The Cultivation of Chelidonium majus L. Increased the Total Alkaloid Content and Cytotoxic Activity Compared with Those of Wild-Grown Plants

Funding Information: Funding: This research was funded by European Regional Development Fund project “Innovative solutions for growing technologies and applications of spring medicinal and aromatic plants” (Grant No. 1.1.1.1/18/A/ 043). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.The effect of cultivation practises on both the phytochemical profile and biological activity of aqueous ethanol extracts of Chelidonium majus L. was studied. Extracts were prepared from aerial parts of the same plant population collected in the wild and grown under organic farming conditions. Both qualitative and quantitative analyses of alkaloids and flavonoid derivatives were performed by LC/MS methods, and the cytotoxicity of lyophilised extracts was studied in B16-F10, HepG2, and CaCo-2 cells. Coptisine was the dominant alkaloid of extracts prepared from wild-grown plants, whereas after cultivation, chelidonine was the most abundant alkaloid. The total alkaloid content was significantly increased by cultivation. Ten flavonol glycoconjugates were identified in C. majus extracts, and quantitative analysis did not reveal significant differences between extracts prepared from wild-grown and cultivated specimens. Treatment with C. majus extracts resulted in a dose-dependent increase in cytotoxicity in all three cell lines. The extracts prepared from cultivated specimens showed higher cytotoxicity than the extracts prepared from wild-grown plants. The strongest cytotoxic effect of cultivated C. majus was observed in B16-F10 cells (IC50 = 174.98 ± 1.12 µg/mL). Cultivation-induced differences in the phytochemical composition of C. majus extracts resulted in significant increases in the cytotoxic activities of the preparations.publishersversionPeer reviewe

LC-MS/MS method for simultaneous quantification of the first-line anti-tuberculosis drugs and six primary metabolites in patient plasma : Implications for therapeutic drug monitoring

Funding Information: This study was funded by the Latvian Council of Science. Project No: lzp-2020/1-0050. Publisher Copyright: © 2021 The AuthorsThe pharmacokinetic profiling of drug substances and corresponding metabolites in the biological matrix is one of the most informative tools for the treatment efficacy assessment. Therefore, to satisfy the need for comprehensive monitoring of anti-tuberculosis drugs in human plasma, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous quantification of first-line anti-tuberculosis drugs (ethambutol, isoniazid, pyrazinamide, and rifampicin) along with their six primary metabolites. Simple single-step protein precipitation with methanol was chosen as the most convenient sample pre-treatment method. Chromatographic separation of the ten analyte mixture was achieved within 10 minutes on a reverse-phase C8 column using mobile phase gradient mode. The multiple reaction monitoring mode (MRM) was used for analyte detection and quantification in patient samples. The chosen quantification ranges fully covered expected plasma concentrations. The method exhibited acceptable selectivity; the within- and between-run accuracy ranged from 87.2 to 113.6%, but within- and between-run precision was between 1.6 and 14.9% (at the LLOQ level CV < 20%). Although the response of the isonicotinic acid varied depending on the matrix source (CV 21.8%), validation results proved that such inconsistency does not affect the accuracy and precision of results. If stored at room temperature plasma samples should be processed within 4 h after collection, temporary storage at −20 °C up to 24 h is acceptable due to stability issues of analytes. The developed method was applied for the patient sample analysis (n = 34) receiving anti-tuberculosis treatment with the first-line drugs.publishersversionPeer reviewe

Wild-Grown and Cultivated Glechoma hederacea L. : Chemical Composition and Potential for Cultivation in Organic Farming Conditions

Funding Information: Funding: This work was supported by the European Regional Development Fund project “Innovative solutions for growing technologies and applications of spring medicinal and aromatic plants” (Nr. 1.1.1.1/18/A/043). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Glechoma hederacea L. is a medicinal plant that is known in traditional medicine for its anti-inflammatory, antibacterial, antiviral, and anticancer properties. This study evaluated the potential for commercial production of G. hederacea and compared the chemical composition and activity of 70% ethanol extracts and steam-distilled essential oils from wild-grown and cultivated G. hederacea collected in different harvesting periods. The main compounds identified in the 70% ethanol extracts were phenolic acids (chlorogenic and rosmarinic acids) and flavonoid O-glycosides. The essential oil varied in the three accessions in the range of 0.32-2.98 mL/kg -1 of dry weight. The extracts possessed potent antioxidant and anti-inflammatory properties in LPS-treated bone-marrow-derived macrophages. The results of flow cytometry show that extracts from different vegetation periods reduced the conversion of macrophages to the proinflammatory phenotype M1. The chemical composition varied the most with the different harvesting periods, and the most suitable periods were the flowering and vegetative phases for the polyphenolic compounds and essential oils, respectively. G. hederacea can be successfully grown under organic farming conditions, and cultivation does not significantly affect the chemical composition and biological activity compared to wild-grown plants.publishersversionPeer reviewe

Efficacy of proanthocyanidins from Pelargonium sidoides root extract in reducing P. gingivalis viability while preserving oral commensal S. salivarius

Funding Information: Funding: This research is a part of the project PELARGODONT (“Engineering and functionalization of delivery system with Pelargonium sidoides biologically active substance on inflamed periodontal surface area”) funded by a grant (No. S-M-ERA.NET-17-2) from the Research Council of Lithuania, the State Education Development Agency of Latvia, and Italian Ministry of Education, University and Research. Publisher Copyright: © 2018 by the authors.Bacterial resistance to antibiotics and the disruption of beneficial microbiota are key problems in contemporary medicine and make the search for new, more efficient infection treatment strategies among the most important tasks in medicine. Multicomponent plant-derived preparations with mild antibacterial activity created by many simultaneous mechanisms together with anti-inflammatory, innate immune and regenerative capacity-stimulating properties are good candidates for this therapy, and proanthocyanidins are among the most promising compounds of this sort. In this study, we have isolated proanthocyanidins from Pelargonium sidoides DC root extract and characterized and compared the composition, antioxidant properties and antibacterial activity of the proanthocyanidin fraction with those of the whole extract. The results revealed that proanthocyanidins had significantly stronger antioxidant capacity compared to the root extract and exhibited a unique antibacterial action profile that selectively targets Gram-negative keystone periodontal and peri-implant pathogenic strains, such as Porphyromonas gingivalis, while preserving the viability of beneficial oral commensal Streptococcus salivarius. The finding suggests that proanthocyanidins from Pelargonium sidoides root extract are good candidates for the prolonged and harmless treatment of infectious diseases.publishersversionPeer reviewe

Single nucleotide polymorphisms in the intergenic region between metformin transporter OCT2 and OCT3 coding genes are associated with short-Term response to metformin monotherapy in type 2 diabetes mellitus patients

Publisher Copyright: © 2016 The authors Published by Bioscientifica Ltd. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.Objective(s): High variability in clinical response to metformin is often observed in type 2 diabetes (T2D) patients, and it highlights the need for identification of genetic components affecting the efficiency of metformin therapy. Aim of this observational study is to evaluate the role of tagSNPs (tagging single nucleotide polymorphisms) from genomic regions coding for six metformin transporter genes with respect to the short-Term efficiency. Design: 102 tagSNPs in 6 genes coding for metformin transporters were genotyped in the group of 102 T2D patients treated with metformin for 3 months. Methods: Most significant hits were analyzed in the group of 131 T2D patients from Slovakia. Pharmacokinetic study in 25 healthy nondiabetic volunteers was conducted to investigate the effects of identified polymorphisms. Results: In the discovery group of 102 patients, minor alleles of rs3119309, rs7757336 and rs2481030 were significantly nominally associated with metformin inefficiency (P = 1.9 × 106 to 8.1 × 106). Effects of rs2481030 and rs7757336 did not replicate in the group of 131 T2DM patients from Slovakia alone, whereas rs7757336 was significantly associated with a reduced metformin response in combined group. In pharmacokinetic study, group of individuals harboring risk alleles of rs7757336 and rs2481030 displayed significantly reduced AUC∞ of metformin in plasma. Conclusions: For the first time, we have identified an association between the lack of metformin response and SNPs rs3119309 and rs7757336 located in the 5 flanking region of the genes coding for Organic cation transporter 2 and rs2481030 located in the 5 flanking region of Organic cation transporter 3 that was supported by the results of a pharmacokinetic study on 25 healthy volunteers.publishersversionPeer reviewe

Mildronate treatment alters γ-butyrobetaine and l -carnitine concentrations in healthy volunteers

Objectives In this study, we aimed to investigate the effects of long-term administration of the cardioprotective drug mildronate on the concentrations of l-carnitine and γ-butyrobetaine in healthy volunteers. Methods Mildronate was administered perorally, at a dosage of 500 mg, twice daily. Plasma and urine samples were collected weekly. Daily meat consumption within an average, non-vegetarian diet was monitored. l-Carnitine, γ-butyrobetaine and mildronate concentrations were measured using the UPLC/MS/MS method. Key findings After 4 weeks, the average concentrations of l-carnitine in plasma significantly decreased by 18%. The plasma concentrations of γ-butyrobetaine increased about two-fold, and this effect was statistically significant in both the male and female groups. In urine samples, a significant increase in l-carnitine and γ-butyrobetaine levels was observed, which provides evidence for increased excretion of both substances during the mildronate treatment. At the end of the treatment period, the plasma concentration of mildronate was 20 μm on average. There were no significant differences between the effects observed in female and male volunteers. Meat consumption partially reduced the l-carnitine-lowering effects induced by mildronate. Conclusions Long-term administration of mildronate significantly lowers l-carnitine plasma concentrations in non-vegetarian, healthy volunteers.publishersversionPeer reviewe

Funkcionalizetu 2,6-di-tres-butilfenola atvasinajumu sinteze un kimisko ipasibu izpete

Separate summaries in Latvian, English, RussianAvailable from Latvian Academic Library / LAL - Latvian Academic LibrarySIGLELVLatvi

Quantitative analysis of phenibut in rat brain tissue extracts by liquid chromatography-tandem mass spectrometry

Phenibut (3-phenyl-4-aminobutyric acid) is a γ-aminobutyric acid mimetic drug, which is used clinically as a mood elevator and tranquilizer. In the present work, a rapid, selective and sensitive liquid chromatography-tandem mass spectrometry method for quantification of phenibut in biological matrices has been developed. The method is based on protein precipitation with acidic acetonitrile followed by isocratic chromatographic separation using acetonitrile-formic acid (0.1% in water; 8:92, v/v) mobile phase on a reversed-phase column. Detection of the analyte was performed by electrospray ionization mass spectrometry in multiple reaction monitoring mode with the precursor-to-product ion transition m/z 180.3 → m/z 117.2. The calibration curve was linear over the concentration range 50-2000 ng/mL. The lower limit of quantification for phenibut in rat brain extracts was 50 ng/mL. Acceptable precision and accuracy were obtained over the whole concentration range. The validated method was successfully applied in a pharmacological study to analyze phenibut concentration in rat brain tissue extract samples.publishersversionPeer reviewe

Metabolomic studies of Experimental Diabetic Urine Samples by 1H NMR Spectroscopy and LC/MS Method

Metabolomic strategies based on nuclear magnetic resonance (NMR) and liquid chromatography coupled with mass spectrometry (LC/MS) have been developed to obtain metabolite profiles for urine samples excreted by male Goto–Kakizaki (G–K) and Wistar rats from 12–20 weeks of age. Multivariate statistical analysis was applied to the generated data sets. The efficiencies of two software packages for LC/MS data processing, MZmine and XCMS, were compared and gave similar results. The extracted data from both analytical methods were subjected to statistical analysis by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). The performance of PLS-DA modeling was compared for both analytical methods and after different data normalization methods were used. The changes in metabolite profile included increased creatinine, glucose, and dimethylamine and decreased creatine, hippurate, formate, phenylalanine, allantoin, fumarate, citrate, acetate, amino acids, and some unidentified metabolites in the urine of G–K rats compared to Wistar rats. The obtained results gave evidence that 1H NMR procedures produce more information about the identity of metabolites. The multivariate analysis allowed the differentiation of the metabolic profiles related to animal age. In conclusion, the metabolomic studies of G–K rat urine samples provided further insights concerning experimental methodologies for data generation and processing, as well as possible markers for diabetes research