Organ-specific volatiles from Sonoran desert Krameria flowers as potential signals for oil-collecting bees.

The evolution of flowers that offer oils as rewards and are pollinated by specialized bees represents a distinctive theme in plant-pollinator co-diversification. Some plants that offer acetylated glycerols as floral oils emit diacetin, a volatile by-product of oil metabolism, which is utilized by oil-collecting bees as an index signal for the presence of floral oil. However, floral oils in the genus Krameria (Krameriaceae) contain ß-acetoxy-substituted fatty acids instead of acetylated glycerols, making them unlikely to emit diacetin as an oil-bee attractant. We analyzed floral headspace composition from K. bicolor and K. erecta, native to the Sonoran Desert of southwestern North America, in search of alternative candidates for volatile index signals. Using solid-phase microextraction, combined with gas chromatography-mass spectrometry, we identified 26 and 45 floral volatiles, respectively, from whole flowers and dissected flower parts of these two Krameria species. As expected, diacetin was not detected. Instead, ß-ionone emerged as a strong candidate for an index signal, as it was uniquely present in dissected oil-producing floral tissues (elaiophores) of K. bicolor, as well as the larval cells and provisions from its oil-bee pollinator, Centris cockerelli. This finding suggests that the floral oil of K. bicolor is perfused with ß-ionone in its tissue of origin and retains the distinctive raspberry-like scent of this volatile after being harvested by C. cockerelli bees. In contrast, the elaiophores of K. erecta, which are not thought to be pollinated by C. cockerelli, produced a blend of anise-related oxygenated aromatics not found in the elaiophores of K. bicolor. Our findings suggest that ß-ionone has the potential to impact oil-foraging by C. cockerelli bees through several potential mechanisms, including larval imprinting on scented provisions or innate or learned preferences by foraging adults.

Synthesis of Green Copper Nanoparticles Using Medicinal Plant Krameria sp. Root Extract and Its Applications.

Nanotechnology is one of the most dynamic research areas and the fastest-growing market. Developing eco-friendly products using available resources to acquire maximum production, better yield, and stability is a great challenge for nanotechnology. In this study, copper nanoparticles (CuNP) were synthesized via the green method using root extract of the medical plant Rhatany (Krameria sp.) as a reducing and capping agent and used to investigate the influence of microorganisms. The maximum production of CuNP was noted at 70 °C after 3 h of reaction time. The formation of nanoparticles was confirmed through UV-spectrophotometer, and the product showed an absorbance peak in the 422-430 nm range. The functional groups were observed using the FTIR technique, such as isocyanic acid attached to stabilize the nanoparticles. The spherical nature and average crystal sizes of the particle (6.16 nm) were determined using Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), and X-ray diffractometer (XRD) analysis. In tests with a few drug-resistant pathogenic bacteria and fungus species, CuNP showed encouraging antimicrobial efficacy. CuNP had a significant antioxidant capacity of 83.81% at 200 g/m-1. Green synthesized CuNP are cost-effective and nontoxic and can be applied in agriculture, biomedical, and other fields.

Antinociceptive and anti-arthritic effects of kramecyne.

AIMS: The aim of this study was to evaluate the antinociceptive (acute assays) and anti-inflammatory (chronic assays) effects of kramecyne (KACY), a peroxide isolated from Krameria cytisoides. MAIN METHODS: The antinociceptive activity of KACY was evaluated using the hot plate, acetic acid and formalin tests. The effects of KACY on heat-induced hemolysis in rat erythrocytes were also evaluated. The in vivo anti-inflammatory assays were performed using the chronic TPA (12-O-tetradecanoylphorbol 13-acetate) method to induce ear edema and carrageenan-kaolin induced arthritis (CKIA). In the CKIA model, the hot plate test was performed, serum samples were obtained for the quantitation of pro-inflammatory (IL-1ß, IL-6, IL-12 and TNF-α) and anti-inflammatory (IL-4 and IL-10) cytokines. KEY FINDINGS: KACY possess antinociceptive effects with comparable activity to naproxen (NPX). KACY inhibited hemolysis (EC50 = 180 µg/mL), in comparison to the untreated group and with a higher potency than NPX (EC50 = 263 µg/mL). KACY at 50 mg/kg decreased inflammation by 38% (chronic TPA-induced edema model) and by 26% (CKIA model), in comparison with the vehicle group and with similar activity to the positive controls 8 mg/kg indomethacin (IND) and 1 mg/kg methotrexate (MTX), respectively. In the CKIA model, KACY increased the release of anti-inflammatory (IL-4 and IL-10) cytokines but reduced the production of pro-inflammatory cytokines (IL-1ß, IL-6, IL-12 and TNF-α). KACY at 50 and 100 mg/kg showed antinociceptive effects by 27% and 23%, respectively, in mice with mono-arthritis. SIGNIFICANCE: KACY might be a good alternative for the treatment of rheumatoid arthritis (RA) due its antinociceptive and anti-inflammatory activities.

In vitro antioxidant and antiproliferative activities of plants of the ethnopharmacopeia from northwest of Mexico.

BACKGROUND: The aim of this study, is to investigate the in vitro antioxidant activity, the total phenols content, the flavonoids content and the antiproliferative activity of methanolic extracts of the plants: Krameria erecta, Struthanthus palmeri, Phoradendron californicum, Senna covesii and Stegnosperma halimifolium, used by different ethnic groups from northwestern Mexico in the treatment and cure of various diseases. METHODS: The in vitro antioxidant activity was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reducing/Antioxidant Power assay (FRAP), the total phenols content was measured by Folin-Ciocalteau assay, the flavonoids content by the AlCl(3) colorimetric method and the antiproliferative activity (line cells HeLa, RAW 264.7, M12A(k).C3.F6 and L929) using MTT method. RESULTS: The K. erecta extract showed the higher radical scavenging activity (67.88%), antioxidant activity by FRAP (1.41 mg Trolox Eq), the highest total phenols content (598.51 mg Galic Acid Eq/g extract), the highest flavonoids content (3.80 mg Quercetin Eq/g extract) and the greatest antiproliferative activity in a dose dependent manner against most Cell line evaluated. A positive correlation was found between the antioxidant activity and the flavonoids content. CONCLUSIONS: This study is the first report on the antioxidant and antiproliferative activities of the five species evaluated. The results demostrate that there is a positive correlation between antioxidant activity and the flavonoids content, indicating that these type of polyphenols could be the major contributors to the observed antioxidant activity in the evaluated plant extracts. Of the extracts evaluated, that of Krameria erecta showed the greatest antioxidant and antiproliferative activities, a discovery that makes this species a promising candidate for future research.

Cycloartanes from Krameria pauciflora and their in vitro PLA2, COX-1, and COX-2 enzyme inhibitory activities.

Krameria pauciflora is a species belonging to the Krameriaceae family. It has been used to treat inflammatory disorders in folkloric Mexican medicine; however, chemistry and pharmacological studies have not been carried out on this species. In this work, from the dichloromethane root extract of K. pauciflora, five cycloartane-type triterpenoids were isolated: cyclomargenyl-3-O-ß-caffeoyl ester (1), cyclomargenyl-3-O-ß-feruloyl ester (2), cyclomargenyl-3-O-ß-coumaroyl ester (3), cyclomargenol (4, polysthicol), and cyclomargenone (5). Additionally, the lignane 6'-methoxyrataniaphenol was isolated. To the best of our knowledge, compounds 1-3 are new natural products, whereas compounds 4 and 5 are isolated for the first time in the Krameria genus and the Krameriaceae family. The structures of all of these compounds were established by 1D and 2D NMR spectroscopy including ¹H, ¹³C, DEPT, COSY, HSQC, and HMBC experiments, as well as by EI mass spectrometry. There is an incomplete previous report about the spectroscopic data of compounds 4 and 5. However, in this work, a complete and unambiguous assignation has been realized. Due to the traditional use of this plant and other species from this genus, such as K. lappacea, cycloartanes isolated herein were evaluated by their inhibition of phospholipase A2, cyclooxygenase-1, and cyclooxygenase-2 enzymes. Cyclomargenyl-3-O-ß-caffeoyl ester (1) showed inhibition of phospholipase A2, cyclooxygenase-1, and cyclooxygenase-2 target enzymes for nonsteroidal anti-inflammatory drugs. Both cyclooxygenases were inhibited by cyclomargenol (4); however, cyclomargenyl-3-O-ß-feruloyl ester (2) showed inhibition only on cyclooxygenase-1.

2-(2,4-dihydroxyphenyl)-5-(E)-propenylbenzofuran promotes endothelial nitric oxide synthase activity in human endothelial cells.

Endothelial nitric oxide synthase (eNOS) mediates important vaso-protective and immunomodulatory effects. Aim of this study was to examine whether lignan derivatives isolated from the roots of the anti-inflammatory medicinal plant Krameria lappacea influence eNOS activity and endothelial nitric oxide (NO) release. The study was performed using cultured human umbilical vein endothelial cells (HUVECs) and HUVEC-derived EA.hy926 cells. Among the eleven isolated compounds only 2-(2,4-dihydroxyphenyl)-5-(E)-propenylbenzofuran (DPPB) was able to increase eNOS enzyme activity. DPPB (1-10 µM) treatment for 24 h induced a significant and dose-dependent increase in eNOS activity as determined by the [(14)C]L-arginine/[(14)C]L-citrulline conversion assay. Immunoblotting studies further revealed a time-dependent DPPB-induced increase in eNOS-Ser(1177) and decrease in eNOS-Thr(495) phosphorylation, as well as increased AMPK phosphorylation at Thr(172), whereas Akt phosphorylation at Ser(473) was not affected. Si-RNA-mediated knockdown of AMPK and inhibition of CaMKKß by STO 609, as well as intracellular Ca(2+) chelation by Bapta AM abolished the stimulating effect of DPPB on eNOS-Ser(1177) and AMPK-Thr(172) phosphorylation. Furthermore, we could show that DPPB increases intracellular Ca(2+) concentrations assessed with the fluorescent dye Fluo-3-AM. DPPB enhances eNOS activity and endothelial NO release by raising intracellular Ca(2+) levels and increases signaling through a CaMKKß-AMPK dependent pathway.

Kramecyne--a new anti-inflammatory compound isolated from Krameria cytisoides.

In the present work we describe the structure and anti-inflammatory activity of a new compound, kramecyne, isolated from a methanol extract of Krameria cytisoides (Krameriaceae). The structure of kramecyne was determined by IR, NMR, MS, and elemental analysis, which indicated that the structure corresponded to a hexamer of cyclic peroxide monomers. This compound exhibited good anti-inflammatory activity in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema (51.8 ± 6.9% inhibition) and carrageenan-induced rat paw edema models at doses of 50 mg/kg. The compound significantly reduced edema to 63.1% after 1.0 h, and the effect was unchanged for 5 h. Kramecyne did not present acute toxicity, even at doses of 5,000 mg/kg.

Ratanhiaphenol III from Ratanhiae radix is a PTP1B inhibitor.

The inhibition of protein tyrosine phosphatase 1B (PTP1B) is considered a valid strategy to combat insulin resistance and type II diabetes. We show here that a dichloromethane extract of Ratanhiae radix ( RR_EX) dose-dependently inhibits human recombinant PTP1B in vitro and enhances insulin-stimulated glucose uptake in murine myocytes. By determination of the PTP1B inhibiting potential of 11 recently isolated lignan derivatives from RR_EX, the observed activity of the extract could be partly assigned to ratanhiaphenol III. This compound inhibited PTP1B in vitro with an IC (50) of 20.2 µM and dose-dependently increased insulin receptor phosphorylation as well as insulin-stimulated glucose uptake in cultured myotubes. This is the first report to reveal an antidiabetic potential for a constituent of rhatany root, traditionally used against inflammatory disorders, by showing its capability of inhibiting PTP1B.

Phytochemical study and anti-inflammatory, antidiabetic and free radical scavenger evaluations of Krameria pauciflora methanol extract.

The plant Krameria pauciflora MOC et. Sessé ex DC. is used as an anti-inflammatory and antidiabetic in traditional medicine. The aim of this study was to evaluate the in vivo anti-inflammatory and antidiabetic effects of a methanol extract from the roots of K. pauciflora. Dichloromethane and ethyl acetate extracts obtained by partitioning the methanol extract were also evaluated. Complete methanol and dichloromethane extracts showed anti-inflammatory effects at 3 mg/kg. An anti-inflammatory effect similar to indomethacin (10 mg/kg) was observed when the methanol and dichloromethane extracts, which contain a cycloartane-type triterpene and an sterol, were administered orally at several doses (3, 10, 30 and 100 mg/kg), whereas no anti-inflammatory effect was observed at any dose for the ethyl acetate extract, which contains catechin-type flavonoids. The antidiabetic effect of each extract was also determined. An antihyperglycaemic effect was observed in diabetic rats, but no effect in normoglycaemic animals was observed when the methanol extract was administrated at 30 mg/kg. All of the extracts exhibited radical scavenger activity. Additionally, constituents from all of the extracts were identified by NMR. This article supports the use of K. pauciflora as an anti-inflammatory because it exhibits a similar effect to indomethacin. However, its antidiabetic effect is not completely clear, although it could be useful for preventing diabetic complications.

Bacterial biofilm formation inhibitory activity revealed for plant derived natural compounds.

Use of herbal plant remedies to treat infectious diseases is a common practice in many countries in traditional and alternative medicine. However to date there are only few antimicrobial agents derived from botanics. Based on microbiological screening tests of crude plant extracts we identified four compounds derived from Krameria, Aesculus hippocastanum and Chelidonium majus that showed a potentially interesting antimicrobial activity. In this work we present an in depth characterization of the inhibition activity of these pure compounds on the formation of biofilm of Staphylococcus aureus as well as of Staphylococcus epidermidis strains. We show that two of these compounds possess interesting potential to become active principles of new drugs.

Lignan derivatives from Krameria lappacea roots inhibit acute inflammation in vivo and pro-inflammatory mediators in vitro.

The roots of Krameria lappacea are used traditionally against oropharyngeal inflammation. So far, the astringent and antimicrobial properties of its proanthocyanidin constituents are considered to account for the anti-inflammatory effect. The aim of the present study was to characterize pharmacologically a lipophilic extract of K. lappacea roots and several isolated lignan derivatives (1-11) in terms of their putative anti-inflammatory activity. The dichloromethane extract (ID50 77 µg/cm²) as well compounds 1-11 (ID50 0.31-0.60 µmol/cm²) exhibited topical antiedematous properties comparable to those of indomethacin (ID50 0.29 µmol/cm²) in a mouse ear in vivo model. Two of the most potent compounds, 2-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxypropyl)benzofuran (5) and (+)-conocarpan (7), were studied regarding their time-dependent edema development and leukocyte infiltration up to 48 h after croton oil-induced dermatitis induction, and they showed activity profiles similar to that of hydrocortisone. In vitro studies of the isolated lignan derivatives demonstrated the inhibition of NF-κB, cyclooxygenase-1 and -2, 5-lipoxygenase, and microsomal prostaglandin E2 synthase-1 as well as antioxidant properties, as mechanisms possibly contributing to the observed in vivo effects. The present findings not only support the ethnopharmacological use of K. lappacea roots but also reveal that the isolated lignan derivatives contribute strongly to the anti-inflammatory activity of this herbal drug.

Quantitative analysis of anti-inflammatory lignan derivatives in Ratanhiae radix and its tincture by HPLC-PDA and HPLC-MS.

Root preparations of Krameria lappacea (Dombey) Burdet et Simpson are traditionally used against oropharyngeal inflammation. Besides antimicrobial and astringent procyanidines, lignan derivatives, including ratanhiaphenol I, II, III and (+)-conocarpan, contribute to the activity of Ratanhiae radix, exerting a significant topical anti-inflammatory activity in vivo, and in vitro by inhibiting NF-κB and the formation of inflammatory prostaglandins and leukotrienes. Besides gravimetrical analysis of the ratanhiaphenols I, II and III, the content of these compounds in the herbal drug has never been determined. The developed HPLC method enables the quantification of twelve active lignan derivatives in the roots, and is also suitable for the determination of the constituents in Tinctura Ratanhiae. Separation was achieved on a phenyl-hexyl column material using a solvent gradient consisting of 0.02% aqueous TFA and a mixture of acetonitrile/methanol (75:25, v/v). Sensitivity, accuracy (recovery rates were between 95% and 105.6%), repeatability (RSD ≤ 4.6%), and precision (intra-day precision ≤ 4.8%; inter-day precision ≤ 3.4%) of the method were determined. HPLC-MS experiments in positive and negative electrospray ionization mode confirmed identity and peak purity of analytes. The analysis of several root and tincture samples revealed that (+)-conocarpan and ratanhiaphenol II dominated with contents of 0.49-0.71% and 0.51-0.53% in the roots and 0.66-0.68 mg/ml and 0.70-0.71 mg/ml in the commercial tinctures, respectively.

Optimization and application of a fluorimetric assay for the identification of histone deacetylase inhibitors from plant origin.

CONTEXT: Histonedeacetylase inhibitors (HDACi) are the focus of enormous interest as a new class of anticancer drugs and discussed as novel treatment in cardiovascular diseases or memory enhancement. In the search for new active substances the structural diversity of secondary plant metabolites provides an indispensable resource. Several molecules from the plant kingdom have gained importance as anticancer drugs. Thus, a search for new therapeutic agents inhibiting histonedeacetylases (HDACs) is an important topic. To accelerate the isolation of potential candidates from plants bioassays well suited for screenings of extracts are an indispensable prerequisite. OBJECTIVE: In the presented study an enzymatic assay was modified, optimized and validated for the search for HDACi from plant origin. MATERIALS AND METHODS: A fluorimetric assay was validated with respect to parameters such as temperature, incubation times, reproducibility, applicability of different enzyme sources and HDAC substrate. For the determination of the HDAC inhibitory potential of extracts the detailed study of the influence of different classes of primary and secondary metabolites probably interfering with the assay was most important. RESULTS: In the experimental design autofluorescent coumarins and tannins were identified to disrupt the assay. Possibilities to avoid disturbances are demonstrated and the applicability of the method in the bioactivity-guided search for new HDACi was proven on the example Leonuri herba (Leonurus cardiaca L.; Lamiaceae). CONCLUSION: The optimization of the assay led to a highly efficient fluorimetric method to study plant extracts and fractions of medium/high polarity for HDAC inhibition. In the bioactivity-guided fractionation of extracts from Leonuri herba the applicability for the aimed purpose was clearly demonstrated.

Protective effect of four Mexican plants against CCl4-induced damage on the Huh7 human hepatoma cell line.

BACKGROUND: Centaurea americana, Krameria ramosissima, Juglans mollis and Turnera diffusa are used by traditional healers in the northeastern region of Mexico to protect against liver damage. However, the hepatoprotective properties of these plants have not been investigated scientifically. This study reports on the protective effects of these plants using an in vitro assay. MATERIAL AND METHODS: Extracts of plants were tested for antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method. The effects of extracts from these plants on a human hepatoma cell line (Huh7) were evaluated according to cell viability and aspartate aminotransferase and malondialdehyde levels before and after exposure of the cells to carbon tetrachloride (CCl(4)). RESULTS: All extracts reduced DPPH levels by more than 50%. C. americana flower and stem/leaf extracts, the aerial part of T. diffusa, and the nut, leaf and bark of J. mollis extracts were used to assess hepatoprotective activity. The extract of the aerial part of K. ramosissima was toxic. Pretreatment of Huh7 cells with extracts from the flower of C. americana (FCA), the stem/leaf fraction of C. americana (S/LCA), the leaf of J. mollis (LJM) and the bark of J. mollis (BJM) prior to the CCl(4) challenge, protected against CCl(4)-induced liver damage, as evidenced by a significant decrease in the activity of the medium enzyme. The FCA, S/LCA, LJM and BJM extracts showed significant antilipid peroxidant effects in vitro. In conclusion, the hepatoprotective effects of the FCA, S/LCA, LJM and BJM extracts observed in this study may result from their antioxidative properties.

[The pollination of Krameria bahiana B.B. Simpson by bees in the Coastal Sand Plains of Bahia, Brazil]. / A polinização de Krameria bahiana B.B. Simpson (Krameriaceae) por Abelhas (Apidae) na Restinga, BA.

The flowers of K. bahiana mainly produce oil as floral resource for their visitors. Oil collecting bees usually show morphological and behavioral adaptation for their collection. This study focused on the analysis of interactions between the flowers of K. bahiana and their visiting bees, aiming for the efficiency of the pollination, in an area of the Coastal Sand Plains of Bahia State, Brazil. From February/2001 to February/2002 and from May to October/2002 observations were accomplished about the phenology and morphology of the plants and the floral visitors' behavior. The flowers of the inflorescences are zigomorphic, small sized, pink and present a pair of petals modified in epithelial elaiophores, which are responsible for the production of oil. These flowers were visited especially by bees of the genus Centris: C. leprieuri Spinola, C. tarsata Smith, C. trigonoides Lepeletier and C. pulchra Moure, Oliveira & Viana. The bees collected only oil in the flowers, by scratching the elaiophores and then transferring it to scopa located on the tibia and basitarsus of the hind legs. During those actions, the bees often contact the reproductive structures of the flowers, resulting in pollination. C. leprieuri was the most frequent bee during this study, thus considered the effective pollinator. Megachile dentipes Vachal also visited the flowers of K. bahiana, collecting only pollen. However, these bees were considered sporadic pollinators because they were not frequent in the flowers of K. bahiana in the months of observation.

A polinização de Krameria bahiana B.B. Simpson (Krameriaceae) por abelhas (Apidae) na restinga, BA / The pollination of Krameria bahiana B.B. Simpson for bees in the Coastal Sand Plains of Bahia, Brazil

As flores de Krameria bahiana B.B. Simpson produzem principalmente óleo como recurso floral para seus visitantes. Abelhas coletoras de óleo usualmente apresentam adaptações morfológicas e comportamentais para sua coleta. Este estudo teve como objetivo a análise das interações entre as flores de K. bahiana e as abelhas visitantes, visando a eficiência da polinização, em uma área de restinga na Bahia. De fevereiro/2001 a fevereiro/2002 e de maio a outubro/2002 foram realizadas observações sobre a fenologia e morfologia das plantas e comportamento dos visitantes florais. As flores das inflorescências são zigomórficas, pequenas, de cor rosa e apresentam um par de pétalas modificadas em elaióforos epiteliais, as quais são responsáveis pela produção de óleo. As flores foram visitadas especialmente por abelhas do gênero Centris, C. leprieuri Spinola, C. tarsata Smith, C. trigonoides Lepeletier e C. pulchra Moure, Oliveira & Viana. Essas espécies coletam apenas óleo nas flores, raspando os elaióforos, posteriormente transferindo o recurso para a escopa localizada na tíbia e basitarso das pernas posteriores. Durante esta ação, as abelhas freqüentemente contatam as estruturas reprodutivas das flores, resultando na polinização. C. leprieuri foi a abelha mais freqüente durante este estudo, sendo considerada o polinizador efetivo. Megachile dentipes Vachal também visitou as flores de K. bahiana, coletando apenas pólen. Entretanto, estas abelhas foram consideradas polinizadoras esporádicas por não serem freqüentes nas flores de K. bahiana nos meses de observação.

The flowers of K. bahiana mainly produce oil as floral resource for their visitors. Oil collecting bees usually show morphological and behavioral adaptation for their collection. This study focused on the analysis of interactions between the flowers of K. bahiana and their visiting bees, aiming for the efficiency of the pollination, in an area of the Coastal Sand Plains of Bahia State, Brazil. From February/2001 to February/2002 and from May to October/2002 observations were accomplished about the phenology and morphology of the plants and the floral visitors' behavior. The flowers of the inflorescences are zigomorphic, small sized, pink and present a pair of petals modified in epithelial elaiophores, which are responsible for the production of oil. These flowers were visited especially by bees of the genus Centris: C. leprieuri Spinola, C. tarsata Smith, C. trigonoides Lepeletier and C. pulchra Moure, Oliveira & Viana. The bees collected only oil in the flowers, by scratching the elaiophores and then transferring it to scopa located on the tibia and basitarsus of the hind legs. During those actions, the bees often contact the reproductive structures of the flowers, resulting in pollination. C. leprieuri was the most frequent bee during this study, thus considered the effective pollinator. Megachile dentipes Vachal also visited the flowers of K. bahiana, collecting only pollen. However, these bees were considered sporadic pollinators because they were not frequent in the flowers of K. bahiana in the months of observation.

Inhibitory effect of the norlignan 2-(2'-hydroxy-4',6'-dimethoxyphenyl)-5-[(E)-propenyl]benzofuran from Krameria tomentosa on acetylcholine-induced relaxation of the rat aorta.

In this work, we studied the effect of the norlignan 2-(2'-hydroxy-4',6'-dimethoxyphenyl)-5-[( E)-propenyl]benzofuran (DMPP) in the rat aorta. In aortic rings with intact endothelium, DMPP inhibited in a concentration-dependent manner the vasodilator effect produced by acetylcholine with an IC50 value of 31.2+/-6.3 microM. DMPP also inhibited basal nitric oxide production. In endothelium-denuded vessels DMPP was without effect whereas superoxide dismutase (SOD) was effective in potentiating responses to the NO donor SIN-1. Contractile effects of carbachol in guinea-pig ileum and trachea were unaffected by DMPP. It is concluded that DMPP inhibits the endothelium-dependent relaxation induced by acetylcholine in the rat aorta without affecting receptor or smooth muscle cells function. Decreased nitric oxide production by endothelial cells seems to be the mechanism involved in the inhibitory effect of DMPP.

Actividad citotóxica in vitro de las fracciones de la mezcla de Annona muricata más Krameria lappacea sobre células cancerosas de glándula mamaria, pulmón y del sistema nervioso central / In vitro cytotoxic activity of a mixture of Annona muricata and Krameria lappacea on breast, lung, and central nervous system cancer cells

Objetivos: Determinar la actividad citotóxica de las fracciones procedentes de la combinación 1:1 del extracto etanólico de hojas de Annona muricata L (guanábana) y el extracto acuoso atomizado de la raíz de Kramerialappacea (ratania) en cultivos de líneas celulares cancerosas de glándula mamaria (MCF-7), pulmón (H-460) ysistema nervioso central (SF-268). Materiales y métodos: Para el fraccionamiento de la mezcla 1:1 de Annona mas Krameria se preparó una columna cromatográfica de 50 cm de longitud empleando diclorometano, diclorometano:acetato de etilo y CHCl3:MeOH como sistemas de elusión de polaridad creciente, obteniéndose 186 fracciones. Se evaluaron las fracciones 2 a 83 en cultivo de células cancerosas de glándula mamaria (MCF-7), de pulmón (H-460) y del sistema nervioso central (SF-268). Todas las fracciones fueron ensayadas en duplicado. Aquellas fracciones que presentaronun porcentaje de crecimiento de células cancerosas (por ciento G) <50 por ciento en alguna de las tres líneas celulares fueron ensayadas nuevamente a cinco concentraciones, para determinar finalmente la concentración a la cual se inhibe el 50 por ciento del crecimiento de las células cancerosas (GI50). Se consideraron activas aquellas fracciones con una GI50 <10 µg/mL. Resultados: Las fracciones 7 a 17 procedentes de la asociación de los dos productos naturales frente a loscultivos de las líneas celulares tumorales MCF-7, H-460 y SF-268 mostraron una GI50 de 1,6, 1,4 y 1,4 µg/mL respectivamente. Conclusiones: Las fracciones 7 a 17 procedentes de la asociación de Annona más Krameriamostraron acción citotóxica in vitro frente al cultivo de células cancerosas de glándula mamaria, pulmón y del sistema nervioso central.

Objectives: To determine cytotoxic activity of fractions from a 1:1 combination of an ethanol extract of Annona muricata leaves (soursop) and atomized aqueous extract of Krameria lappacea root (Ratania) in breast (MCF-7), lung (H-460), and central nervous system (SF-268) cancer cell cultures. Material and methods: For fractionating the 1:1 mixture of Annona and Krameria a 50-cm long chromatographic column was prepared using dichloromethane, dicholoromethane: ethyl acetate and ChCl3:MeOH as increasing polarity eluting systems and 186 fractions were obtained. Fractions 2 to 83 were assessed in breast (MCF-7), lung (H-460), and central nervous system (SF-268) cancer cell cultures. All fractions were assessed two times. Those fractions that showed <50% growth of cancer cells (%G) in any of the three cell lines were assayed once again using five different concentrations, in order to determine the concentration where there was a 50% inhibition of cancer cell growth (GI50). Those fractions with a <10 ìg/mL GI50 were considered to be active against cancer cell lines. Results: Fractions 7 to 17 of the association of the two aforementioned natural products has GI50 values reported as 1,6, 1,4, and 1,4 ìg/mL against MCF-7, H-460, and SF-268 cancer cell lines, respectively. Conclusions: Fractions 7 to 17 of the Annona and Krameria combination showed in vitro cytotoxic activity against breast, lung, and central nervous system cancer cultured cells.

Total synthesis of norneolignans from Krameria species.

The total synthesis of nomeolignans isolated from Krameria species, 2-aryl-5-(E)-propenylbenzofurans (5, 11), is described. The key step involves the one-pot reaction for 2-arylbenzofurans (2, 7) from 4-hydroxyphenylacetone with 4'-acetoxy-2-chloro-2-(methylthio)acetophenone (1) and 2-chloro-2-methylthio-(2',4',6'-trimethoxy)acetophenone (6) under Friedel-Crafts reactionconditions.