TEAC assays. The most prominent antimicrobial potency of optimized extracts was displayed against Bacillus cereus, while against Gram-(+) bacteria, a moderate efficacy was observed. Furthermore, anti-cancer, anti-inflammatory, and antioxidant potential were assessed on normal fibroblasts and prostate carcinoma cell lines. From the evaluated optimized extracts, E. angustifolium aerial parts had the highest selectivity toward killing cancerous cells, followed by E. hirsutum aerial parts extract. For the antioxidant effect, E. hirsutum leaves and E. hirstum aerial parts extracts displayed the highest potency, decreasing ROS at the level observed for the positive control. The highest anti-inflammatory potential, based on the IL-6 and IL-8 levels, was displayed by E. dodonaei aerial parts and E. angustifolium leaves extracts. In conclusion, all five endemic species of Epilobium harvested from Romanian flora possess a diverse phytochemical composition, which supports complex biological activities.

The aim of this study was to identify possible influences of extraction methods as well as extraction parameters on the phytochemical and biological profiles of Xanthium spinosum L. extracts. Extraction methods were chosen as follows: classical methods, maceration and Soxhlet extraction; innovative extraction methods, turboextraction, ultrasound-assisted extraction, and a combination of the latter two. Extracts were subjected to total polyphenolic and flavonoid content spectrophotometric analysis. The phytochemical profile was determined for the best-yielding extracts using HPLC-MS analysis. Following the newly acquired data, another sorting of the extracts was performed. Biological activities such as antimicrobial and anti-inflammatory actions were evaluated, as well as oxidative stress reduction potential, on a Wistar rats inflammation model. Comparable results were achieved with Soxhlet extraction and ultrasound-assisted extraction, both surpassing all other tested methods in terms of yields. Bioactive compound concentrations tended to increase with the increase in extraction time and temperature. These maximal values lowered once the degradation points of the bioactive compounds were reached. Extracts demonstrated good protection against Gram-negative bacteria. Additionally, they provided good cellular protection and increased the antioxidant defense in the analyzed rat plantar tissue.

The development of hybrid molecules with significant human therapeutic properties is one of the main approaches of pharmaceutical research. One of the most important pharmacophores is the quinazolin-4(3H)-one heterocycle moiety, due to its wide range of biological activities. By its derivatization with polyphenolic compounds, in our previous research, it proved to possess a good antiradical activity of ortho-diphenolic derivatives of quinazolin-4(3H)-one. In this study, we developed two new series of compounds, with an additional phenolic group or with a methyl group on the thioacetohydrazone fragment. The methods used to evaluate the activity of the compounds were radical scavenging, reduction of oxidizing reagents and transition metals’ ions chelation assays. Quantum descriptors were also calculated in order to evaluate the influence of substituents and their position on the activity of the compounds. The cytotoxic activity was evaluated using normal human foreskin fibroblast cells (BJ) and two cancerous cell lines, lung adenocarcinoma cells (A549) and prostate carcinoma cells (LNCaP). The results obtained for the pyrogallol derivatives showed a high antioxidant activity compared to ascorbic acid and Trolox. All the synthesized compounds displayed a higher cytotoxicity against the cancerous cell types and a high cytocompatibility with the normal cells. The antioxidant activity was deeply influenced by the addition of the third phenolic group in the synthesized molecules.

Improving aroma profile represents one of the principal goals in winemaking. This paper focuses to evaluate the influence of enzymes applied before alcoholic fermentation of Fetească regală and Sauvignon blanc wines, even if most studies analyze their use in different winemaking stages. Fetească regală wines are described by higher proportions (1.07–4.28%) of ethyl octanoate (exotic fruits), 3-methylbutyl acetate (pear, banana), hexanoic acid (creamy, phenolic, exotic fruits), propan-2-yl acetate (ripe fruits, banana), and ethyl decanoate (floral, fruity, woody), while Sauvignon blanc wines are distinguished by significant proportions (2.77–42.15%) of 3-methylbutan-1-ol (exotic fruits), acetic acid (vegetal, sour), 1-phenylethanol (floral, honey), and diethyl butanedioate (fruity, floral). Variables as 3-methylbutyl acetate-ethyl decanoate, ethyl decanoate-hexanoic acid (r > 0.8) showed proportional levels in Fetească regală wines. In Sauvignon blanc samples, positive correlations were observed for 2-ethyl hydroxypropanoate-diethyl butanedioate or 2,3-butanediol-ethyl 4-hydroxybutanoate (r > 0.7). Data confirmed a significant influence of enzymes on wine’s aroma profile (p < 0.05). The higher proportions of the most volatile compounds were obtained in samples treated with pectinases, for both varieties. In correlation with the sensory analysis, these variants showed the lowest intensity for negative descriptors such as phenolic sensation, the mineral or bitter taste, demonstrating that pectinases can give more acceptable results regarding the sensory perception compared to β-glycosidases.

Quinoa is an Andean grain known for its gluten-free grains, which are used as a functional food. The aim of this research was to study the possibility of introducing quinoa as a vegetable crop grown for young leaves as a source of polyphenols and phytosterols. To achieve this goal, a field experiment was performed with three quinoa cultivars (Titicaca, Puno, and Vikinga) grown in a split plot design. The experimental factors included three densities (160, 320, and 760 plants·m−2) and two harvest dates (52 and 62 days after sowing (DAS)). The content of phytosterols (ergosterol, stigmasterol, β-sitosterol and campesterol) and polyphenols (ferulic acid, isoquercitrin and rutozid) in quinoa leaves were determined by HPLC method. The phytosterol content varied within the limits: ergosterol 0–7.62 µg·100 g−1 dw, stigmasterol 79.9–175.3 µg·100 g−1 dw, β-sitosterol 425.7–623.1 µg·100 g−1 dw and campesterol 0–5.25 µg·100 g−1 dw. Ferulic acid varied greatly from 38.0 to 63.3 µg·g−1 dw, isoquercitrin ranged from 63 to 101.6 µg·g−1 dw and rutozid varied widely from 32.9 to 162.8 µg·g−1 dw. The total phytosterols and the total phenolic compounds decreased with decreasing plant number density and DAS. This research demonstrated that young quinoa leaves are a good source of phytosterols and phenolics for human consumption.

Ascaris suum is present in traditionally managed indoor pig herds and in industrialized farms, especially in older fatteners and sows. The increasing resistance to common antihelminthic drugs redirected research towards alternative and traditional therapies, which also include medicinal plants. This study comparatively evaluated the in vitro antiparasitic effects of Allium sativum L., Artemisia absinthium L., Cucurbita pepo L., Coriandrum sativum L., Satureja hortensis L. and Calendula officinalis L. against A. suum egg hatching and larval development. A. suum eggs were sampled from randomized fecal specimens collected from traditionally raised swine. The egg suspension (ES, 12 × 103/mL) was divided into two controls (C) (1C—1 mL ES + 1 mL distilled water, 2C—five plates of 1 mL ES + 1 mL ethanol of 70%, 35%, 17.5%, 8.75%, and 4.375%, respectively) and six experimental groups, and placed in 3 mL cell plates. The experimental groups (EG, 1–6) included ES + each alcoholic plant extract (10%, 5%, 2.5%, 1.25%, 0.625%). Both C and EG were performed in quintuplicate. All variants were incubated at 27 °C for a total of 21 days. A. suum eggs were examined after 2, 14 (L1), and 21 (L2/L3) days of incubation. The efficacy of all tested plant extracts increased with concentration. Anti-embryogenic effects on A. suum eggs were expressed by all plants. A superior influence was observed in A. sativum L., A. absinthium L., C. pepo L. and S. hortensis L. extracts, at all concentrations tested. A. sativum L. and A. absinthium L. extracts showed the strongest antihelminthic activity, while C. sativum L. and C. officinalis L. were the weakest ascaricids. Future in-depth phytochemical studies are required to identify the compounds responsible for the anthelminthic properties of these plant species.

Aging is an intricate process and an important risk factor in the development and advancement of many disorders [...]

The effects of two lyophilized extracts obtained from the aerial parts of Thymus marschallianus Willd. and harvested from wild flora (TMW) and obtained from culture (TMC) were evaluated in Wistar rats with experimentally induced hyperglycemia. The hyperglycemia was induced by streptozotocin (STZ) administration and the obtained results were evaluated in comparison for TMW and TMC. The polyphenolic composition of extracts was evaluated by spectrophotometrical and LC-MS methods. In vitro antioxidant capacity assays (DPPH, FRAP, EPR) were performed in order to preliminary establish the ability of tested samples to protect against free radical induced damage. Afterwards, the effects of these extracts were assessed in vivo on rats with experimental-induced hyperglycemia. Oxidative stress biomarkers (e.g. malondialdehyde—MDA), phosphorylated transcription factor subunit of nuclear kappaB (NF-kB) p65, methyl CpG binding protein (MECP) 2 and histone deacetylase 1 (HDAC1) expressions in hippocampus and frontal lobe were assessed. Open Field Test (OFT) and Elevated Plus Maze (EPM) were conducted on tested animals. Malondialdehyde (MDA) levels and HDAC1and MeCP2 expressions increased significantly in hippocampus (p

The pathophysiology of inflammation and oxidative stress generated during different types of cancers and anticancer treatments is well documented. Traditionally, grape pomace is used for animal feed, organic fertilizers, ethanol production or is disposed as waste. Because grape pomace is a rich source of antioxidant compounds, the purpose of the study was to evaluate the antioxidant, anti-inflammatory, and antiproliferative effects of fresh and fermented grape pomace extracts of two Vitis vinifera L. varieties Fetească neagră and Pinot noir cultivated in Romania. Firstly, grape pomace phytochemical analysis and in vitro antioxidant tests were performed. Secondly, the effect of a seven-day pretreatment with grape pomace extracts on the turpentine oil-induced inflammation in rats was assessed by measuring total oxidative status, total antioxidant response, oxidative stress index, malondialdehyde, total thiols, nitric oxide and 3-nitrotyrosine. Thirdly, the antiproliferative properties were evaluated on human lung carcinoma (A549), human breast adenocarcinoma (MDA-MB-231), murine melanoma (B164A5), and keratinocyte (HaCat) cell lines. Fetească neagră and Pinot noir grape pomace extracts have a rich content of polyphenols and in vitro antioxidant effect. Fermented samples had higher polyphenol content, but fresh samples had better antioxidant activity. Pretreatment with grape pomace extracts reduced inflammation-induced oxidative stress in a concentration-dependent way, fresh samples being more efficient. The malignant cells’ proliferation was inhibited by all grape pomace extracts, fermented Fetească neagră extracts having the strongest effect. Conclusion: fresh and fermented pomace extracts of Vitis vinifera L. varieties Fetească neagră and Pinot noir cultivated in a Romanian wine region have antioxidant, anti-inflammatory and antiproliferative effects.

Polyphenols have attained pronounced attention due to their ability to provide numerous health benefits and prevent several chronic diseases. In this study, we designed, synthesized and analyzed a water-soluble molecule presenting a good antioxidant activity, namely catechol hydrazinyl-thiazole (CHT). This molecule contains 3′,4′-dihydroxyphenyl and 2-hydrazinyl-4-methyl-thiazole moieties linked through a hydrazone group with very good antioxidant activity in the in vitro evaluations performed. A preliminary validation of the CHT developing hypothesis was performed evaluating in silico the bond dissociation enthalpy (BDE) of the phenol O-H bonds, compared to our previous findings in the compounds previously reported by our group. In this paper, we report the binding mechanism of CHT to human serum albumin (HSA) using biophysical methods in combination with computational studies. ITC experiments reveal that the dominant forces in the binding mechanism are involved in the hydrogen bond or van der Waals interactions and that the binding was an enthalpy-driven process. NMR relaxation measurements were applied to study the CHT–protein interaction by changing the drug concentration in the solution. A molecular docking study added an additional insight to the experimental ITC and NMR analysis regarding the binding conformation of CHT to HSA.

The aim of the present study was to investigate the polyphenolic profile and the anti-inflammatory and anti-nociceptive activities of four traditionally used medicinal plants from Burkina Faso: Parkia biglobosa, Detarium microcarpum, Vitellaria paradoxa and Sclerocarya birrea. The analysis of the main phenolic compounds was performed by the HPLC-UV-MS method. The anti-inflammatory effect of the aqueous bark extracts was investigated by the λ-carrageenan-induced rat paw edema test. The anti-nociceptive activity was evaluated by the Randall–Selitto test under inflammatory conditions. Seven phenolic acids (gallic, protocatechuic, gentisic, vanillic, p-coumaric, ferulic, and syringic acids), and three flavonoids (catechin, epicatechin, and quercitrin) were identified in the plant samples. High contents of gallic acid were determined in the D. microcarpum, P. biglobosa and S. birrea extracts (190–300 mg/100 g), and V. paradoxa extract was the richest in epicatechin (173.86 mg/100 g). The λ-carrageenan-induced inflammation was significantly reduced (p < 0.001) by the P. biglobosa and D. microcarpum extracts (400 mg/kg p.o.). Under the inflammatory conditions, a significant anti-nociceptive activity (p < 0.001) was obtained after 2–3 h from the induction of inflammation. The effects of the tested extracts could be related to the presence of polyphenols and could be useful in the management of certain inflammatory diseases.

Considering the important damage caused by the reactive oxygen (ROS) and nitrogen (RNS) species in the human organism, the need for new therapeutic agents, with superior efficacy to the known natural and synthetic antioxidants, is crucial. Quinazolin-4-ones are known for their wide range of biological activities, and phenolic compounds display an important antioxidant effect. Linking the two active pharmacophores may lead to an increase of the antioxidant activity. Therefore, we synthesized four series of new hybrid molecules bearing the quinazolin-4-one and phenol scaffolds. Their antioxidant potential was evaluated in vitro, considering different possible mechanisms of action: hydrogen atom transfer, ability to donate electrons and metal ions chelation. Theoretical quantum and thermodynamical calculations were also performed. Some compounds, especially the ortho diphenolic ones, exerted a stronger antioxidant effect than ascorbic acid and Trolox.

Abstract Background Although Galanthus nivalis L. (snowdrop) is known for the galanthamine content, used in the treatment of Alzheimer disease, the polyphenolic compounds of Amaryllidaceae species are less studied. Proper understanding of the polyphenolics in these extracts and of their antioxidant and antimicrobial properties may allow a reconsideration of their medicinal uses. Methods The polyphenolic content of four selected Amaryllidaceae species harvested from Romania (Galanthus nivalis L., Narcissus pseudonarcissus L., N. poeticus L. and Leucojum vernum L.) was determined by spectrophotometric methods; the identification of phenolic compounds was performed by a HPLC-MS method, in order to establish their polyphenolic fingerprints. For the evaluation of the antioxidant potential the following methods were employed: DPPH radical scavenging, FRAP, hemoglobin ascorbate peroxidase activity inhibition (HAPX), inhibition of lipid peroxidation catalyzed by cytochrome c, and electron paramagnetic resonance (EPR) spectroscopy assays. Antimicrobial activity was assessed using the disc diffusion method. Results Qualitative and quantitative analyses highlight important amount of polyphenols (over 15 mg/g); the main identified compounds are chlorogenic and p-coumaric acids in all species. Only G. nivalis shows antioxidant activity by all the used methods. G. nivalis and L. vernum strongly inhibits the growth of S. aureus, while N. poeticus shows a very good antifungal activity. Conclusions The results of this study provide a new approach to the properties and therapeutic uses of some Romanian widespread Amaryllidaceae species that could be considered sources of developing new medicinal products with anti anti-staphylococcal and antifungal activity.

A judicious antibiotic therapy is one of the challenges in the therapy of critically ill patients with sepsis and septic shock. The pathophysiological changes in these patients significantly alter the antibiotic pharmacokinetics (PK) and pharmacodynamics (PD) with important consequences in reaching the therapeutic targets or the risk of side effects. The use of linezolid, an oxazolidinone antibiotic, in intensive care is such an example. The optimization of its therapeutic effects, administration in intermittent (II) or continuous infusion (CI) is gaining increased interest. In a systematic review of the main databases, we propose a detailed analysis of the main PK/PD determinants, their relationship with the clinical therapeutic response and the occurrence of adverse effects following II or CI of linezolid to different classes of critically ill patients or in Monte Carlo simulations.

In this study, the biological activities of four extracts from Vitis vinifera by-products: two pomace extracts, white (WPE) and red (RPE), a canes extract (CE), and their combination (CoE), were evaluated, to be included in freeze-drying mouthwashes formulations. The cytocompatibility and anticancerous potential of the four extracts were tested on three cancerous cell lines, as well as the cytoprotective activity against nicotine-induced cytotoxicity and the antioxidant potential determined on a human gingival fibroblasts (HGF) cell line. Additionally, the anti-inflammatory activity and the antimicrobial activity against several microorganisms from the oral microbiome were tested. Freeze-dried mouthwashes with CoE were prepared and characterized, both as lyophilizates and after reconstitution. The four tested extracts showed the highest cytotoxicity on MDA-kb2 cell line. The antioxidant potential was demonstrated for WPE, RPE, CE, and CoE, both in non-stimulated and H2O2 stimulated conditions. The four extracts reduced the levels of proinflammatory cytokines (IL-6, IL-8, and IL-1β) in a dose-dependent manner, confirming their anti-inflammatory activity. The antimicrobial activity of tested extracts was shown against pathogenic bacteria from the oral microbiome. Mouthwashes of CoE with poloxamer-407, xylitol, and different ratios of mannitol were prepared by freeze-drying leading to porous formulations with interesting mechanical properties and reconstitution times.

The wound-healing capacity of ointments based on bee products was investigated in vivo on three experimental models of incision, excision and heat burn. For this purpose, four ointments were prepared with propolis, honey, apilarnil (drone brood homogenate) and a mixture of these three apitherapy products. The ointments were applied topically for 21 days. Clinical and macroscopic evaluation was performed throughout the experiment, with the recording of the re-epithelialization period and determination of the wound contraction rate on days 6 and 9. The histopathological examination was performed on days 1, 3, 12 and 21 of the treatment. The topical formulations were also characterized from a rheological point of view in order to verify their stability. HPLC analysis of propolis revealed the presence of phenolic compounds, particularly ferulic acid and p-coumaric which were found in high amounts. All ointments had beneficial effects on wound contraction and the re-epithelialization period, but the most significant result, both macroscopically and especially in terms of histological architecture, was presented by the ointment that contains all three apitherapy products, due to their synergistic effect.

Oxidative stress represents the underlying cause of many chronic diseases in human; therefore, the development of potent antioxidant compounds for preventing or treating such conditions is useful. Starting from the good antioxidant and antiradical properties identified for the previously reported Dihydroxy-Phenyl-Thiazol-Hydrazinium chloride (DPTH), we synthesized a congeneric series of phenolic thiazoles. The radical scavenging activity, and the antioxidant and chelation potential were assessed in vitro, a series of quantum descriptors were calculated, and the electrochemical behavior of the synthesized compounds was studied to evaluate the impact on the antioxidant and antiradical activities. In addition, their antibacterial and antifungal properties were evaluated against seven aerobic bacterial strains and a strain of C. albicans, and their cytotoxicity was assessed in vitro. Compounds 5a-b, 7a-b and 8a-b presented remarkable antioxidant and antiradical properties, and compounds 5a-b, 7a and 8a displayed good Cu+2 chelating activity. Compounds 7a and 8a were very active against P. aeruginosa ATCC 27853 compared to norfloxacin, and proved less cytotoxic than ascorbic acid against the human keratinocyte cell line (HaCaT cells, CLS-300493). Several phenolic compounds from the synthesized series presented excellent antioxidant activity and notable anti-Pseudomonas potential.

Abstract Many herbal products have a long history of use, but there are increasing concerns over product efficacy, safety and quality in the wake of recent cases exposing discrepancies between labeling and constituents. When it comes to St. John’s wort (Hypericum perforatum L.) herbal products, there is limited oversight, frequent off-label use and insufficient monitoring of adverse drug reactions. In this study, we use amplicon metabarcoding (AMB) to authenticate 78 H. perforatum herbal products and evaluate its ability to detect substitution compared to standard methods using thin-layer chromatography (TLC) and high performance liquid chromatography coupled with mass spectrometry (HPLC-MS). Hypericum perforatum was detected in 68% of the products using AMB. Furthermore, AMB detected incongruence between constituent species and those listed on the label in all products. Neither TLC nor HPLC-MS could be used to unambiguously identify H. perforatum. They are accurate methods for authenticating presence of the target compounds, but have limited efficiency in detecting infrageneric substitution and do not yield any information on other plant ingredients in the products. Random post-marketing AMB of herbal products by regulatory agencies could raise awareness among consumers of substitution and would provide an incentive to manufacturers to increase quality control from raw ingredients to commercialized products.

Vancomycin (VAN) is a glycopeptide antibiotic, active against Gram-positive bacteria resistant to other antibiotics. VAN therefore needs to be monitored for maximum efficacy and minimum toxicity. Electrochemical sensors can be used for this purpose, using the direct electrochemical signal of VAN. Due to its molecular complexity and the need for analysis from complex matrices, the electrochemical detection of VAN requires the development of a complex electrochemical fingerprint (CEF), which covers a large variety of possible combinations of samples and interferents at concentrations of interest.The objective of this study was to develop a CEF for VAN, involving a battery of tests and the elucidation of the mechanism of anodic oxidation of VAN, using high-performance liquid chromatography coupled with mass-spectrometric analysis of the products obtained after small-scale electrolysis.A CEF for VAN was obtained, describing the electrochemical behavior of VAN at different commercially available screen-printed electrodes, with several electrolytes, considering successive analyses, after simple pretreatments, and examining both anodic and cathodic peaks. The concept was successfully applied to analysis of VAN in real samples and in the presence of some common interferents. Furthermore, a two-step combined electrochemical–chemical mechanism was proposed for the electrooxidation of VAN. Keywords: Vancomycin, Screen printed electrodes, Antibiotic detection, Electrochemical fingerprint, Electrooxidation mechanism

Backround:Ajuga species have been used in traditional medicine for their diuretic, anti-inflammatory, wound-healing, and hepatoprotective properties.Purpose: The phytochemical profile and anticancer potential of three Ajuga sp. (A. genevensis, A. chamaepitys, and A. laxmannii) from Romania was investigated.Materials and Methods: The phytochemicals were extracted from the aerial parts of Ajuga sp. by using different solvents and methods. The hydroalcoholic extracts were examined for total phenolic, flavonoid and iridoid contents, and HPLC/MS was used to analyze the polyphenolic compounds and iridoids. The phytochemical profile was also evaluated by principal component analysis in connection with antitumor efficacy of extracts. The antiproliferative potential was evaluated using the ELISA BrdU-colorimetric immunoassay. Western Blot with regard to inflammatory protein NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) p65 subunit expression in cell lysates was performed. Quantification of oxidative stress marker malondialdehyde (MDA) was determined by high-performance liquid chromatography (HPLC). Enzymatic and non-enzymatic antioxidant capability was assessed by measuring catalase activity and by evaluating the total antioxidant capacity (TAC) of treated cells.Results:Ajuga laxmannii ethanol extract showed the highest total phenolic and flavonoid content, while A. genevensis ethanol extract was more abundant in iridoids. The overall cytostatic effect of the investigated plant extracts was exerted through strong inhibitory actions on NF-κB, the key molecule involved in the inflammatory response and via oxidative stress modulatory effects in both murine colon carcinoma and melanoma cell lines.Conclusion:Ajuga laxmannii showed the most significant antitumor activity and represents an important source of bioactive compounds, possibly an additional form of treatment alongside conventional anticancer drugs.

The extraction of bioactive compounds present in walnut (Juglans regia L.) male flowers (WMFs) was performed based on an experimental design using ultrasonic-assisted extraction. Solvent nature, extraction time, and water content were selected as experimental variables, and phenolic, flavonoidic, and condensed tannins contents and antioxidant properties were evaluated. Acetone was the solvent with the highest extraction performance, with the extracts obtained using this solvent displaying an increased concentration of bioactive compounds and increased antioxidant activities. For several extracts with high bioactive content, individual polyphenolic and tocopherolic compounds were evaluated by means of LC-MS and LC-MS/MS. The best extraction conditions for polyphenolic (2.86 mg gallic acid equivalents/g WMF) and tocopherolic compounds (29.4 µg/g WMF) were acetone with 40% water content (N20) and acetone with 20% water content (N15), respectively. Although the total tocopherol concentrations were lower than in other Juglans regia parts, most of the total tocopherol quantity was provided by the highly biologically active δ-tocopherol (84%). Significant quantities of quercetin (101.9 µg/g), hyperoside (2662.9 µg/g), quercitrin (405.7 µg/g), and isoquercitrin (1293.7 µg/g) were determined in WMF (N20). Both extracts inhibited the enzymatic activity of α-glucosidase and tyrosinase; however, an increased inhibition was observed for N20, the extract with the higher polyphenolic content. Conversely, N15 had higher anticancerous activity on the cell lines used, with a moderate selectivity towards the cancerous phenotype being observed for both extracts. At non-cytotoxic concentrations, both extracts displayed good antioxidant activities in cellular cultures, decreasing basal and H2O2-induced oxidative stress. This is the first characterization of both hydrophilic and lipophilic phytochemicals in WMF extracts. The outcomes of our study reveal that walnut male flowers have strong biological activities, thus justifying further research to demonstrate their usefulness in the food, pharmaceutical, and/or cosmetic industries.

Objective: To assess the antioxidant and anti-inflammatory activities as well as to determine the flavonoids and phenolic acids content of active fractions. Methods: Two medicinal plant samples were extracted successively in Soxhlet apparatus with n-hexane, dichloromethane, acetonitrile, ethyl acetate, methanol and n-butanol. Five methods were used to evaluate the antioxidant activity. Anti-inflammatory activity was done through the inhibition of the cyclooxygenase enzymes (COX-1 and COX-2). Polyphenolic compounds were analyzed by using a spectrophotometrical and high performance liquid chromatography-mass spectrometry (HPLC-MS) methods. Results: The data showed that the stem leaves extracts of Commiphora africana and Loeseneriella africana possessed significant in vitro antioxidant and anti-inflammatory activities. Polar extracts had radical scavenging effects and they reduced iron (III). The prostaglandin production was significantly stopped by acetonitrile and methanol extracts. These biological activities were supported by some bioactive compounds quantified by using the HPLC-MS. p-Coumaric acid, ferulic acid, isoquercitrin, quercitrin, quercetin, rutin, kaempferol and apigenin were the most metabolites quantified. Conclusions: The present study may explain the effectiveness of plants in traditional medicine of Burkina Faso, singularly Commiphora africana and Loeseneriella africana. The next investigation was to sub-fractionate the methanol fraction in order to isolate new antioxidant and/or anti-inflammatory compounds.

Background: Taraxacum officinale (TO) or dandelion has been frequently used to prevent or treat different liver diseases because of its rich composition in phytochemicals with demonstrated effect against hepatic injuries. This study aimed to investigate the possible preventing effect of ethanolic TO root extract (TOERE) on a rat experimental acute on chronic liver failure (ACLF) model. Methods: Chronic liver failure (CLF) was induced by human serum albumin, and ACLF was induced in CLF by D-galactosamine and lipopolysaccharide (D-Gal-LPS). Five groups (n = 5) of male Wistar rats (200–250 g) were used: ACLF, ACLF-silymarin (200 mg/kg b.w./day), three ACLF-TO administered in three doses (200 mg, 100 mg, 50 mg/kg b.w./day). Results: The in vivo results showed that treatment with TOERE administered in three chosen doses before ACLF induction reduced serum liver injury markers (AST, ALT, ALP, GGT, total bilirubin), renal tests (creatinine, urea), and oxidative stress tests (TOS, OSI, MDA, NO, 3NT). Histopathologically, TOERE diminished the level of liver tissue injury and 3NT immunoexpression. Conclusions: This paper indicated oxidative stress reduction as possible mechanisms for the hepatoprotective effect of TOERE in ACLF and provided evidence for the preventive treatment.

The present study analyzed the methanol extract and tincture obtained from the spontaneous Romanian Cichorium intybus species, in order to evaluate polyphenols content and some biological properties. Chromatographic and spectrophotometric methods were used for the analysis of polyphenols and the antioxidant capacity was assessed in vitro with DPPH● (2,2-diphenyl-picrylhydrazil) and FRAP (ferric-reducing antioxidant power) tests. The cardio-protective effects of Cichorii herba tincture on myocardial ischemia induced by isoprenaline and nephroprotection on renal failure induced by gentamicin were evaluated on rats. Also, aspartate aminotrasferase (AST), alanine aminotransferase (ALT), creatine kinase-MB (CK-MB) and creatinine clearance (CrCl) were measured. The antioxidant effect was evaluated by determining total oxidative stress (TOS), oxidative stress index (OSI, total antioxidant capacity (TAC), malondyaldehide (MDA), total thiols (SH) and total nitrites and nitrates (NOx). Cichoric acid was the main polyphenolic compound. The extracts had moderate in vitro antioxidant activity but the in vivo antioxidant and anti-inflammatory effects were significant and associated with myocardial and renal dysfunction improvement. The results were attributed to the content of polyphenols in the extracts, for which reason C. intybus may be considered an important raw material for pharmaceuticals formulations recommended in the prevention or treatment of heart or kidney diseases.

The present paper aims to formulate and characterize four phytotherapeutic ointments based on Hippophae fructus, Calendulae flos, Bardanae folium, and Millefolii herba, which are included in a novel ointment base. In order to investigate the healing properties of the ointments, in vivo experimental wound models of linear incision, circular excision, and thermal burn were performed on Wistar rats. Topical treatment was performed daily for 21 days. Determination of the wound contraction rate (WCR), the period of reepithelization, and histopathological examination were achieved. Additionally, for the tested ointments, oscillatory and rotational rheological tests were carried out, and for the extracts, HPLC analysis was performed. The results demonstrate that the tested novel ointments are safe for use and the most effective ointment proved to be the one based on Arctium lappa, followed by that of Calendulae flos.