Vasorelaxant effects of ellagitannins isolated from Cuphea carthagenensis.

Cuphea carthagenensis (Jacq.) J. F. Macbr. is a popular plant in Brazilian folk medicine owing to its hypotensive and central nervous system depressant effects. This study aimed to validate the hypotensive effect of the plant's aqueous extract (AE) in rats and examine the vascular actions of three hydrolyzable tannins, oenothein B, woodfordin C, and eucalbanin B, isolated from AE. Systolic blood pressure in unanesthetized rats was determined using the non-invasive tail-cuff method. Oral treatment of normotensive rats with 0.5 and 1.0 g/kg/day AE induced a dose-related hypotensive effect after 1 week. In rat aortic rings pre-contracted with noradrenaline, all ellagitannins (20 - 180 µM) induced a concentration-related vasorelaxation. This effect was blocked by either removing the endothelium or pre-incubating with NG-nitro-l-arginine methyl ester (10 µM), an inhibitor of nitric oxide (NO) synthase. In KCl-depolarized rat portal vein preparations, the investigated compounds did not affect significantly the maximal contractile responses and pD2 values of the concentration-response curves to CaCl2. Our results demonstrated the hypotensive effect of C. carthagenensis AE in unanesthetized rats. All isolated ellagitannins induced vasorelaxation in vitro via activating NO synthesis/NO release from endothelial cells, without altering the Ca2+ influx in vascular smooth muscle preparations. Considering the low oral bioavailability of ellagitannins, the determined in vitro actions of these compounds are unlikely to account for the hypotensive effect of AE in vivo. It remains to be determined the role of the bioactive ellagitannin-derived metabolites in the hypotensive effect observed after oral treatment of unanesthetized rats with the plant extract.

The Genus Cuphea P. Browne as a Source of Biologically Active Phytochemicals for Pharmaceutical Application and Beyond-A Review.

Cuphea P. Browne (Lythraceae) is a monophyletic taxon comprising some 240-260 species that grow wild in the warm, temperate, and tropical regions of South and Central America and the southern part of North America. They have been valued as traditional medicinal remedies for numerous indications, including treating wounds, parasitic infections, hypertension, digestive disorders, cough, rheumatism, and pain. Modern pharmacological research provides data that support many of these traditional uses. Such a wide array of medicinal applications may be due to the exceptionally rich phytochemical profile of these plants, which includes bioactive compounds classified into various metabolite groups, such as polyphenols, triterpenes, alkaloids, and coumarins. Furthermore, Cuphea seed oils, containing medium-chain fatty acids, are of increasing interest in various industries as potential substitutes for coconut and palm oils. This review aims to summarize the results of phytochemical and pharmacological studies on Cuphea plants, with a particular focus on the therapeutic potential and molecular mechanisms of the action of polyphenolic compounds (especially flavonoids and tannins), which have been the subject of many recently published articles.

Biogeneration of silver nanoparticles from Cuphea procumbens for biomedical and environmental applications.

Nanotechnology is one of the most important and relevant disciplines today due to the specific electrical, optical, magnetic, chemical, mechanical and biomedical properties of nanoparticles. In the present study we demonstrate the efficacy of Cuphea procumbens to biogenerate silver nanoparticles (AgNPs) with antibacterial and antitumor activity. These nanoparticles were synthesized using the aqueous extract of C. procumbens as reducing agent and silver nitrate as oxidizing agent. The Transmission Electron Microscopy demonstrated that the biogenic AgNPs were predominantly quasi-spherical with an average particle size of 23.45 nm. The surface plasmonic resonance was analyzed by ultraviolet visible spectroscopy (UV-Vis) observing a maximum absorption band at 441 nm and Infrared Spectroscopy (FT IR) was used in order to structurally identify the functional groups of some compounds involved in the formation of nanoparticles. The AgNPs demonstrated to have antibacterial activity against the pathogenic bacteria Escherichia coli and Staphylococcus aureus, identifying the maximum zone of inhibition at the concentration of 0.225 and 0.158 µg/mL respectively. Moreover, compared to the extract, AgNPs exhibited better antitumor activity and higher therapeutic index (TI) against several tumor cell lines such as human breast carcinoma MCF-7 (IC50 of 2.56 µg/mL, TI of 27.65 µg/mL), MDA-MB-468 (IC50 of 2.25 µg/mL, TI of 31.53 µg/mL), human colon carcinoma HCT-116 (IC50 of 1.38 µg/mL, TI of 51.07 µg/mL) and melanoma A-375 (IC50 of 6.51 µg/mL, TI of 10.89 µg/mL). This fact is of great since it will reduce the side effects derived from the treatment. In addition, AgNPs revealed to have a photocatalytic activity of the dyes congo red (10-3 M) in 5 min and malachite green (10-3 M) in 7 min. Additionally, the degradation percentages were obtained, which were 86.61% for congo red and 82.11% for malachite green. Overall, our results demonstrated for the first time that C. procumbens biogenerated nanoparticles are excellent candidates for several biomedical and environmental applications.

In vitro cytotoxic activity of Cuphea ingrata Cham. & Schltdl. extracts related to the oenothein B content.

Cuphea ingrata is a traditional medicinal plant species of the Lythraceae family. This work reports on the cytotoxic activity of the methanolic extract from the aerial parts of C. ingrata and the n-butanol and ethyl acetate fractions against human skin and prostate cancer cells. The selectivity of action was tested in normal skin keratinocytes HaCaT and prostate epithelial cells PNT2. The ethyl acetate fraction showed the highest activity in all three human skin cancer cell lines: A375, HTB-140, WM793, with IC50 = 15.90; 3.40; 18.75 µg/mL, respectively. To obtain comparative information on the chemical composition, a quantitative analysis of oenothein B was performed using the UHPLC-PDA method. An analysis of its cytotoxic activity was also carried out.

Ecofriendly phytofabrication of silver nanoparticles using aqueous extract of Cuphea carthagenensis and their antioxidant potential and antibacterial activity against clinically important human pathogens.

The green synthesis of nanoparticles (NPs) is the safest, ecofriendly, cost-effective, and non-hazardous approach of nanotechnology. In the current study, we described the green synthesis of silver nanoparticles (AgNPs) using Cuphea carthagenensis aqueous leaf extract as a reducing, capping, and stabilizing agent. The study aims at the synthesis, characterization, optimization, and determination of the antibacterial activity of Cc-AgNPs against clinically important human pathogens. Coating of cotton fabrics with Cc-AgNPs and their efficacy against skin infection causing organisms was also evaluated. Furthermore, antioxidant activity, growth assay and time kill assay of Cc-AgNPs were also performed in the study. The biosynthesized Cc-AgNPs were characterized by UV-visible spectrometry, energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FTIR). The spectroscopic and microscopic analysis demonstrated biosynthesis of face-centered cubic (fcc) crystalline spherical Cc-AgNPs with an average particle size of 10.65 ± 0.1 nm. Optimized peak synthesis of Cc-AgNPs was reported at pH7, 55 °C, 4 mM silver nitrate, and 5:45 (plant extract: silver nitrate). Cc-AgNPs exhibited potent antioxidant effect and antibacterial activity against both Gram-positive and Gram-negative bacteria. The lowest MIC (15 µg/ml) and MBC (25 µg/ml) values were reported against S. typhimurium. The Cc-AgNPs coated fabrics demonstrated potent antibacterial activity against tested strains. This application could be helpful in wound healing management. Furthermore, the hemolytic analysis demonstrated that Cc-AgNPs exhibit non-toxic nature against Red Blood Cells (RBCs) at the tested concentrations. In conclusion, the investigation demonstrated a fast, stable, and eco-friendly approach to the biosynthesis of Cc-AgNPs along with their antibacterial and antioxidant properties.

UHPLC-PDA-ESI-MS profile of phenolic compounds in the aerial parts of Cuphea ingrata Cham. & Schltdl.

The purpose of the current study was a qualitative UHPLC-PDA-ESI-MS analysis of phenolic compounds in the aerial parts of Cuphea ingrata, which led to detection of over sixty constituents: tannins, flavonoids, phenolic acids and their derivatives. The presence of oenothein B-type macrocyclic dimeric ellagitannins seems to be of particular importance. Quercetin sulfate, that has been previously identified as characteristic chemotaxonomic marker in Cuphea carthagenensis, was found in C. ingrata, as well.

Polyphenolic Composition and in Vitro Antihypertensive and Anti-Inflammatory Effects of Cuphea lindmaniana and Cuphea urbaniana.

The present study investigates the chemical composition, anti-inflammatory, and antihypertensive activities, in vitro, from extracts of Cuphea lindmaniana and Cuphea urbaniana leaves. The extraction was performed ultrasound-assisted, and UHPLC/MS analysis was in positive mode ionization. The anti-inflammatory activity of the extracts and miquelianin were assayed at concentrations 0.001-10 µg/mL by chemotaxis on rat polymorphonuclear neutrophils. The antihypertensive activity was performed by angiotensin-converting enzyme (ACE) inhibition. From the nineteen proposed compounds, six of them are described for the first time in this genus. The extracts displayed antichemotactic effect with a reduction of 100 % of the neutrophil migration, in vitro, in most concentrations. The ACE-inhibition presented results ranging from 19.58 to 22.82 %. In conclusion, C. lindmaniana and C. urbaniana extracts contain a rich diversity of flavonoids and display in vitro anti-inflammatory and antihypertensive potential. Thus, this study could serve as a scientific baseline for further investigation, on developmental novel products with therapeutic actions.

Cuphea calophylla var. mesostemon (Koehne) S.A. Graham: A Whole-Ethnopharmacological Investigation.

Several species of Cuphea are used medicinally and are reported to have cardioprotective, diuretic, and antihypertensive properties. In Brazil, Cuphea species are collectively called "sete-sangrias" due to their similar appearances and are also used interchangeably for the same therapeutic purposes. So the aim of the study was to characterize morphoanatomy of leaves and stems, evaluate the safety, and investigate the diuretic, hypotensive, vasodilatory, and antioxidant properties of ethanol-soluble fraction of Cuphea calophylla var. mesostemon (Koehne) S.A. Graham. Initially, the morphoanatomical characterization of the leaves and stems of C. calophylla var. mesostemon was performed. For the pharmacological evaluation, the ethanol-soluble fraction from Cuphea calophylla (ESCC) was obtained and chemically characterized by high-performance liquid chromatography coupled with a diode array detector and tandem mass spectrometry techniques. Then, acute toxicity, diuretic, hypotensive, antioxidant, and vasodilatory effects were evaluated in Wistar rats. The main chemical compounds identified from ESCC were gallic acid derivatives, ellagitannins, and flavonoids. ESCC showed no acute toxic effect. ESCC showed no acute toxic effect and the estimated median lethal dose (LD50) was above 2000 mg/kg. ESCC treatment (30, 100, and 300 mg/kg) did not present any significant acute diuretic or hypotensive effects. However, an important reduction in the elimination of electrolytes was observed after the acute administration, and a significant increase in renal sodium elimination was observed after 7 days of treatment. In the cardiac tissue, the groups treated with ESCC presented significant increase in superoxide dismutase activity.

Cuphea spp.: antichemotactic study for a potential anti-inflammatory drug.

Cuphea genus (Lythraceae) popularly known in Brazil as "sete-sangrias", it's described as antimicrobial, anti-inflammatory, diuretic and antihypertensive mainly. Investigating the chemotactic ability plays an important role in the identification of new anti-inflammatory agents. Thus, this research aims to assay the antichemotactic activity of hydroethanolic extracts of C. calophylla, C. carthagenensis, C. glutinosa, and C. racemosa as well as the compounds miquelianin and myricitrin. The antichemotactic activity of the hydroethanolic extracts, miquelianin, and myricitrin were assayed at concentrations 0.001 to 10 µg/mL in the lipopolysaccharide-induced chemotaxis on rat polymorphonuclear neutrophils. All the assayed samples displayed antichemotactic activity with reduction of the neutrophil migration in the range of 4.46-100%, and an IC50 value in the range of 0.30-1.24 µg/mL. Thus, this study demonstrates that the extracts hydroethanolic of Cuphea species, miquelianin, and myricitrin display a significant antichemotactic activity. Therefore, in future studies, extracts from Cuphea spp. could be used as anti-inflammatory drugs.

Antinociceptive and anti-inflammatory effects of Cuphea aequipetala Cav (Lythraceae).

Cuphea aequipetala Cav (Lythraceae) is an herb used in folk treatment for pain and inflammation. The aim of this study was to evaluate the antinociceptive and anti-inflammatory actions of an ethanol extract from the leaves and stem of Cuphea aequipetala (CAE). The antinociceptive actions of CAE (10-200 mg/kg p.o.) were assessed with the acetic acid-induced writhing, hot plate, and formalin tests. The possible mechanism of action of CAE was evaluated using inhibitors. The effects of CAE on motor coordination were assessed by the rotarod test. The in vitro anti-inflammatory actions of CAE were evaluated using LPS-stimulated primary murine macrophages, and the in vivo anti-inflammatory actions were assessed by the TPA-induced ear oedema and the carrageenan-induced paw oedema tests. The production of inflammatory mediators was estimated from both in vitro and in vivo assays. CAE showed antinociception (ED50 = 90 mg/kg) in the acetic acid test and in the second phase of the formalin test (ED50 = 158 mg/kg). Pretreatment with glibenclamide or L-NAME partially reversed the antinociception shown by the plant extract. CAE (50-200 mg/kg) did not affect motor coordination in mice. CAE increased the production of IL-10 in LPS-stimulated macrophages (EC50 = 10 pg/ml) and, in the carrageenan-induced paw oedema test (threefold increase). In conclusion, CAE induced antinociceptive effects without affecting motor coordination, probably due to the involvement of nitric oxide and ATP-sensitive K+ channels. CAE also exerts in vitro and in vivo anti-inflammatory effects by increasing the release of IL-10.

Inhibition of biofilm and quorum sensing-regulated virulence factors in Pseudomonas aeruginosa by Cuphea carthagenensis (Jacq.) J. F. Macbr. Leaf extract: An in vitro study.

ETHNOPHARMCOLOGICAL RELEVANCE: Microbial biofilm formation, a quorum sensing (QS) regulated process, is one of the major causes of nosocomial and chronic infections, foodborne diseases, and associated deaths. Various approaches have been used to eradicate the menace of biofilm. Ethnomedicinal plants as potent antibiofilm agents are gaining a lot of interest in an era where the drug resistance is increasing and the availability of potent antibiotics is no longer promised. In this context, the methanol extract of Cuphea carthagenensis (CCMD), an ethno-medicinal and culinary herb, was evaluated as an antibiofilm and anti-QS agent against Pseudomonas aeruginosa. AIM OF THE STUDY: The aim of the study is to evaluate the antibiofilm and anti-QS activity of an ethnomedicinal plant against a strong biofilm forming microorganism, P. aeruginosa. METHODS: Antibiofilm activity of CCMD was demonstrated at different concentrations by Tissue Culture Plate, Test Tube method and other microscopic techniques. The effect of CCMD on QS and QS-related virulence factors viz. Pyocyanin, exopolymeric substance matrix (EPS), total protease, elastase, pyoverdin and swimming motility in P. aeruginosa were also evaluated. Antioxidant activity (DPPH & FRAP), total phenolic and flavonoid content were also checked. In order to determine the composition of the extract HPLC analysis was also performed. RESULTS: In vitro study demonstrated a significant inhibition of biofilm formation (81.88 ± 2.57%) as well as production of QS-dependent virulence factors in P. aeruginosa. The extract also inhibited violacein production (83.31 ± 2.77%) in Chromobacterium violaceum which correlates with the reduction in QS-mediated virulence factors. The extract showed 64.79% ± 0.83% DPPH scavenging activity and reduction of ferricyanide complex (Fe3+) to the ferrous form (Fe2+) in DPPH and FRAP assay, respectively. Furthermore, the extract showed thermal stability and does not have any growth inhibitory effect on P. aeruginosa. The HPLC analysis demonstrated the presence of ellagic acid, ascorbic acid and hippuric acid in the extract. CONCLUSION: This work is the first to demonstrate that C. carthagenensis can attenuate biofilm formation and QS-mediated virulence factors of P. aeruginosa. Further investigation is required to use this ethnomedicinal plant (CCMD) as an important source of antibiofilm agents.

Antimicrobial and Antioxidant Activities of Two Medicinal Plants Cuphea aequipetala var. hispida (Cav.) Koehne and Eryngium comosum Delaroche F Against Bacteria Related to Equine Infections.

Functional biocompounds beneficial for animals and humans are in Mexican folk herbs. Cuphea and Eryngium species presented antimicrobial potential. Natural antibiotic uses by ethnoveterinary research with medicinal plants in equine infection or digestive diseases need more scientific evidence. Staphylococcus aureus, Escherichia coli, Salmonella enterica serotype Enteritidis are etiological agents in horses responsible for stable infections, abortions, fetal or perinatal deaths, and resistant intrahospital infections. The main objective of the present research was to evaluate the potential of antimicrobial and antioxidant activities of two Mexican medicinal plants Cuphea aequipetala var. hispida (Cav.) Koehne and Eryngium comosum Delaroche F over Listeria monocytogenes ATCC 19115, Staphylococcus sp., E. coli ATCC 25922, and S. enterica serotype Enteritidis ATCC 13076 bacterium reference strains related to equine infections. Determination of total phenol, saponins, antioxidant activity (ABTS), and antimicrobial activity with diffusion-sensitive discs was performed in triplicate. All the strains were sensitive for both extracts except for E. coli strain that was inhibited only by C. aequipetala. Staphylococcus sp. and S. enterica strains were inhibited equally by both extracts. E. comosum extracts tested have shown the highest effect over L. monocytogenes. In summary, antimicrobial activity was similar to the reported activity of Eryngium species extracts with other different solvents. Present extracts are suggested as a potential alternative antibiotic; definitely, more specific equine pathogen inhibition tests are needed in feed additives for horse nutrition research. In conclusion, antimicrobial activities of Cuphea aequipetala var. hispida (Cav.) Koehne and Eryngium comosum Delaroche F over reference strains related to equine infections suggested these medicinal plants as potential antibiotic sources for horse diseases.

Ultrasound-assisted extraction optimization and validation of ultra-performance liquid chromatographic method for the quantification of miquelianin in Cuphea glutinosa leaves.

Cuphea glutinosa is a medicinal species abundant in South of Brazil, known because of its flavonoids, which have pharmacological properties as antioxidant, anti-hypertensive, diuretic, and antimicrobial. The present study aimed to optimize the extraction and validate an ultra-performance liquid chromatographic method coupled to a photodiode array detector (UPLC-PDA) method for the quantification of a chemical marker miquelianin in C. glutinosa leaves. The optimum conditions for the extraction of miquelianin from leaves of C. glutinosa were determined using a fractional factorial design (FFD) and a central composite design (CCD). An UPLC-PDA method was validated, following the ICH guidelines and RDC 166/2017 of ANVISA (Brazil). The extraction-optimization methodology was obtained with the following parameters: plant:solvent 1:60 (w/v), percentage solvent 38% ethanol, 60 min time, five extractions and particle size ≤ 180 µm. The validation parameters of the quantification method were satisfactory. The results revealed a method with excellent selectivity, linearity, precision (repeatability and intermediate precision were below 2.18 and 1.40%, respectively) and accuracy (mean recovery 90.6%). The average content of miquelianin was 1.03%. Briefly, the optimization of the extractive method in the leaves of C. glutinosa increased the concentration of miquelianin in the crude extract and the method was validated according to the current legislation.

Polyphenols composition from leaves of Cuphea spp. and inhibitor potential, in vitro, of angiotensin I-converting enzyme (ACE).

ETHNOPHARMACOLOGICAL RELEVANCE: Cuphea is the largest genus of the Lythraceae family. It is popularly known as "sete-sangrias" in Brazil used in folk medicine as a diuretic, antipyretic, anti-inflammatory, laxative and antihypertensive agent. The raw material of Cuphea has shown promising results in the production of fitotherapics, which are chemically characterized by quercetin core flavonoids. AIMS OF THE STUDY: Present work aims to investigate the chemical composition of Cuphea calophylla, Cuphea carthagenensis, Cuphea glutinosa and Cuphea racemosa by UHPLC-MS using ESI-Q-TOF, and also to investigate the inhibition of angiotensin-converting enzyme (ACE) in vitro. MATERIALS AND METHODS: Leaves extraction was conducted by an ultrasound-assisted system under the following conditions: 40% ethanol, particle size ≤180 µm, plant:solvent ratio 1:20 (w/v) for 30 min. The leaf extracts were analyzed by UHPLC-MS positive mode ionization. For the inhibition of ACE, the leaf extracts used were obtained from different Cuphea species collected from several regions of Rio Grande do Sul (Brazil). RESULTS: In total 26 polyphenolic compounds were proposed, which were mostly derived from quercetin, myricetin, and kaempferol. Of these compounds, ten are described in the genus for the first time. The ACE-inhibiting activities are presented in descending order: miquelianin (32.41%), C. glutinosa 1 (31.66%), C. glutinosa 5 (26.32%) and C. carthagenensis 1 (26.12%). CONCLUSION: The obtained results suggest that the ACE-inhibiting potential may be increased by the interactions among the different phytoconstituents present in the crude extract. These results corroborate with the popular usage of Cuphea genus as diuretic and antihypertensive agents in folk medicine.

Antiulcerogenic effect of Cuphea ignea extract against ethanol-induced gastric ulcer in rats.

BACKGROUND: Cuphea ignea is one of the herbal resources belonging to Lythraceae family. Some species of this family have been used traditionally in South and Central America's folk medicine for treating stomach disorders. Therefore, the present study was performed to evaluate the gastropreventive effect of aqueous ethanolic extract of C. ignea aerial parts on ethanol-induced gastric ulcer. METHODS: Gastric ulcers were induced in Sprague Dawley rats using one oral dose of absolute ethanol (1.5 mL/rat). The C. ignea aerial parts extract at doses of 250 and 500 mg/kg body weight and ranitidine (a reference drug) at a dose of 30 mg/kg body weight were orally administrated daily for 7 days before ulcer induction. One hour after ethanol administration blood samples were collected and then stomachs of sacrificed rats were subjected to biochemical, macroscopic and microscopic studies. RESULTS: Oral administration of C. ignea extract significantly attenuated gastric ulcer as revealed by significant reduction in the gastric ulcer index and volume of gastric juice while significantly increased preventive percentage, gastric pH value and pepsin activity. Pre-treatment of C. ignea extract markedly improved the serum level of TNF-α, the gastric MPO activity and NO content. Furthermore, C. ignea pre-treatment significantly increased the gastric levels of enzymatic and non- enzymatic antioxidants namely CAT, SOD, GSH-Px, and GSH with concomitant reduction in MDA level compared with those in the ethanol group. These results were further supported by histopathological findings which revealed the curing effect of C. ignea on the hemorrhagic shock induced by ethanol toxicity. CONCLUSIONS: C. ignea extract showed a potential gastroprotective effect on ethanol-induced gastric ulcer, and its effect may be mediated through suppression of oxidative stress and gastric inflammation.

Inhibitory Effect of Cuphea aequipetala Extracts on Murine B16F10 Melanoma In Vitro and In Vivo.

Cuphea aequipetala (C. aequipetala) has been used in Mexican traditional medicine since prehispanic times to treat tumors. In this paper, we evaluated the antiproliferative and apoptotic effect of the methanolic and aqueous extracts of C. aequipetala on several cancer cell lines including the B16F10 cell line of murine melanoma and carried a murine model assay. In vitro assay analyzed the effect in the cellular cycle and several indicators of apoptosis, such as the caspase-3 activity, DNA fragmentation, phosphatidylserine exposure (Annexin-V), and induction of cell membrane permeabilization (propidium iodide) in the B16F10 cells. In vivo, groups of C57BL/6 female mice were subcutaneously injected with 5x105 B16F10 cells and treated with 25 mg/mL of C. aequipetala extracts via oral. Aqueous and methanolic extracts showed a cytotoxic effect in MCF-7, HepG2, and B16F10 cell lines. The methanolic extract showed more antiproliferative effect with less concentration, and for this reason, the in vitro experiments were only continued with it. This extract was able to induce accumulation of cells on G1 phase of the cell cycle; moreover, it was able to induce DNA fragmentation and increase the activity of caspase-3 in B16F10 cells. On the other hand, in the murine model of melanoma, the aqueous extract showed a greater reduction of tumor size in comparison with the methanolic extract, showing an 80% reduction versus one of around 31%, both compared with the untreated control, indicating a better antitumor effect of C. aequipetala aqueous extract via oral administration. In conclusion, the in vitro data showed that both C. aequipetala extracts were able to induce cytotoxicity through the apoptosis pathway in B16F10 cells, and in vivo, the oral administration of aqueous extract reduces the melanoma tumoral mass, suggesting an important antitumoral effect and the perspective to search for effector molecules involved in it.

A phytochemical study of the Cuphea glutinosa from Southern Brazil: Na+,K+-ATPase activity inhibition and antioxidant properties.

This study investigated the antioxidant activity of Cuphea glutinosa (CG) and its effect on Na+, K+-ATPase from cardiac muscle. The ethanolic extract showed higher antioxidant capacity compared to aqueous and ethyl acetate fraction. Ethyl acetate fraction showed ß-sitosterol-3-O-ß-glucoside, kaempferol, quercetin, isoquercetin, gallic acid methyl ester, and gallic acid. The ethanolic extract also reduced the Na+,K+-ATPase activity. CG presented a promising antioxidant activity and inhibitory effect on the Na+, K+-ATPase activity, supporting biochemical evidences the popular use of this plant in the treatment of heart failure.

Caracterización de compuestos fenólicos del extracto metanólico de hojas y tallos de Cuphea ciliata Ruiz & Pav. (hierba del toro) / Characterization of phenolic compounds of the metallic extract of stems and leaves of Cuphea ciliata Ruiz & Pav. (hierba del toro)

Objetivos. Caracterizar los compuestos fenólicos presentes en el extracto metanólico de hojas y tallos de Cuphea ciliata Ruiz & Pav. "hierba del toro". Materiales y métodos. Se preparó un extracto metanólico de las hojas y tallos de Cuphea ciliata Ruiz & Pav. Se evaluó la solubilidad del extracto en solventes de alta polaridad, mediana polaridad y no polares. Se detectaron los componentes químicos del extracto metanólico mediante un tamizaje fitoquímico empleando gelatina, tricloruro férrico, reacción de Mayer, reacción de Shinoda, entre otros. Se realizó cromatografía en capa fina y reveladores cromatográficos. Finalmente, mediante el uso del espectrofotómetro UV/Vis se hizo la propuesta de las estructuras de los flavonoides presentes en el extracto metanólico. Resultados. El extracto metanólico presentó una mejor solubilidad en solventes de alta polaridad. El tamizaje fitoquímico dio resultados positivos para la presencia de taninos, compuestos fenólicos, flavonoides, glicósidos y quinonas. Se propuso la estructura química de siete flavonoides obtenidos del extracto estudiado. Conclusiones. Se caracterizó la posible estructura química de siete flavonoides presentes en el extracto metanólico de hojas y tallos de Cuphea ciliata Ruiz & Pav. "hierba del toro".

Objectives. Characterize the phenolic compounds present in the methanolic extract of leaves and stems of Cuphea ciliata Ruiz & Pav. "Bull grass." Materials and methods. A methanolic extract was prepared from the leaves and stems of Cuphea ciliata Ruiz & Pav. The solubility of the extract in solvents of high polarity, medium polarity and non-polar was evaluated. The chemical components of the methanolic extract were detected by phytochemical screening using gelatin, ferric trichloride, Mayer reaction, Shinoda reaction, among others. Thin layer chromatography, chromatographic developers were performed. Finally, through the use of the UV / Vis spectrophotometer, the proposal of the flavonoid structures present in the methanolic extract was made. Results. The methanolic extract showed a better solubility in solvents of high polarity. Phytochemical screening gave positive results for the presence of tannins, phenolic compounds, flavonoids, glycosides and quinones. The chemical structure of seven flavonoids obtained from the studied extract was proposed. Conclusions. The possible chemical structure of seven flavonoids present in the methanolic extract of leaves and stems of Cuphea ciliata Ruiz & Pav. "Bull grass" was characterized.

Redox regulation and NO/cGMP plus K+ channel activation contributes to cardiorenal protection induced by Cuphea carthagenensis (Jacq.) J.F. Macbr. in ovariectomized hypertensive rats.

BACKGROUND: One of the medicinal plants widely used by the population in the treatment of hypertension, atherosclerosis and circulatory disorders is Cuphea carthagenensis (Jacq.) J.F. Macbr. (Lythraceae), popularly known as 'sete sangrias', being found in Brazil, Hawaii and in South Pacific Islands. Despite the widespread use of this species by the population, its long-term antihypertensive and cardioprotective activities have not yet been scientifically evaluated. PURPOSE: To evaluate the possible cardioprotective effects of an ethanol-soluble fraction obtained from C. carthagenensis (ESCC) using ovariectomized hypertensive rats to simulate a broad part of the female population over 50 years of age affected by hypertension. In addition, the molecular mechanism that may be responsible for its cardiorenal protective effects was also explored. METHODS: Female Wistar rats were submitted to surgical procedures of bilateral ovariectomy and induction of renovascular hypertension (two-kidneys, one-clip model). The sham-operated group was used as negative control. ESCC was obtained and a detailed phytochemical investigation about its main secondary metabolites was performed. ESCC was orally administered at doses of 30, 100 and 300  mg/kg, daily, for 28 days, 5 weeks after surgery. Enalapril (15  mg/kg) was used as standard antihypertensive drug. Renal function was evaluated on days 1, 7, 14, 21 and 28. At the end of the experimental period, systolic, diastolic, mean arterial pressure and heart rate were recorded. The activity of the tissue enzymatic antioxidant system, thiobarbituric acid reactive substances, nitrotyrosine, nitrite, aldosterone and vasopressin levels, in addition to the activity of the angiotensin-converting enzyme were also evaluated. Additionally, vascular reactivity to acetylcholine, sodium nitroprusside, and phenylephrine, and the role of nitric oxide, prostaglandins, and K+ channels in the vasodilator response of ESCC on the mesenteric vascular bed were also investigated. RESULTS: ESCC-treatment induced an important cardiorenal protective response, preserving renal function and preventing elevation of blood pressure and heart rate in ovariectomized hypertensive rats. In addition, prolonged treatment with ESCC recovered mesenteric vascular reactivity at all doses used. This effect was associated with an important modulation of the antioxidant defense system with a possible increase in NO bioavailability. Additionally, NO/cGMP activation and K+ channel opening-dependent vasodilator effect was observed on the mesenteric vascular bed, indicating a potential mechanism for the cardiovascular effects of ESCC. CONCLUSION: A 28-days ESCC treatment reduces the progression of the cardiorenal disease in ovariectomized hypertensive rats. These effects seem to be involved with an attenuation of oxidative and nitrosative stress, affecting endothelial nitric oxide production and K+ channel opening in smooth muscle cells.

Identification of active site residues implies a two-step catalytic mechanism for acyl-ACP thioesterase.

In plants and bacteria that use a Type II fatty acid synthase, isozymes of acyl-acyl carrier protein (ACP) thioesterase (TE) hydrolyze the thioester bond of acyl-ACPs, terminating the process of fatty acid biosynthesis. These TEs are therefore critical in determining the fatty acid profiles produced by these organisms. Past characterizations of a limited number of plant-sourced acyl-ACP TEs have suggested a thiol-based, papain-like catalytic mechanism, involving a triad of Cys, His, and Asn residues. In the present study, the sequence alignment of 1019 plant and bacterial acyl-ACP TEs revealed that the previously proposed Cys catalytic residue is not universally conserved and therefore may not be a catalytic residue. Systematic mutagenesis of this residue to either Ser or Ala in three plant acyl-ACP TEs, CvFatB1 and CvFatB2 from Cuphea viscosissima and CnFatB2 from Cocos nucifera, resulted in enzymatically active variants, demonstrating that this Cys residue (Cys348 in CvFatB2) is not catalytic. In contrast, the multiple sequence alignment, together with the structure modeling of CvFatB2, suggests that the highly conserved Asp309 and Glu347, in addition to previously proposed Asn311 and His313, may be involved in catalysis. The substantial loss of catalytic competence associated with site-directed mutants at these positions confirmed the involvement of these residues in catalysis. By comparing the structures of acyl-ACP TE and the Pseudomonas 4-hydroxybenzoyl-CoA TE, both of which fold in the same hotdog tertiary structure and catalyze the hydrolysis reaction of thioester bond, we have proposed a two-step catalytic mechanism for acyl-ACP TE that involves an enzyme-bound anhydride intermediate.