The Genus Hyssopus: Traditional Use, Phytochemicals and Pharmacological Properties.

According to modern concepts, the genus Hyssopus L. includes seven plant species (Hyssopus ambiguus (Trautv.) Iljin ex Prochorov. & Lebel; Hyssopus cuspidatus Boriss; Hyssopus latilabiatus C.Y.Wu & H.W. Li; Hyssopus macranthus Boriss.; Hyssopus officinalis L.; Hyssopus seravschanicus (Dubj.) Pazij; Hyssopus subulifolius (Rech.f.) Rech.f.). The plants are rich in various groups of biologically active substances with a wide spectrum of pharmacological action. This review presents a modern comprehensive overview of the botanical research, extraction methods, chemical composition and pharmacological activity of plants of the genus Hyssopus L. As a result of the review, it was established that the chemical composition of plant extracts of the genus Hyssopus L. depends on various factors (place of growth, weather conditions, chemotypes, extraction methods, etc.). For the further use of the plants, the extraction methods and low-molecular metabolites isolated from them (mono- and sesquiterpenoids, flavonoids, alkaloids, etc.) are discussed. The data from the review provide an assessment of the relevance.

Acute Toxicity of Dental Gel Based on Origanum vulgare in Mice.

Objectives: The creation of new herbal medicines for their use in dentistry is relevant. The purpose of this work is to study the acute toxicity of the anticaries dental gel (ACDG3) developed by us based on Origanum vulgare. Results: In case of studying the safety of anticaries dental gel "ACDG3" in animals, that with a single dose of up to 2000 mg/kg, the absence of pathological changes in the behavior of animals was noted. Biochemical studies indicate that the studied doses of dental gel did not lead to significant deviations in the blood parameters of mice and deviations fluctuated within the reference values. According to the results of a morphometric study conducted 15 days after the administration of the drug, no deviations were found. The histological evaluation of organs showed little change in the cardiac architecture in animals treated with ACDG3 at doses of 1000 mg/kg and 2000 mg/kg. On the other hand, no significant changes in the cardiac function were observed in all treated mice. Conclusion: As follows from the results obtained, in case of determining acute toxicity, the studied anticaries gel, ACDG3, showed low toxicity. For mice, LD50 was 2000 mg/kg intragastrically. So, according to the generally accepted classification of the toxicity of substances, ACDG3 can be attributed to the class of low-toxic substances (IV class of toxicity, LD50 > 5000 mg/kg, intragastric administration), that is, to practically nontoxic compounds.

Salvia dumetorum essential oil: GC-MS analysis, antibacterial activity and effect on the formation of Streptococcus mutans biofilms.

Salvia dumetorum essential oil (SDEO) was obtained using a Clevenger apparatus by hydrodistillation approach. The chemical composition of the essential oil was determined by GC-MS analysis. In this study SDEO was screened for its antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Candida albicans and the amount of biofilm formed by Streptococcus mutans bacteria. For the first time the chemical composition of SDEO growing in Central Kazakhstan was established. The results obtained from GC-MS showed the predominance of sesquiterpenoids (54.15%). The antibacterial study results showed that SDEO exhibited strong antibacterial activity against B. subtilis and S. aureus in vitro and also demonstrated an inhibitory effect on S. mutans biofilm formation on 1% sucrose medium. During the study, no antibacterial activity was detected against E. coli and C. albicans. These results demonstrated that SDEO can be used in the development of new antibacterial and anti-caries therapeutic dental products.

Prunella vulgaris L.: An Updated Overview of Botany, Chemical Composition, Extraction Methods, and Biological Activities.

Prunella vulgaris L. (PV) is a well-known renewable drug resource full of different groups of biologically active substances with a wide range of pharmacological actions and applications in medicine. In this review, we present an updated comprehensive overview of the botany, extracting methods, chemical composition, and pharmacological activity of different parts of PV extracts. As a result of this review, it was found that chemical composition of PV depends on various factors ranging from the part of the plant to the method of extraction. We also highlight extraction methods that have not been previously used for obtaining PV extracts and may have high scientific interest. With this review, we hope to guide present and future professionals and provide possible previously unexplored areas to find new solutions associated with PV plant.

HPLC and GC/MS analysis of Prunus ulmifolia Franch. (syn. Aflatunia ulmifolia (Franch.) Vassilcz.) leaves growing in South-Eastern Kazakhstan.

Prunus ulmifolia Franch. (Rosaceae) was investigated for its phytochemical composition from South-Eastern Kazakhstan for the first time. HPLC analysis confirmed rutin (0.88%) in ethanol extract, and the extract also exhibited antioxidant activity. The GC/MS analysis identified total 44 components from main groups e.g. oxygenated monoterpenes (51.06%), oxygenated sesquiterpenes (20.33%), non-terpene derivatives (18.71%), and sesquiterpene hydrocarbons (7.89%), and the maximum content was of acyclic alcoholic monoterpenoid citronellol (36.58%). The hierarchical cluster analysis (HCA) from previous reports and present study was used to demonstrate the variations between essential oil compositions in different Prunus species. It formed three main clusters, cluster I consisted of species with benzaldehyde as dominant component. Cluster II included plants with benzaldehyde as secondary component, and cluster III was of P. ulmifolia in which benzaldehyde was not detected. Further, the essential oil was assessed for cytotoxic and antimicrobial activities too, and it showed better cytotoxic but poor antimicrobial activities.

Formulation of an Origanum vulgare based dental gel with antimicrobial activity.

OBJECTIVES: This study aims to formulate a new Origanum vulgare anti-caries dental gel with high antimicrobial activity. METHODS: O. vulgare essential oil was extracted using hydro-distillation, ethanol extraction, gas chromatography/mass spectrometry, and high-performance liquid chromatography methods. Antimicrobial activity of the produced gels with oregano oil and extract was determined through the disco-diffusion method. The effectiveness of O. vulgare essential oil was tested in vitro for Streptococcus mutans biofilm using colorimetric analysis. RESULTS: O. vulgare essential oil inhibited the growth of S. mutans biofilm by 98% compared with unexposed control bacteria (p <0.05). Five samples of anti-caries gel (ACDG1, ACDG2, ACDG3, ACDG4, ACDG5) were formulated using the obtained oregano essential oil and extract. Based on the microbiological study results, the ACDG1 and ACDG3 gel samples exhibited high antimicrobial activity against the gram-positive bacterial strains of Staphylococcus aureus and Bacillus subtilis and the yeast fungus Candida albicans and moderate antimicrobial activity against the gram-negative strains of Escherichia coli and Pseudomonas aeruginosa. CONCLUSION: Based on the results of this study, the ACDG3 sample may be considered an anti-caries gel owing to its high antimicrobial activity. This sample has good organoleptic properties compared to other samples, produces relatively high antimicrobial activity, and guards against cariogenic biofilms of S. mutans.

Composition of essential oil of the aerial parts of Viola canina L. growing wild in Northern Kazakhstan.

The aim of the study was to investigate volatile compounds from the aerial parts of Viola canina L. of the family Violaceae grown wild in Northern Kazakhstan for the first time. Viola canina is a common and widespread species of the temperate northern hemisphere. The oil from the aerial parts of V. canina, was obtained by hydrodistillation and investigated by gas chromatography combined with mass spectrometry. The main component of V. canina essential oil was phytol (55.2%). The obtained results showed differences in the composition of already studied Viola essential oils, such as essential oil of V. odorata L., V. etrusca Erben, V. tricolor L., V. arvensis Murr., V. tianshanica Maxim., V. serpens Wall. and V. hamiltoniana D. Don. There is a certain similarity with the composition of the essential oil of V. arvensis where phytol was also found as one of the main component (11.4%).

Inhibition of T Cell Receptor Activation by Semi-Synthetic Sesquiterpene Lactone Derivatives and Molecular Modeling of Their Interaction with Glutathione and Tyrosine Kinase ZAP-70.

A variety of natural compounds have been shown to modulate T cell receptor (TCR) activation, including natural sesquiterpene lactones (SLs). In the present studies, we evaluated the biological activity of 11 novel semi-synthetic SLs to determine their ability to modulate TCR activation. Of these compounds, α -epoxyarglabin, cytisinyl epoxyarglabin, 1 ß ,10 α -epoxyargolide, and chloroacetate grosheimin inhibited anti-CD3-induced Ca2+ mobilization and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in Jurkat T cells. We also found that the active SLs depleted intracellular glutathione (GSH) in Jurkat T cells, supporting their reactivity towards thiol groups. Because the zeta-chain associated tyrosine kinase 70 kDa (ZAP-70) is essential for TCR signaling and contains a tandem SH2 region that is highly enriched with multiple cysteines, we performed molecular docking of natural SLs and their semi-synthetic derivatives into the ZAP-70 binding site. The docking showed that the distance between the carbon atom of the exocyclic methylene group and the sulfur atom in Cys39 of the ZAP-70 tandem SH2 module was 3.04⁻5.3 Å for active compounds. Furthermore, the natural SLs and their derivatives could be differentiated by their ability to react with the Cys39 SH-group. We suggest that natural and/or semi-synthetic SLs with an α -methylene- γ -lactone moiety can specifically target GSH and the kinase site of ZAP-70 and inhibit the initial phases of TCR activation.

The natural sesquiterpene lactones arglabin, grosheimin, agracin, parthenolide, and estafiatin inhibit T cell receptor (TCR) activation.

Inhibition of the T cell receptor (TCR) pathway represents an effective strategy for the treatment of T cell-mediated inflammatory and autoimmune diseases. To identify natural compounds that could inhibit inflammatory T cell responses, we screened 13 sesquiterpene lactones, including achillin, arglabin, argolide, argracin, 3ß-hydroxyarhalin, artesin, artemisinin, estafiatin, grosheimin, grossmisin, leucomisine, parthenolide, and taurine, for their ability to modulate activation-induced Ca2+ mobilization in Jurkat T cells. Five of the compounds (arglabin, grosheimin, argracin, parthenolide, and estafiatin) inhibited anti-CD3-induced mobilization of intercellular Ca2+ ([Ca2⁺]i) in Jurkat cells, with the most potent being parthenolide and argacin (IC50 = 5.6 and 6.1 µM, respectively). Likewise, phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in activated Jurkat cells was inhibited by these five compounds, with the most potent being parthenolide and estafiatin (IC50 = 13.8 and 15.4 µM, respectively). These compounds also inhibited ERK1/2 phosphorylation in primary human T cells and depleted intracellular glutathione. In contrast, none of the sesquiterpene lactones inhibited ERK1/2 phosphorylation in HL60 cells transfected with N-formyl peptide receptor 2 (FPR2) and stimulated with the FPR2 peptide agonist WKYMVM, indicating specificity for T cell activation. Estafiatin, a representative sesquiterpene lactone, was also profiled in a cell-based phosphokinase array for 43 kinase phosphorylation sites, as well as in a cell-free competition binding assay for its ability to compete with an active-site directed ligand for 95 different protein kinases. Besides inhibition of ERK1/2 phosphorylation, estafiatin also inhibited phosphorylation of p53, AMPKα1, CREB, and p27 elicited by TCR activation in Jurkat cells, but it did not bind to any of 95 kinases evaluated. These results suggest that arglabin, grosheimin, agracin, parthenolide, and estafiatin can selectively inhibit initial phases of TCR activation and may be natural compounds with previously undescribed immunotherapeutic properties.

Chemical Composition of the Essential Oil of the Boreal Relict of Pyrola rotundifolia L. from Northern Kazakhstan.

In Kazakhstan Pyrola rotundifolia L. is the plant-relict in the flora of insular pine forests of the region of low hillocks and declivities in Kazakhstan - a group of insular pine forests of Kokshetau, Bayanaul and Karkaralinsk. In this study, the essential oils from dried aerial parts of P. rotundifolia, collected in natural habitats of the State National Natural Park "Burabay" (Akmola oblast, Northern Kazakhstan), were extracted by hydrodistillation and analyzed by gas chromatography - mass spectrometry. The yield of the essential oil amounted to 0.057 % in relation to the mass of the air-dry raw material. The major components in dried plant oil were 2,6-dimethyl-1,4-naphthoquinone (12.99-93.49%) and dibutyl phthalate (4.42-40.48%), depending on the growth conditions.

(1S*,3R*,5S*,7S*)-4,4,8,8-Tetra-chloro-1-isopropyl-5-methyl-tri-cyclo-[5.1.0.0(3,5)]octa-ne.

The title compound, C12H16Cl4, is a derivative of the natural product 1-isopropyl-4-methyl-cyclo-hexa-1,4-diene, and represents a diastereomer with two trans-fused cyclo-propane rings. Both enanti-omers are present in the non-centrosymmetric polar space group Pna21. The central cyclo-hexane ring is planar within 0.02 (1) Å. The C atoms of di-chloro-methyl-ene groups deviate from this plane by 1.19 (1) and -1.26 (1) Å, whereas the isopropyl and methyl groups are oriented more equatorially, deviating by 0.71 (1) and -0.87 (1) Å, respectively.