Phytochemical and Micro-Morphological Characterization of Atraphaxis pyrifolia Bunge Growing in the Republic of Kazakhstan.

Atraphaxis pyrifolia is a native species of Central Asia, known for curing several disorders. The species has little knowledges about its chemical composition and any information about its morphological characteristics despite its importance in traditional Asian medicine. This is one of the first approaches to the phytochemical and morphological characterization of this species. Micro-morphology was performed on the stem, and leaf parts of this plant to profile the morpho-anatomical characters using brightfield, fluorescence, polarized and scanning electron microscopy. Leaves were extracted with hexane and methanol. The hexane extract was analyzed using GC-MS analysis revealing the major presence of γ-sitosterol and nonacosane. The methanolic extract was submitted to Vacuum Liquid Chromatography and Sephadex LH-20. HPTLC, HR-ESI-MS and NMR techniques were used to identify the main compounds. Four glycosylated flavonoids were isolated: 8-O-acetyl-7-O-methyl-3-O-α-l-rhamnopyranosylgossypetin (Compound 1), and 7-O-methyl-3-O-α-l-rhamnopyranosylgossypetin (Compound 3), and two other compounds reported for the first time in the literature (Compounds 2 and 4). The findings presented herein furnish pertinent information essential for the identification and authentication of this medicinal plant. Such insights are invaluable for facilitating robust quality control measures and serve as a foundational framework for subsequent endeavours in metabolic, pharmacological, and taxonomical analyses.

Ultrastructural, Energy-Dispersive X-ray Spectroscopy, Chemical Study and LC-DAD-QToF Chemical Characterization of Cetraria islandica (L.) Ach.

The lichen Cetraria islandica (L.) Ach. has been used in traditional and modern medicines for its many biological properties such as immunological, immunomodulating, antioxidant, antimicrobial, and anti-inflammatory activities. This species is gaining popularity in the market, with interest from many industries for selling as medicines, dietary supplements, and daily herbal drinks. This study profiled the morpho-anatomical features by light, fluorescence, and scanning electron microscopy; conducted an elemental analysis using energy-dispersive X-ray spectroscopy; and phytochemical analysis was performed using high-resolution mass spectrometry combined with a liquid chromatography system (LC-DAD-QToF) of C. islandica. In total, 37 compounds were identified and characterized based on comparisons with the literature data, retention times, and their mass fragmentation mechanism/s. The identified compounds were classified under five different classes, i.e., depsidones, depsides, dibenzofurans, aliphatic acids, and others that contain simple organic acids in majority. Two major compounds (fumaroprotocetraric acid and cetraric acid) were identified in the aqueous ethanolic and ethanolic extracts of C. islandica lichen. This detailed morpho-anatomical, EDS spectroscopy, and the developed LC-DAD-QToF approach for C. islandica will be important for correct species identification and can serve as a useful tool for taxonomical validation and chemical characterization. Additionally, chemical study of the extract of C. islandica led to isolation and structural elucidation of nine compounds, namely cetraric acid (1), 9'-(O-methyl)protocetraric acid (2), usnic acid (3), ergosterol peroxide (4), oleic acid (5), palmitic acid (6), stearic acid (7), sucrose (8), and arabinitol (9).

Regioselective Claisen-Schmidt Adduct of 2-Undecanone from Houttuynia cordata Thunb as Insecticide/Repellent against Solenopsis invicta and Repositioning Plant Fungicides against Colletotrichum fragariae.

The U.S. Department of Agriculture (USDA) has established research programs to fight the phytopathogen Colletotrichum fragariae and the invasive red imported fire ant, Solenopsis invicta. C. fragariae is known to cause anthracnose disease in fruits and vegetables, while S. invicta is known for its aggressive behavior and painful stings and for being the cause of significant damage to crops, as well as harm to humans and animals. Many plants have been studied for potential activity against C. fragariae and S. invicta. Among the studied plants, Houttuynia cordata Thunb has been shown to contain 2-undecanone, which h is known for its antifungal activity against Colletotrichum gloesporioides. Based on the mean amount of sand removed, 2-undecanone showed significant repellency at 62.5 µg/g, similar to DEET (N,N-diethyl-meta-toluamide), against S. invicta. The 2-Undecanone with an LC50 of 44.59 µg/g showed toxicity against S. invicta workers. However, neither H. cordata extract nor 2-undecanone had shown activity against C. fragariae despite their known activity against C. gloesporioides, which in turn motivates us in repositioning 2-undecanone as a selected candidate for a Claisen-Schmidt condensation that enables access to several analogs (2a-f). Among the prepared analogs, (E)-1-(3-methylbenzo[b]thiophen-2-yl)dodec-1-en-3-one (2b) and (E)-1-(5-bromothiophen-2-yl)dodec-1-en-3-one (2f) showed promising activity against C. fragariae, revealing a distinctive structural activity relationship (SAR). The generated analogs revealed a clear regioselectivity pattern through forming the C=C alkene bond at position C-1. These data open the window for further lead optimization and product development in the context of managing C. fragariae and S. invicta.

Pharmacological Properties of Four Plant Species of the Genus Anabasis, Amaranthaceae.

The genus Anabasis is a member of the family Amaranthaceae (former name: Chenopodiaceae) and includes approximately 102 genera and 1400 species. The genus Anabasis is one of the most significant families in salt marshes, semi-deserts, and other harsh environments. They are also renowned for their abundance in bioactive compounds, including sesquiterpenes, diterpenes, triterpenes, saponins, phenolic acids, flavonoids, and betalain pigments. Since ancient times, these plants have been used to treat various diseases of the gastrointestinal tract, diabetes, hypertension, and cardiovascular diseases and are used as an antirheumatic and diuretic. At the same time, the genus Anabasis is very rich in biologically active secondary metabolites that exhibit great pharmacological properties such as antioxidant, antibacterial, antiangiogenic, antiulcer, hypoglycemic, hepatoprotective, antidiabetic, etc. All of the listed pharmacological activities have been studied in practice by scientists from different countries and are presented in this review article to familiarize the entire scientific community with the results of these studies, as well as to explore the possibilities of using four plant species of the genus Anabasis as medicinal raw materials and developing medicines based on them.

Component Composition and Antimicrobial Activity of CO2 Extract of Portulaca oleracea, Growing in the Territory of Kazakhstan.

In the medicine of many countries, the use of herbal healing agents included a significant contribution to improving human health and well-being. Many antibiotics have been widely used to treat infectious diseases caused by various pathogenic bacteria. However, increased multidrug resistance has led to increased severity of diseases caused by bacterial pathogens. Bacteria remain the main causative agents of diseases that cause human death, even in the present day. This cause prompted scientists to investigate alternative new molecules against bacterial strains. The significant interest for the study is Portulaca oleracea L. (family Portulacaceae), a widespread annual plant used in folk medicine. Thus, the production and study of CO2 extract of Portulaca oleracea is an actual problem. Methods. Raw materials were collected from Almaty and Zhambyl regions (Southeast and South Kazakhstan) in phase flowering. Portulaca oleracea herb's CO2 extract was obtained by subcritical carbon dioxide extraction (installation of carbon dioxide flow-through extraction- 5L). The Wiley 7th edition and NIST'02 library were used to identify the mass spectra obtained. The antimicrobial activity study was conducted by the micromethod of serial dilution and disco-diffuse method. Standard test strains of microorganisms were used: Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 6538-P, Candida albicans ATCC 10231, and Escherichia coli ATCC 8739. Results. The use of carbon dioxide extraction (further CO2 extract) is a promising direction of obtaining total medicinal substances containing biologically active substances, from fractions of volatile esters of various composition and functional purpose until a fraction of fatty acids and fat-soluble vitamins. In the current study, we obtained CO2 extract at subcritical conditions from aboveground organs of Portulaca oleracea and investigated the component composition for the first time. From 41 to 66 components were identified in the composition of Portulaca oleracea's CO2 extract. Studies of antimicrobial activity showed that CO2 extract of Portulaca oleracea had the expressed effect against clinically significant microorganisms such as Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Candida albicans. Conclusions. This study showed that CO2 extract of Portulaca oleracea's raw material contained biological active compounds exhibiting a significant antimicrobial effect.

Study of Cold-Pressed Tobacco Seed Oil Properties by Gas Chromatography Method.

A special place among vegetable oils was occupied by natural tobacco oil. Natural tobacco oil in folk medicine is used as an antiseptic and antibacterial agent. To determine the possible alternative use of tobacco, the seeds representing Kazakhstan tobacco cultivars, extracted from ground Nicotiana tabacum seeds, were investigated by using the cold press. The quality of the oil was assessed in terms of free fatty acid content. The percentage oil yield was 36.75 ± 0.50%. Tobacco seed oil is highly unsaturated, nonacidic, and would require little purification. The oil can be used for the production of soap, antiwrinkle cream for the face, hair shampoo, shoe cream, and as a high-resolution base oil for perfumes and light industry and can be commercialized due to its high oil yield, for use as anti-inflammatory drugs.

Isolation of Chemical Compounds and Essential Oil from Agrimonia asiatica Juz. and Their Antimicrobial and Antiplasmodial Activities.

Agrimonia asiatica is a perennial plant with deep green color and covered with soft hairs and has a slightly aromatic odor. This genus Agrimonia has been used in traditional medicines of China, Greece, and European countries. It was mainly used as a haemostatic, a tonic for asthenia, and an astringent for diarrhea. Agrimony is part of the division Magnoliophyta; class is represented by order Rosales, family Rosaceae, of the genus Agrimonia. Family Rosaceae-or pink eels-is one of the largest families of flowering plants, including about 100 genera and 3000 species. Rosaceae is common in almost all areas of the globe where flowering plants can grow, but most of them are concentrated in the temperate and subtropical zones of the Northern Hemisphere. Phytochemical investigation on ethanolic extract of A. asiatica led to isolation of four flavonoid derivatives (kaempferol-3-glycoside, quercetin-3-O-α-arabinofuranosyl-ß-D-galactopyranoside, 3-O-kaempherol 2,3-di-O-acetyl-4-O-(cis-p-coumaroyl)-6-O-(trans-p-coumaroyl)-ß-D-glucosopyranoside, and catechin) alongside of sucrose. All the extracts, fractions, and isolated compounds were tested for antimicrobial and antiplasmodial activities. We also studied the chemical composition of essential oil obtained from the aerial part of A. asiatica. The essential oil constituents from the aerial part of A. asiatica were obtained using a steam-distillation method in wild growing conditions in Kazakhstan. The essential oil extracted from the aerial part of the plant was analyzed by gas chromatography-mass spectroscopy and its major components amounting to 100% were found to be ß-selinene (36.370%), α-panasinsene (21.720%), hexadecanoic acid (7.839%), and 1,2-nonadiene (6.199%). Neither the extract nor the isolated compounds showed antimicrobial and antiplasmodial activities.

General Toxicity and Antifungal Activity of a New Dental Gel with Essential Oil from Abies Sibirica L.

BACKGROUND The aim of this study was to analyze the antifungal activity and the general toxicity of a new dental gel containing essential oil from the tree Abies sibirica L., which grows in the Republic of Kazakhstan. MATERIAL AND METHODS The essential oil from Abies sibirica L. was obtained by microwave heating method using the STARTE Microwave Extraction System. Adjutants used to prepare the oil were carbomer 974P, glycerin, polysorbate 80, xylitol, triethanolamine, and purified water, all allowed for medical usage. The antifungal activity of the essential oil was assessed by monitoring the optical density of Candida albicans in a microplate reader. The safety was determined by analyzing the acute and subacute toxicity. RESULTS The essential oil obtained by the microwave heating method revealed a higher antifungal activity in comparison with the essential oil obtained by the steam distillation method. No obvious changes were detected in guinea pigs following cutaneous application of the gel. Enteral administration of the essential oil caused minimal functional and histological changes in mice after 4 weeks. The new harmless dental gel containing pine oil from Abies sibirica L. was provided for the purposes of this particular clinical research. CONCLUSIONS The high antifungal activity of the gel is the basis for more in-depth studies on its safety and pharmacological activity.

Phytochemical studies of white mulberry fruits (Morus alba L.).

Medicinal preparations made from plant materials have been widely used for many years due to their high pharmacological efficacy and safety of use. Therefore, a study of white mulberry fruits (Morus alba L.) for the content of substances is very important for the pharmaceutical industry such as flavonoids, alkaloids, polysaccharides, minerals, vitamins, and amino acids. White mulberry has a wide distribution area around the world, including in Kazakhstan, especially in the southern regions of the country (Almaty, Zhambyl, and Turkestan regions). The composition of the fruits of this plant is significantly influenced by the area where the trees grow, and therefore, the establishment of a specific composition of biologically active substances is very important. In the course of this study, such methods as gas chromatography were used-mass spectrometry of an extract obtained using carbon dioxide under subcritical conditions, atomic absorption, gravimetric, and spectrophotometric methods. As a result, for the first time in Kazakhstan, the composition of white mulberry fruits (Morus alba L.), namely, biologically active substances, has been identified, such as alkaloids, flavonoids, vitamins, macro- and microelements, and amino acids and fatty acids; in addition, the percentage composition of the above compounds has been determined. The results of the study show a comparative analysis of the component composition of white mulberry fruits (Morus alba L.) in various areas of tree growth, including outside of Kazakhstan. The obtained data testify to the great possibilities of using this raw material in medicine, pharmacology, and the food industry.

GC/MS chemical profiling and isolation of secondary metabolites from Leontice ewersmannii.

GC/MS chemical profiling of the aerial parts of Leontice ewersmannii revealed the presence of various bioactive compounds of which 20 compounds were in n-hexane fraction and 3 compounds in basic DCM fraction. Among the identified compounds alkaloids, fatty acids and their esters, fatty alcohols, hydrocarbons, and sterol were detected. Phytochemical investigation of the aerial parts of L. ewersmannii led to isolation of 17 compounds including 1-heptacosanol (1), phytol (2), lupenone (3), palmitic acid (4), oleic acid (5), stigmasterol (6), stigmast-7-en-3-ol (7), methyl palmitate (8), methyl linoleate (9), butyl palmitate (10), butyl linoleate (11), dimethyl dodecanedioate (12), methyl cerebronate (13), ß-sitosterol (14), ß-sitosterol 3-O-ß-glucopyranoside (15), sophoridine (16) and camoensine (17). The structures of the isolated compounds were determined by 1D NMR, HR-ESI-MS, and GC-MS. All methyl esters of fatty acids are possible artifacts during extraction. Additionally, the antimicrobial activity of the total extract and different fractions was screened, and they exhibited no inhibition of the growth at the tested concentration ranging from 8 to 200 µg/mL.

Prevalence of chronic kidney disease in Kazakhstan: evidence from a national cross-sectional study.

To date, there have been no large-scale national studies of the prevalence of chronic kidney disease in Kazakhstan. It includes the research based on the analysis of the estimated glomerular filtration rate (eGFR). The aim of this study was to investigate the population prevalence of CKD and associated risk factors in Kazakhstan. The cross-sectional study consisted of a nationally representative sample of n = 6 720 adults aged 18 to 69 from 14 regions and 3 major cities in Kazakhstan. The study covered the period from October 2021 to May 2022. The WHO STEPS questionnaire was used for the survey. For the diagnosis of CKD, creatinine levels in collected blood samples were measured to assess eGFR. Demographic characteristics were collected and studied. The total and adjusted prevalence of factors associated with the presence of CKD were calculated and analysed using logistic regression. 73.5% (n = 4940) of participants had normal eGFR, while 25.2% (n = 1695) had mild CKD (eGFR = 60-89 mL/min/1.7 m2). The overall prevalence of CKD with eGFR < 60 ml/min/1.7 m2 was 1.3% (n = 85), of which 0.2% (n = 15) had eGFR < 45 ml/min/1.7 m2. A mild degree of CKD was most often determined in residents of the East Kazakhstan region in 10.4%, and in 7.8-8.0% of cases. The majority of CKD patients was detected in the East Kazakhstan region and Almaty city, 15.3% and 10.6% of cases respectively. In mild and CKD with GFR < 60 ml/min/1.7 m2, the age of participants was 50-69 years in 61.5% and 78.8% of cases, respectively (p < 0.001). In addition to the association with the place of residence, a statistically significant relationship was found between the risk of developing CKD and underweight (OR 1.43, 95% CI (1.09-1.88), p < 0.001), as well as the presence of obesity (OR 1.24, 95% CI (0.99-1.53), p = 0.04). We observed the prevalence of CKD with eGFR < 60 ml/min/1.7 m2 at the level of 1.3%. However, a fairly large part of study participants had a mild CKD (25.2%). The results of this study can be used for the optimization of the doctors workload and the timely provision of care to patients with CKD.

Unraveling the Complex Web of Mechanistic Regulation of Versatile NEDD4 Family by Non-Coding RNAs in Carcinogenesis and Metastasis: From Cell Culture Studies to Animal Models.

Discoveries related to an intriguing feature of ubiquitination have prompted a detailed analysis of the ubiquitination patterns in malignant cells. How the "ubiquitinome" is reshaped during multistage carcinogenesis has garnered significant attention. Seminal studies related to the structural and functional characterization of NEDD4 (Neuronal precursor cell-expressed developmentally downregulated-4) have consolidated our understanding at a new level of maturity. Additionally, regulatory roles of non-coding RNAs have further complicated the complex interplay between non-coding RNAs and the members of NEDD4 family. These mechanisms range from the miRNA-mediated targeting of NEDD4 family members to the regulation of transcriptional factors for a broader range of non-coding RNAs. Additionally, the NEDD4-mediated degradation of different proteins is modulated by lncRNAs and circRNAs. The miRNA-mediated targeting of NEDD4 family members is also regulated by circRNAs. Tremendous advancements have been made in the identification of different substrates of NEDD4 family and in the comprehensive analysis of the molecular mechanisms by which various members of NEDD4 family catalyze the ubiquitination of substrates. In this review, we have attempted to summarize the multifunctional roles of the NEDD4 family in cancer biology, and how different non-coding RNAs modulate these NEDD4 family members in the regulation of cancer. Future molecular studies should focus on the investigation of a broader drug design space and expand the scope of accessible targets for the inhibition/prevention of metastasis.

Investigation of CO2 Extract of Portulaca oleracea for Antioxidant Activity from Raw Material Cultivated in Kazakhstan.

Medicinal plants remain as an important resource in the fight against many diseases, especially in developing countries. Antioxidants are substances capable of delaying, retarding, and preventing the oxidation of lipids or substances that delay or prevent free radical reactions during lipid oxidation. Natural antioxidants such as ascorbic acid, tocopherol, phenolic compounds, and flavonoids are a safe alternative to chemical antioxidants. In present work, results of antioxidant activity of raw materials from the cultivated plant Portulaca oleracea are presented. The extraction time was optimized to 780 minutes; the yield of extractive substances was 1.25% in the production of CO2 extract under subcritical conditions. For the first time, the antioxidant activity of Portulaca oleracea CO2 extract was determined by the amperometric method. Gas chromatography-mass spectrometry (GC-MS) chemical analysis of Portulaca oleracea CO2 extract dissolved in hexane revealed 37 components, including a complex mixture of aldehydes, alkanes, alkenes, esters, diterpenes, steroids, vitamin E, and carbohydrates. The investigation results showed that the Portulaca oleracea CO2 extract was promising for pharmaceutical, cosmetic, and food industries and had great potential for the prevention and treatment of diseases caused by oxidative stress.

Regulation of RUNX proteins by long non-coding RNAs and circular RNAs in different cancers.

RUNX proteins have been shown to behave as "double-edge sword" in wide variety of cancers. Discovery of non-coding RNAs has played linchpin role in improving our understanding about the post-transcriptional regulation of different cell signaling pathways. Several new mechanistic insights and distinct modes of cross-regulation of RUNX proteins and non-coding RNAs have been highlighted by recent research. In this review we have attempted to provide an intricate interplay between non-coding RNAs and RUNX proteins in different cancers. Better conceptual and mechanistic understanding of layered regulation of RUNX proteins by non-coding RNAs will be helpful in effective translation of the laboratory findings to clinically effective therapeutics.

Chemical and biological studies on Cichorium intybus L.

Cichorium intybus L. (Asteraceae family) is a world-wide grown plant known as chicory. In traditional medicine, this plant is used as diuretic, anti-inflammatory, digestive, cardiotonic and liver tonic. Chromatographic purification of the supercritical fluid extract of aerial parts of C. intybus on silica gel column led to isolation of three compounds: new compound, 28ß-hydroxytaraxasterol (I), and two known compounds usnic acid (II) and ß-sitosterol (III). Purification of the ethanolic extract of aerial parts of this plant on silica gel column chromatography yielded four compounds: 1,3-dioleylglycerate (IV), sitoindoside II (V), 11ß-13-dihydrolactucin (VI) and ß-sitosterol-3-O-glucoside (VII). The structures of the isolated compounds were determined by their 1D, 2D NMR and MS spectral data. All the fractions and isolated compounds were tested for cannabinoid and opioid receptor binding, as well as antibacterial, antifungal and antimalarial activities. Compound I showed moderate activity (60.5% displacement) towards CB1 receptor.

Isolation and Biological Evaluation of Prenylated Flavonoids from Maclura pomifera.

Phytochemical analysis of the ethanolic extract of Maclura pomifera fruits yielded four new compounds (I-IV) along with eleven known compounds (V-XV). The crude extract exhibited significant activity towards cannabinoid receptors (CB1: 103.4% displacement; CB2: 68.8% displacement) and possibly allosteric interaction with δ and µ opioid receptors (-49.7 and -53.8% displacement, resp.). Compound I was found to be possibly allosteric for κ and µ opioid receptors (-88.4 and -27.2% displacement, resp.) and showed moderate activity (60.5% displacement) towards CB1 receptor. Compound II exhibited moderate activity towards cannabinoid receptors CB1 and CB2 (47.9 and 42.3% displacement, resp.). The known compounds (V-VIII) exhibited prominent activity towards cannabinoid receptors: pomiferin (V) (IC50 of 2.110 and 1.318 µM for CB1 and CB2, resp.), auriculasin (VI) (IC50 of 8.923 µM for CB1), warangalone (VII) (IC50 of 1.670 and 4.438 µM for CB1 and CB2, resp.), and osajin (VIII) (IC50 of 3.859 and 7.646 µM for CB1 and CB2, resp.). The isolated compounds were also tested for inhibition of human monoamine oxidase-A and monoamine oxidase-B enzymes activities, where all the tested compounds showed fewer inhibitory effects on MAO-A compared to MAO-B activities: auriculasin (VI) (IC50 of 1.91 and 45.98 µM for MAO-B and MAO-A, resp.).