Cholinesterase and Tyrosinase Inhibitory Potential and Antioxidant Capacity of Lysimachia verticillaris L. and Isolation of the Major Compounds.

OBJECTIVES: The scope of the present study was to specify the therapeutic potential for neurodegenerative diseases through evaluating cholinesterase and tyrosinase (TYR) inhibitory and antioxidant activity of Lysimachia verticillaris (LV), and to isolate the major compounds considering the most active fraction. MATERIALS AND METHODS: The methanol extract (ME) of LV and the chloroform, ethyl acetate (EtOAC), and aqueous fractions obtained from it were used for biological activity and isolation studies. The ME and all fractions were tested for their acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and TYR inhibitory and antioxidant potentials using ELISA microtiter assays. Seven major compounds were isolated from the active EtOAC fraction by semi-preparative high performance liquid chromatography. The structures of the compounds were elucidated by several spectroscopic methods. RESULTS: Marked AChE inhibitory activity was observed in the EtOAC fraction (6337±1.74%), BChE inhibitory activity in the ME and EtOAC fraction (85.84±3.01% and 83.82±3.93%), total phenol content in the EtOAC fraction (261.59±3.95 mg equivalent of gallic acid/1 g of extract) and total flavonoid contents in the EtOAC fraction (515.54±2.80 mg equivalent of quercetin/1 g of extract), and 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and ferric-reducing antioxidant power values in the aqueous and EtOAC fractions (92.54±0.67%, 92.11±0.30%; 2.318±0.054, 2.224±0.091, respectively). Accordingly, the isolation studies were carried out on the EtOAC fractions. Compounds 1-7 (gallic acid, (+)-catechin, myricetin 3-O-arabinofuranoside, myricetin 3-O-α-rhamnopyranoside, quercetin 3-O-ß-glucopyranoside, quercetin 3-O-arabinofuranoside, and quercetin 3-O-α-rhamnopyranoside, respectively) were isolated from the active EtOAC fraction. CONCLUSION: LV may be a potential herbal source for treatment of neurodegenerative diseases based on its strong antioxidant activity and significant cholinesterase inhibition similar to that of the reference.

Schisandra chinensis and its phytotherapeutical applications.

Schisandra (Schisandra chinensis) has been used for centuries as a plant of traditional Chinese medicine. Its biological activity and pharmacological use are associated with dibenzocyclooctadiene lignans, while specific polysaccharides may also be involved. The lignans of schisandra are genus-specific. Their activity has been investigated in hundreds of studies that have confirmed adaptogenic effects, central nervous system stimulation, hepatoprotective effects and potential anticancer potential. This summary review of the literature synthesizes the current state-of-the-art in research on bioactivities of schisandra constituents, description of folk use of extracts, overview of clinical studies and additional information on in vitro tests bringing insight into mechanisms of action.

Kazakh Ziziphora Species as Sources of Bioactive Substances.

Ziziphora species represent the prototypical example of the Lamiaceae family. The phytochemicals present in Ziziphora include monoterpenic essential oils, triterpenes and phenolic substances belonging to the flavonoids. In Kazakh traditional medicine, Ziziphora species possess several medicinal uses. In particular, Z. bungeana Lam. and Z. clinopodioides Lam. are used for the treatment of illnesses related to the cardiovascular system or to combat different infections. Unfortunately, the majority of the information about the complex Ziziphora species is only available in Russian and Chinese language, therefore, we decided gather all available information on Kazakhstan Ziziphora, namely its content compounds, medicinal uses and published patents, to draw the attention of scientists to this very interesting plant with high medicinal potential.

Plant-Derived Urease Inhibitors as Alternative Chemotherapeutic Agents.

Inhibition of the metalloenzyme urease has important pharmacologic applications in the field of antiulcer and antigastric cancer agents. Urease is involved in many serious infections caused by Helicobacter pylori in the gastric tract as well as by Proteus and related species in the urinary tract. Although numerous studies have described several novel urease inhibitors (UIs) used for the treatment of gastric and urinary infections, all these compounds have exhibited severe side effects, toxicity, and instability. Therefore, to overcome such problems, it is necessary to search for new sources of UIs, such as natural products, that provide reduced side effects, low toxicity, greater stability, and bioavailability. As limited studies have been conducted on plant-derived UIs, this paper aims to highlight and summarize the most promising compounds isolated and identified from plants, such as terpenoids, phenolic compounds, alkaloids, and other substances with inhibitory activities against plant and bacterial ureases; these are in vitro and in vivo studies with an emphasis on structure-activity relationship studies and types of inhibition that show high and promising levels of anti-urease activity. This will aid medicinal chemists in the design and synthesis of novel and pharmacologically potent UIs useful for the development of antiulcer drugs.

Hepatoprotective and proapoptotic effect of Ecballium elaterium on CCl4-induced hepatotoxicity in rats.

OBJECTIVES: To investigate the effects of perorally administered juice on tetrachloromethane (CCl4)-induced hepatotoxicity model in rats. METHODS: Male Wistar rats were tube-administrated silymarin, Ecballium juice at 0.2 mL/kg and 0.7 mL/kg daily for 3 consequent days, i.e., 3.28 µg and 11.48 µg of cucurbitacin B per kg of body weight respectively. On the third day, liver damage was induced by intraperitoneal application of CCl4. On the fourth day, abdominal cavity was macroscopically examined and liver samples were taken for histopathological and immunochemical evaluation. HPLC was used to determine the content of the active substance cucurbitacin B. RESULTS: The experiment revealed that 0.7 ml/kg juice concentration expressed the highest pro-apoptotic activity, but with prevailing negative effects. Compared with the lower concentration, there was an observable vasodilatation with consequent interstitial hemorrhages and a larger scope of inflammatory damage, which suppressed the hepatoprotective effect. In the 0.2 mL/kg concentration, there was a smaller pro-apoptotic activity but other parameters had better results, and the liver parenchyma damage was reversible. CONCLUSIONS: No reactions confirming the potentially allergic effect on laboratory rats were observed; its hepatoprotective and anti-inflammatory effect was confirmed on a model of acute liver damage.

[Preparation and evaluation of the oral gel containing the essential oil from Siberian fir (Abies sibirica Ledeb.)]. / Príprava a hodnocení orálního gelu obsahujícího silici z jedle sibirské (Abies sibirica Ledeb.).

Essential oil of the Siberian fir (Abies sibirica Ledeb.) ranks among the substances with potential use in prevention and treatment of oral candidiasis. Therefore, the aim of the study was the formulation, preparation and evaluation of an oral gel containing 0.3% of this essential oil. Carbopol 974P NF in 1% concentration was used as the gelling agent, some samples were additionally stabilized by an addition of polysorbate 80 (0.1-0.5%). Xylitol in concentrations of 10% or 20% was added with the aim to modify the taste properties of the gel. Following microscopic evaluation (mean oil droplet size, degree of dispersity) immediately after preparation and after 6-month storage, it has been found that the optimal concentration of polysorbate 80 is 0.3%. The results of the experiment also demonstrated that xylitol was not only an excipient adjusting the organoleptic properties of the preparation - its use enabled significant improvement of the quality parameters and stability.

Antiurease activity of plants growing in the Czech Republic.

The antiurease activity of the aqueous extracts of 42 plants growing in the Czech Republic was investigated. A phenol-hypochlorite reaction was used for the determination of ammonia produced by urease. The inhibitory activity of the extracts at a concentration of 0.2 mg/mL varied from 17.8% to 80.0%. Extracts from six Potentilla species expressed inhibitory activity against jack bean urease. They were further investigated for their phenolic constituents and the major compounds were subjected to molecular docking. The results revealed that both jack bean urease and Helicobacter pylori urease were inhibited by quercetin-3-O-ß-D-galactopyranoside-6″-gallate (1), myricetin-3-O-ß-D-glucuronide (2), tiliroside (3) and B-type procyanidin (4). The antiurease activity of the investigated Potentilla species is probably due to the presence of complex phenolic constituents such as flavonoid glycosides and catechin dimers.

Natural compound cudraflavone B shows promising anti-inflammatory properties in vitro.

Cudraflavone B (1) is a prenylated flavonoid found in large amounts in the roots of Morus alba, a plant used as a herbal remedy for its reputed anti-inflammatory properties. The present study shows that this compound causes a significant inhibition of inflammatory mediators in selected in vitro models. Thus, 1 was identified as a potent inhibitor of tumor necrosis factor α (TNFα) gene expression and secretion by blocking the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus in macrophages derived from a THP-1 human monocyte cell line. The NF-κB activity reduction resulted in the inhibition of cyclooxygenase 2 (COX-2) gene expression. Compound 1 acts as a COX-2 and COX-1 inhibitor with higher selectivity toward COX-2 than indomethacin. Pretreatment of cells by 1 shifted the peak in an regulatory gene zinc-finger protein 36 (ZFP36) expression assay. This natural product has noticeable anti-inflammatory properties, suggesting that 1 potentially could be used for development as a nonsteroidal anti-inflammatory drug lead.

Antiradical and cytoprotective activities of several C-geranyl-substituted flavanones from Paulownia tomentosa fruit.

Antiradical and cytoprotective activities of several flavanones isolated from Paulownia tomentosa (Thunb.) Steud. (Scrophulariaceae) have been evaluated using different in vitro and in vivo methods. The capacity of flavanones to scavenge radicals was measured in vitro by means of DPPH and ABTS assays, the inhibition of hydroxyl radicals produced in Fenton reactions, FRAP, scavenging superoxide radicals using enzymatic and nonenzymatic assays and the inhibition of peroxynitrite-induced nitration of tyrosine. The in vivo testing involved measuring the cytoprotective effect of chosen flavanones against alloxan-induced diabetes in mice. The activity of tested compounds was expressed either as a Trolox® equivalent or was compared with rutin or morine as known antioxidant compounds. The highest activity in most tests was observed for diplacone and 3´-O-methyl-5´-hydroxydiplacone, and the structure vs. the antioxidant activity relationship of geranyl or prenyl-substituted flavonoids with different substitutions at the B and C ring was discussed.

Analgesic compounds from Scorzonera latifolia (Fisch. and Mey.) DC.

ETHNOPHARMACOLOGICAL RELEVANCE: A traditional mastic named yaki sakizi prepared from the roots of Scorzonera latifolia (Fisch. and Mey.) DC. is used as a folk remedy for treatment of pain in Turkish folk medicine. AIM OF THE STUDY: To isolate and identify the compounds responsible for the antinociceptive activity of S. latifolia using bioassay-guided fractionation. MATERIALS AND METHODS: The methanolic extract of the S. latifolia roots was prepared and subjected to isolation procedures such as solvent-solvent partitioning and column chromatography. Writhing and tail-flick tests were used to determine the antinociceptive activity. RESULTS: The n-hexane fraction of the S. latifolia root methanolic extract showed potent antinociceptive activity in both writhing and tail-flick tests. Three compounds were isolated from n-hexane fraction using bioassay-guided chromatographic purification. Isolated compounds were the triterpene taraxasteryl myristate, taraxasteryl acetate, and fern-7-en-3-beta-one, structures were elucidated by means of MS and NMR techniques. Both taraxasterol derivatives showed promising antinociceptive activity when compared to reference compounds. CONCLUSION: Results of the present study support the usage of S. latifolia in Turkish folk medicine. Both plant root extract and the isolated compounds showed promising antinociceptive activities. Our results suggested that antinociceptive activity of the plant extract is probably caused by the synergistic interaction of the isolated compounds.

Evaluation of the antiradical activity of Schisandra chinensis lignans using different experimental models.

The in vitro antiradical activity of Schisandra chinensis lignans was investigated using DPPH, ABTS+, Fenton reaction inhibition and tyrosine-nitration inhibition assays, as were the in vivo antidiabetic activities of selected lignans in an animal model of alloxan-induced diabetes. Different degrees of antiradical activity were found, depending upon the structural parameters of the tested compounds. Unfortunately, the compounds showed no antidiabetic activity in concentration range tested.

Glycosylated nervogenic acid derivatives from Liparis condylobulbon (Reichb.f.) leaves.

Three new nervogenic acid glycosides, 1-O-alpha-L-rhamnopyranosyl 3,5-bis(3-methyl-but-2-enyl)-4-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl]-benzoate, 3,5-bis(3-methyl-but-2-enyl)-4-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl]-benzoic acid, and bis{3,5-bis(3-methyl-but-2-enyl)-4-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl]-benzoyl} 1,2-O-beta-d-glucopyranose, which we named condobulbosides A-C, were isolated from a methanol extract of the leaves of Liparis condylobulbon together with an apigenin C-glycoside, schaftoside. Their structures were established on the basis of spectral techniques, namely, UV, IR, HR-MS spectroscopy, both 1D and 2D NMR experiments, and chemical reactions.

Cytotoxic activity of C-geranyl compounds from Paulownia tomentosa fruits.

The newly discovered 5,7-dihydroxy-6-geranylchromone ( 1) was isolated from PAULOWNIA TOMENTOSA fruit and subsequently characterized. The structure of the isolated compound was elucidated on the basis of extensive NMR experiments including HMQC, HMBC, COSY, and NOESY, as well as HR-MS, IR, and UV. The cytotoxicity of 1 was evaluated using a plant cell model represented by tobacco BY-2 cells. The other phytoconstituents ( 2 - 8) previously isolated from P. TOMENTOSA were similarly evaluated together with the known flavanones 10 and 11. The cytotoxicity (human erythro-leukaemia cell line K562) and activity on erythroid differentiation of compounds 2 - 9 and 12 and 13 have also been evaluated. Acteoside ( 2) was determined to be the most toxic of the compounds tested on BY-2 cells, diplacone ( 6) on the K562 cell line. Some aspects of the relationship between the flavanone skeleton substitution and the metabolic activation necessary for a toxic effect are discussed.

Electrochemical and spectrometric study of antioxidant activity of pomiferin, isopomiferin, osajin and catalposide.

The antioxidant properties of pomiferin, isopomiferin, osajin and catalposide are evaluated. The electrochemical behaviour of these compounds at a carbon paste electrode was studied using square wave voltammetry. Oxidative signals, optimized frequencies and appropriate pH acetate buffer conditions were determined. The detection limits (3S/N) for pomiferin, isopomiferin, osajin and catalposide were estimated to be 50 pg/ml, 800 pg/ml, 40 pg/ml and 10 ng/ml, respectively. Furthermore, spectrometric test was employed with 2,2-diphenyl-1-picrylhydrazyle (DPPH) to evaluate the antioxidant activities of these compounds. Based on the obtained results, the highest antioxidant activity measured by DPPH tests was found at pomiferin followed by isopomiferin. The activities of osajin and catalposide were undetectable. The protective effects of pomiferin, isopomiferin, osajin and catalposide on DNA exposed to oxygen radicals in vitro were also studied. Changes in height of oxidative signals for the four bases (guanine, thymine, adenine and cytosine) were measured for DNA exposed to oxygen radicals, generated by Fenton's reaction, non-oxidized ssDNA (50 microg/ml) displayed well developed signals; however, after oxidative damage the observed oxidative signals decreased. Significant protective effects were observed for pomiferin and osajin. Decreased effect was observed for isopomiferin while a further reduced protective effect was seen for DNA exposed to catalposide. Based on the obtained results, pomiferin had the highest antioxidant activity followed by isopomiferin, osajin and catalposide.

Antioxidant activity of Catalpa bignonioides.

Antioxidant activity of methanolic extracts from inflorescence rachises, corollas, calyxes, leaves, valves of capsules and hypertrophied placenta of Catalpa bignonioides by 1,1-diphenyl-2-picrylhydrazyl reduction (DPPH) and tyrosine nitration inhibition induced by peroxynitrite was tested.

Antioxidative and EROD activities of osajin and pomiferin.

The major constituents of fruits of Maclura pomifera are the prenylated isoflavones, osajin (1) and pomiferin (2). Since significant biological activities of extracts from the wood of M. pomifera were previously reported, the peroxynitrite scavenging activity, inhibition of lipid peroxidation, scavenging of DPPH and EROD activity of these two major substances were studied.

Pomiferin.

The crystal structure of pomiferin, 3-(3,4-dihydroxyphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-enyl)-4H,8H-pyrano[2,3-h]chromen-4-one, C(25)H(24)O(6), has been determined. The benzopyranone ring system is nearly planar and the dihedral angle between the phenyl ring and the benzopyranone moiety is 40.85 (4) degrees. The crystal structure is stabilized by a one-dimensional chain of inter- and intramolecular O-H...O hydrogen bonds, with O...O distances in the range 2.5546 (15)-2.7999 (16) A.