In Vitro Hypoxia/Reoxygenation Induces Mitochondrial Cardiolipin Remodeling in Human Kidney Cells.

Renal ischemia/reperfusion is a serious condition that not only causes acute kidney injury, a severe clinical syndrome with high mortality, but is also an inevitable part of kidney transplantation or other kidney surgeries. Alterations of oxygen levels during ischemia/reperfusion, namely hypoxia/reoxygenation, disrupt mitochondrial metabolism and induce structural changes that lead to cell death. A signature mitochondrial phospholipid, cardiolipin, with many vital roles in mitochondrial homeostasis, is one of the key players in hypoxia/reoxygenation-induced mitochondrial damage. In this study, we analyze the effect of hypoxia/reoxygenation on human renal proximal tubule epithelial cell (RPTEC) cardiolipins, as well as their metabolism and mitochondrial functions. RPTEC cells were placed in a hypoxic chamber with a 2% oxygen atmosphere for 24 h to induce hypoxia; then, they were replaced back into regular growth conditions for 24 h of reoxygenation. Surprisingly, after 24 h, hypoxia cardiolipin levels substantially increased and remained higher than control levels after 24 h of reoxygenation. This was explained by significantly elevated levels of cardiolipin synthase and lysocardiolipin acyltransferase 1 (LCLAT1) gene expression and protein levels. Meanwhile, hypoxia/reoxygenation decreased ADP-dependent mitochondrial respiration rates and oxidative phosphorylation capacity and increased reactive oxygen species generation. Our findings suggest that hypoxia/reoxygenation induces cardiolipin remodeling in response to reduced mitochondrial oxidative phosphorylation in a way that protects mitochondrial function.

Impact of CYP2C19 Gene Variants on Long-Term Treatment with Atorvastatin in Patients with Acute Coronary Syndromes.

The effectiveness of lipid-lowering therapies may be insufficient in high-risk cardiovascular patients and depends on the genetic variability of drug-metabolizing enzymes. Customizing statin therapy, including treatment with atorvastatin, may improve clinical outcomes. Currently, there is a lack of guidelines allowing the prediction of the therapeutic efficacy of lipid-lowering statin therapy. This study aimed to determine the effects of clinically significant gene variants of CYP2C19 on atorvastatin therapy in patients with acute coronary syndromes. In total, 92 patients with a confirmed diagnosis of ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI) were sequenced for target regions within the CYP2C19 gene on the Illumina Miniseq system. The CYP2C19 poor metabolizer phenotype (carriers of CYP2C19*2, CYP2C19*4, and CYP2C19*8 alleles) was detected in 29% of patients. These patients had significantly lower responses to treatment with atorvastatin than patients with the normal metabolizer phenotype. CYP2C19-metabolizing phenotype, patient age, and smoking increased the odds of undertreatment in patients (∆LDL-C (mmol/L) < 1). These results revealed that the CYP2C19 phenotype may significantly impact atorvastatin therapy personalization in patients requiring LDL lipid-lowering therapy.

Phenolic Compounds of Rhodiola rosea L. as the Potential Alternative Therapy in the Treatment of Chronic Diseases.

The roots and rhizomes of Rhodiola rosea L. (Crassulaceae), which is widely growing in Northern Europe, North America, and Siberia, have been used since ancient times to alleviate stress, fatigue, and mental and physical disorders. Phenolic compounds: phenylpropanoids rosavin, rosarin, and rosin, tyrosol glucoside salidroside, and tyrosol, are responsible for the biological action of R. rosea, exerting antioxidant, immunomodulatory, anti-aging, anti-fatigue activities. R. rosea extract formulations are used as alternative remedies to enhance mental and cognitive functions and protect the central nervous system and heart during stress. Recent studies indicate that R. rosea may be used to treat diabetes, cancer, and a variety of cardiovascular and neurological disorders such as Alzheimer's and Parkinson's diseases. This paper reviews the beneficial effects of the extract of R. rosea, its key active components, and their possible use in the treatment of chronic diseases. R. rosea represents an excellent natural remedy to address situations involving decreased performance, such as fatigue and a sense of weakness, particularly in the context of chronic diseases. Given the significance of mitochondria in cellular energy metabolism and their vulnerability to reactive oxygen species, future research should prioritize investigating the potential effects of R. rosea main bioactive phenolic compounds on mitochondria, thus targeting cellular energy supply and countering oxidative stress-related effects.

Investigation of Bioactive Complexes of Chitosan and Green Coffee Bean or Artichoke Extracts.

The formation of water-insoluble complexes between chitosan (ChS) and caffeoylquinic acid (CQ) derivatives present in artichoke (AE) and green coffee bean (GCBE) extracts was investigated by the equilibrium adsorption method. The UPLC/HPLC analysis revealed that the phenolic compounds accounted for 8.1% and 74.6% of AE and GCBE respectively, and CQ derivatives were the predominant compounds. According to the applied Langmuir adsorption model, anionic compounds present in natural extracts were adsorbed onto the active centers of ChS, i.e., primary amino groups. The driving forces of adsorption were electrostatic interactions between cationic groups of ChS and anionic compounds of natural extracts. Chromatographic analysis revealed that not only CQ derivatives, but also other phenolic compounds of natural extracts were attached to ChS. The release of adsorbed compounds into different media as well as the bioactive properties of complexes were also studied. With the immobilization of bioactives onto ChS, increased and prolonged ABTS•+ radical scavenging activity and decreased antifungal activity against Fusarium graminearum and Botrytis cinerea were observed compared to those of ChS. The findings of the current study highlight that the adsorption approach could be used to successfully prepare water-insoluble complexes of ChS and components of natural extracts with prolonged antioxidant activity.

Fermented, ultrasonicated, and dehydrated bovine colostrum: Changes in antimicrobial properties and immunoglobulin content.

This study evaluated the influence of fermentation with Lactobacillus plantarum LUHS135 and Lactobacillus paracasei LUHS244, ultrasonication, and different methods of dehydration on the content of IgG, IgA, and IgM in bovine colostrum (BC), as well as the antimicrobial activity of the treated and fresh BC samples [fresh = BC; freeze dried = BClyoph; vacuum dried (+45°C) = BCvacdried; BC fermented with LUHS135 = BCLUHS135; BC fermented with LUHS244 = BCLUHS244; BC fermented with LUHS135 and freeze dried = BCLUHS135lyoph; BC fermented with LUHS244 and freeze dried = BCLUHS244 lyoph; BC fermented with LUHS135 and vacuum dried = BCLUHS135 vacdried; BC fermented with LUHS244 and vacuum dried = BCLUHS244 vacdried; BC ultrasonicated and freeze dried = BCultr lyoph; BC ultrasonicated and vacuum dried = BCultr vacdried]. The antimicrobial activity was assessed against Klebsiella pneumoniae, Salmonella enterica, Pseudomonas aeruginosa, Acinetobacter baumanni, Proteus mirabilis, methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Bacillus cereus, Streptococcus mutans, Enterobacter cloacae, Citrobacter freundii, Staphylococcus epidermis, Staphylococcus haemolyticus, and Pasteurella multocida using the agar well diffusion method, as well as in liquid medium. In liquid medium analysis showed that the fermented BC samples had the broadest antimicrobial spectrum (of 15 tested pathogenic strains, BCLUHS135 vacdried and BCLUHS135lyoph inhibited 13; BCLUHS244 vacdried inhibited 12; and BCLUHS135, BCLUHS244, and BCLUHS244 lyoph inhibited 11). Based on the inhibition zones, BCLUHS135lyoph samples exhibited the broadest inhibition spectrum, inhibiting the growth of 12 of the 15 tested pathogenic strains). According to the lactic acid bacteria strain selected for BC fermentation, different properties of the BC will be obtained. To ensure a broad antimicrobial spectrum and high IgG content, fermentation with LUHS135 can be recommended (IgG concentration in BCLUHS135 was retained), whereas fermentation with LUHS244 will provide a high IgM concentration (IgM concentration increased by 48.8 and 21.6% in BCLUHS244 and BCLUHS244lyoph samples, respectively). However, IgA is very sensitive for fermentation, and further studies are needed to increase IgA stability in BC. Finally, fermented BC can be recommended as a food/beverage ingredient, providing safety, as well as improved functionality through displaying a broad spectrum of antimicrobial activities.

Fatty Acid Synthesis and Degradation Interplay to Regulate the Oxidative Stress in Cancer Cells.

Both cytosolic fatty acid synthesis (FAS) and mitochondrial fatty acid oxidation (FAO) have been shown to play a role in the survival and proliferation of cancer cells. This study aimed to confirm experimentally whether FAS and FAO coexist in breast cancer cells (BCC). By feeding cells with 13C-labeled glutamine and measuring labeling patterns of TCA intermediates, it was possible to show that part of the cytosolic acetyl-CoA used in lipid synthesis is also fed back into the mitochondrion via fatty acid degradation. This results in the transfer of reductive potential from the cytosol (in the form of NADPH) to the mitochondrion (in the form of NADH and FADH2). The hypothesized mechanism was further confirmed by blocking FAS and FAO with siRNAs. Exposure to staurosporine (which induces ROS production) resulted in the disruption of simultaneous FAS and FAO, which could be explained by NADPH depletion.

Microencapsulation of Elsholtzia ciliata Herb Ethanolic Extract by Spray-Drying: Impact of Resistant-Maltodextrin Complemented with Sodium Caseinate, Skim Milk, and Beta-Cyclodextrin on the Quality of Spray-Dried Powders.

Spray-drying is the most popular encapsulation method used for the stabilization and protection of biologically active compounds from various environmental conditions, such as oxidation, moisture, pH, and temperature. Spray-drying increases the bioavailability of the natural active compounds and improves the solubility of low-soluble compounds. The aim of this work was to study the effects of different wall materials and optimize wall material solution's composition on physicochemical properties of microcapsules loaded with phenolics, extract rich in volatile compounds and essential oil from Elsholtzia ciliata herb. For encapsulation of elsholtzia and dehydroelsholtzia ketones, more suitable wall materials were used-beta-cyclodextrin and sodium caseinate. Four phenolics-sodium caseinate, skim milk, beta-cyclodextrin, and resistant-maltodextrin-were used. A D-optimal mixture composition design was used to evaluate the effect of wall material solution's composition using sodium caseinate (0.5-1 g), skim milk (6-10 g), resistant-maltodextrin (8-12 g), and beta-cyclodextrin (0.5-1 g) for the encapsulation efficiency, drying yield, and physicochemical properties. The optimal mixture composition was 0.54 g of sodium caseinate, 10 g of skim milk, 8.96 g of resistant-maltodextrin, and 0.5 g of beta-cyclodextrin. These encapsulating agents had a good performance in the microencapsulation of E. ciliata ethanolic extracts by the spray-drying technique. It is proven that the produced microparticles have a good potential to be included in various pharmaceutical forms or food supplements.

Improvement of the antimicrobial activity of lactic acid bacteria in combination with berries/fruits and dairy industry by-products.

BACKGROUND: By-products from berries/fruits (B/F) and the dairy industry (DI) are an important environmental issue in many countries. In the present study, the concept of an improvement of the antimicrobial activity of lactic acid bacteria (LAB) in combination with B/F (raspberries, blackcurrants, apples, rowanberries) and DI by-products was analysed. Antimicrobial activities of the B/F by-products and LAB (13 LAB strains were estimated against 15 pathogenic strains) were evaluated, with whey substrate being used for the selected and the highest antimicrobial activities showing LAB cultivation. RESULTS: The broadest spectrum of pathogenic bacteria inhibition was shown by lyophilised blackcurrant and apple by-products, which inhibited 13 and 12 pathogenic strains of the 15 strains analysed, respectively. The strongest inhibition of the tested pathogens were shown by the Lactobacillus uvarum LUHS245 and Lactobacillus casei LUHS210 and, for the abovementioned LAB biomass preparation, whey enriched with 2.5 g 100 g-1 glucose, 2.0 g 100 g-1 yeast extract and 0.5 g 100 g-1 saccharose is a suitable and sustainable substrate. The B/F by-product's antimicrobial activity can be enhanced in combination with the LUHS245 and LUHS210 strains. CONCLUSION: LAB, B/F and DI by-products can be used for preparation of antimicrobial products because the combination of compounds from different origins showed higher antimicrobial properties. © 2019 Society of Chemical Industry.

The effects of ultrasonication, fermentation with Lactobacillus sp., and dehydration on the chemical composition and microbial contamination of bovine colostrum.

The aim of this study was to evaluate the influence of ultrasonication, fermentation with Lactobacillus plantarum LUHS135 and Lactobacillus paracasei LUHS244, and different methods of dehydration on the chemical composition of bovine colostrum (BC), including the fatty acid and free amino acid profile and the content of micro- and macroelements. In addition, we analyzed the changes in lactic acid bacteria count, microbial contamination (aerobic mesophilic spore-forming bacteria, enterobacteria including Escherichia coli, and fungi/yeasts), the abundance of biogenic amines, and the concentration of nucleotide monophosphates. Significant effects of different treatments on the free amino acid profile were established, and an increase of lysine concentration by 1.2 to 95.9% was observed in treated BC. All of the treatments reduced the concentration of cadaverine, histamine, and tyramine in BC. The concentrations of macro- and microelements in BC followed the following order Ca > Na > K > Mg and Zn > Fe > Sr > Ba > Mn > Cu > Al > Se > Mo > Cr > Ni > Sn > Co > Pb > Cd. By combining the fermentation with Lactobacillus plantarum strain LUHS135 and vacuum drying, it was possible to increase the abundance of nucleotide monophosphates by more than 100%. All of the treatments reduced the microbial contamination of BC. Thus, the combination of ultrasonication, fermentation, and dehydration can be used for improving the properties and safety of BC.

Evaluation of phenolic antioxidant content in organically and conventionally grown buckwheat herb crop and its regrowth.

BACKGROUND: Buckwheat herb is known in the pharmaceutical industry as a material rich in phenolics. Buckwheat is also capable of regrowing and producing an additional harvest in the same year. Although buckwheat herb is a popular material, it is not known whether the regrowth has features of the same quality as the first harvest. Therefore, using the herb of 15 varieties of buckwheat cultivated in Lithuania, the present study aimed to examine biometric properties, phenolic content and antioxidant activity as material quality indicators for buckwheat herb and its regrowth under organic and conventional farming conditions. RESULTS: The highest amount of rutin was indicated in the organically cultivated regrowth of 2015. Buckwheat material accumulated significantly (P < 0.05) lower amounts of other phenolics. A significant correlation between phenolic content and antioxidant activity was observed in the herb and its regrowth in both farming systems. CONCLUSION: Regrowth was of similar quality to the first harvest in terms of phenolic content and antioxidant activity, although a downward trend in several biometric features was observed: the height of the regrowth plants was up to two-fold smaller and biomass was five- to nine-fold lower compared to that of the first harvest plants. Organic and industrial farming systems were determined to produce plants of similar quality. © 2016 Society of Chemical Industry.

Rosmarinus officinalis L. extract and some of its active ingredients as potential emulsion stabilizers: a new approach to the formation of multiple (W/O/W) emulsion.

Nowadays, novel topical formulations loaded with natural functional actives are under intense investigations. Therefore, the aim of our study was to evaluate how the rosemary extract and some of its active ingredients [rosmarinic acid (RA), ursolic acid (UA) and oleanolic acid (OA)] affect technological characteristics of multiple emulsion. Formulation has been prepared by adding investigated solutions (10%) in water/oil/water (W/O/W) multiple emulsion consisting of different lipophilic phases: olive oil and liquid paraffin, with 0.5% emulsifying agent (complex of sodium polyacrylate and polysorbate 20) under constant stirring with mechanical stirrer at room temperature. The emulsion parameters were evaluated using centrifugation test, freeze-thaw cycle test, microscopical and texture analyses. Rosemary's triterpenic saponins UA and OA showed the highest emulsion stabilizing properties: they decreased CI from 3.26% to 10.23% (p < 0.05). According to obtained interfacial tension data, the effect of rosemary active ingredients is not surfactant-like. Even though emulsifier itself at low concentration intends to form directly the multiple emulsion, the obtained results indicate that rosemary extract containing active ingredients does not only serve as functional cosmetic agent due to a number of biological activities, but also offer potential advantages as a stabilizer and an enhancer of W/O/W emulsions formation for dermopharmaceutical and cosmetic preparations.

Secondary metabolites of seven Hypericum species growing in Turkey.

Context The genus Hypericum (Hypericaceae) has attracted remarkable scientific interest as its members have yielded many bioactive compounds. Objective The current study presents investigations on the accumulation of hypericin, pseudohypericin, hyperforin, adhyperforin, chlorogenic acid, neochlorogenic acid, caffeic acid, 2,4-dihydroxybenzoic acid, 13,118-biapigenin, hyperoside, isoquercitrin, quercitrin, quercetin, avicularin, rutin, (+)-catechin and (-)-epicatechin in seven Hypericum (Hypericaceae) species growing wild in Turkey, namely, H. aviculariifolium Jaup. and Spach subsp. aviculariifolium (Freyn and Bornm.) Robson var. albiflorum (endemic), H. bithynicum Boiss., H. calycinum L., H. cardiophyllum Boiss., H. elongatum L. subsp. microcalycinum (Boiss. and Heldr.) Robson, H. hirsutum L. and H. xylosteifolium (Spach) N. Robson. Materials and methods The plant materials were collected at flowering period and dissected in different tissues. Air-dried plant material including stems, leaves and flowers was mechanically powdered with a laboratory mill and samples (0.1 g) were extracted in 10 mL of 100% methanol by ultrasonication at 40 °C for 30 min for HPLC-PDA analyses. Results Accumulation levels of the investigated compounds varied greatly depending on species and plant part. Discussion For the first time, the detailed chemical profiles of corresponding Turkish Hypericum species were reported and the results were discussed from a phytochemical point of view. Conclusions The present data have importance in evaluation of plant resources of Hypericum genus in selecting the new potential sources of bioactive compounds.

APPLICATION OF DRY HAWTHORN (CRATAEGUS OXYACANTHA L.) EXTRACT IN NATURAL TOPICAL FORMULATIONS.

There is a great potential for a semi-solid preparation for topical application to the skin that would use materials of natural origin not only as an active substance but also as its base. The aim of this research was to model semisolid preparations containing hawthorn extract and to determine the effect of their bases (carriers) on the release of active components from experimental dosage forms, based on the results of the in vitro studies of the bioactivity of hawthorn active components and ex vivo skin penetration studies. The active compounds of hawthorn were indentified and quantified by validated HPLC method. The antimicrobial and anti-radical activity of dry hawthorn extract were evaluated by methods in vitro. The penetration of active substances into the full undamaged human skin was evaluated by method ex vivo. Natural topical composition was chosen according to the results of release of active compounds. Release experiments were performed with modified Franz type diffusion cells. B.ceieus was the most sensitive bacteria for the hawthorn extract. Extract showed antiradical activity, however the penetration was limited. Only traces of hyperoside and isoquercitrin were founded in epidermis. Protective topical preparation with shea butter released 41.4-42.4% of active substances. Four major compounds of dry hawthorn extract were identified. The research showed that extract had antimicrobial and antiradical activity, however compounds of hawthorn stay on the surface of the undamaged human skin. Topical preparation containing beeswax did not release active compounds. Beeswax was identified as suspending agent. Topical preparations released active compounds when shea butter was used instead of beeswax.

The effect of Leonurus cardiaca herb extract and some of its flavonoids on mitochondrial oxidative phosphorylation in the heart.

Motherwort (Leonurus cardiaca) possesses antibacterial, antioxidant, anti-inflammatory, and analgesic activities, and is used as a complementary remedy to improve heart function and blood circulation. Since cardiovascular diseases are often associated with an alteration of mitochondria, the main producers of ATP in cardiac muscle cells, the aim of our work was to determine bioactive constituents present in motherwort aerial parts extract in ethanol and investigate their effects on the functions of cardiac mitochondria. Quantitative determination of polyphenols in L. cardiaca herb extract was performed by HPLC. Mitochondrial respiration rates were evaluated using a Clark-type oxygen electrode. Mitochondrial ROS generation was determined fluorimetrically with Amplex Red and horseradish peroxidase. The results showed that constituents (chlorogenic acid, orientin, quercetin, hyperoside, and rutin) of L. cardiaca herb extract uncouple (by 20-90 %) mitochondrial oxidation from phosphorylation, partially inhibit (by ~ 40 %) the mitochondrial respiratory chain in cases of pyruvate and malate as well as succinate oxidation, and effectively attenuate the generation of free radicals in mitochondria. Since partial uncoupling of mitochondria, respiratory inhibition, and decreased ROS production are proposed as possible mechanisms of cardioprotection, our results imply that L. cardiaca herb extract could be a useful remedy to protect cardiac muscles from the effects of pathogenic processes.

Phytochemical, Technological, and Pharmacological Study on the Galenic Dry Extracts Prepared from German Chamomile (Matricaria chamomilla L.) Flowers.

Galenic preparations of German chamomile are used to treat mild skin diseases, inflammation, and spasms, and they have also been reported to have anxiolytic and sedative effects. The medicinal use of chamomile is well known in ethnomedicine. After obtaining its galenic preparations, there is lots of waste left, so it is expedient to develop waste-free technologies. The aims of this study were to gain knowledge of the ethnomedical status of chamomile in the past and present, develop methods for preparing essential oils and dry extracts from German chamomile flowers using complex processing, reveal the phytochemical composition of such extracts, and verify the analgesic and soporific activity of the extracts. Two methods for the complex processing of German chamomile flowers were developed, which allowed us to obtain the essential oil and dry extracts of the tincture and aqueous extracts as byproducts. A total of 22 phenolic compounds (7 hydroxycinnamic acids, 13 flavonoids, and 2 phenolic acids) were found in the dry extracts by using UPLC-MS/MS. In total, nine main terpenoids were identified in the chamomile oil, which is of the bisabolol chemotype. During the production of chamomile tincture, a raw material-extractant ratio of 1:14-1:16 and triple extraction are recommended for its highest yield. In in vivo studies with mice and rats, the extracts showed analgesic activity and improvements in sleep. The highest sedative and analgesic effects in rodents were found with the dry extract prepared by using a 70% aqueous ethanol solution for extraction at a dose of 50 mg/kg. The developed methods for the complex processing of German chamomile flowers are advisable for implementation into the pharmaceutical industry to reduce the volume of waste during the production of its essential oil and tincture, and to obtain new products.

Phytochemical, Pharmacological, and Molecular Docking Study of Dry Extracts of Matricaria discoidea DC. with Analgesic and Soporific Activities.

Pineapple weed (Matricaria discoidea DC.) is a widespread plant in Europe and North America. In ethnomedicine, it is well-known for its anti-inflammatory and spasmolytic activities. The aim of this research was to develop novel methods of M. discoidea processing to obtain essential oil and dry extracts and to investigate their phytochemical compositions. Moreover, the molecular docking of the main substances and the in vivo studies on their soporific and analgesic activities were conducted. The essential oil and two dry extracts from M. discoidea were prepared. A total of 16 phenolic compounds (seven flavonoids, seven hydroxycinnamic acids, and two phenolic acids) in the dry extracts were identified by means of UPLC-MS/MS. In the essential oil, nine main terpenoids were identified by gas chromatography (GC). It was shown that phenolic extraction from the herb was successful when using 70% ethanol in a triple extraction method and at a ratio of 1:14-1:16. The in vivo studies with rodents demonstrated the analgesic activity of the M. discoidea extracts and improvements in the sleep of animals. The dry extracts of M. discoidea did not show any toxicity. The molecular docking analysis showed a high probability of COX-1,2 inhibition and NMDA receptor antagonism by the extracts.

Enterobacterales Biofilm-Specific Genes and Antimicrobial and Anti-Inflammatory Biomarkers in the Blood of Patients with Ischemic Heart Disease.

BACKGROUND: Ischemic heart disease (IHD) is the most prevalent type of cardiovascular disease. The main cause of IHD is atherosclerosis, which is a multifactorial inflammatory disease of blood vessels. Studies show that bacteria might have a significant impact on the pathogenesis of atherosclerosis and plaque rupture. This study aimed to evaluate the complexity of interactions between bacteria and the human body concerning metabolites and bacterial genes in patients with ischemic heart disease. METHODS: Bacterial 16S rDNA and wcaF, papC, and sdhC genes were detected in whole blood using a real-time PCR methodology. An enzyme-linked immunosorbent assay was used to measure the concentration of the LL-37 protein. An analysis of ARA in blood plasma was performed. RESULTS: Bacterial 16S rDNA was detected in 31% of the study patients, and the genes wcaF and sdhC in 20%. Enterobacterales genes were detected more frequently in patients younger than 65 years than in patients aged 65 years and older (p = 0.018) and in patients with type 2 diabetes (p = 0.048). Concentrations of the human antimicrobial peptide LL-37 and 12S-HETE concentrations were determined to be higher if patients had 16S rDNA and biofilm-specific genes. CONCLUSIONS: The results of this study enhance the understanding that Enterobacterales bacteria may participate in the pathogenesis of atherosclerosis and IHD. Bacterial DNA and host metabolites in higher concentrations appear to be detected.

Fractionation and Characterization of Triterpenoids from Vaccinium vitis-idaea L. Cuticular Waxes and Their Potential as Anticancer Agents.

Fruit and leaf cuticular waxes are valuable source materials for the isolation of triterpenoids that can be applied as natural antioxidants and anticancer agents. The present study aimed at the semi-preparative fractionation of triterpenoids from cuticular wax extracts of Vaccinium vitis-idaea L. (lingonberry) leaves and fruits and the evaluation of their cytotoxic potential. Qualitative and quantitative characterization of obtained extracts and triterpenoid fractions was performed using HPLC-PDA method, followed by complementary analysis by GC-MS. For each fraction, cytotoxic activities towards the human colon adenocarcinoma cell line (HT-29), malignant melanoma cell line (IGR39), clear renal carcinoma cell line (CaKi-1), and normal endothelial cells (EC) were determined using MTT assay. Furthermore, the effect of the most promising samples on cancer spheroid growth and viability was examined. This study allowed us to confirm that particular triterpenoid mixtures from lingonberry waxes may possess stronger cytotoxic activities than crude unpurified extracts. Fractions containing triterpenoid acids plus fernenol, complexes of oleanolic:ursolic acids, and erythrodiol:uvaol were found to be the most potent therapeutic candidates in the management of cancer diseases. The specificity of cuticular wax extracts of lingonberry leaves and fruits, leading to different purity and anticancer potential of obtained counterpart fractions, was also enclosed. These findings contribute to the profitable utilization of lingonberry cuticular waxes and provide considerable insights into the anticancer effects of particular triterpenoids and pharmacological interactions.

American Cranberry (Oxycoccus macrocarpus (Ait.) Pursh) Leaves Extract and Its Amino-Acids Preparation: The Phytochemical and Pharmacological Study.

The liver is an organ with several important biofunctions, for which there are very few effective and safe preparations that promote the functioning, protection, and regeneration of cells. Sufficiently safe preparations with hepatoprotective activity can be found in plants. The aim of our study was to investigate the chemical composition of an extract made from American cranberry (Oxycoccus macrocarpus (Ait.) Pursh) leaves and its amino-acids preparations as well as their possible hepatoprotective activity. Using the UPLC-MS/MS method, we identified 19 phenolic compounds (8 flavonoids (flavones and flavonols), 4 anthocyanins, 3 hydroxycinnamic acids, and 2 catechins). The prophylactic and therapeutic administration of the American cranberry-leaves extracts led to a decrease in the lipid-peroxidation process during a study of tetrachloromethane acute toxic damage in the liver of rats. As a result of animal studies, the most effective hepatoprotective activity was found in the extract preparations with valine and arginine.

Optimization of Delivery and Bioavailability of Encapsulated Caffeic Acid.

Caffeic acid is a widely distributed phenolic acid. It is described in the scientific literature that caffeic acid has poor solubility. The aim of this study was to improve the solubility of caffeic acid for better dissolution kinetics when administered orally. During the study, oral capsules of different compositions were modeled. The results of the disintegration test revealed that the excipients affected the disintegration time of the capsules. The excipient hypromellose prolonged the disintegration time and dissolution time of caffeic acid. The dissolution kinetics of caffeic acid from capsules depend on the chosen excipients. P407 was more effective compared to other excipients and positively affected the dissolution kinetics of caffeic acid compared to other excipients. When the capsule contained 25 mg of ß-cyclodextrin, 85% of the caffeic acid was released after 60 min. When the capsule contained 25-50 mg poloxamer 407, more than 85.0% of the caffeic acid was released from capsules after 30 min. The research results showed that in order to improve the dissolution kinetics of caffeic acid, one of the important steps is to improve its solubility.