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This article posits lusmore or foxglove (Digitalis purpurea) as a border herb par excellence.1 It presents a bilingual example of a locus, source and resource of different knowledges sometimes expressed oppositionally as indigenous and scientific. It traces a genealogy of ways of knowing through the filters of a number of reified modern historically determined concepts such as nature, culture, supernatural and folklore. Discussing indigenous names and associated domains, it traces a few apparently obvious similarities and differences, but also moves further upstream to a time and place in which these may not always have been familiar in the same way. This suggests an eco-cosmology involving non-passive ancestral human and nonhuman, often feminine, adumbrating important knowledge, later folklorized as fairyland, that undergoes a complex process of transitions and translations leading, not necessarily originally, inevitably or finally, to masculine rationalist discoveries. [ABSTRACT FROM AUTHOR]

Digitalis purpurea (foxglove, common foxglove, purple foxglove or lady's glove) is a species of flowering plant in the plantain family Plantaginaceae. The objective of this study were analysis of the secondary metabolite products and investigation of its anti-microbial Activity. GC-MS analysis of methanolic extract of Digitalis purpurea revealed the existence of the 4H-Benzopyran-4-one, 6,7-dimethoxy-3-phenyl, Eucalyptol, 7,8-Dihydro-7-methyl-2-phenyl-6-p-tosylamino-pyrido[4,3-d], Octanoic acid, 6-hydroxy-8-methoxy-,e-lactone,1,3-Dioxolane, 2,2-dimethyl-4-[[(2-methylhexadecyl)oxy]meth, Bicyclo[2.2.1]heptane-2,5-diol, 1,7,7-trimethyl-, (2-endo, 5-ex, 1-Hydroxy-4,4-dimethylcyclohexanecarbonitrile, Bicyclo[3.1.1] hept-2-en-4-ol, 2,6,6-trimethyl-,acetate, 12,15-Octadecadiynoic acid, methyl ester, 2-Cyclohexene-1-methanol, 2,6,6-trimethyl, 1-(Cyclopropyl-nitro-methyl)-cyclopentanol, 11-Oxa-dispiro[4.0.4.1]undecan-1-ol, Muramic acid, 10-Chlorotricyclo[4.2.1.1(2,5)]deca-3,7-dien-9-ol, D-Fructose, diethyl mercaptal, pentaacetate, 10-Octadecenoic acid, methyl ester, 9,12-Octadecadienoic acid (Z,Z), 3h-Naphtho[2,3-b] furan-2-one, 4-hydroxy-4a, 5-dimethyl-3, 9,12,15-Octadecatrienoic acid, 2-phenyl-1,3-dioxan-5-yl ester, and a-Tocopheryl acetate. Digitalis purpurea has maximum zone against Streptococcus faecalis (4.671±0.21). [ABSTRACT FROM AUTHOR]

Digitonin, a steroidal saponin obtained from the foxglove plant (Digitalis purpurea), displays a wide spectrum of biological properties and is often used as a model in mechanistic investigations of the biological activity of saponins. In the present study, Langmuir monolayers of zwitterionic (DPPC, DMPE, POPC, POPE, DSPC, DSPE, and DPPE) and ionic (DPPS and DPPG) phospholipids were employed in order to better understand the effect of digitonin on the lipid organization. For this purpose, a combination of surface pressure relaxation, infrared reflection absorption spectroscopy (IRRAS), and fluorescence microscopy measurements was used. The observed increase in surface pressure (π) suggests that digitonin can adsorb at the air/water interface, both bare and covered with the uncompressed phospholipid monolayers. However, the detailed analysis of IRRAS and fluorescence microscopy data shows that digitonin interacts with the lipid monolayers in a very selective way, and both the headgroup and the lipid tails affect this interaction. Nevertheless, it should be noted that in no case did digitonin cause any disruptive effects on the monolayers. The DPPE and DPPS monolayers get disordered by penetration with digitonin, despite an increase in surface pressure, leading to an unprecedented LC-LE transition. Interestingly, saponin could be easily squeezed out of these monolayers by mechanical compression. [ABSTRACT FROM AUTHOR]

Digitalis purpurea L. is one of the two unique species of economic interest in the genus Digitalis. It is important because is one of the principal source of cardenolides, irreplaceable drugs in the treatment of heart failure. The present work was done with the objective to determinate the effect of inoculum density and gaseous atmosphere renovation in D. purpurea plants cultivated in Temporal Immersion Systems (TIS). To do this, several parameters like inoculums density (6, 12, 18 explants per TIS) and the use forced ventilation were studied. The highest biomass production was obtained when 12 explants were inoculated (104.03 gFW and 5.74 gDW). On the contrary, the lower inoculum density caused a negative effect in plant development and the biomass did not increase. On the other hand, the renovation of atmosphere mediated by forced ventilation induced a higher oxidative stress associated to an increase of digitoxin synthesis. Both factors are of great importance for biomass and secondary metabolites production in plants with pharmaceutical interest. [ABSTRACT FROM AUTHOR]

Genetic transformation is a tool of special interest for developing new biotechnological strategies for the production of bio-active compounds such as cardenolides, which are exclusively obtained from plants. To date, Digitalis plants are the main economically viable source of cardenolides for the pharmaceutical industry. This study describes the development of efficient plant regeneration and Agrobacterium-mediated genetic transformation protocols for Digitalis purpurea L. First, a plant regeneration procedure starting from leaf segments of in vitro-cultivated plants was established and the minimal inhibitory concentration of G-418 (geneticin) for callus induction was determined. Both leaf segments and callus tissue were sensitive to G-418 70 mg l. Afterwards, two Agrobacterium strains were used to test their T-DNA transfer ability on D. purpurea leaf tissues, EHA105 and C58C1Rif (pMP90), both harboring the binary vector pTJK136. Strain C58C1Rif (pMP90) yielded a higher number of transformed plants than EHA105. Successful transformation was confirmed by histochemical β-glucuronidase (GUS) assays of the putative transgenic tissues and PCR analyses using β- glucuronidase ( uidA)- and neomycin phosphotransferase II ( nptII)-specific primers. Southern blot hybridization confirmed the stable integration of the nptII gene in the transgenic plants. In total, 518 independent transgenic lines were regenerated with an average of 6.91 transgenic lines per initial leaf segment infected with A. tumefaciens strain C58C1Rif (pMP90). To date, only a few studies have been published on the genetic transformation of Digitalis species. The protocols for plant regeneration and genetic transformation described in this paper will contribute to functional studies for a better understanding of cardenolide biosynthetic pathways and the metabolic engineering of cardenolides to develop high-yielding improved genotypes. [ABSTRACT FROM AUTHOR]

Digitalis purpurea (D. purpurea) is one of the most important medicinal plants and is well known in the treatment of heart failure because of the cardiac glycosides that are its main active compounds. However, in the absence of strand specific sequencing information, the post-transcriptional mechanism of gene regulation in D. purpurea thus far remains unknown. In this study, a strand-specific RNA-Seq library was constructed and sequenced using Illumina HiSeq platforms to characterize the transcriptome of D. purpurea with a focus on alternative splicing (AS) events and the effect of AS on protein domains. De novo RNA-Seq assembly resulted in 48,475 genes. Based on the assembled transcripts, we reported a list of 3,265 AS genes, including 5,408 AS events in D. purpurea. Interestingly, both glycosyltransferases and monooxygenase, which were involved in the biosynthesis of cardiac glycosides, are regulated by AS. A total of 2,422 AS events occurred in coding regions, and 959 AS events were located in the regions of 882 unique protein domains, which could affect protein function. This D. purpurea transcriptome study substantially increased the expressed sequence resource and presented a better understanding of post-transcriptional regulation to further facilitate the medicinal applications of D. purpurea for human health. [ABSTRACT FROM AUTHOR]

The extraction methods of genomic DNA are usually laborious and hazardous to human health and the environment by the use of organic solvents (chloroform and phenol). In this work a protocol for in situ extraction of genomic DNA by alkaline lysis is validated. It was used in order to amplify regions of DNA in four species of plants and fungi by polymerase chain reaction (PCR). From plant material of Saccharum officinarum L., Carica papaya L. and Digitalis purpurea L. it was possible to extend different regions of the genome through PCR. Furthermore, it was possible to amplify a fragment of avr-4 gene DNA purified from lyophilized mycelium of Mycosphaerella fijiensis. Additionally, it was possible to amplify the region ap24 transgene inserted into the genome of banana cv. 'Grande naine' (Musa AAA). [ABSTRACT FROM AUTHOR]

The article presents a study on the phytochemical examination of the flowering plant Digitalis purpurea's seeds which resulted in the isolation of 15 cardenolide glycosides including three new compounds showing cytotoxicity against leukemia cells and human liver cancer cells. It mentions that the structure of glycosides was determined by nuclear magnetic resonance (NMR) spectroscopy. It reveals that the cytotoxic activity of cardenolide glycosides was reduced by addition of a hydroxy group.

Digitalis purpurea L. (Scrophulariaceae; Foxglove) is a source of cardiotonic glycosides such as digitoxin and digoxin which are commercially applied in the treatment to strengthen cardiac diffusion and to regulate heart rhythm. This investigation deals with in vitro propagation and elicited production of cardiotonic glycosides digitoxin and digoxin in shoot cultures of D. purpurea L. In vitro germinated seedlings were used as a primary source of explants. Multiple shoot formation was achieved for three explant types (nodal, internodal, and leaf) cultured on Murashige and Skoog (MS) medium with several treatments of cytokinins (6-benzyladenine-BA; kinetin-Kin; and thidiazuron-TDZ) and auxins (indole-3-acetic acid-IAA; α-naphthaleneacetic acid-NAA; and 2,4-dichlorophenoxy acetic acid-2,4-D). Maximum multiple shoots (12.7 ± 0.6) were produced from nodal explants on MS + 7.5 μM BA. Shoots were rooted in vitro on MS containing 15 μM IAA. Rooted plantlets were successfully acclimatized. To further maintain the multiple shoot induction, mother tissue was cut into four equal parts and repeatedly sub-cultured on fresh shoot induction liquid medium after each harvest. On adaptation of this strategy, an average of 18 shoots per explant could be produced. This strategy was applied for the production of biomass and glycosides digitoxin and digoxin in shoot cultures on MS medium supplemented with 7.5 μM BA and several treatments with plant growth regulators, incubation period, abiotic (salicylic acid, mannitol, sorbitol, PEG-6000, NaCl, and KCl), biotic ( Aspergillus niger, Helminthosporium sp., Alternaria sp., chitin, and yeast extract) elicitors, and precursors (progesterone, cholesterol, and squalene). The treatment of KCl, mycelial mass of Helminthosporium sp., and progesterone were highly effective for the production of cardenolides. In the presence of progesterone (200 to 300 mg/l), digitoxin and digoxin accumulation was enhanced by 9.1- and 11.9-folds respectively. [ABSTRACT FROM AUTHOR]

The plants of the genus Digitalis are characterized by the production of cardenolides, drugs widely used worldwide in the treatment of heart failure. In previous research a transformation protocol was developed from leaf disc of Digitalis purpurea L., using geneticin as selection marker. However some escapes in the selection process were obtained. So it is necessary to develop a more efficient selection scheme using another selective agent. Therefore, the aim of the present research was to select the minimum lethal concentration of hygromycin B during callus induction and shoots multiplication of D. purpurea. For callus induction we studied five concentrations of hygromycine B (3, 6, 9, 12, 15 mg l-1) during 28 days. Besides, the effect in shoot multiplication of four concentrations of hygromycine B (25, 50, 75, 100 mg l-1) was studied during 30 days. The minimal lethal concentration for callus formation was 12 mg l-1. In the case of shoot multiplication, 100% mortality was showed at 75 mg l-1 strictly after 30 days. The proposed selection scheme is recommended for future work at genetic transformation in this species. [ABSTRACT FROM AUTHOR]

Specialization in plant-pollinator systems represents an important issue for both the ecological understanding and conservation of these systems. We investigated the extent to which the bumblebee Bombus hortorum (Linnaeus) is the main potential pollinator of Common Foxglove, Digitalis purpurea L. Twenty D. purpurea patches were selected in North Yorkshire, U.K., ten each in woodland and garden or park habitat. All insects visiting D. purpurea within the patches were recorded over seventy 30-min bouts. The relative frequency of insect visitors to other flowering plant species within 15 m of each patch was also determined. B. hortorum and B. pascuorum were the two most frequent visitors to D. purpurea , accounting for 82 - 92% and 3 -17%, respectively, of all insect visits (n = 1682), depending on habitat. B. hortorum showed a significant preference for visiting D. purpurea relative to its frequency of visits to other available plant species. The relationship of D. purpurea with B. hortorum, which pollinates several plant species with long corollas, therefore represents a potential case of asymmetric specialization, albeit one that may vary spatially. Because D. purpurea reproduction appears dependent on insect pollination, B. hortorum and B. pascuorum may help underpin the viability of D. purpurea populations. [ABSTRACT FROM AUTHOR]

Abstract: Urbanization of natural habitats is considered to have large impacts on local plant populations and their associated pollinator faunas, which are expected to cause changes in both plant-pollinator interactions and increased pollen limitation. This study investigated the effects of increasing intensity of urban land use on pollinator diversity, flower visitation rates and reproductive success in Digitalis purpurea. To this end, we set up experimental populations of D. purpurea in three urban–rural gradients and contrasted these against two large, natural populations. In the experimental populations we quantified the number of flower visits per 20min and applied supplemental hand-pollinations to determine the impact of pollen limitation on fruit-level seed set. We found no impact of urbanization intensity on pollinator diversity at all locations studied, and also the number of flower visits did not differ significantly between urban and rural populations. Reproductive success appeared, however, pollen limited in all sites, even in the large and optimal reference populations. This led us to conclude that the pollen limitation was caused by a bet-hedging strategy of the species rather than by insufficient pollination. [Copyright &y& Elsevier]

The survival of seedlings in temperate climate habitats depends on both temporal and spatial factors. The interaction between an internal seed dormancy mechanism and the ruling environmental conditions allows accurate cueing of germination. We analysed how environmental signals interact in seeds of temperate forest pioneer species, increasing the seed's chances of germinating in the right place at the right time. Digitalis purpurea and Scrophularia nodosa are two small-seeded herbaceous species that typically grow in vegetation gaps in European temperate forests. Seeds of both species are partially dormant at the time of dispersal in summer. This primary dormancy is released in autumn and early winter, resulting in a minimal level of physiological dormancy by late winter and early spring. We observed that physiological dormancy was induced again in seeds exhumed in late spring and in summer. Experiments in laboratory conditions revealed that primary dormancy in seeds of S nodosa was broken by cold stratification, whereas primary dormancy in D. purpurea seeds was broken by both a cold and a warm stratification. The two species differed in their response to the tested gap-detection signals, as light was the most important factor stimulating germination of D. purpurea, and seeds of S. nodosa germinated best when subjected to daily fluctuating temperatures. This study clearly indicates that the ability to germinate in response to gap-detection signals changes seasonally in temperate forest pioneers. Additionally, seeds of both species responded differently to these environmental signals, probably reflecting differences in the regeneration niche. [ABSTRACT FROM AUTHOR]

Background: Functional traits play important roles in plant growth and survival. According to functional traits, there are several classification types for plants such as adaptive and demographic strategies. Materials and Methods: In this study, eight endemic taxa were collected from the Amasya Kirklar Mountain in Turkey and were classified and evaluated by Grime's CSR (Competitive, Stress tolerant, Ruderal) strategy scheme. Results: These plants are in the LR(lc) (Lower risk/least concern) red list category and they are hemicryptophytes according to Raunkiaer's life forms. The CSR strategies of Asyneuma limonifolium subsp. pestalozzae, Digitalis lamarckii, and Paracaryum ancyritanum were CR, Linaria corifolia and Scutellaria salviifolia were CR/CSR, Phlomis armeniaca was C/CR, and Sideritis dichotoma and Jurinea pontica were SC. Conclusions: CR, CR/CSR, and C/CR plants are resistant to competition and disturbance such as grazing, trampling, mowing, soil erosion, and fire, whereas, SC are resistant to competition and stress, for example drought [ABSTRACT FROM AUTHOR]

Background: Digitalis purpurea is an important ornamental and medicinal plant. There is considerable interest in exploring its transcriptome. Results: Through high-throughput 454 sequencing and subsequent assembly, we obtained 23532 genes, of which 15626 encode conserved proteins. We determined 140 unigenes to be candidates involved in cardiac glycoside biosynthesis. It could be grouped into 30 families, of which 29 were identified for the first time in D. purpurea. We identified 2660 mRNA-like npcRNA (mlncRNA) candidates, an emerging class of regulators, using a computational mlncRNA identification pipeline and 13 microRNA-producing unigenes based on sequence conservation and hairpin structure-forming capability. Twenty five protein-coding unigenes were predicted to be targets of these microRNAs. Among the mlncRNA candidates, only 320 could be grouped into 140 families with at least two members in a family. The majority of D. purpurea mlncRNAs were species-specific and many of them showed tissue-specific expression and responded to cold and dehydration stresses. We identified 417 protein-coding genes with regions significantly homologous or complementary to 375 mlncRNAs. It includes five genes involved in secondary metabolism. A positive correlation was found in gene expression between protein-coding genes and the homologous mlncRNAs in response to cold and dehydration stresses, while the correlation was negative when protein-coding genes and mlncRNAs were complementary to each other. Conclusions: Through comprehensive transcriptome analysis, we not only identified 29 novel gene families potentially involved in the biosynthesis of cardiac glycosides but also characterized a large number of mlncRNAs. Our results suggest the importance of mlncRNAs in secondary metabolism and stress response in D. purpurea. [ABSTRACT FROM AUTHOR]

Serially diluted and agitated (SAD) drugs available commercially are in use with great faith because of the astonishing results they produce. The scientific viewpoint attached to the centuries-old therapy with SAD drugs, as in homeopathy, remained doubtful for want of appropriate research and insufficient evidence base. The conflicting points related to SAD drug mostly related to the level of concentrations/dilutions, use of drug in contradictory clinical conditions compared to the modern system of medicine, identification of medicinally active ingredient in concentrations and dilutions used in commercially available SAD drugs, and lack of laboratory-based pharmacological data vis-`a-vis modern medicine. Modus operandi of SAD drug is also unknown. To address some of these issues an analytical study was carried out wherein commercially available SAD drug Digitalis purpurea, commonly used in different systems of medicine, was put to test. Various concentrations of commercially available Digitalis purpurea were analyzed using analytical methods: cyclic voltammetry, emission spectroscopy, and UV-VIS spectroscopy. These analytical methods apparently identified the medicinal ingredients and effect of serial dilution in commercial preparation of the drugs. [ABSTRACT FROM AUTHOR]

One major characteristic of invasive alien species is their occurrence at high abundances in their new habitat. Flowering invasive plant species that are visited by native insects and overlap with native plant species in their pollinators may facilitate or disrupt native flower visitation and fertilisation by forming large, dense populations with high numbers of flowers and copious rewards. We investigated the direction of such a proposed effect for the alien invasive Rhododendron ponticum in Irish habitats. Flower visitation, conspecific and alien pollen deposition, fruit and seed set were measured in a self-compatible native focal plant, Digitalis purpurea, and compared between field sites that contained different relative abundances of R. ponticum. Flower visitation was significantly lower at higher alien relative plant abundances than at lower abundances or in the absence of the alien. Native flowers experienced a significant decrease in conspecific pollen deposition with increasing alien abundance. Heterospecific pollen transfer was very low in all field sites but increased significantly with increasing relative R. ponticum abundance. However, lower flower visitation and lower conspecific pollen transfer did not alter reproductive success of D. purpurea. Our study shows that indirect interactions between alien and native plants for pollination can be modified by population characteristics (such as relative abundance) in a similar way as interactions among native plant species. In D. purpurea, only certain aspects of pollination and reproduction were affected by high alien abundances which is probably a result of high resilience due to a self-compatible breeding system. Native species that are more susceptible to pollen limitation are more likely to experience fitness disadvantages in habitats with high relative alien plant abundances. [ABSTRACT FROM AUTHOR]

Angiosperms exhibit staggering diversity in floral form, and evolution of floral morphology is often correlated with changes in pollination syndrome. The showy, bilaterally symmetrical flowers of the model species Antirrhinum majus (Plantaginaceae) are highly specialized for bee pollination. In A. majus, CYCLOIDEA (CYC), DICHOTOMA (DICH), RADIALIS (RAD), and DIVARICATA (DIV) specify the development of floral bilateral symmetry. However, it is unclear to what extent evolution of these genes has resulted in flower morphological divergence among closely related members of Plantaginaceae differing in pollination syndrome. We compared floral symmetry genes from insect-pollinated Digitalis purpurea, which has bilaterally symmetrical flowers, with those from closely related Aragoa abietina and wind-pollinated Plantago major, both of which have radially symmetrical flowers. We demonstrate that Plantago, but not Aragoa, species have lost a dorsally expressed CYC-like gene and downstream targets RAD and DIV. Furthermore, the single P. major CYC-like gene is expressed across all regions of the flower, similar to expression of its ortholog in closely related Veronica serpyllifolia. We propose that changes in the expression of duplicated CYC-like genes led to the evolution of radial flower symmetry in Aragoa/Plantago, and that further disintegration of the symmetry gene pathway resulted in the wind-pollination syndrome of Plantago. This model underscores the potential importance of gene loss in the evolution of ecologically important traits. [ABSTRACT FROM AUTHOR]

Abstract: We developed a highly sensitive and selective reversed-phase HPLC-pulsed amperometric detection (RP-HPLC-PAD) method for cardiac glycoside detection. Eight cardiac glycosides were completely separated within 45min on a reversed-phase column using a water–acetonitrile gradient, and were detected using a PAD under NaOH alkaline conditions. The detection (S/N =3) and quantification (S/N =10) limits for the cardiac glycosides were 0.1–0.3 and 0.3–0.8ng, respectively. The linear regression coefficient was 0.9962–0.9998 for concentrations of 1–25μg/mL. Cardiac glycosides in the Digitalis purpurea leaf displayed intra- and inter-day precisions (RSDs) of <9.30% and average recoveries of 98.63–99.94%. The contents of gitoxin, digitonin, and digitoxin in the D. purpurea were 0.197, 0.11, and 0.379mg/g for leaf dried at 60°C, 0.058, 0.11, and 0.090mg/g for leaf dried at ambient temperature, and N.D. (not detected), and 18.379mg/g, N.D. for seed, respectively. We conclude that our method shows good precision and accuracy. [ABSTRACT FROM AUTHOR]

Cardenolides are secondary metabolites produced by plants of the genus Digitalis. These are widely used in treatments of congestive heart failure. Failed attempts to obtain suitable cardenolide levels from in vitro culture of Digitalis plants have pointed genetic transformation as a promising strategy to obtain highly productive plants. Transformation systems have been already developed for Digitalis minor and Digitalis lanata to achieve this aim, whereas related investigations have been done in other species of the same genus. Selection of candidate genes for transformation depends on the analysis of the cardenolide biosynthesis pathway. The latter is partially established, from phytosterol oxidative degradation to progesterone reduction. Many authors point this reaction as the first specific key step of the pathway. However, the recent discovery of two genes encoding this enzyme activity in Digitalis purpurea, with different expression patterns, calls this statement into question. Pathway flexibility and possible connections with other hormone-related processes imply an additional challenge in this regard. Therefore, functional studies of these genes and their signaling pathways are required to improve design Digitalis transformation strategies, maximizing cardenolide productivity as well as minimizing hazardous side effects on transformed plants viability. [ABSTRACT FROM AUTHOR]

Objective. To report a case of cardiac arrhythmia related to a low dose of endovenous lanatoside C. Case report. A 23-year-old pregnant woman with mitral regurgitation complicated with preeclampsia and pulmonary edema presented 2 episodes of atrial tachycardia induced by a intravenous digitalis (2 mg, IV and 1 mg, IV, respectively). Conclusion. This case calls attention to the need for further studies analysing the security of digoxin use in preeclampsia. [ABSTRACT FROM AUTHOR]

• The stereospecific 5β-reduction of progesterone is a required step for cardiac glycoside biosynthesis in foxglove plants. Recently, we have isolated the gene P5βR, and here we investigate the function and regulation of P5βR2, a new progesterone 5β-reductase gene from Digitalis purpurea. • P5βR2 cDNA was isolated from a D. purpurea cDNA library and further characterized at the biochemical, structural and physiological levels. • Like P5βR, P5βR2 catalyzes the 5β-reduction of the Δ4 double bond of several steroids and is present in all plant organs. Under stress conditions or on treatment with chemical elicitors, P5βR expression does not vary, whereas P5βR2 is highly responsive. P5βR2 expression is regulated by ethylene and hydrogen peroxide. • The correlation between P5βR2 expression and cardenolide formation demonstrates the key role of this gene in cardenolide biosynthesis, and therefore in the chemical defense of foxglove plants. [ABSTRACT FROM AUTHOR]

Comfrey (Symphytum officinale) leaves resemble those of foxglove (Digitalis purpurea) when the plant is not in bloom and, therefore, cardiac glycoside poisoning may occur when people confuse foxglove with comfrey. We report an outbreak of foxglove leaf poisoning following the use of alleged “comfrey” herbal tea. Nine patients were involved and initially presented with nausea, vomiting, diarrhea and dizziness. Significant cardiotoxicity developed later among the 3 patients who also had mild hyperkalemia. Peak serum digoxin concentration measured by immunoassay was elevated in all patients and ranged from 4.4 ng/mL to 139.5 ng/mL. Patients with severe cardiotoxicity were treated with temporary cardiac pacing. Moreover, 40–80 mg of digoxin-specific antibody therapy was given without any effect. All patients recovered uneventfully. Our report highlights the potential risk of misidentification of herbs; in this case, D. purpurea was mistaken for S. officinale. Physicians should be aware that cardiac glycoside poisoning could arise from such misidentification. Public education about the toxicity of D. purpurea poisoning may reduce the risk of misidentification and subsequent poisoning. [Copyright &y& Elsevier]

Abstract: (Na++K+)-ATPase is a target receptor of digitalis (cardiac glycoside) drugs. It has been demonstrated that the H1-H2 domain of the α-subunit of the (Na++K+)-ATPase is one of the digitalis drug interaction sites of the enzyme. Despite the extensive studies of the inhibitory effect of digitalis on the (Na++K+)-ATPase, the functional property of the H1-H2 domain of the enzyme and its role in regulating enzyme activity is not completely understood. Here we report a surprise finding: instead of inhibiting the enzyme, binding of a specific monoclonal antibody SSA78 to the H1-H2 domain of the (Na++K+)-ATPase elevates the catalytic activity of the enzyme. In the presence of low concentration of ouabain, monoclonal antibody SSA78 significantly protects enzyme function against ouabain-induced inhibition. However, higher concentration of ouabain completely inactivates the (Na++K+)-ATPase even in the presence of SSA78. These results suggest that the H1-H2 domain of the (Na++K+)-ATPase is capable of regulating enzyme function in two distinct ways for both ouabain-sensitive and -resistant forms of the enzyme: it increases the activity of the (Na++K+)-ATPase during its interaction with an activator; it also participates in the mechanism of digitalis or ouabain-induced inhibition of the enzyme. Understanding the dual activity of the H1-H2 domain will help better understand the structure–function relationships of the (Na++K+)-ATPase and the biological processes mediated by the enzyme. [Copyright &y& Elsevier]

Abstract: Insect herbivores search for their host plants in heterogeneous environments, and the efficiency of host location may be influenced by plant architecture and abundance. In this study, we ask how plant and habitat characteristics traditionally thought to attract pollinators are related to attack rates by floral herbivores. Patterns of floral herbivory by the moth larva Eupithecia pulchellata were studied in relation to inflorescence size and local plant density in two years in a natural population of the facultative biennial Digitalis purpurea. Overall levels of herbivory were low, 84% of the infested plants lost less than 10% of their flowers. Only 9% of the plants lost more than 20% of their flowers. Probability of herbivory at the plant level increased strongly with inflorescence height, and it was considerably higher in dense patches compared to sparse ones. There was no effect of local plant density on the functional relationship between inflorescence size and probability of herbivory. Both number and proportion of damaged flowers per plant increased with inflorescence height. The results suggest that E. pulchellata is attracted to dense patches and large individuals of D. purpurea, and that negative effects of herbivory increase with plant size. This implies diminishing returns for investment in more flowers in D. purpurea, and indicates that herbivory may select for smaller flowering size and flower number in this monocarpic species. [Copyright &y& Elsevier]

Digitalis purpurea L. produces cardiatonic glycosides such as digoxin and digitoxin, which are widely used for congestive heart failure. Genomic studies of this species are limited because there is no efficient genetic transformation system. One of the first steps to launch a transgene technology is to obtain the method and agent to select transformed out of non-transformed cells. In the current study, the Geneticin G-418 minimal inhibitory concentration was determined for leaf explants on callus formation. Besides, the effect of concentrations of this antibiotic between 10 and 50 mg·l-1 on leaf fragments was evaluated. An evaluation scale, taking into account the percentage of the explants which did not form callus, was proposed. No explant developed callus when leaf fragments were cultured at 50 mg·l-1. This concentration was considered as the minimal inhibitory and was selected for future works on genetic transformation. [ABSTRACT FROM AUTHOR]

1. Plant ecologists have long since realized that the persistence of many facultative biennial plants depends upon disturbance. However, we still have a limited knowledge of the population-level effects of disturbance, and the connection between adult and seed bank dynamics. 2. Using data from a 3-year demographic study combined with experimental gap-opening in a large population of Digitalis purpurea, we parameterized stochastic transition matrix models in ‘disturbed’ vs. ‘undisturbed’ areas. We simulated different gap sizes (fraction of population that was disturbed) and temporal disturbance patterns (constant, random, regular and irregular return intervals) and evaluated the effects on population growth rate and seed bank dynamics. To explore seed bank importance we used two alternatives for seed bank survival rate (0.75/0.35) and three alternatives for seed bank recruitment fraction (0.9/0.5/0.1). 3. Observed background recruitment levels were insufficient to ensure a positive population growth rate. Increased amounts of gap-opening led to higher growth rates, and population persistence was predicted at moderate disturbance levels if seed bank survival was high (0.75). 4. Temporal disturbance pattern affected model results; random and interval scenarios resulted in lower population growth rates and higher extinction risks than constant scenarios of the same average disturbance level. Small and frequent disturbances led to considerably higher growth rates than large and rare disturbances. 5. Stochastic elasticity analyses identified the seed bank as the most important life cycle stage with respect to population growth and persistence in most scenarios, and its relative impact was positively related to seed bank survival rate and negatively related to disturbance level. Variation in the recruitment fraction from seed bank vs. seed rain affected both population growth rate and elasticity patterns, indicating the large impact of spatial variation in seed bank density. 6. Synthesis: Despite the existence of a large seed bank, our data suggest that recruitment may be locally seed-limited due to a patchy seed bank structure. Local population development may consequently differ widely from gap to gap. These results illustrate how spatial structures in both seed bank, adult population and gap formation interact to shape plant population dynamics, as well as the occurrence of microsite- vs. seed-limitation. [ABSTRACT FROM AUTHOR]

Despite recent, strong interest in the modelling of monocarpic perennial flowering strategies, little is known about how variation in demographic rates affects selection on optimal timing of flowering. Temporal variation may yield fluctuating selective pressures, or, if individuals experience time trends, selection for phenotypic plasticity. Here we report the results of a 3-year study in a large field population of the facultative biennial herb Digitalis purpurea, where we use field data on size-dependent growth, survival and fecundity to parameterize an existing optimisation model. We compare results from models using either deterministic or individually varying demographic rates to address the degree of fluctuating selection on the flowering strategy. In addition, we explore whether recent growing conditions influence the size-specific liability to flower. Model results differed widely between years; immediate onset of reproduction was predicted in 1999, strongly delayed reproduction in 2000. This reflected large differences in both growth and survival rates between years. Observed flowering sizes also varied between years, but were larger in 1999 than in 2000, contrary to model predictions. Incorporating individual variation in growth increased predicted optimal flowering sizes compared to models using deterministic growth, whereas the inclusion of individual survival variation had little effect. There was no significant effect of recent growth rate on flowering probability. Taken together, these results indicate highly fluctuating selection on the flowering strategy in D. purpurea, but no evidence of adaptive plasticity in response to current growing conditions. Fluctuating selection may contribute to maintain genetic variation for threshold size for flowering, and may partly explain the large within-season size-variation in flowering individuals found in natural populations of D. purpurea. [ABSTRACT FROM AUTHOR]

Chrysoeriol is a flavonoid with antioxidant and anti-inflammatory activities. Despite the large number of studies performed on its biological activities, no clear picture of its mode of action has emerged. In the present study, we isolated chrysoeriol from the leaves of Digitalis purpurea (foxglove), and studied its effect on the induction of the inducible nitric oxide synthase (iNOS) gene, and the mechanism of this induction in Raw264.7 macrophages. Chrysoeriol pretreatment potently inhibited the release of NO in the cells treated with lipopolysaccharide (LPS), and Western blot and RT-PCR analyses revealed that chrysoeriol inhibited the LPS-induced inductions of iNOS gene. Moreover, it is known that the activations of nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) are crucial steps in the transcriptional activation of the iNOS gene. Here, we found that chrysoeriol selectively suppressed AP-1 activation, and that activation of AP-1 is likely to be essential for iNOS induction in LPS-treated macrophages. This presumed inhibitory effect on AP-1 activation by chrysoeriol may be associated with its potent NO blocking and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

The mechanisms by which digitalis causes its therapeutic and toxic actions have been studied for nearly a half century, revealing a great deal about cardiac cell regulation of intracellular ions via the Na-K-ATPase (NKA) and how it is altered by cardiac glycosides. However, recent observations suggest that digitalis may have additional effects on cardiac cell function in both the short and long term that include intracellular effects, interactions with specific NKA isoforms in different cellular locations, effects on intracellular (including nuclear) signaling, and long-term regulation of intracellular ionic balances through circulating ouabain-like compounds. The purpose of this review is to examine the current status of a number of the newest and most interesting developments in the study of digitalis with a particular focus on cardiac function, although we will also discuss some of the new advances in other relevant cardiovascular effects. This new information has important implications for both our understanding of ionic regulation in normal and diseased hearts as well as for potential avenues for the development of future therapeutic interventions for the treatment of heart failure. [ABSTRACT FROM AUTHOR]

1 Density-dependent effects on vital rates may vary in both magnitude and direction at different stages of the life cycle. In monocarpic perennials, however, it is often assumed that recruitment is the stage most affected by density. 2 The spatial pattern of newly emerged individuals of the facultative biennial Digitalis purpurea was recorded and followed in five 0.5-m2 plots censused twice during each of three seasons. 3 To examine effects of local density on growth and survival, a plant's neighbourhood was defined as the number of individuals inside a circle of fixed radius around it. Species identity of the nearest neighbour was established to see whether the effects of intra- and interspecific interactions differed. 4 Relative growth rate (RGR) was negatively related to local density during both of the first two summers, but not during winter. In 1998 the negative effects were stronger when the closest neighbour was conspecific. 5 Contrasting patterns of size-dependent growth were found during summer and winter, with summer RGR an increasing, and winter RGR a decreasing, function of size. 6 Summer survival was generally high, and was positively related to spring size. There was a significant negative effect of increasing local density on survival probability in 1998. No effect of neighbour identity was detected. 7 Winter survival was low, and mainly dependent on autumn size, with no significant effects of local density in any season. During the first winter, individuals with a conspecific as the nearest neighbour had lower survival probabilities. 8 There was no evidence of a tradeoff between summer RGR and survival probability. 9 Density-dependent effects may be significant beyond the recruitment stage in monocarpic perennials such as D. purpurea. Density dependence was strongest at early life stages although, because effects on growth persisted into the second year, it is likely that local density may influence timing of reproduction in this population. The use of detailed studies investigating the timing and magnitude of density dependence across the entire life cycle may provide new insight into life history evolution. Journal of Ecology (2005) doi: 10.1111/j.1365-2745.2005.01008.x [ABSTRACT FROM AUTHOR]

Abstract: Despite controversy over their use and the potential for toxic side effects, cardiac glycosides have remained an important clinical component for the treatment for congestive heart failure (CHF) and supraventricular arrhythmias since the effects of Digitalis purpurea were first described in 1785. While there is a wealth of information available with regard to the effects of these drugs on their pharmacological receptor, the Na+, K+-ATPase, the exact molecular mechanism of digitalis binding and inhibition of the enzyme has remained elusive. In particular, the absence of structural knowledge about Na+, K+-ATPase has thwarted the development of improved therapeutic agents with larger therapeutic indices via rational drug design approaches. Here, we propose a binding mode for digoxin and several analogues to the Na+, K+-ATPase. A 3D-structural model of the extracellular loop regions of the catalytic α1-subunit of the digitalis-sensitive sheep Na+, K+-ATPase was constructed from the crystal structure of an E1Ca2+ conformation of the SERCA1a and a consensus orientation for digitalis binding was inferred from the in silico docking of a series of steroid-based cardiotonic compounds. Analyses of species-specific enzyme affinities for ouabain were also used to validate the model and, for the first time, propose a detailed model of the digitalis binding site. [Copyright &y& Elsevier]

1. Pollinator visitation patterns in relation to variation in floral display size may be modified both quantitatively and qualitatively by local plant density. In this study four measures of pollinator response by Bombus spp. (plant visitation rate, bout length, proportion of flowers visited, flower visitation rate) were investigated under two or three different plant densities in two consecutive years in a natural population of Digitalis purpurea L. 2. Plant visitation rate increased with floral display size in both years, and was higher in dense patches compared with sparse ones in 1999. Bout lengths increased with display size in 1999, and bouts were longer in sparse patches. However, the actual rate of increase with display size was independent of plant density for both response measures. 3. The proportion of flowers visited decreased with floral display size in both years, and in 1999 the decline was faster in high-density patches. As a result, the proportion visited was higher in dense patches for the smallest display sizes, and higher in sparse patches for larger display sizes. 4. Flower visitation rate decreased with floral display size in both years. This is inconsistent with the idea that bees achieve an ideal free distribution across flowers. There was no significant effect of plant density. 5. These results demonstrate that local plant density variation may modify the functional relationship between floral display size and pollinator visitation rate, and potentially influence plant mating patterns. Functional Ecology (2005) doi: 10.1111/j.1365-2435.2005.00988.x [ABSTRACT FROM AUTHOR]

Digitalis minor L. is illustrated. A description is provided, its taxonomic relationships are discussed and recommendations for its successful cultivation are presented. [ABSTRACT FROM AUTHOR]

The cardiac glycoside, digitoxin, from Digitalis purpurea L (Scrophulariaceae), a cardiac glycosidal (cardenolide) extract from Calotropis procera (Ait) R Br (Asclepiadaceae), azadirachtin and neem oil from Azadirachta indica A Juss (Meliaceae) were tested for their effects against larvae and adult stages of the camel tick, Hyalomma dromedarii Koch (Acari: Ixodidae). The contact LC[sub50] values of the first three materials against adults were 4.08, 9.63 and >40.7 µg cm][sup-2], respectively, whereas the dipping LC[sub50] values of the four materials were 409.9, 1096, > 5000 and > 5000 mg litre[sup-1], respectively. Contact and dipping LC[sub50] values of the extract and azadirachtin against larvae were 6.16, >20.3 μg cm[sub-2] and 587.7 and >2500mg litre[sup-1], respectively. Azadirachtin had no effects on egg production or feeding of adults up to 5000mg litre[sup-1]; however at 2500mg litre[sup-1], it caused significant reduction in feeding activity of larve, prolonged the period for moulting to nymphal stage, and caused 60% reduction in moultability. Results of the two cardiac glycoside materials are comparable with those of several commercial acaricides. The risks and benefits associated with the use of cardiac glycosides are considered. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a risk factor for congestive heart failure. Diabetics with congestive heart failure should have good glycemic control, treatment of hypertension and dyslipidemia, and treatment with diuretics, angiotensin-converting enzyme inhibitors, and β blockers as well as digoxin, if the left ventricular ejection fraction is abnormal. Patients with chronic obstructive pulmonary disease may have left ventricular failure because of a coexistent cardiac disorder or right ventricular failure from pulmonary hypertension. An acute respiratory tract infection may precipitate right ventricular failure and should be treated. Alveolar hypoxia should be corrected by improving alveolar ventilation through relieving airflow obstruction with bronchodilators and by increasing inspired oxygen concentration. Loop diuretics should be used cautiously. Beta blockers may be given to patients with chronic obstructive pulmonary disease and left ventricular failure if bronchospasm is not present. Angiotensin-converting enzyme inhibitors should be used to treat left ventricular failure. Digitalis should not be used in patients with right ventricular failure due to chronic obstructive pulmonary disease. Nonsteroidal anti-inflammatory drugs are contraindicated in patients with congestive heart failure. There are controversial data about the negative interaction between aspirin and angiotensin-converting enzyme inhibitors in patients with congestive heart failure. Patients with arthritis and congestive heart failure needing large doses of aspirin for pain relief may be treated instead with acetaminophen, tramadol, or Percocet if necessary for chronic severe pain. [ABSTRACT FROM AUTHOR]

Summary 1 Monocarpy in facultative biennials can be favoured by selection when there is a more than proportional increase in fitness with size. The possible contributions of larger reproductive output and higher offspring quality to such an increase were investigated in the facultative biennial plant Digitalis purpurea . Straw mass (rosette leaves and flowering stem excluding fruits and seeds) was determined for 100 individuals of varying size and correlated with the number of flowers and seeds per flower to examine whether sex-allocation is size dependent. 2 To determine whether maternal size influences offspring growth, and whether this effect is more pronounced in the presence of competition, seeds from 32 maternal plants were grown alone, and with one, two or four competitors. 3 Total seed number increased proportionally with size. Seed quality, measured as seed size, germination percentage and speed also increased with maternal size. The combined fitness measures of total seed mass (seed number × seed size), number of seedlings (seed number × germination percentage) and total female fitness (seed number × germination percentage × mean offspring dry mass after 14 weeks) all increased disproportionally with size. 4 Sex-allocation was size dependent, with large plants emphasizing the female function. 5 Offspring dry mass after both 8 and 14 weeks of growth was strongly influenced by competition, whereas the effect of maternal size was significant only at the first harvest date. Competition did not accentuate the effects of maternal size. 6 The results support that monocarpy exists in D. purpurea because of increased offspring quality rather than a disproportionate advantage in seed output of large individuals. [ABSTRACT FROM AUTHOR]

The bioconversion of [14]atrazine to dealkylated and hydroxylated products was studied in heterotrophic cell-suspension cultures of carrot (Daucus carota L.), Agrostemina githago L. (corn cockle), Digitalis purpurea L. (purple foxglove), soyabean (Glycine max L. Merr,; four different cultivars). Datura stramonium L. (thorn-apple) and wheat (Triticum aestivum L.). During 48 h of incubation, the herbicide was biotransformed by all species; turnover yields differed considerably and were between 10.1% and 88.0% of applied C. Differences were also observed among the soyabean cultivars (10.1–71.5%). Hydroxyatrazine, de-ethyl-deisopropyl- and de-ethytdeisopropylatrazine formed in the cultures were identified by thin-layer chromatography (tlc) (cochromatography with reference compounds); dealkylated metabolites were also proved by gas chromatography-mass spectrometry (gc-ms). In addition, highly polar transformation products emerged that were not identified. Portions of non-extractable residues were below 5% (one soyabean cultivar: 8.9%). Atrazine was metabolized by the cells, mainly to its dealkylated derivatives and hydroxyatrazine (totals of 9.4–54.5%), whereas portions of highly polar products were lower (0.1–26.1%). Exceptions were A. githago (26.0 and 13.6%, respectively) and D. purpurea (4.5 and 25.2% respectively). Thus, plants generally contribute to the environmental degradation of atrazine. [ABSTRACT FROM AUTHOR]

Progesterone 5β-reductase, which catalyzes the reduction of progesterone to 5β-pregnane-3,20-dione, was purified 770-fold to homogeneity from the cytosolic fraction of shoot cultures of Digitalis purpurea. This purification involved DEAE-Sephacel, affinity chromatography (Blue-Sepharose CL-6B and adenosine 2′,5′-bisphosphate-Sepharose 4B) and elution from a gel matrix after non-dissociating PAGE. The molecular mass determined by SDS/PAGE was 43 kDa and the molecular mass determined by gel-filtration chromatography on calibrated Sephadex G-200 was 280 kDa, thus indicating that the native protein is a polymer consisting of several subunits. The purified enzyme had a Km value of 6 μM for NADPH and 34 μM for progesterone. The enzyme had a strong substrate specificity for progesterone. The relative rates for other steroids such as testosterone, cortisone and cortisol were much lower. The trypsin digestion of the purified progesterone 5β-reductase resulted in 100 peptide fragments. The largest fragment after trypsin digestion and sequence analysis consisted of 13 amino acids. [ABSTRACT FROM AUTHOR]

(1) Field observations on the life cycles of species with continental, oceanic, montane and arctic-alpine patterns of distribution have demonstrated that low winter survival prevents the establishment of Digitalis purpurea (oceanic) and Eupatorium cannabinum (continental), at altitudes above their present limits. (2) Computer simulations of population densities have predicted that Potentilla reptans (continental) should also become extinct, after a longer period of time at the same altitude. In this case, failure to extend the attitudinal range is a result of the combined influences of low seed germination, winter survival and seed production. (3) Observations of germination plant survival and seed production in the arctic alpine species, Oxyria digyna and Saxifraga stellaris provided no clue to their absence from the Welsh lowlands. Both species demonstrated and were predicted to show continued and successful population survival. Slow leaf area expansion resulting in low competitive ability is likely to be the key to their restriction. [ABSTRACT FROM AUTHOR]

During digitalis-induced, sustained, monomorphic ventricular tachycardia, programmed electrical stimulation was performed and the effect on the first post-pacing QRS morphology was determined. Ventricular tachycardia was induced in nine conscious dogs with chronic complete atrioventricular block by administering digoxin i.v. 0.1 mg/kg given in 1–1½ hour. Spontaneous ventricular tachycardia most frequently had a right bundle branch block morphology and an extreme left axis suggesting an origin in the apex of the left ventricle. Less frequently, a left bundle branch block-like configuration with an intermediate axis was observed, compatible with an origin in the basal part of the right ventricle. Following pacing close to one of these predilection sites, the first post-pacing QRS morphology suggested an origin close to the site of stimulation. Pacing distant from these predilection sites resulted in fusion complexes between electrical activation from these predilection sites and the stimulation site. The amount of fusion depended on interstimulus interval and the number of stimuli. Long interstimulus intervals and few stimuli induced a QRS complex similar to that of the spontaneous tachycardia. The faster and longer the stimulation train, the more the QRS complex became similar to the paced QRS complex. Similar findings were also observed on decreasing the last paced interval only. Our findings suggest that triggered activity is the underlying mechanism for the first post-pacing QRS complex. QRS configuration and the relation between the R-H interval and QRS configuration during tachycardia suggest that triggered activity is also the mechanism for the spontaneously occurring ventricular tachycardia during digitalis intoxication. These observations may have important clinical implications. [ABSTRACT FROM AUTHOR]

The article focuses on the study of the influence of rabbits on the vegetation of various hill-grazing districts of Scotland. The rabbit burrows are in sand, light soil, usually with small stones or rubbles. Pentland Hills have extreme rabbit pressures, where vegetations like Ulex europaeus and Digitalis purpurea have been severely grazed. In Moorfoot Hills the burrows are scattered, so the pressure is not severe and a good grassy vegetation prevails. The vegetation in this region comprises of short dense Calluna vulgaris and small patches of Pteridium aquilinum. The chief changes that took place in this region are increase of grass and the plant species Galium saxatile. The first stage in destruction was the partial destruction of the vegetation covering the soil.

The article reflects on the censorship of manuscripts that use natural products, submitted to the "Canadian Journal of Physiology and Pharmacology." It mentions about English botanist William Withering's description on the benefits of extracts from foxglove Digitalis purpurea, determination of the active compound digitalis, and a study which identified elusive endothelium-derived relaxation factor (EDRF) as nitric oxide (NO).