Chemical Profiling and Antioxidant Activity of Tanacetum vulgare L. Wild-Growing in Latvia

Funding Information: This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 857287 and European Agricultural Fund for Rural Development—development of the medication form from the extract of the leaves of the Latvian traditional medicinal plant tansy and its impact on the sheep digestive tract microbiome and antiparasitic control (22-00-A01612-000007). The project is supported by the Ministry of Agriculture and Rural Support Service Republic of Latvia, project no: 22-00-A01612-000007. Publisher Copyright: © 2023 by the authors.The Tanacetum vulgare L. (Tansy) has several ethnobotanical uses, mostly related to the essential oil and sesquiterpene lactones, whereas information regarding other compounds is scarce. This research is designed to characterize the phenolic compounds (flavonoids, phenolic acids, and tannins) to analyze the thujone (which is toxic in high concentrations) content and to detect the antioxidant activity (DPPH assay) of extracts. The main highlights of our work provide a chemical profile of phenolic compounds of T. vulgare harvested from different regions of Latvia, as well as simultaneously support the ethnomedicinal uses for wild T. vulgare through the integration of phenolic compounds as one of the value constituents of leaves and flowers. The extraction yield was 18 to 20% for leaves and 8 to 16% for flowers. The total phenol content in the extracts of T. vulgare as well as their antioxidant activity was different between collection regions and the aerial parts ranging from 134 to 218 mg GAE/g and 32 to 182 mg L−1, respectively. A remarkable variation in the thujone (α + β) content (0.4% up to 6%) was detected in the extracts. T. vulgare leaf extracts were rich in tannins (up to 19%). According to the parameters detected, the extracts of T. vulgare could be considered promising for the development of new herbal products.publishersversionPeer reviewe

Oregonin from Alnus incana bark affects DNA methyltransferases expression and mitochondrial DNA copies in mouse embryonic fibroblasts

Oregonin is an open-chain diarylheptanoid isolated from Alnus incana bark that possesses remarkable antioxidant and anti-inflammatory properties, inhibits adipogenesis, and can be used in the prevention of obesity and related metabolic disorders. Here, we aimed to investigate the effects of oregonin on the epigenetic regulation in cells as well as its ability to modulate DNA methylating enzymes expression and mitochondrial DNA (mtDNA) copies. Our results show that oregonin altered the expression of DNA methyltransferases and mtDNA copy numbers in dependency on concentration and specificity of cells genotype. A close correlation between mtDNA copy numbers and mRNA expression of the mtDnmt1 and Dnmt3b was established. Moreover, molecular modeling suggested that oregonin fits the catalytic site of DNMT1 and partially overlaps with binding of the cofactor. These findings further extend the knowledge on oregonin, and elucidate for the first time its potential to affect the key players of the DNA methylation process, namely DNMTs transcripts and mtDNA

Antibacterial Activity of Tanacetum vulgare L. Extracts against Clinical Isolates of Bovine Mastitis

Funding Information: This research was funded by the European Union’s Horizon 2020 research and innovation program under the grant agreement No 857287 and this research is supported by the Ministry of Agriculture and Rural Support Service Republic of Latvia with the European Agricultural Fund for Rural Development—Development of herbal plant containing medical extracts with anti-parasitic effect No 18-00-A01620-000028. Publisher Copyright: © 2023 by the authors.A bovine mastitis is an infectious disease, which is usually treated with antibiotics. Alternatively, herbal medicine has been proposed due to bacterial resistance. The aim of this study was to determine the antibacterial activity of the acetonic and ethanolic extracts of dried flowers and leaves of Tanacetum vulgare L. against bovine mastitis-inducing clinical isolates such as Escherichia coli, Streptococcus agalactiae, Streptococcus uberis, Serratia liquefaciens, Staphylococcus aureus, and reference cultures of S. aureus and E. coli. The extracts of T. vulgare showed partial antibacterial activity against tested strains of S. aureus. The MIC and MBC values of a 70% ethanol extract of flowers (MIC = 3.4 mg/mL, MBC = 3.4–6.8 mg/mL) were lower than for the 70% ethanol extract of leaves (MIC = 15.7–31.4 mg/mL, MBC = 62.9–125.9 mg/mL). The flower extracts showed low activity against E. coli (MIC = 53.9 mg/mL, MBC = 53.9–107.8 mg/mL) and S. agalactiae (MIC, MBC = 53.9 mg/mL). T. vulgare leaf extracts had minimal antibacterial effects against Streptococcus strains (MIC = 31.4–62.9 mg/mL, MBC = 53.9–125.9 mg/mL) and Serratia liquefaciens (MIC, MBC = 125.9 mg/mL). However, flower extracts had a higher phenolic content that did not correlate with antibacterial effects. T. vulgare flower and leaf extracts could be combined to obtain broader antibacterial effects.publishersversionPeer reviewe

Genetic inactivation of the sigma-1 chaperone protein results in decreased expression of the R2 subunit of the GABA-B receptor and increased susceptibility to seizures

Funding Information: This study was supported by European Regional Development Fund Project No. 1.1.1.2/VIAA/2/18/376 (PostDoc Latvia), “Sigma chaperone protein as a novel drug target”. We thank Laboratorios Dr. Esteve, S.A. (Barcelona, Spain) for providing CD-1 background sigma-1 receptor knockout mice. We thank Associate Professors Inga Kadisha and Thomas van Groen (University of Alabama at Birmingham, Birmingham, Alabama, USA) for fruitful discussions regarding immunohistochemistry. We also thank Dr. biol. Dace Pjanova (Latvian Biomedical Research and Study Centre, Riga, Latvia) for the help with confocal imaging and Abberior Instruments (Göttingen, Germany) for a kind gift of fluorescently labeled Abberior STAR antibodies. Publisher Copyright: © 2020 The Author(s)There is a growing body of evidence demonstrating the significant involvement of the sigma-1 chaperone protein in the modulation of seizures. Several sigma-1 receptor (Sig1R) ligands have been demonstrated to regulate the seizure threshold in acute and chronic seizure models. However, the mechanism by which Sig1R modulates the excitatory and inhibitory pathways in the brain has not been elucidated. The aim of this study was to compare the susceptibility to seizures of wild type (WT) and Sig1R knockout (Sig1R−/−) mice in intravenous pentylenetetrazol (PTZ) and (+)-bicuculline (BIC) infusion-induced acute seizure and Sig1R antagonist NE-100-induced seizure models. To determine possible molecular mechanisms, we used quantitative PCR, Western blotting and immunohistochemistry to assess the possible involvement of several seizure-related genes and proteins. Peripheral tissue contractile response of WT and Sig1R−/− mice was studied in an isolated vasa deferentia model. The most important finding was the significantly decreased expression of the R2 subunit of the GABA-B receptor in the hippocampus and habenula of Sig1R−/− mice. Our results demonstrated that Sig1R−/− mice have decreased thresholds for PTZ- and BIC-induced tonic seizures. In the NE-100-induced seizure model, Sig1R−/− animals demonstrated lower seizure scores, shorter durations and increased latency times of seizures compared to WT mice. Sig1R-independent activities of NE-100 included downregulation of the gene expression of iNOS and GABA-A γ2 and inhibition of KCl-induced depolarization in both WT and Sig1R−/− animals. In conclusion, the results of this study indicate that the lack of Sig1R resulted in decreased expression of the R2 subunit of the GABA-B receptor and increased susceptibility to seizures. Our results confirm that Sig1R is a significant molecular target for seizure modulation and warrants further investigation for the development of novel anti-seizure drugs.publishersversionPeer reviewe

Reduced GFAP expression in Bergmann glial cells in the cerebellum of sigma-1 receptor knockout mice determines the neurobehavioral outcomes after traumatic brain injury

Funding Information: Funding: This study was supported by EU-ERA-NET NEURON project TRAINS No. 9642151 and the European Union’s Horizon 2020 research and innovation program under grant agreement No. 857394. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Neuroprotective effects of Sigma-1 receptor (S1R) ligands have been observed in multiple animal models of neurodegenerative diseases. Traumatic brain injury (TBI)-related neurodegeneration can induce long-lasting physical, cognitive, and behavioral disabilities. The aim of our study was to evaluate the role of S1R in the development of neurological deficits after TBI. Adult male wild-type CD-1 (WT) and S1R knockout (S1R-/-) mice were subjected to lateral fluid percussion injury, and behavioral and histological outcomes were assessed for up to 12 months postinjury. Neurological deficits and motor coordination impairment were less pronounced in S1R-/-mice with TBI than in WT mice with TBI 24 h after injury. TBI-induced short-term memory impairments were present in WT but not S1R-/-mice 7 months after injury. Compared to WT animals, S1R-/-mice exhibited better motor coordination and less pronounced despair behavior for up to 12 months postinjury. TBI induced astrocyte activation in the cortex of WT but not S1R-/-mice. S1R-/-mice presented a significantly reduced GFAP expression in Bergmann glial cells in the molecular layer of the cerebellum compared to WT mice. Our findings suggest that S1R deficiency reduces TBI-induced motor coordination impairments by reducing GFAP expression in Bergmann glial cells in the cerebellum.publishersversionPeer reviewe

Sea Buckthorn (Hippophae rhamnoides) Waste Biomass after Harvesting as a Source of Valuable Biologically Active Compounds with Nutraceutical and Antibacterial Potential

Funding Information: Funding: This research was funded by ERDF project nr. Nr.1.1.1.1/19/A/146 “Biorefinery processing of sea buckthorn non-fruit biomass using innovative techniques and comprehensive analytical investigation, for obtaining prospective for Latvian bioeconomy high value-added products, including serotonin”. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.For sustainable sea buckthorn (Hippophae rhamnoides) berry production, the task at hand is to find an application for the large amount of biomass waste arising at harvesting. Sea buckthorn (SBT) vegetation is currently poorly studied. The purpose of this research was to assess the composition and potential of SBT twigs as a source of valuable biologically active substances. Water and 50% EtOH extracts of twigs of three Latvian SBT cultivars with a high berry yield and quality, popular for cultivation in many countries (H. rhamnoides ‘Maria Bruvele', ‘Tatiana', ‘Botanicheskaya Lubitelskaya'), were investigated for the first time. The phytochemical composition (UHPLC-ESI-MS/MS analysis) and biological activity of the obtained hydrophilic extracts were determined. The highest yield of polyphenolic compounds and serotonin was observed for ‘Maria Bruvele'. Hydrophilic extracts were investigated for radical scavenging activity (DPPH' test), antibacterial/antifungal activity against five pathogenic bacteria/yeast, cytotoxicity, and the enzymatic activity of alpha-amylase (via in vitro testing), which is extremely important for the treatment of people with underweight, wasting, and malabsorption. The results showed a high potential of sea buckthorn biomass as a source of valuable biologically active compounds for the creation of preparations for the food industry, nutraceuticals, and cosmetics.publishersversionPeer reviewe

A Comparative Assessment of Sea Buckthorn (Hippophae rhamnoides L.) Pruning Waste as a Potential Source of Serotonin

Sea buckthorn (Hippophae rhamnoides L.) twigs, remaining after harvesting and pruning, are an underutilized and little-explored biomass resource. This study investigated the content of serotonin in 10 sea buckthorn cultivars (‘Maria Bruvele’, ‘Botanicheskaya Lubitelskaya’, ‘Tatiana’, ‘Otto’, ‘Leikora’, ‘Duet’, ‘Clara’, ‘Lord’, ‘Eva’, ‘Tarmo’) for the first time, and for further adjustment of the extraction conditions, cultivar ‘Maria Bruvele’ was extracted by water and water/ethanol solution with 20-25, 50, 70, and 96% ethanol at different temperatures. The results showed that 50% water/ethanol solutions are the most suitable for extraction, which makes it possible to increase the yield of serotonin. The 2-year-old twigs and bark from ‘Maria Bruvele’ collected in autumn contained higher serotonin content compared to spring-collected biomass. Serotonin sequential purification allowed the serotonin content in the fraction to increase to 26%/DM. The serotonin-rich fraction showed antimicrobial activity against gram-positive and gram-negative bacteria. In tests with salivary amylase, a serotonin-rich fraction at the amount of 0.1-0.4 mg/mL of saliva, under normal physiological conditions, tended to increase amylase activity, resulting in acceleration of starch degradation to glucose. Thus, the results support further study of the serotonin fraction for the treatment of people having underweight, malnutrition, and malabsorption conditions