RESUMEN
KEY MESSAGE: A highly specialized function for individual LTPs for different products from the same terpenoid biosynthesis pathway is described and the function of an LTP GPI anchor is studied. Sequiterpenes produced in glandular trichomes of the medicinal plant Tanacetum parthenium (feverfew) accumulate in the subcuticular extracellular space. Transport of these compounds over the plasma membrane is presumably by specialized membrane transporters, but it is still not clear how these hydrophobic compounds are subsequently transported over the hydrophilic cell wall. Here we identified eight so-called non-specific Lipid transfer proteins (nsLTPs) genes that are expressed in feverfew trichomes. A putative function of these eight nsLTPs in transport of the lipophilic sesquiterpene lactones produced in feverfew trichomes, was tested in an in-planta transport assay using transient expression in Nicotiana benthamiana. Of eight feverfew nsLTP candidate genes analyzed, two (TpLTP1 and TpLTP2) can specifically improve extracellular accumulation of the sesquiterpene costunolide, while one nsLTP (TpLTP3) shows high specificity towards export of parthenolide. The specificity of the nsLTPs was also tested in an assay that test for the exclusion capacity of the nsLTP for influx of extracellular substrates. In such assay, TpLTP3 was identified as most effective in blocking influx of both costunolide and parthenolide, when these substrates are infiltrated into the apoplast. The TpLTP3 is special in having a GPI-anchor domain, which is essential for the export activity of TpLTP3. However, addition of the TpLTP3 GPI-anchor domain to TpLTP1 resulted in loss of TpLTP1 export activity. These novel export and exclusion assays thus provide new means to test functionality of plant nsLTPs.
Asunto(s)
Sesquiterpenos , Tanacetum parthenium , Tanacetum parthenium/química , Tanacetum parthenium/genética , Tanacetum parthenium/metabolismo , Sesquiterpenos/metabolismo , LípidosRESUMEN
Nanomaterials can be used as elicitors for improving the biosynthesis of secondary metabolites in medicinal plants. The present study was conducted to assay the titanium dioxide-nanoparticles (TiO2-NPs) effects on feverfew (Tanacetum parthenium) as an anti-cancer plant. The study showed that TiO2-NPs application increased the amounts of the main compounds and oxygenated monoterpene in essential oils, thereby causing an improvement in the quantity and quality of the essential oils compared to control. The highest effect was related to 1500 ppm TiO2-NPs concentration. Regarding parthenolide, TiO2-NPs had no positive effect on parthenolide content and the highest content was observed in control. Increasing the concentrations over 1500 ppm resulted in a decrease in chlorophyll content, capitule diameter, flower yield, and harvest index compared to other concentrations and control. Additionally, the results indicated that TiO2-NPs foliar spray reduced flower number, biological yield, fresh weight, and dry weights compared with untreated plants. The increase in quality and content of essential oil and lack of increase in parthenolide content, and reproductive and vegetative characteristics showed that TiO2-NPs mainly affected the content and composition of essential oil. Totally, the application of TiO2-NPs in terms of positive effect on the yield and metabolites (without damaging biological effects) can be recommended and followed up to the concentration of 1000 ppm. Overall, the results indicated that improving the synthesis of valuable medicinal metabolites using TiO2-NPs has promising results depending on the type of species, concentration used and target metabolites.
Asunto(s)
Nanopartículas , Aceites Volátiles , Tanacetum parthenium/química , Tanacetum parthenium/metabolismo , Titanio/farmacología , Fitoquímicos/metabolismo , Aceites Volátiles/metabolismoRESUMEN
Parthenolide (PTL) is a sesquiterpene lactone derived from medicinal plant feverfew (Tanacetum parthenium). Recent studies have demonstrated that it has multiple pharmacological activities, especially in the treatment of various hematological and solid cancers. The superior anticancer activity of PTL suggests that it has the potential to be a first-line drug. However, due to the limited physical and chemical properties, as well as bioavailability, structural modification strategies are strongly recommended to improve the anticancer activity. This review describes representative PTL derivatives obtained by different modification strategies, which are reported to exert antiproliferative activities superior to the parent compound PTL. Furthermore, we also summarize their basic mechanisms on cancer-related signaling pathways, so as to explain the potential and characteristics of PTL and its derivatives in cancer therapy.
Asunto(s)
Antineoplásicos , Neoplasias , Sesquiterpenos , Sesquiterpenos/farmacología , Sesquiterpenos/uso terapéutico , Sesquiterpenos/química , Tanacetum parthenium/química , Tanacetum parthenium/metabolismo , Antineoplásicos/farmacología , Extractos Vegetales , Neoplasias/tratamiento farmacológicoRESUMEN
Feverfew is an herb used to treat different diseases such as migraine headaches. Due to the economic aspect of its metabolites in the pharmaceutical industry, establishing new approaches to produce the compounds on a large scale is essential. To investigate the effects of stimulators on parthenolide synthesis, feverfew plants were treated with different elicitors, including methyl jasmonate, salicylic acid, NaCl, aluminum oxide, and magnesium aluminate spinel nanoparticles. The expression of genes, E-beta-caryophyllene synthase, Germacrene A synthase, and Costunolide Synthase in the metabolite biosynthesis pathway was examined using qRT-PCR. In addition, parthenolide content, total flavonoids, and polyphenols antioxidant activity were evaluated by HPLC and spectrophotometry. Our results indicated that methyl jasmonate and salicylic acid were more effective on the final concentration of parthenolide, but magnesium aluminate spinel affected the genes' expression, positively. The results show that the elicitors can be used to increase the metabolite in the plant, commercially.
Asunto(s)
Sesquiterpenos , Tanacetum parthenium , Tanacetum parthenium/genética , Tanacetum parthenium/metabolismo , Vías Biosintéticas/genética , Sesquiterpenos/farmacología , Extractos Vegetales/farmacología , Ácido Salicílico/farmacologíaRESUMEN
Acetylcholinesterase (AChE) is an enzyme that catalyzes acetylcholine into choline and acetic acid. Conventional pesticides, including organophosphates and carbamates target and inhibit the activity of AChE. To obtain more pesticide precursors that meet the safety requirements, more than 200 compounds were screened. Tirotundin and parthenolide identified as potential neurotoxins to nematodes were isolated from Tithonia diversifolia and Chrysanthemum parthenium, respectively. Their IC50 values were 6.89 ± 0.30 and 5.51 ± 0.23 µg/mL, respectively against the AChE isolated from Caenorhabditis elegans. AChE was inhibited in a dose-dependent manner using the two compounds. And the Lineweaver-Burk and Dixon plots indicated that tirotundin and parthenolide were reversible inhibitors against AChE, both inhibiting AChE in a mixed-type competitive manner and demonstrating these compounds may possess dual binding site AChE inhibitors. LC50 values of tirotundin and parthenolide against C. elegans were 9.16 ± 0.21 and 7.23 ± 0.48 µg/mL, respectively. These results provide a certain theoretical basis for the development and utilization of novel pesticides.
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Acetilcolinesterasa , Plaguicidas , Acetilcolinesterasa/metabolismo , Animales , Caenorhabditis elegans , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Lactonas , Plaguicidas/toxicidad , Sesquiterpenos , Tanacetum parthenium/metabolismo , TithoniaRESUMEN
Continuous use of glyphosate in citrus groves in the Gulf of Mexico region has selected for resistant Parthenium hysterophorus L. populations. In this study, the target-site and non-target-site resistance mechanisms were characterized in three putative glyphosate-resistant (GR) P. hysterophorus populations, collected in citrus groves from Acateno, Puebla (GR1 and GR2) and Martínez de la Torre, Veracruz (GR3), and compared with a susceptible population (GS). Based on plant mortality, the GR populations were 9.2-17.3 times more resistant to glyphosate than the GS population. The low shikimate accumulation in the GR population confirmed this resistance. Based on plant mortality and shikimate accumulation, the GR3 population showed intermediate resistance to glyphosate. The GR populations absorbed 15-28% less 14C-glyphosate than the GS population (78.7% absorbed from the applied) and retained 48.7-70.7% of 14C-glyphosate in the treated leaf, while the GS population translocated ~68% of absorbed herbicide to shoots and roots. The GR3 population showed the lowest translocation and absorption rates, but was found to be susceptible at the target site level. The 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene sequence of the GR1 and GR2 populations showed the Pro106-Ser mutation, conferring 19- and 25-times more resistance in comparison to the GS population, respectively. Reduced absorption and impaired translocation conferred glyphosate resistance on the GR3 population, and contributed partially to the resistance of the GR1 and GR2 populations. Additionally, the Pro-106-Ser mutation increased the glyphosate resistance of the last two P. hysterophorus populations.
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Glicina/análogos & derivados , Herbicidas/farmacología , Tanacetum parthenium/efectos de los fármacos , Tanacetum parthenium/metabolismo , 3-Fosfoshikimato 1-Carboxiviniltransferasa , Glicina/farmacología , Resistencia a los Herbicidas , Mutación/genética , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Brotes de la Planta/efectos de los fármacos , Brotes de la Planta/metabolismo , GlifosatoRESUMEN
Feverfew (Parthenium hysterophorus), an invasive weed from the Asteraceae family, has been reported as allergen source. Despite its relevance, knowledge of allergens is restricted to a partial sequence of a hydroxyproline-rich glycoprotein. We aimed to obtain the entire sequence for recombinant production and characterize feverfew pollen using proteomics and immunological assays. Par h 1, a defensin-proline fusion allergen was obtained by cDNA cloning and recombinantly produced in E. coli. Using two complementary proteomic strategies, a total of 258 proteins were identified in feverfew pollen among those 47 proteins belonging to allergenic families. Feverfew sensitized patients' sera from India revealed IgE reactivity with a pectate lyase, PR-1 protein and thioredoxin in immonoblot. In ELISA, recombinant Par h 1 was recognized by 60 and 40% of Austrian and Indian sera, respectively. Inhibition assays demonstrated the presence of IgE cross-reactive Par h 1, pectate lyase, lipid-transfer protein, profilin and polcalcin in feverfew pollen. This study reveals significant data on the allergenic composition of feverfew pollen and makes recombinant Par h 1 available for cross-reactivity studies. Feverfew might become a global player in weed pollen allergy and inclusion of standardized extracts in routine allergy diagnosis is suggested in exposed populations.
Asunto(s)
Alérgenos/metabolismo , Polen/metabolismo , Proteoma , Proteómica , Tanacetum parthenium/metabolismo , Alérgenos/genética , Alérgenos/inmunología , Secuencia de Aminoácidos , Inmunoglobulina E/inmunología , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/inmunología , Proteínas de Plantas/metabolismo , Polen/inmunología , Proteómica/métodos , Tanacetum parthenium/genética , Tanacetum parthenium/inmunologíaRESUMEN
A balanced nutrient supply is a critical factor affecting accumulation of terpenoids in plants, yet data related to the interactive effects of two essential nutrients for the biosynthesis of sesquiterpenes are scarce. Here, the interactional effects between magnesium (Mg) and manganese (Mn) on plant growth, oxidative status, parthenolide accumulation and expression of key genes involved in parthenolide biosynthesis including 1-deoxy-d-xylulose-5-phosphate reductoisomerase (DXR), hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase (HDR), 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGR), germacrene A synthase (GAS), germacrene A oxidase (GAO), costunolide synthase (COS) and parthenolide synthase (PTS) in the leaves of feverfew plants grown at different Mn and Mn levels were assessed. Plant growth and leaf pigment concentrations were associated with the amount of applied Mg but could be modified by the Mn level. Deprivation and the addition of both Mg and Mn induce oxidative stress. Mg supply also alleviated the adverse effects of Mn excess on plant growth and oxidative status. In addition, parthenolide biosynthesis decreased under deprivation of Mg or Mn, but the addition of Mn up to 50µM under 2mM Mg supply considerably increased its accumulation. The parthenolide accumulation trend might reflect the up-regulation of terpenoid-related genes and enzyme activities as well as the oxidative status of feverfew leaves. Our data suggest a profound effect of the combined supply of Mg and Mn on parthenolide biosynthesis through the activation of terpene synthases, which concomitantly modulate by oxidative status.
Asunto(s)
Magnesio/farmacología , Manganeso/farmacología , Hojas de la Planta/metabolismo , Sesquiterpenos/metabolismo , Tanacetum parthenium/metabolismo , Antioxidantes/metabolismo , Vías Biosintéticas/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Malondialdehído/metabolismo , Redes y Vías Metabólicas/efectos de los fármacos , Pigmentos Biológicos/metabolismo , Hojas de la Planta/efectos de los fármacos , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Brotes de la Planta/efectos de los fármacos , Brotes de la Planta/metabolismo , Prolina/metabolismo , Tanacetum parthenium/efectos de los fármacos , Tanacetum parthenium/genética , Tanacetum parthenium/crecimiento & desarrolloRESUMEN
KEY MESSAGE: Up-regulation of germacrene A synthase and down-regulation of parthenolide hydroxylase genes play key role in parthenolide accumulation of feverfew plants treated with methyl jasmonate and salicylic acid. Parthenolide is an important sesquiterpene lactone due to its anti-migraine and anti-cancer properties. Parthenolide amount was quantified by high-performance liquid chromatography after foliar application of methyl jasmonate (100 µM) or salicylic acid (1.0 mM) on feverfew leaves in time course experiment (3-96 h). Results indicate that exogenous application of methyl jasmonate or salicylic acid activated parthenolide biosynthesis. Parthenolide content reached its highest amount at 24 h after methyl jasmonate or salicylic acid treatments, which were 3.1- and 1.96-fold higher than control plants, respectively. Parthenolide transiently increased due to methyl jasmonate or salicylic acid treatments until 24 h, but did not show significant difference compared with control plants at 48 and 96 h time points in both treatments. Also, the transcript levels of early pathway (upstream) genes of terpene biosynthesis including 3-hydroxy-3-methylglutaryl-coenzyme A reductase, 1-deoxy-D-xylulose-5-phosphate reductoisomerase and hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase and the biosynthetic genes of parthenolide including germacrene A synthase, germacrene A oxidase, costunolide synthase and parthenolide synthase were increased by methyl jasmonate and salicylic acid treatments, but with different intensity. The transcriptional levels of these genes were higher in methyl jasmonate-treated plants than salicylic acid-treated plants. Parthenolide content measurements along with expression pattern analysis of the aforementioned genes and parthenolide hydroxylase as side branch gene of parthenolide suggest that the expression patterns of early pathway genes were not directly consistent with parthenolide accumulation pattern; hence, parthenolide accumulation is probably further modulated by the expression of its biosynthetic genes, especially germacrene A synthase and also its side branch gene, parthenolide hydroxylase.
Asunto(s)
Acetatos/farmacología , Ciclopentanos/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Oxilipinas/farmacología , Ácido Salicílico/farmacología , Sesquiterpenos/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología , Tanacetum parthenium/efectos de los fármacos , Tanacetum parthenium/genética , Tanacetum parthenium/metabolismoRESUMEN
Photoaging is a leading concern for patients and many of these patients will express a desire to utilize natural ingredients as treatment. Mushrooms, feverfew, green tea, licorice, olive oil, soy, and coffee berry have been shown to have antioxidant properties and may play a role in the treatment and prevention of photoaging. In this manuscript, the most recent select basic science and clinical studies examining the mechanisms and efficacy of these ingredients will be discussed.
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Productos Biológicos/administración & dosificación , Fitoterapia/métodos , Envejecimiento de la Piel/efectos de los fármacos , Agaricales/metabolismo , Animales , Antioxidantes/administración & dosificación , Antioxidantes/metabolismo , Productos Biológicos/metabolismo , Humanos , Envejecimiento de la Piel/patología , Tanacetum parthenium/metabolismo , Té/metabolismoRESUMEN
Parthenolide, a naturally occurring sesquiterpene lactone derived from feverfew (Tanacetum parthenium), exhibits exceptional anti-cancer and anti-inflammatory properties, making it a prominent candidate for further studies and drug development. In this review, we briefly investigate molecular events and cell-specific activities of this chemical in relation to cytochrome c, nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), signal transduction and activation of transcription (STAT), reactive oxygen species (ROS), TCP, HDACs, microtubules, and inflammasomes. This paper reports that parthenolide shows strong NF-κB- and STAT-inhibition-mediated transcriptional suppression of pro-apoptotic genes. This compound acts both at the transcriptional level and by direct inhibition of associated kinases (IKK-ß). Similarly, this review discusses parthenolide-induced ROS-mediated apoptosis of tumor cells via the intrinsic apoptotic signaling pathway. The unique ability of this compound to not harm normal cells but at the same time induce sensitization to extrinsic as well as intrinsic apoptosis signaling in cancer cells provides an important, novel therapeutic strategy for treatment of cancer and inflammation-related disorders.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos/farmacología , Inflamación/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Sesquiterpenos/farmacología , Apoptosis/efectos de los fármacos , Citocromos c/metabolismo , Humanos , Quinasa I-kappa B/antagonistas & inhibidores , Quinasa I-kappa B/biosíntesis , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno , Factores de Transcripción STAT/antagonistas & inhibidores , Factores de Transcripción STAT/metabolismo , Sesquiterpenos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Tanacetum parthenium/química , Tanacetum parthenium/metabolismo , Transcripción Genética/efectos de los fármacosRESUMEN
Feverfew (Tanacetum parthenium) is a perennial medicinal herb and is a rich source of sesquiterpene lactones. Parthenolide is the main sesquiterpene lactone in feverfew and has attracted attention because of its medicinal potential for treatment of migraine and cancer. In the present work the parthenolide content in different tissues and developmental stages of feverfew was analyzed to study the timing and localization of parthenolide biosynthesis. The strongest accumulating tissue was subsequently used to isolate sesquiterpene synthases with the goal to isolate the gene encoding the first dedicated step in parthenolide biosynthesis. This led to the isolation and charachterization of a germacrene A synthase (TpGAS) and an (E)-ß-caryophyllene synthase (TpCarS). Transcript level patterns of both sesquiterpene synthases were analyzed in different tissues and glandular trichomes. Although TpGAS was expressed in all aerial tissues, the highest expression was observed in tissues that contain high concentrations of parthenolide and in flowers the highest expression was observed in the biosynthetically most active stages of flower development. The high expression of TpGAS in glandular trichomes which also contain the highest concentration of parthenolide, suggests that glandular trichomes are the secretory tissues where parthenolide biosynthesis and accumulation occur.
Asunto(s)
Transferasas Alquil y Aril/metabolismo , Antiinflamatorios no Esteroideos/metabolismo , Extractos Vegetales/química , Sesquiterpenos/metabolismo , Tanacetum parthenium/metabolismo , Transferasas Alquil y Aril/genética , Secuencia de Aminoácidos , Antiinflamatorios no Esteroideos/análisis , ADN Complementario/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Flores/genética , Frutas/genética , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Especificidad de Órganos , Filogenia , Hojas de la Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/genética , Tallos de la Planta/genética , Plantas Medicinales , ARN Mensajero/genética , ARN de Planta/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alineación de Secuencia , Sesquiterpenos/análisis , Tanacetum parthenium/química , Tanacetum parthenium/enzimología , Tanacetum parthenium/crecimiento & desarrolloRESUMEN
In a new approach to microbial gallic acid production by Aspergillus fischeri MTCC 150, 40gL-1 oftannic acid was added in two installments during the bioconversion phase of the process (25gL-1 and 15gL-1 at 32 and 44h respectively). The optimum parameters for the bioconversion phase were found to be temperature: 35ºC, pH: slightly acidic (3.3-3.5), aeration: nil and agitation: 250 rpm. A maximum of 71.4 percent conversion was obtained after 71h fermentation with 83.3 percent product recovery. The yield was 7.35 g of gallic acid per g of biomass accumulated and the fermenter productivity was 0.56 g of gallic acid produced per liter of medium per hour.
Em uma nova abordagem para produção de ácido gálico por Aspergillus fischeri MTCC 150, adiciona-se 40 g.L-1 de ácido tânico em dois momentos da fase de bioconversão do processo (25 g.L-1 e 15 g.L-1 a 32h e 44h, respectivamente). Os parâmetros ótimos para a fase de bioconversão foram: temperatura 35ºC, pH levemente ácido (3,3 a 3,5), nenhuma aeração e agitação 250 rpm. Um máximo de 71,4 por cento de conversão foi obtido após 71h de fermentação, com 83,3 por cento de recuperação do produto. O rendimento foi 7,35g de ácido gálico por g de biomassa acumulada e a produtividade do fermentador foi 0,56g de ácido gálico por litro de meio por hora.
Asunto(s)
Ácido Gálico/análisis , Ácido Gálico/metabolismo , Biomasa , Eficiencia , Fermentación , Tanacetum parthenium/metabolismo , Biotransformación , Métodos , Estándares de Referencia , MétodosRESUMEN
The effect of harvest time, shading prior to harvest and water stress on parthenolide (PRT) concentration in feverfew and its possible connection with the abscisic acid (ABA) pathway were investigated. In plants harvested at different times of the day, acetumar the PRT levels were highest during late afternoon while ABA levels were greatest during morning hours. Shading plants during the afternoon prior to harvest caused a two-fold increase in ABA and no significant difference in PRT levels. ABA was higher in water-stressed plants while PRTcontent increased in plants following recovery from a water stress event. ABA inhibitors, norflurazon, sodium tungstate, naproxen and sodium bisulfite, were used to determine the connection between the biosynthesis of PRTand ABA. Norflurazon and naproxen reduced PRT concentration in cut flowers and in 2-month old plants. Sodium bisulfite and sodium tungstate reduced PRT only in cut flowers. Application of 2,4-D, a promoter of ABA synthesis, to potted plants resulted in a 2.5 fold increase in PRT levels. The inhibition of PRT formation in response to ABA inhibitors and the increase in PRT concentration observed with 2,4-D application indicated that PRT is derived from carotenoid synthesis similarly to ABA and not directly from farnesyl pyrosphosphate (FPP) as suggested for other sesquiterpene Lactones. However, PRT and ABA levels are affected dissimilarly by environmental conditions. The overall results of the study indicated that simple agricultural practices, such as harvesting during afternoon and subjecting plants to a single water stress event, can increase PRT concentration in the final feverfew product with no additional costs of production prior to harvest.