Triterpene Compounds Research Articles

Bioassay-guided Isolation of Triterpene Compounds from Dillenia suffruticosa and Their Cytotoxic Activities Against Cancer Cells

Previous studies showed the ability of Dillenia suffruticosa to inhibit the growth of cancer cells by means of cell cycle arrest and apoptosis, thus validating the traditional use of the plant in treating cancer. Therefore, the present study was designed to isolate and elucidate the bioactive compounds responsible for the anticancer properties of D. suffruticosa extract. Bioassay-guided fractionation of the most potent fractions of DCM and EtOAc extract of D. suffruticosa was performed via column chromatography followed by purification using preparative HPLC. The structures of the isolated compounds were elucidated by NMR spectroscopy. Biological experiment by MTT assay and a series of column chromatography resulted in the isolation of three triterpene compounds. However, only the structure of compound (3) was confirmed as 1-isopropenyl-4α, 4β, 8, 10, 14-pentamethyl-icosahydro-cyclopenta[a]chrysene-3, 17-diol. Another two compounds were labelled as (1) and (2), which currently are unidentified due to unsuccessfulness in the full analysis of the spectroscopic data that enable the assignment of all protons, carbons, and confirmation of the structure. Compound (2) isolated from DCM extract of D. suffruticosa was most cytotoxic towards the selected cancer cells compared to the other two compounds and selected chemotherapeutic drugs, tamoxifen, and cisplatin. The ability of the isolated compounds to inhibit the growth of cancer cells indicates that these compounds are the bioactive constituents in D. suffruticosa that is mainly responsible for the cytotoxic activities. For this reason, these isolated compounds could be used as a means for the standardisation of herbal product from D. suffruticosa.

Production features of duckweed (Lemna L.) as an object of cultivation in integrated technologies

The issues of exploitation of duckweed communities, selection of the most promising species from the genus duckweed and determination of its productivity in the second zone of fish farming are considered. Duckweed is an aquatic, free-floating or submerged, mostly perennial higher plants, distributed throughout the Earth, with the exception of hot dry deserts and cold polar regions. Duckweed can withstand a large temperature range, from heat to frost, light-loving. It contains (in terms of dry matter): 20–38% protein, up to 5% fat, fiber, vitamins A, C and group B, anthocyanins, triterpene compounds, as well as iodine, iron, biogens, calcium, silicon, magnesium, heavy metals, trace elements. The experiments were carried out at the experimental production base of VNIIR in fiberglass baths of 6.0×0.7×0.6 m in the period from June 6 to the end of August, and observations of the state of the duckweed biotope in a reservoir with an area of 60 acres and an average depth of 1.6 m from the end of April to the third decade of September, The results obtained during the research allow us to conclude that the exploitation of duckweed biotopes (Lemna minor L.) in the second zone of fish farming has good prospects, which is expressed in obtaining about 50 tons/ha or more of biomass in raw form during the growing season. This makes it possible to create a raw material base for the production of duckweed feed and feed additives in the form of flour, powder, granulate, pastes, etc.

Triterpene Content in Flesh and Peel of Apples Grown on Different Rootstocks.

Advancements in rootstock breeding and selection have revolutionized the manner in which apples are grown throughout the world. Fruit tree breeding has typically focused on key horticultural characteristics. Even though agents with health benefits have been investigated more frequently during the recent years, information about the effect of different cultivation factors, such as the rootstock, on triterpene concentration is still lacking. The present study aimed to evaluate triterpene profiles and the quantitative composition of different parts of apple fruit that was grown on 17 various origin and vigor rootstocks. HPLC analyses of triterpenes in apple samples were performed. The highest total content of triterpenes (7.72 ± 0.39 mg/g) was found in peel samples of apples grown on the dwarf rootstock 62-396-B10®. Depending on the rootstock, apple peel samples accumulated 3.52 to 4.74 times more triterpene compounds than apple flesh samples. Ursolic acid was the predominant triterpene compound in apple peel and flesh samples. The highest content of ursolic acid (5.84 ± 0.29 mg/g) was found in peel samples of apples grown on the dwarf rootstock 62-396-B10®. Meanwhile, the lowest amount of ursolic acid (3.25 ± 0.16 mg/g) was found in apple peel samples grown on the dwarf rootstock Cepiland-Pajam®2. A proper match of a cultivar and a rootstock can program a fruit tree to grow larger amounts of higher quality, antioxidant-rich, and high-nutrition-value fruit.

Characterization of Triterpene Saponin Glycyrrhizin Transport by Glycyrrhiza glabra.

Glycyrrhizin (GL), a triterpene compound produced by Glycyrrhiza species, is a crucial pharmacologically active component of crude drugs. In contrast to the biosynthesis of GL in plants, little is known about GL transport and accumulation in plants. The transport mechanism of GL was characterized using cultured cells of Glycyrrhiza glabra. Cultured cells of G. glabra efficiently incorporated exogenously supplied GL. Proton pump inhibitors, such as probenecid and niflumic acid, as well as a protonophore (carbonylcyanide m-chlorophenylhydrazone), markedly inhibited GL uptake by cultured cells, whereas vanadate exhibited a moderate inhibition. Furthermore, GL transport by G. glabra tonoplast vesicles is dependent not on a H+-electrochemical gradient but MgATP and is markedly inhibited by vanadate. These results suggest that GL uptake by cultured cells is mediated by a H+-symporter in the plasma membrane and an ATP-binding cassette transporter, which has high specificity for the aglycone structure of GL on the tonoplast.

Obtaining biologically active substances from Amaranthus caudatus L. seeds in one technological cycle.

Nowadays, amaranth is a valuable multipurpose crop and a source of a number of very important biologically active substances. The aim of this study was to develop a comprehensive scheme for obtaining fatty oil, triterpenoids and lectin from the seeds of Amaranthus caudatus L. in one technological cycle. Two variants of the lectin and triterpene compound purification method from amaranth seeds were tested. It was determined that the extraction of triterpene compounds should be carried out after purification of the lectin from degreased seeds. The rationality of this sequence of technological operations is explained by the lability of the lectin and the insolubility in water of triterpene compounds from amaranth seeds. The study also presents a scheme for obtaining squalene from amaranth oil by chromatography on silica gel and proposes a more effective affinity sorbent for purification of the lectin. The use of such a sorbent also opens up the possibility of preserving other water-soluble substances from amaranth seeds. The physicochemical characteristics and carbohydrate specificity of the lectin are described and new data on the results of the interaction of lectin with human and animal erythrocytes are given. The obtained results are discussed in the light of the complex use of raw materials.

Molecular Mechanisms Underlying the Effects of Olive Oil Triterpenic Acids in Obesity and Related Diseases.

Dietary components exert protective effects against obesity and related metabolic and cardiovascular disturbances by interfering with the molecular pathways leading to these pathologies. Dietary biomolecules are currently promising strategies to help in the management of obesity and metabolic syndrome, which are still unmet medical issues. Olive oil, a key component of the Mediterranean diet, provides an exceptional lipid matrix highly rich in bioactive molecules. Among them, the pentacyclic triterpenic acids (i.e., oleanolic acid) have gained clinical relevance in the last decade due to their wide range of biological actions, particularly in terms of vascular function, obesity and insulin resistance. Considering the promising effects of these triterpenic compounds as nutraceuticals and components of functional foods against obesity and associated complications, the aim of our review is to decipher and discuss the main molecular mechanisms underlying these effects driven by olive oil triterpenes, in particular by oleanolic acid. Special attention is paid to their signaling and targets related to glucose and insulin homeostasis, lipid metabolism, adiposity and cardiovascular dysfunction in obesity. Our study is aimed at providing a better understanding of the impact of dietary components of olive oil in the long-term management of obesity and metabolic syndrome in humans.

Potential of Triterpenic Natural Compound Betulinic Acid for Neglected Tropical Diseases New Treatments.

Neglected tropical diseases are one of the most important public health problems in many countries around the world. Among them are leishmaniasis, Chagas disease, and malaria, which contribute to more than 250 million infections worldwide. There is no validated vaccine to prevent these infections and the treatments available are obsolete, highly toxic, and non-effective due to parasitic drug resistance. Additionally, there is a high incidence of these diseases, and they may require hospitalization, which is expensive to the public health systems. Therefore, there is an urgent need to develop new treatments to improve the management of infected people, control the spread of resistant strains, and reduce health costs. Betulinic acid (BA) is a triterpene natural product which has shown antiparasitic activity against Leishmania, Trypanosoma cruzi, and Plasmodium. Here, we review the main results regarding the in vitro and in vivo pharmacological activity of BA and its derivatives against these parasites. Some chemical modifications of BA have been shown to improve its activities against the parasites. Further improvement on studies of drug-derived, as well as structure–activity relationship, are necessary for the development of new betulinic acid-based treatments.

Total triterpene content, antioxidant activity and acute toxicity study of Securidaca longepedunculara Fresen

Plants are widely used in developing countries for traditional medicine. Knowledge of biological activities and phytochemistry is necessary for the safe use of these plants in traditional medicine. Securidaca longepedunculata is a medicinal plant whose roots are widely used in the treatment of several diseases. In this study the content of total triterpenes in leaf and root bark was assessed. The antioxidant activity by the ABTS method was evaluated as well as the effect of the extracts on lipid peroxidation of mice liver cell membranes. Acute toxicity was evaluated at the dose of 2000 mg / mL administered to the mouse. The results showed that the maximum values of the triterpenes contents of the leaves and of the root bark are 58 and 21 mg UAE / 100 mg respectively. Methanolic and chloroform extracts from leaves and root bark inhibited more than 50% of lipid peroxidation. The same extracts showed strong ABTS cation reduction activity. The leaf extract did not induce signs of acute toxicity in mice at a dose of 2000 mg / mL. The leaves of S. longepedunculata could be used in the management of pathologies associated with oxidative stress or which require biological properties relating to triterpene compounds.
 Keywords: Securidaca longepedunculata, triterpenes, peroxidation, toxicity

A novel natural PPARγ agonist, Gypenoside LXXV, ameliorates cognitive deficits by enhancing brain glucose uptake via the activation of Akt/GLUT4 signaling in db/db mice.

Targeting the PPARγ might be a potential therapeutic strategy for diabetes-associated cognitive decline (DACD). In this study, Gypenoside LXXV (GP-75), a dammarane-type triterpene compound isolated from Gynostemma pentaphyllum, was found to be a novel PPARγ agonist using a dual-luciferase reporter assay system. However, whether GP-75 has protective effects against DACD remains unknown. Interestingly, intragastric administration of GP-75 (40 mg/kg/day) for 12 weeks significantly attenuated the cognitive deficit in db/db mice. GP-75 treatment significantly improved the glucose tolerance and lipid metabolism, and suppressed neuroinflammation. Notably, GP-75 treatment dramatically increased the uptake of glucose by the brain, as detected by 18 F-FDG PET. Incubation of primary cortical neurons with GP-75 significantly increased 2-deoxyglucose uptake. In addition, GP-75 treatment markedly increased the p-Akt (Ser 473)/total Akt levels and the expression levels of PPARγ and GLUT4, while decreasing the levels of p-IRS-1 (Ser 616)/total IRS-1. Importantly, all of these protective effects mediated by GP-75 were abolished by cotreatment with the PPARγ antagonist, GW9662. However, GP-75-mediated PPARγ upregulation was not affected by coincubation with the phosphatidylinositol 3-kinase inhibitor, LY294002. Collectively, GP-75 might be a novel PPARγ agonist that ameliorates cognitive deficit by enhancing brain glucose uptake via the activation of Akt/GLUT4 signaling in db/db mice.

POSTHARVEST BIOCHEMICAL CHANGES IN APPLE SAMPLES

Apples are seasonal fruits, and it is relevant to prepare them adequately for storage and ensure proper storage conditions. In this study, we used ‘Rubin’ apple cultivar. We studied the qualitative and quantitative composition of phenolic and triterpenic compounds in the apple before placing them in the controlled atmosphere chambers and against at the end of the experiment, eight months later. Different concentrations of oxygen, carbon dioxide and nitrogen, constant temperature, relative humidity, and removal of endogenous ethylene were continually maintained. HPLC analysis showed that in the apple samples stored of variant II (5 % - O2, 1 % - CO2, 94 % - N2) conditions the total amount of triterpenes changed the least, dropped by 20 %. The study showed that the total content of phenolic compounds has increased in apple samples stored under controlled atmospheric conditions. The highest content of phenolic compounds increased in apple samples stored under IV (5 % - O2, 5 % - CO2, 90 % - N2) conditions. Evaluating the optimal storage parameters is useful to providing the consumers with apples that have a known and minimally altered phytochemical composition of phenolic compounds and triterpenes, which estimate the use of apples in the healthy food chain.

Asiatic Acid Alleviates Myocardial Ischemia-Reperfusion Injury by Inhibiting the ROS-Mediated Mitochondria-Dependent Apoptosis Pathway.

Myocardial ischemia-reperfusion injury (MIRI) is a major cause of heart failure in patients with coronary heart disease (CHD). Mitochondrial dysfunction is the crucial factor of MIRI; oxidative stress caused by mitochondrial reactive oxygen species (ROS) aggravates myocardial cell damage through the mitochondria-dependent apoptosis pathway. Asiatic acid (AA) is a type of pentacyclic triterpene compound purified from the traditional Chinese medicine Centella asiatica, and its protective pharmacological activities have been reported in various disease models. This study is aimed at investigating the protective effects of AA and the underlying mechanisms in MIRI. To achieve this goal, an animal model of MIRI in vivo and a cell model of oxygen-glucose deprivation/reperfusion (OGD/R) in vitro were established. The results show that AA exerts a protective effect on MIRI by improving cardiac function and reducing cardiomyocyte damage. Due to its antioxidant properties, AA alleviates mitochondrial oxidative stress, as evidenced by the stable mitochondrial structure, maintained mitochondrial membrane potential (MMP), and reduced ROS generation, otherwise due to its antiapoptotic properties. AA inhibits the mitogen-activated protein kinase (MAPK)/mitochondria-dependent apoptosis pathway, as evidenced by the limited phosphorylation of p38-MAPK and JNK-MAPK, balanced proportion of Bcl-2/Bax, reduced cytochrome c release, inhibition of caspase cascade, and reduced apoptosis. In conclusion, our study confirms that AA exerts cardiac-protective effects by regulating ROS-induced oxidative stress via the MAPK/mitochondria-dependent apoptosis pathway; the results provide new evidence that AA may represent a potential treatment for CHD patients.

Phytogenics From Sage and Lemon Verbena Promote Growth, Systemic Immunity and Disease Resistance in Atlantic Salmon (Salmo salar)

The transcriptomic response of the head kidney, the main lymphohematopoietic tissue of the body, was evaluated in Atlantic salmon (Salmo salar) smolts fed a functional feed containing a phytogenic rich in verbascoside and triterpenic compounds like ursolic acid. Fish (initial body weight = 55.0 ± 0.1 g) were fed two experimental diets (40% crude protein, 22% crude fat; 21.6 MJ/kg gross energy) that only differed in the phytogenic content (0.1% inclusion). Each diet has six replicates and was tested over a period of 133 days. The tested zootechnical feed additive a medicinal plant leaf extract (MPLE) obtained from sage (Salvia officinalis) and lemon verbena (Lippia citriodora). At the end of the trial, smolts fed the MPLE diet were heavier than their congeners from the control group (271.5 ± 7.9 g vs. 240.2 ± 19.3 g, respectively; P < 0.05). Feed conversion ratio (FCR) values in fish fed the control diet were higher than those in fish fed the MPLE diet (FCRcontrol diet = 1.27 ± 0.08 vs. FCR0.1% MPLE diet = 1.08 ± 0.05; P < 0.05). The immunomodulatory properties of the functional diet were evaluated by means of an in vivo challenge with Aeromonas salmonicida subsp. salmonicida (1 × 107 CFU mL–1). The microarray analysis of head kidney samples from both dietary groups revealed 1,178 differentially expressed genes (802 upregulated and 376 downregulated). Among them, several biological processes related to immunity were identified in fish fed the MPLE diet (i.e., interferon-gamma-mediated signaling pathway, antigen processing and presentation of peptide antigen via MHC class II, autophagy, regulation of i-kappaB kinase/NF-kappaB signaling, and leukocyte activation). Results from the bacterial challenge showed that survival rates were higher in smolts from the MPLE group (90.6 ± 6.4%) in comparison to the control group (60.7 ± 13.5%), confirming the functional benefits of the phytogenic in terms of host’s immunity and disease resistance. Biological processes such as cytoskeleton organization and regulation of cellular protein metabolic process detected in fish fed the MPLE diet supported the metabolic changes related to increased somatic growth promoted. The present findings showed that the inclusion at 0.1% of the tested MPLE obtained from sage and lemon verbena in diets for Atlantic salmon smolts promoted somatic growth, and enhanced their systemic immune response and reduced mortality when fish were challenged with A. salmonicida cumulative, the causative agent of furunculosis in salmonids.

Chemical composition analysis, antioxidant activity, and target cell‐based screening of the potential active components in jujube and its fermented product

In this study, the chemical constituents of jujube and jujube fermentation broth were compared by chromatography tandem high-resolution mass spectrometry for the first time. A total of 68 compounds were detected, and six of them were quantified. The results showed that rutin was hydrolyzed and converted into quercetin during the fermentation process. Further, the antioxidant experiments in vitro were carried out, and the IC50 value of the fermentation broth was lower than that of the jujube extract. Twenty-three potential bioactive components from jujube samples were identified by a target cell-based screening method, and triterpenic acid compounds exhibited high cell binding property. These results will help to understand the different biological activities of jujube and its fermented products and will benefit the discovery of new functional components.

Chemical Profile of Lipophilic Fractions of Different Parts of Zizyphus lotus L. by GC-MS and Evaluation of Their Antiproliferative and Antibacterial Activities.

Zizyphus lotus L. is a perennial shrub particularly used in Algerian folk medicine, but little is known concerning the lipophilic compounds in the most frequently used parts, namely, root bark, pulp, leaves and seeds, which are associated with health benefits. In this vein, the lipophilic fractions of these morphological parts of Z. lotus from Morocco were studied by gas chromatography–mass spectrometry (GC–MS), and their antiproliferative and antimicrobial activities were evaluated. GC–MS analysis allowed the identification and quantification of 99 lipophilic compounds, including fatty acids, long-chain aliphatic alcohols, pentacyclic triterpenic compounds, sterols, monoglycerides, aromatic compounds and other minor components. Lipophilic extracts of pulp, leaves and seeds were revealed to be mainly composed of fatty acids, representing 54.3–88.6% of the total compounds detected. The leaves and seeds were particularly rich in unsaturated fatty acids, namely, (9Z,12Z)-octadeca-9,12-dienoic acid (2431 mg kg−1 of dry weight) and (9Z)-octadec-9-enoic acid (6255 mg kg−1 of dry weight). In contrast, root bark contained a high content of pentacyclic triterpenic compounds, particularly betulinic acid, accounting for 9838 mg kg−1 of dry weight. Root bark extract showed promising antiproliferative activity against a triple-negative breast cancer cell line, MDA-MB-231, with a half-maximal inhibitory concentration (IC50) = 4.23 ± 0.18 µg mL−1 of extract. Leaf extract displayed interesting antimicrobial activity against Escherichia coli, methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermis, presenting minimum inhibitory concentration (MIC) values from 1024 to 2048 µg mL−1 of extract. Our results demonstrate that Zizyphus lotus L. is a source of promising bioactive components, which can be exploited as natural ingredients in pharmaceutical formulations.

Apple Fruit Growth and Quality Depend on the Position in Tree Canopy.

Modern apple orchard systems should guarantee homogeneity of fruit internal and external qualities and fruit maturity parameters. However, when orchards reach productive age, a variation of these parameters takes place and mostly it is related to uneven light distribution within the tree canopy. The aim of the study was to evaluate the canopy position’s effect on fruit internal and external quality parameters. This is the first study where all the main fruit quality and maturation parameters were evaluated on the same trees and were related to the light conditions and photosynthetic parameters. Four fruit positions were tested: top of the apple tree, lower inside part of the canopy, and east and west sides of the apple tree. Fruit quality variability was significant for fruit size, blush, colour indices, total sugar content, dry matter concentration, accumulation of secondary metabolites and radical scavenging activity. Fruit position in the canopy did not affect flesh firmness and fruit maturity parameters such as the starch index, Streif index and respiration rate. At the Lithuanian geographical location (55°60′ N), significantly, the highest fruit quality was achieved at the top of the apple tree. The tendency was established that apple fruits from the west side of the canopy have better fruit quality than from the east side and it could be related to better light conditions at the west side of the tree. Inside the canopy, fruits were distinguished only by the higher accumulation of triterpenic compounds and higher content of malic acid. Light is a main factor of fruit quality variation, thus all orchard management practices, including narrow two-dimensional tree canopies and reflecting ground covers which improve light penetration through the tree canopy, should be applied.

The Role of Cyclodextrins in the Design and Development of Triterpene-Based Therapeutic Agents.

Triterpenic compounds stand as a widely investigated class of natural compounds due to their remarkable therapeutic potential. However, their use is currently being hampered by their low solubility and, subsequently, bioavailability. In order to overcome this drawback and increase the therapeutic use of triterpenes, cyclodextrins have been introduced as water solubility enhancers; cyclodextrins are starch derivatives that possess hydrophobic internal cavities that can incorporate lipophilic molecules and exterior surfaces that can be subjected to various derivatizations in order to improve their biological behavior. This review aims to summarize the most recent achievements in terms of triterpene:cyclodextrin inclusion complexes and bioconjugates, emphasizing their practical applications including the development of new isolation and bioproduction protocols, the elucidation of their underlying mechanism of action, the optimization of triterpenes’ therapeutic effects and the development of new topical formulations.

Remediation of zearalenone mycotoxin contamination in rumen fluid by phytochemical compounds of Zataria multiflora.

Zearalenone (ZEA), which is one of the most prevalent wheat and corn seeds mycotoxins causes acute and chronic toxicities in ruminants, poultry, and aquatic animals. Among commercial toxin binders, only a few active charcoals have the significant ability to adsorb ZEA contamination; nevertheless, active charcoal is not considered a sound additive by the feed industry. This study aimed to screen and identify the ZEA-degradation compounds of the Zataria multiflora (Shirazi thyme) in the cattle rumen fluid. In this investigation, essential oil and different extracts (n-hexane, ethyl acetate, and methanol) of the aerial part of Shirazi thyme (at three concentrations of 0.5, 1, and 2 mg/ml) were screened to reduce ZEA contamination conditions (2 µg/ml) in rumen fluid. ZEA-content was analyzed by high-performance liquid chromatography (HPLC) with a fluorescence detector. In addition, Shirazi thyme phytochemical compounds responsible for eliminating ZEA were localized by HPLC-based activity profiling and then identified by mass spectrometry (LC-MS). Both n-hexane and methanol extracts of Z. multiflora, considerably remediated ZEA (63-78%) from rumen fluid. According to HPLC-based activity profiling of Z. multiflora extract and LC-MS analysis, two triterpene compounds, including ursolic and oleanolic acids were introduced as ZEA degradation agents. Z. multiflora could be recommended as a new botanical source, and ursolic and oleanolic acids could be introduced as new phytochemical compounds that degrade ZEA.

Natural and Semisynthetic Triterpenes from Combretum leprosum Mart. with Antiplasmodial Activity

Malaria is responsible for thousands of deaths each year. Currently, artemisinin combination therapy (ACT) is used as first-choice medication against the disease. However, the emergence of resistant strains prompts the search for alternative compounds. The present study aimed to investigate the antiplasmodial activities of natural triterpenes (compounds 1 and 2), and semisynthetic derivatives 1a, 1b, 1c, and 1d. Antiplasmodial assays were carried out using the SYBR Green technique, whereas cytotoxicity was evaluated by the MTT (3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide) method. Hemolytic assays were performed on human erythrocytes. An in silico analysis of the compounds against PfENR (Plasmodium falciparum 2-trans-enoyl-reductase) was carried out by molecular docking. Experiments with 1, and its derivatives against P. falciparum showed that 1a was very similar in terms of biological activity to compound 1 (half maximal inhibitory concentration (IC50) ca. 4 μM), whereas 1b, 1c, and 1d had reduced antiplasmodial activities (IC50 between 8-103 μM). The selectivity indexes of 1 and 1d for HepG2, and Vero cells were > 10. Docking results partially agreed with the in vitro experiments, with 1 and 1c having the best and worst affinities with PfENR, respectively. In conclusion, the results showed that 1 and 1d may serve as biotechnological tools in the development of antimalarial drugs.

EFFECT OF AN EXTRAGENT ON THE COMPOSITION OF THE LIPOPHILIC CONSTITUENTS OF THE EXTRACTS OF RHODIOLA ROSEA L. AND ON THE EXTRACTS ACTIVITY

The composition of the plant Rhodiola rosea L. lipophylic substances was studied. Acidic and neutral components were identified by gas-chromatography-mass-spectrometry. With methyl-tert-butyl ether (MTBE) as an extractant instead of the volatile solvent diethyl ether, lipophylic extract was obtained. Methyl-tert-butyl ether used as an extraction solvent for raw materials has all the advantages of diethyl ether, being free of its disadvantages. It does not form peroxides or produce elevated partial gas pressure due to its higher boiling point. As a result, comparison with databases identified some triterpene, phenolic and aliphatic acids with chain lengths 12 to 30 carbon atoms, including saturated, unsaturated, and dibasic acids. In addition to the components known from the literature, more than 50 triterpene and aliphatic compounds were detected in the unsaponifiable residue and acidic fractions for the first time. The hexane extract and the product obtained by the stepwise extraction of MTBE after the extraction of low-polarity compounds with hexane were investigated in a similar way. In the case of an extract obtained using MTBE after the extraction of low-polarity components with hexane, there was shown a more efficient extraction of benzoic and cinnamic acids compared to the exhaustive extraction of MTBE. These acids are absent in the hexane extract. Ethanol extraction was also carried out to test bioactivity: exhaustive and after hexane and MTBE extraction. Extracts obtained using MTBE and ethanol showed anti-virus activity against Ebola psevdovirus.

Novel betulin dicarboxylic acid ester derivatives as potent antiviral agents: Design, synthesis, biological evaluation, structure-activity relationship and in-silico study.

The search for new methods of antiviral therapy is primarily focused on the use of substances of natural origin. In this context, a triterpene compound, betulin 1, proved to be a good starting point for derivatization. Thirty-eight betulin acid ester derivatives were synthetized, characterized, and tested against DNA and RNA viruses. Several compounds exhibited 4- to 11-fold better activity against Enterovirus E (compound 5 EC50: 10.3μM) and 3- to 6-fold better activity against Human alphaherpesvirus 1 (HHV-1; compound 3c EC50: 17.2μM). Time-of-addition experiments showed that most of the active compounds acted in the later steps of the virus replication cycle (e.g., nucleic acid/protein synthesis). Further in-silico analysis confirmed in-vitro data and demonstrated that interactions between HHV-1 DNA polymerase and the most active compound, 3c, were more stable than interactions with the parent non-active betulin 1.