The health benefits associated with a diet rich in fruit and vegetables include reduction of the risk of chronic diseases such as cardiovascular disease, diabetes and cancer, that are becoming prevalent in the aging human population. Triterpenoids, polycyclic compounds derived from the linear hydrocarbon squalene, are widely distributed in edible and medicinal plants and are an integral part of the human diet. As an important group of phytochemicals that exert numerous biological effects and display various pharmacological activities, triterpenoids are being evaluated for use in new functional foods, drugs, cosmetics and healthcare products. Screening plant material in the search for triterpenoid-rich plant tissues has identified fruit peel and especially fruit cuticular waxes as promising and highly available sources. The chemical composition, abundance and biological activities of triterpenoids occurring in cuticular waxes of some economically important fruits, like apple, grape berry, olive, tomato and others, are described in this review. The need for environmentally valuable and potentially profitable technologies for the recovery, recycling and upgrading of residues from fruit processing is also discussed.
Cuticular waxes; Fruit peel; Health benefits; Triterpenoids
Artemisia annua L. produces the sesquiterpene lactone, artemisinin, a potent antimalarial drug that is also effective in treating other parasitic diseases, some viral infections and various neoplasms. Artemisinin is also an allelopathic herbicide that can inhibit the growth of other plants. Unfortunately, the compound is in short supply and thus, studies on its production in the plant are of interest as are low cost methods for drug delivery. Here we review our recent studies on artemisinin production in A. annua during development of the plant as it moves from the vegetative to reproductive stage (flower budding and full flower formation), in response to sugars, and in concert with the production of the ROS, hydrogen peroxide. We also provide new data from animal experiments that measured the potential of using the dried plant directly as a therapeutic. Together these results provide a synopsis of a more global view of regulation of artemisinin biosynthesis in A. annua than previously available. We further suggest an alternative low cost method of drug delivery to treat malaria and other neglected tropical diseases.
Artemisinin pharmacokinetics; ROS; DMSO; Artemisia annua development; Trichomes
The deep waters surrounding the coastline of the northern parts of Norway represent an exciting biotope for marine exploration. Dark and cold Arctic water generates a hostile environment where the ability to adapt is crucial to survival. These waters are nonetheless bountiful and a diverse plethora of marine organisms thrive in these extreme conditions, many with the help of specialised chemical compounds. In comparison to warmer, perhaps more inviting shallower tropical waters, the Arctic region has not been as thoroughly investigated. MabCent is a Norwegian initiative based in Tromsø that aims to change this. Since 2007, scientists within MabCent have focussed their efforts on the study of marine organisms inhabiting the Arctic waters with the long term goal of novel drug discovery and development. The activities of MabCent are diverse and range from sampling the Arctic ice shelf to the chemical synthesis of promising secondary metabolites discovered during the screening process. The current review will present the MabCent pipeline from isolation to identification of new bioactive marine compounds via an extensive screening process. An overview of the main activities will be given with particular focus on isolation strategies, bioactivity screening and structure determination. Pitfalls, hard earned lessons and the results so far are also discussed.
Pharmacognosy; Arctic; Cold adaption; Psychrophile; Screening; Bioprospecting; Norway; MabCent
Chalcone synthase (CHS, EC 188.8.131.52) is a key enzyme of the flavonoid/isoflavonoid biosynthesis pathway. Besides being part of the plant developmental program the CHS gene expression is induced in plants under stress conditions such as UV light, bacterial or fungal infection. CHS expression causes accumulation of flavonoid and isoflavonoid phytoalexins and is involved in the salicylic acid defense pathway. This review will discuss CHS and its function in plant resistance.
Chalcone synthase; Flavonoids; Plant resistance
A large percentage of allergenic proteins are of plant origin. Hence, plant-based expression systems are considered ideal for the recombinant production of certain allergens. First attempts to establish production of plant-derived allergens in plants focused on transient expression in Nicotiana benthamiana infected with recombinant viral vectors. Accordingly, allergens from birch and mugwort pollen, as well as from apple have been expressed in plants. Production of house dust mite allergens has been achieved by Agrobacterium-mediated transformation of tobacco plants. Beside the use of plants as production systems, other approaches have focused on the development of edible vaccines expressing allergens or epitopes thereof, which bypasses the need of allergen purification. The potential of this approach has been convincingly demonstrated for transgenic rice seeds expressing seven dominant human T cell epitopes derived from Japanese cedar pollen allergens. Parallel to efforts in developing recombinant-based diagnostic and therapeutic reagents, different gene-silencing approaches have been used to decrease the expression of allergenic proteins in allergen sources. In this way hypoallergenic ryegrass, soybean, rice, apple, and tomato were developed.
Allergy; Expression system; Green biotechnology; Molecular farming; Recombinant protein
Knowledge about members of the flowering plant family Clusiaceae occurring in the tropical mountain regions of the world is limited, in part due to endemism and restricted distributions. High altitude vegetation habitats (Páramos) in Central and South America are home to numerous native Hypericum species. Information related to the phytochemistry of páramo Hypericum, as well as ecological factors with the potential to influence chemical defenses in these plants, is briefly reviewed. Results of the phytochemical analysis of Hypericum irazuense, a species collected in the páramo of the Cordillera de Talamanca in Costa Rica, are presented. Lastly, guidelines for the viable and sustainable collections of plant material, to facilitate future investigations of these interesting plants, are given.
Clusiaceae; Hypericum; Montane; Páramo; Phytochemistry; Xanthone
The understanding of the selection factors that drive chemical diversification of secondary metabolites of constitutive defence systems in plants, such as pyrrolizidine alkaloids (PAs), is still incomplete. Historically, plants always have been confronted with microorganisms. Long before herbivores existed on this planet, plants had to cope with microbial pathogens. Therefore, plant pathogenic microorganisms may have played an important role in the early evolution of the secondary metabolite diversity. In this review, we discuss the impact that plant-produced PAs have on plant-associated microorganisms. The objective of the review is to present the current knowledge on PAs with respect to anti-microbial activities, adaptation and detoxification by microorganisms, pathogenic fungi, root protection and PA induction. Many in vitro experiments showed effects of PAs on microorganisms. These results point to the potential of microorganisms to be important for the evolution of PAs. However, only a few in vivo studies have been published and support the results of the in vitro studies. In conclusion, the topics pointed out in this review need further exploration by carrying out ecological experiments and field studies.
Anti-microbial activity; Adaptation; Pathogens; Plant defence; Secondary metabolites
The diversity of secondary metabolites (SMs) has been poorly understood from both a mechanistic and a functional perspective. Hybridization is suggested to contribute to the evolution of diversity of SMs. In this paper we discuss the effects of hybridization on SMs and herbivore resistance by evaluating the literature and with special reference to our own research results from the hybrids between Jacobaea vulgaris (syn. Senecio jacobaea) and Jacobaea aquatica (syn. Senecio aquaticus). We also review the possible genetic mechanism which causes the variation of SMs and herbivore resistance in hybrids. Most SMs in hybrids are present in the parents as well. But hybrids may miss some parental SMs or have novel SMs. The concentration of parental SMs in hybrids generally is constrained by that in parental plants, but transgressive expression was present in some hybrids. Hybrids may be as susceptible (resistant) as the parents or more susceptible than the parents, but rarely more resistant than the parents. However, different hybrid classes (F1, F2, backcrossing and mixed genotypes) show different patterns in relation to herbivore resistance. The variation in SMs and herbivore resistance occurring in hybrids could be explained by complicated genetic mechanisms rather than a simple one-gene model. Most previous work in this field only reported mean trait values for hybrid classes and few studies focused on genotype differences within hybrid classes. Our study in Jacobaea hybrids showed transgressive segregation in most SMs and herbivore resistance. To summarize, our article shows that hybridization may increase the variation of SMs and affect herbivore resistance, which may partially explain the evolution of chemical diversity in plants.
Chemical defense; Pyrrolizidine alkaloids; Jacobaea vulgaris; Jacobaea aquatica
Several theories have been developed to explain why invasive species are very successful and develop into pest species in their new area. The shifting defence hypothesis (SDH) argues that invasive plant species quickly evolve towards new defence levels in the invaded area because they lack their specialist herbivores but are still under attack by local (new) generalist herbivores. The SDH predicts that plants should increase their cheap, toxic defence compounds and lower their expensive digestibility reducing compounds. As a net result resources are saved that can be allocated to growth and reproduction giving these plants a competitive edge over the local plant species. We conducted a literature study to test whether toxic defence compounds in general are increased in the invaded area and if digestibility reducing compounds are lowered. We specifically studied the levels of pyrrolizidine alkaloids, a toxin which is known for its beneficial and detrimental impact against specialists and generalists, respectively. Digestibility reducers did not show a clear trend which might be due to the small number of studies and traits measured. The meta analysis showed that toxic compounds in general and pyrrolizidine alkaloid levels specifically, increased significantly in the invaded area, supporting the predictions of the SDH that a fast evolution takes place in the allocation towards defence.
Defence; EICA; Invasion; PAs; SDH
Marine natural products have become a major source of new chemical entities in the discovery of potential anticancer agents that potently suppress various antitumor molecular targets. As a consequence of insufficient vascularization, hypoxic regions form within rapidly growing solid tumor masses. Specific alterations of gene expression in these hypoxic tumor cells help facilitate the survival and metastatic spread of solid tumors. The transcriptional response to cellular hypoxia is primarily mediated by the transcription factor hypoxia-inducible factor-1 (HIF-1) that regulates the expression of more than 100 genes involved in cellular adaptation and survival under hypoxic stress. Clinical studies in cancer patients indicate that HIF-1 activation is directly correlated with advanced disease stages and treatment resistance. HIF-1 has emerged as an important tumor-selective molecular target for anticancer drug discovery. As a result, natural product-based inhibitors of HIF-1 activation have been identified from plants and microorganisms. Recently, structurally unique natural products from marine sponges, crinoids, and algae have been identified as HIF-1 activation inhibitors. The US National Cancer Institute’s Open Repository of marine invertebrate and algae extracts has proven to be a valuable source of natural product HIF-1 inhibitors. Among the active compounds identified, certain marine natural products have also been shown to suppress the hypoxic induction of HIF-1 target genes such as vascular endothelial growth factor (VEGF). Some of these marine HIF-1 inhibitors act by interfering with the generation of mitochondrial signaling molecules in hypoxic cells. However, the precise mechanisms of action for many newly identified marine natural product HIF-1 inhibitors remain unresolved.
cellular signaling; crinoids; gene expression; HIF-1 inhibitors; hypoxia-inducible factor-1; marine natural products; molecular-targeted antitumor agents; sponges; transcription factor; tumor hypoxia; tunicates
Biosynthesis of the anticancer drug Taxol in Taxus (yew) species involves 19 steps from the universal diterpenoid progenitor geranylgeranyl diphosphate derived by the plastidial methyl erythritol phosphate pathway for isoprenoid precursor supply. Following the committed cyclization to the taxane skeleton, eight cytochrome P450-mediated oxygenations, three CoA-dependent acyl/aroyl transfers, an oxidation at C9, and oxetane (D-ring) formation yield the intermediate baccatin III, to which the functionally important C13-side chain is appended in five additional steps. To gain further insight about Taxol biosynthesis relevant to the improved production of this drug, and to draw inferences about the organization, regulation, and origins of this complex natural product pathway, Taxus suspension cells (induced for taxoid biosynthesis by methyl jasmonate) were used for feeding studies, as the foundation for cell-free enzymology and as the source of transcripts for cDNA library construction and a variety of cloning strategies. This approach has led to the elucidation of early and late pathway segments, the isolation and characterization of over half of the pathway enzymes and their corresponding genes, and the identification of candidate cDNAs for the remaining pathway steps, and it has provided many promising targets for genetically engineering more efficient biosynthetic production of Taxol and its precursors.
baccatin; cytochrome P450 taxoid hydroxylases; paclitaxel; Taxaceae; taxadiene synthase; taxane diterpenoids; taxoid acyl transferases; taxoids; Taxol; Taxus; yew
Cytochrome P450 monooxygenases play a prominent role in the biosynthesis of the diterpenoid anticancer drug Taxol, as they appear to constitute about half of the 19 enzymatic steps of the pathway in yew (Taxus) species. A combination of classical biochemical and molecular methods, including cell-free enzyme studies and differential-display of mRNA-reverse transcription polymerase chain reaction (RT-PCR) combined with a homology-based searching and random sequencing of a cDNA library from induced T. cuspidata cells, led to the discovery of six novel cytochrome P450 taxoid (taxane diterpenoid) hydroxylases. These genes show unusually high sequence similarity with each other (>70%) but low similarity (<30%) to, and significant evolutionary distance from, other plant P450s. Despite their high similarity, functional analysis of these hydroxylases demonstrated distinctive substrate specificities responsible for an early bifurcation in the biosynthetic pathway after the initial hydroxylation of the taxane core at C5, leading into a biosynthetic network of competing, but interconnected, branches. The use of surrogate substrates, in cases where the predicted taxoid precursors were not available, led to the discovery of two core oxygenases, the 2α- and the 7β-hydroxylase. This general approach could accelerate the functional analysis of candidate cDNAs from the extant family of P450 genes to identify the remaining oxygenation steps of this complex pathway.
Taxoid hydroxylases; Taxane diterpenoid; Taxadiene; Taxusin; Taxus
The aim of this review is to combine the knowledge of studies on effects of nutrients on pyrrolizidine alkaloids (PAs) in Senecio with those studies of effects of PAs on herbivores and pathogens in order to predict the effects that nutrients may have on herbivores and pathogens via changes in PAs. We discuss whether these predictions match with the outcome of studies where the effect of nutrients on herbivores and insects were measured. PA concentrations in S. jacobaea, S. vulgaris and S. aquaticus were mostly reduced by NPK fertilization, with genotype-specific effects occurring. Plant organs varied in their response to increased fertilization; PA concentrations in flowers remained constant, while shoot and roots were mostly negatively affected. Biomass change is probably largely responsible for the change in concentrations. Nutrients affect both the variety and the levels of PAs in the plant. The reduced PA concentrations after NPK fertilization was expected to benefit herbivores, but no or negative responses from insect herbivores were observed. Apparently other changes in the plant after fertilization are overriding the effect of PAs. Pathogens do seem to benefit from the lower PA concentrations after fertilization; they were more detrimental to fertilized plants than to unfertilized control plants. Future studies should include the effect of each element of nutrients separately and in combinations in order to gain more insight in the effect of specific nutrients on PA content in Senecio plants.
Senecio; Jacobaea; Nitrogen; Tyria; Puccinia
Saponins are natural glycosides which possess a wide range of pharmacological properties including cytotoxic activity. In this review, the recent studies (2005–2009) concerning the cytotoxic activity of saponins have been summarized. The correlations between the structure and the cytotoxicity of both steroid and triterpenoid saponins have been described as well as the most common mechanisms of action.
Cytotoxic mechanisms; Glycosides; Sar; Steroid; Triterpenoid
Pyrrolizidine alkaloids (PAs) are the major defense compounds of plants in the Senecio genus. Here I will review the effects of PAs in Senecio on the preference and performance of specialist and generalist insect herbivores. Specialist herbivores have evolved adaptation to PAs in their host plant. They can use the alkaloids as cue to find their host plant and often they sequester PAs for their own defense against predators. Generalists, on the other hand, can be deterred by PAs. PAs can also affect survival of generalist herbivores. Usually generalist insects avoid feeding on young Senecio leaves, which contain a high concentration of alkaloids. Structurally related PAs can differ in their effects on insect herbivores, some are more toxic than others. The differences in effects of PAs on specialist and generalists could lead to opposing selection on PAs, which may maintain the genetic diversity in PA concentration and composition in Senecio species.
Evolution; Performance; Preference; Tyria jacobaeae; Jacobaea vulgaris
Secondary metabolites provide a potential source for the generation of host plant resistance and development of biopesticides. This is especially important in view of the rapid and vast spread of agricultural and horticultural pests worldwide. Multiple pests control tactics in the framework of an integrated pest management (IPM) programme are necessary. One important strategy of IPM is the use of chemical host plant resistance. Up to now the study of chemical host plant resistance has, for technical reasons, been restricted to the identification of single compounds applying specific chemical analyses adapted to the compound in question. In biological processes however, usually more than one compound is involved. Metabolomics allows the simultaneous detection of a wide range of compounds, providing an immediate image of the metabolome of a plant. One of the most universally used metabolomic approaches comprises nuclear magnetic resonance spectroscopy (NMR). It has been NMR which has been applied as a proof of principle to show that metabolomics can constitute a major advancement in the study of host plant resistance. Here we give an overview on the application of NMR to identify candidate compounds for host plant resistance. We focus on host plant resistance to western flower thrips (Frankliniella occidentalis) which has been used as a model for different plant species.
Eco-metabolomic approach; Host plant resistance; NMR metabolomics; Secondary plant metabolites; Thrips (Frankliniella occidentalis)
The ragwort species common or tansy ragwort (Jacobaea vulgaris, formerly Senecio jacobaea), marsh ragwort (S. aquaticus), Oxford ragwort (S. squalidus) and hoary ragwort (S. erucifolius) are native in Europe, but invaded North America, Australia and New Zealand as weeds. The abundance of ragwort species is increasing in west-and central Europe. Ragwort species contain different groups of secondary plant compounds defending them against generalist herbivores, contributing to their success as weeds. They are mainly known for containing pyrrolizidine alkaloids, which are toxic to grazing cattle and other livestock causing considerable losses to agricultural revenue. Consequently, control of ragwort is obligatory by law in the UK, Ireland and Australia. Commonly used management practices to control ragwort include mechanical removal, grazing, pasture management, biological control and chemical control. In this review the biology of ragwort species is shortly described and the different management practices are discussed.
Jacobaea vulgaris; Senecio aquaticus; Mechanical control; Pasture management; Biological control; Chemical control
With a realistic threat against biodiversity in rain forests and in the sea, a sustainable use of natural products is becoming more and more important. Basic research directed against different organisms in Nature could reveal unexpected insights into fundamental biological mechanisms but also new pharmaceutical or biotechnological possibilities of more immediate use. Many different strategies have been used prospecting the biodiversity of Earth in the search for novel structure–activity relationships, which has resulted in important discoveries in drug development. However, we believe that the development of multidisciplinary incentives will be necessary for a future successful exploration of Nature. With this aim, one way would be a modernization and renewal of a venerable proven interdisciplinary science, Pharmacognosy, which represents an integrated way of studying biological systems. This has been demonstrated based on an explanatory model where the different parts of the model are explained by our ongoing research. Anti-inflammatory natural products have been discovered based on ethnopharmacological observations, marine sponges in cold water have resulted in substances with ecological impact, combinatory strategy of ecology and chemistry has revealed new insights into the biodiversity of fungi, in depth studies of cyclic peptides (cyclotides) has created new possibilities for engineering of bioactive peptides, development of new strategies using phylogeny and chemography has resulted in new possibilities for navigating chemical and biological space, and using bioinformatic tools for understanding of lateral gene transfer could provide potential drug targets. A multidisciplinary subject like Pharmacognosy, one of several scientific disciplines bridging biology and chemistry with medicine, has a strategic position for studies of complex scientific questions based on observations in Nature. Furthermore, natural product research based on intriguing scientific questions in Nature can be of value to increase the attraction for young students in modern life science.
Pharmacognosy; Geodia; COX-2; ChemGPS-NP; Chemical space; Phylogeny; Cyclotide; Viola; Truffle; Tuber; Lateral gene transfer; Trypanosoma
The numerous uses of the grapevine fruit, especially for wine and beverages, have made it one of the most important plants worldwide. The phytochemistry of grapevine is rich in a wide range of compounds. Many of them are renowned for their numerous medicinal uses. The production of grapevine metabolites is highly conditioned by many factors like environment or pathogen attack. Some grapevine phytoalexins have gained a great deal of attention due to their antimicrobial activities, being also involved in the induction of resistance in grapevine against those pathogens. Meanwhile grapevine biotechnology is still evolving, thanks to the technological advance of modern science, and biotechnologists are making huge efforts to produce grapevine cultivars of desired characteristics. In this paper, important metabolites from grapevine and grape derived products like wine will be reviewed with their health promoting effects and their role against certain stress factors in grapevine physiology.
Grapevine; Medicinal importance; Phytochemistry; Resistance