Sample records for sesquiterpene lactone dermatitis
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Jacob, Mathias; Brinkmann, Jürgen; Schmidt, Thomas J
2012-05-01
Two preparations are currently in use for the diagnosis of allergic contact dermatitis caused by Asteraceae: (i) Sesquiterpene lactone (SL) mix [three pure sesquiterpene lactones (STLs)], whose use has been questioned, owing to an insufficient rate of true-positive results; and (ii) Compositae mix, consisting of five Asteraceae extracts, which is problematic because of lack of standardization and questionable reproducibility. To analyse the reasons for the narrow sensitivity of SL mix from a chemoinformatic point of view, and to propose a solution by rational selection of alternative constituents for a new SL mix II covering a broader cohort of allergic patients. Structural and biological information on allergenic STLs was retrieved from databases and the literature, and molecular modelling and chemoinformatic computations were performed. An explanation for the insufficient hit rate of SL mix is that the three constituents possess extremely similar molecular structures/properties and do not represent well the structural diversity of allergenic STLs. STLs that are known as constituents of Compositae mix plants show much a wider diversity, which explains the higher positive rate. On the basis of their positions in chemical property space, a new collection of STLs that more evenly cover the overall structural diversity spectrum is proposed. SL mix II is likely to detect a larger number of patients sensitized to Asteraceae. © 2012 John Wiley & Sons A/S.
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De, Dipankar; Khullar, Geeti; Handa, Sanjeev
2015-01-01
Parthenium hysterophorus is the leading cause of phytogenic allergic contact dermatitis in India. The Indian Standard Series currently supplied by Systopic Laboratories Ltd and manufactured by Chemotechnique Diagnostics ® contains parthenolide as the only allergen representing plant allergens. The study was conducted to assess the performance of the Chemotechnique plant series (PL-1000), consisting of 14 allergens, in patients with clinically suspected occupational contact dermatitis to plant allergens. Ninety patients were patch tested with the Chemotechnique plant series from 2011 to 2013. Demographic details, clinical diagnosis and patch test results were recorded in the contact dermatitis clinic proforma. Of 90 patients, 24 (26.7%) showed positive reactions to one or more allergens in the plant series. Positive patch tests were elicited most commonly by sesquiterpene lactone mix in 19 (78.6%) patients, followed by parthenolide in 14 (57.1%), Achillea millefolium in 10 (42.9%) and others in decreasing order. The plant allergen series prepared by Chemotechnique Diagnostics is possibly not optimal for diagnosing suspected allergic contact dermatitis to plants in north Indians. Sesquiterpene lactone mix should replace parthenolide as the plant allergen in the Indian Standard Series until relevant native plant extracts are commercially available for patch testing.
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Sesquiterpene lactone dermatitis in the young: is atopy a risk factor?
Paulsen, Evy; Otkjaer, Aksel; Andersen, Klaus E
2008-07-01
Screening for Compositae contact allergy has documented fairly high prevalence in adults, and recent studies indicate that the allergy may be more common in children than previously believed. However, detailed information on sensitization in this age group is sparse. The objective of this study was to present another 2 cases in children and review the literature. Screening with sesquiterpene lactone (SL) mix has shown prevalence of 0.5% and 1.8% in 2 studies, while screening with 2 different Compositae mixes detected 4.2% and 2.6% positives among children and adolescents. All individual case reports describe sensitization in atopic children, and the largest screening study showed a prevalence of Compositae mix sensitization that was significantly higher in children with atopic dermatitis compared with non-atopics. Compositae sensitization should be considered in children with a family or personal history of atopy, summer-related, or -exacerbated dermatitis of any kind, and a history of plant exposure. Screening with SL mix is recommended but should be supplemented with plant extracts based on exposure history. Compositae weeds, especially dandelions, seem to be important sensitizers in children.
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Jovanović, Marina; Poljacki, Mirjana
2003-01-01
Compositae dermatitis is an allergic contact dermatitis caused by plant species of the Compositae family. The first report of a cutaneous reaction to the Chrysanthemum genus was made by Howe JS in 1887. In 1895 Maiden JH reported about skin lesions among men working with Tagetes minuta. Case reports of contact allergic-ragweed dermatitis appeared in the American literature as early as 1919. The North American feverfew--Parthenium Hysterophorus was brought to India from America in 1956 and it caused thousands of cases of so-called parthenium dermatitis. Ragweed and parthenium dermatitis became prototypes for the classic, so-called "airborne" Compositae dermatitis, that affects primarily exposed skin surfaces, and produces a universal erythroderma. The frequency of contact allergy to Compositae in Europe is higher than previously believed. It occurs most frequently in middle-aged and elderly persons, but also in all age groups. During the two past decades a more equal sex ratio has been established. The prevalence varies from 0.7-1.4% in the general population, up to 4.5% among occupationally exposed persons. Compositae allergy is among the top ten contact sensitivities in Europe. In North Europe plants were the cause of 4.4% cases of occupational allergic contact dermatitis. ETIOLOGY AND PATHOGENESIS: Among cultivated Compositae plants, Chrysanthemum is considered to be a major sensitizer in Europe (60%). Among the edible types, it is lettuce--Lactuca sativa and endive Cichorium endivia (20-30%), and wild-growing feverfew--Tanace--tum parthenium (70-90%), tansy--Tanacetum vulgare (54%), and dandelion--Taraxacum officinale (65%). Sesquiterpene lactones are the main sensitizers of the Compositae family. Other components, thiophenes and acetylenes are said to elicit only phytophotodermatitis, but recent studies have demonstrated that some thiophenes and benzofuran derivates possess not only phototoxic activity, but also sensitizing properties. Photosensitivity is present in 22-75% Compositae sensitive individuals. Extracts from Compositae are known to be phototoxic in vitro. Photoreactivity of alpha-methylene-gamma-la-ctone group of sesquiterpene-lactone directed towards the DNA base thymine, thus producing intermolecular 2 + 2 photoadducts (antigen within the cell), was also thought to be related to photosensitivity. Clinical manifestations vary from generalized eczema (20-30%), eczema of hands and face (24%), hand (36-44%), or facial eczema (11-28%). 65% of patients have vesicular hand eczema. Routine patch testing with sesquiterpene lactone mix, aimed testing with Compositae extracts screening mix, Compositae plants, and with their extracts, whereas the treatment of choice is a specific allergen-immunotherapy.
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Sesquiterpene lactone stereochemistry influences herbivore resistance and plant fitness in the field
Ahern, Jeffrey R.; Whitney, Kenneth D.
2014-01-01
Background and Aims Stereochemical variation is widely known to influence the bioactivity of compounds in the context of pharmacology and pesticide science, but our understanding of its importance in mediating plant–herbivore interactions is limited, particularly in field settings. Similarly, sesquiterpene lactones are a broadly distributed class of putative defensive compounds, but little is known about their activities in the field. Methods Natural variation in sesquiterpene lactones of the common cocklebur, Xanthium strumarium (Asteraceae), was used in conjunction with a series of common garden experiments to examine relationships between stereochemical variation, herbivore damage and plant fitness. Key Results The stereochemistry of sesquiterpene lactone ring junctions helped to explain variation in plant herbivore resistance. Plants producing cis-fused sesquiterpene lactones experienced significantly higher damage than plants producing trans-fused sesquiterpene lactones. Experiments manipulating herbivore damage above and below ambient levels found that herbivore damage was negatively correlated with plant fitness. This pattern translated into significant fitness differences between chemotypes under ambient levels of herbivore attack, but not when attack was experimentally reduced via pesticide. Conclusions To our knowledge, this work represents only the second study to examine sesquiterpene lactones as defensive compounds in the field, the first to document herbivore-mediated natural selection on sesquiterpene lactone variation and the first to investigate the ecological significance of the stereochemistry of the lactone ring junction. The results indicate that subtle differences in stereochemistry may be a major determinant of the protective role of secondary metabolites and thus of plant fitness. As stereochemical variation is widespread in many groups of secondary metabolites, these findings suggest the possibility of dynamic evolutionary histories within the Asteraceae and other plant families showing extensive stereochemical variation. PMID:24380844
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Ahern, Jeffrey R; Whitney, Kenneth D
2014-03-01
Stereochemical variation is widely known to influence the bioactivity of compounds in the context of pharmacology and pesticide science, but our understanding of its importance in mediating plant-herbivore interactions is limited, particularly in field settings. Similarly, sesquiterpene lactones are a broadly distributed class of putative defensive compounds, but little is known about their activities in the field. Natural variation in sesquiterpene lactones of the common cocklebur, Xanthium strumarium (Asteraceae), was used in conjunction with a series of common garden experiments to examine relationships between stereochemical variation, herbivore damage and plant fitness. The stereochemistry of sesquiterpene lactone ring junctions helped to explain variation in plant herbivore resistance. Plants producing cis-fused sesquiterpene lactones experienced significantly higher damage than plants producing trans-fused sesquiterpene lactones. Experiments manipulating herbivore damage above and below ambient levels found that herbivore damage was negatively correlated with plant fitness. This pattern translated into significant fitness differences between chemotypes under ambient levels of herbivore attack, but not when attack was experimentally reduced via pesticide. To our knowledge, this work represents only the second study to examine sesquiterpene lactones as defensive compounds in the field, the first to document herbivore-mediated natural selection on sesquiterpene lactone variation and the first to investigate the ecological significance of the stereochemistry of the lactone ring junction. The results indicate that subtle differences in stereochemistry may be a major determinant of the protective role of secondary metabolites and thus of plant fitness. As stereochemical variation is widespread in many groups of secondary metabolites, these findings suggest the possibility of dynamic evolutionary histories within the Asteraceae and other plant families showing extensive stereochemical variation.
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Jones, Samuel B; Burnett, William C; Coile, Nancy C; Mabry, Tom J; Betkouski, M F
1979-01-01
Sesquiterpene lactone glaucolide-A from Vernonia, incorporated in the rearing diets of five species of Lepidoptera, significantly reduced the rate of growth of larvae of the southern armyworm, Spodoptera eridania; fall armyworm, S. frugiperda; and yellowstriped armyworm, S. ornithogalli. Quantitative feeding tests demonstrated that decreased feeding levels and reduced growth resulted from ingestion of a sesquiterpene lactone. Ingestion of glaucolide-A increased the number of days to pupation in four of the species. In the southern armyworm, it significantly reduced pupal weight. Glaucolide-A decidedly reduced percentage of survival of southern and fall armyworms. Yellow woollybear, Diacrisia virginica, and cabbage looper, Trichoplusia ni, larvae were essentially uneffected by the ingestion of the sesquiterpene lactone. Sesquiterpene lactones adversely affect growth rate and survival of certain insects that feed upon plants containing them. They apparently function as defensive products, screening out a portion of the potential herbivores.
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Sessa, R A; Bennett, M H; Lewis, M J; Mansfield, J W; Beale, M H
2000-09-01
Wounding leaves or stems of Lactuca species releases a milky latex onto the plant surface. We have examined the constituents of latex from Lactuca sativa (lettuce) cv. Diana. The major components were shown to be novel 15-oxalyl and 8-sulfate conjugates of the guaianolide sesquiterpene lactones, lactucin, deoxylactucin, and lactucopicrin. The oxalates were unstable, reverting to the parent sesquiterpene lactone on hydrolysis. Oxalyl derivatives have been reported rarely from natural sources. The sulfates were stable and are the first reported sesquiterpene sulfates from plants. Unusual tannins based on 4-hydroxyphenylacetyl conjugates of glucose were also identified. Significant qualitative and quantitative variation was found in sesquiterpene lactone profiles in different lettuce varieties and in other Lactuca spp. The proportions of each conjugate in latex also changed depending on the stage of plant development. A similar profile was found in chicory, in which oxalyl conjugates were identified, but the 8-sulfate conjugates were notably absent. The presence of the constitutive sesquiterpene lactones was not correlated with resistance to pathogens but may have a significant bearing on the molecular basis of the bitter taste of lettuce and related species. The induced sesquiterpene lactone phytoalexin, lettucenin A, was found in the Lactuca spp. but not in chicory.
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New sources and antifungal activity of sesquiterpene lactones.
Barrero, A F; Oltra, J E; Alvarez, M; Raslan, D S; Saúde, D A; Akssira, M
2000-02-01
In the search for new sources of sesquiterpene lactones, six Centaurea species have been analyzed. The activity against the fungus Cunninghamella echinulata of (+)-cnicin (1) and (+)-salonitenolide (2), isolated from the Centaurea plants, as well as that of (+)-costunolide (3), (-)-dehydrocostuslactone (4), (-)-lychnopholide (5) and (-)-eremantholide C (6), has been evaluated. Compounds 3 and 4 showed noticeable EC50 values, whilst more polar lactones were inactive. These results suggest that a relatively low polarity is one of the molecular requirements for the antifungal activity of sesquiterpene lactones.
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Sesquiterpenoids Lactones: Benefits to Plants and People
Chadwick, Martin; Trewin, Harriet; Gawthrop, Frances; Wagstaff, Carol
2013-01-01
Sesquiterpenoids, and specifically sesquiterpene lactones from Asteraceae, may play a highly significant role in human health, both as part of a balanced diet and as pharmaceutical agents, due to their potential for the treatment of cardiovascular disease and cancer. This review highlights the role of sesquiterpene lactones endogenously in the plants that produce them, and explores mechanisms by which they interact in animal and human consumers of these plants. Several mechanisms are proposed for the reduction of inflammation and tumorigenesis at potentially achievable levels in humans. Plants can be classified by their specific array of produced sesquiterpene lactones, showing high levels of translational control. Studies of folk medicines implicate sesquiterpene lactones as the active ingredient in many treatments for other ailments such as diarrhea, burns, influenza, and neurodegradation. In addition to the anti-inflammatory response, sesquiterpene lactones have been found to sensitize tumor cells to conventional drug treatments. This review explores the varied ecological roles of sesquiterpenes in the plant producer, depending upon the plant and the compound. These include allelopathy with other plants, insects, and microbes, thereby causing behavioural or developmental modification to these secondary organisms to the benefit of the sesquiterpenoid producer. Some sesquiterpenoid lactones are antimicrobial, disrupting the cell wall of fungi and invasive bacteria, whereas others protect the plant from environmental stresses that would otherwise cause oxidative damage. Many of the compounds are effective due to their bitter flavor, which has obvious implications for human consumers. The implications of sesquiterpenoid lactone qualities for future crop production are discussed. PMID:23783276
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Sunflower seeds as eliciting agents of Compositae dermatitis.
Paulsen, Evy; El-Houri, Rime B; Andersen, Klaus E; Christensen, Lars P
2015-03-01
Sunflowers may cause dermatitis because of allergenic sesquiterpene lactones (SLs). Contact sensitization to sunflower seeds has also been reported, but the allergens are unknown. To analyse sunflower seeds for the presence of SLs and to assess the prevalence of sunflower sensitization in Compositae-allergic individuals. Sunflower-sensitive patients were identified by aimed patch testing. A dichloromethane extract of whole sunflower seeds was analysed by liquid chromatography-mass spectrometry and high-performance liquid chromatography. The prevalence of sensitivity to sunflower in Compositae-allergic individuals was 56%. A solvent wash of whole sunflower seeds yielded an extract containing SLs, the principal component tentatively being identified as argophyllin A or B, other SLs being present in minute amounts. The concentration of SLs on the sunflower seeds is considered high enough to elicit dermatitis in sensitive persons, and it seems appropriate to warn Compositae-allergic subjects against handling sunflower seeds. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Structural and Sensory Characterization of Novel Sesquiterpene Lactones from Iceberg Lettuce.
Mai, Franziska; Glomb, Marcus A
2016-01-13
Lactuca sativa var. capitate (iceberg lettuce) is a delicious vegetable and popular for its mild taste. Nevertheless, iceberg lettuce is a source of bitter substances, such as the sesquiterpene lactones. Chemical investigations on the n-butanol extract led to the isolation of three novel sesquiterpene lactones. All compounds were isolated by multilayer countercurrent chromatography followed by preparative high-performance liquid chromatography. The structures were verified by means of spectroscopic methods, including NMR and mass spectrometry techniques. For the first time 11ß,13-dihydrolactucin-8-O-sulfate (jaquinelin-8-O-sulfate) was structurally elucidated and identified in plants. In addition, the sesquiterpene lactones cichorioside B and 8-deacetylmatricarin-8-O-sulfate were identified as novel ingredients of iceberg lettuce. Further flowering plants in the daisy family Asteraceae were examined for the above three compounds. At least one of the compounds was identified in nine plants. The comparison between the lettuce butt end and the leaves of five types of the Cichorieae tribe showed an accumulation of the compounds in the butt end. Further experiments addressed the impact of sesquiterpene lactones on color formation and bitter taste.
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Variability of sesquiterpene lactones in Neurolaena lobata of different origin.
Passreiter, C M; Aldana, B E
1998-06-01
Leaves of Neurolaena lobata (L.) R. Br. originating from Guatemala, were analyzed using HPLC for their qualitative and quantitative sesquiterpene lactone contents. Significant differences in the individual amounts of neurolenins and furanoheliangolides were found between four natural populations. When plants were cultivated on proving fields at two different localities in Guatemala, their sesquiterpene lactone patterns matched the natural population, but differed quantitatively. The meaning of these differences for the use of N. lobata in traditional medicine and its cultivation is discussed.
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Sesquiterpene Lactones from Artemisia Genus: Biological Activities and Methods of Analysis
Miron, Anca; Corciova, Andreia
2015-01-01
Sesquiterpene lactones are a large group of natural compounds, found primarily in plants of Asteraceae family, with over 5000 structures reported to date. Within this family, genus Artemisia is very well represented, having approximately 500 species characterized by the presence of eudesmanolides and guaianolides, especially highly oxygenated ones, and rarely of germacranolides. Sesquiterpene lactones exhibit a wide range of biological activities, such as antitumor, anti-inflammatory, analgesic, antiulcer, antibacterial, antifungal, antiviral, antiparasitic, and insect deterrent. Many of the biological activities are attributed to the α-methylene-γ-lactone group in their molecule which reacts through a Michael-addition with free sulfhydryl or amino groups in proteins and alkylates them. Due to the fact that most sesquiterpene lactones are thermolabile, less volatile compounds, they present no specific chromophores in the molecule and are sensitive to acidic and basic mediums, and their identification and quantification represent a difficult task for the analyst. Another problematic aspect is represented by the complexity of vegetal samples, which may contain compounds that can interfere with the analysis. Therefore, this paper proposes an overview of the methods used for the identification and quantification of sesquiterpene lactones found in Artemisia genus, as well as the optimal conditions for their extraction and separation. PMID:26495156
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Antimalarial activity of sesquiterpene lactones from Vernonia cinerea.
Chea, Aun; Hout, Sotheara; Long, Christophe; Marcourt, Laurence; Faure, Robert; Azas, Nadine; Elias, Riad
2006-10-01
Two new sesquiterpene lactones, vernolides C and D as well as six known ones were isolated from the dichloromethane fraction of an aqueous extract from Vernonia cinerea. Their structures were elucidated by spectroscopic methods. Among the known sesquiterpene lactones, three of them were described in this plant for the first time. In vitro antiplasmodial evaluation showed that the three major compounds 1, 7 and 8 were active against chloroquine resistant Plasmodium falciparum strain (W2) with IC(50) 3.9, 3.7 and 3.5 microM, respectively.
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Sesquiterpene lactones from Centaurea tweediei.
Fortuna, A M.; de Riscala, E C.; Catalan, C A.N.; Gedris, T E.; Herz, W
2001-10-01
Aerial parts of Centaurea tweediei from Argentina afforded as the main constituent the sesquiterpene lactone onopordopicrin and minor amounts of a new heliangolide, a new guaianolide, a new eudesmanolide, a new eudesmane acid and the lignans arctigenin and matairesinol.
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Clauser, Maria; Aiello, Nicola; Scartezzini, Fabrizio; Innocenti, Gabbriella; Dall'Acqua, Stefano
2014-01-01
The flower heads of fourteen wild Arnica montana L. populations were collected in the summer of 2010 in the provinces of Trento, Brescia and Bergamo (Italy). The dried flowers were analyzed to assess their chemical diversity. HLPC-MS analysis led to the identification of phenolic derivatives and sesquiterpene lactones in the samples, confirming literature data. Quali-quantitative analysis of the flower heads showed similar qualitative patterns both for the phenolic as well as sesquiterpene lactone derivatives, while significant variability was obtained in the amounts (HPLC-DAD) of sesquiterpene lactones (0.45-2.31%), phenolic acids (1.44-2.88%) and flavonoids (0.96-2.44%). The highest quantities of sesquiterpene lactones, flavonoids and phenolic acids were found in Malga Fregasoga (1703 m above sea level), Rifugio Camini (1608 m a.s.l.) and Malga Sass (1817 m a.s.l.) samples, respectively.
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Mode of Action of the Sesquiterpene Lactones Psilostachyin and Psilostachyin C on Trypanosoma cruzi
Papademetrio, Daniela; Batlle, Alcira; Martino, Virginia S.; Frank, Fernanda M.; Lombardo, María E.
2016-01-01
Trypanosoma cruzi is the causative agent of Chagas’ disease, which is a major endemic disease in Latin America and is recognized by the WHO as one of the 17 neglected tropical diseases in the world. Psilostachyin and psilostachyin C, two sesquiterpene lactones isolated from Ambrosia spp., have been demonstrated to have trypanocidal activity. Considering both the potential therapeutic targets present in the parasite, and the several mechanisms of action proposed for sesquiterpene lactones, the aim of this work was to characterize the mode of action of psilostachyin and psilostachyin C on Trypanosoma cruzi and to identify the possible targets for these molecules. Psilostachyin and psilostachyin C were isolated from Ambrosia tenuifolia and Ambrosia scabra, respectively. Interaction of sesquiterpene lactones with hemin, the induction of oxidative stress, the inhibition of cruzipain and trypanothione reductase and their ability to inhibit sterol biosynthesis were evaluated. The induction of cell death by apoptosis was also evaluated by analyzing phosphatidylserine exposure detected using annexin-V/propidium iodide, decreased mitochondrial membrane potential, assessed with Rhodamine 123 and nuclear DNA fragmentation evaluated by the TUNEL assay. Both STLs were capable of interacting with hemin. Psilostachyin increased about 5 times the generation of reactive oxygen species in Trypanosoma cruzi after a 4h treatment, unlike psilostachyin C which induced an increase in reactive oxygen species levels of only 1.5 times. Only psilostachyin C was able to inhibit the biosynthesis of ergosterol, causing an accumulation of squalene. Both sesquiterpene lactones induced parasite death by apoptosis. Upon evaluating the combination of both compounds, and additive trypanocidal effect was observed. Despite their structural similarity, both sesquiterpene lactones exerted their anti-T. cruzi activity through interaction with different targets. Psilostachyin accomplished its antiparasitic effect by interacting with hemin, while psilostachyin C interfered with sterol synthesis. PMID:26939119
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Staneva, Jordanka; Denkova, Pavletta; Todorova, Milka; Evstatieva, Ljuba
2011-01-05
(1)H NMR spectroscopy was used as a method for quantitative analysis of sesquiterpene lactones present in a crude lactone fraction isolated from Arnica montana. Eight main components - tigloyl-, methacryloyl-, isobutyryl- and 2-methylbutyryl-esters of helenalin (H) and 11α,13-dihydrohelenalin (DH) were identified in the studied sample. The method allows the determination of the total amount of sesquiterpene lactones and the quantity of both type helenalin and 11α,13-dihydrohelenalin esters separately. Furthermore, 6-O-tigloylhelenalin (HT, 1), 6-O-methacryloylhelenalin (HM, 2), 6-O-tigloyl-11α,13-dihydrohelenalin (DHT, 5), and 6-O-methacryloyl-11α,13-dihydrohelenalin (DHM, 6) were quantified as individual components. Copyright © 2010 Elsevier B.V. All rights reserved.
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[Facial allergic contact dermatitis. Data from the IVDK and review of literature].
Schnuch, A; Szliska, C; Uter, W
2009-01-01
The face is exposed to many foreign substances and may thus be a site of allergic contact dermatitis. Our aim is to elucidate the spectrum of factors associated with facial dermatitis by analyzing data of patients patch tested in the Information Network of Departments of Dermatology (IVDK) between 1995 and 2007. In 18,572 patients the main anatomical site of dermatitis was the face. Among these, the proportion of females and of patients with past or present atopic eczema was increased, while probable occupational causation was less common than in the overall group. Cosmetic allergens, as well as nickel, were significantly more common in women than men, including fragrance mix (10.8% vs. 8.3%), p-phenylenediamine (4.0% vs. 2.8%), lanolin alcohols (3.0% vs. 2.2%), Lyral(TM) (3.1% vs. 2.0%) and bufexamac (1.8% vs. 1.1%). In comparison, only epoxy resin contact allergy was diagnosed significantly more often in men than women: In patients with airborne contact dermatitis, over-represented allergens included sesquiterpene lactone mix, compositae mix, epoxy resin, (chloro-) methylisothiazolinone and oil of turpentine. In the clinical approach to patients with facial dermatitis, occupational airborne causation should be considered in addition to non-occupational (e.g., cosmetic) allergen exposure.
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Antibacterial and cytotoxic activities of the sesquiterpene lactones cnicin and onopordopicrin.
Bach, Sandra M; Fortuna, Mario A; Attarian, Rodgoun; de Trimarco, Juliana T; Catalán, César A N; Av-Gay, Yossef; Bach, Horacio
2011-02-01
The antimicrobial and cytotoxic activities of chloroform extracts from the weeds Centaurea tweediei and C. diffusa, and the main sesquiterpene lactones isolated from these species, onopordopicrin and cnicin, respectively, were assayed. Results show that the chloroform extracts from both Centaurea species possess antibacterial activities against a panel of Gram-positive and Gram-negative bacteria. Remarkable antibacterial activity against methicillin-resistant Staphylococcus aureus was also measured. Both the extracts and the purified sesquiterpene lactones show high cytotoxicity against human-derived macrophages. Despite this cytotoxicity, C. diffusa chloroform extract and cnicin are attractive candidates for evaluation as antibiotics in topical preparations against skin-associated pathogens.
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2013-01-01
Human trypanosomiasis is a parasitic disease among poor people in Africa and Latin America. Therapy against African and American trypanosomiasis is based on a few drugs that often cause severe side-effects. Therefore, it is essential to develop drug discovery especially from natural origins. Sesquiterpenes, a diverse group of natural terpenoids, are found in essential oils of many plants and show a broad range of bioactivities. They act through multiple mechanisms in the chemotherapy of trypanosomiasis. Some of these active compounds contain hydroperoxides, aldehydes, alcohols, α,β-unsaturated γ-lactone and even halogenated moieties. Among the compounds reported, sesquiterpene lactones showed a potent anti-trypanosoma effect comparable with commercial trypanocidal drugs. Trypanocidal activity of sesquiterpene lactones mostly depends on the reaction between γ-lactone moieties and nucleophile groups of trypanithione, which is essential for Trypanosoma defense against the oxidative stresses. Elatol is a sesquiterpenoid from marine algae, with a different structure and considerable trypanocidal activity which could be an interesting candidate for further antiprotozoal investigations. To develop novel drugs with higher efficacy and lower toxicity from natural products, this review summarizes the more recent information on trypanocidal activities of various sesquiterpenes. PMID:23676125
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Torres, Ascensión; Molinillo, José M G; Varela, Rosa M; Casas, Lourdes; Mantell, Casimiro; Martínez de la Ossa, Enrique J; Macías, Francisco A
2015-10-02
Four novel compounds (1-4) with an unprecedented skeleton that combines a sesquiterpene lactone and a kaurane diterpene acid were isolated from Helianthus annuus L. var. Arianna extract, which was obtained under supercritical conditions. The structures of 1-4 were elucidated by NMR and MS analyses. The biosynthetic routes involve sesquiterpene lactones and kauranic acid, both of which were previously isolated from this species.
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Sesquiterpene lactones from Taraxacum obovatum.
Michalska, Klaudia; Kisiel, Wanda
2003-02-01
Two new guaianolide glucosides, deacetylmatricarin 8-O-beta-glucopyranoside and 11beta-hydroxyleukodin 11-O-beta-glucopyranoside, were isolated from roots of Taraxacum obovatum, along with four known sesquiterpene lactones, deacetylmatricarin, sonchuside A, taraxinic acid beta-glucopyranosyl ester and its 11beta,13-dihydro derivative. Their structures were established by spectral methods.
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Jovanović, M; Poljacki, M; Mimica-Dukić, N; Boza, P; Vujanović, Lj; Duran, V; Stojanović, S
2004-09-01
We investigated the value of patch testing with dandelion (Compositae) extract in addition to sesquiterpene lactone (SL) mix in selected patients. After we detected a case of contact erythema multiforme after patch testing with dandelion and common chickweed (Caryophyllaceae), additional testing with common chickweed extract was performed. A total of 235 adults with a mean age of 52.3 years were tested. There were 66 men and 169 women: 53 consecutive patients with allergic contact dermatitis (ACD); 43 with atopic dermatitis (AD); 90 non-atopics suffering from non-allergic chronic inflammatory skin diseases; 49 healthy volunteers. All were tested with SL mix 0.1% petrolatum (pet.) and diethyl ether extracts from Taraxacum officinale (dandelion) 0.1 and 3.0% pet. and from Stellaria media (common chickweed) 0.1 and 3% pet. A total of 14 individuals (5.9%) showed allergic reaction (AR) to at least 1 of the plant allergens, 4 (28.6%) to common chickweed extract, and 11 (78.6%) to Compositae allergens. These 11 persons made the overall prevalence of 4.7%: 8 (3.4%) were SL-positive and 3 (1.3%) reacted to dandelion extract. 5 persons (45.5%) had AD, 2 had ACD, 2 had psoriasis and 2 were healthy controls. The Compositae allergy was relevant in 8 cases (72.7%). The highest frequency of SL mix sensitivity (9.3%) was among those with AD. Half the SL mix-sensitive individuals had AD. ARs to dandelion extract were obtained only among patients with eczema. A total of 9 irritant reactions (IRs) in 9 individuals (3.8%) were recorded, 8 to SL mix and 1 to common chickweed extract 3.0% pet. No IR was recorded to dandelion extract (P = 0.007). Among those with relevant Compositae allergy, 50.0% had AR to fragrance mix and balsam of Peru (Myroxylon pereirae resin) and colophonium. SLs were detected in dandelion but not in common chickweed. Our study confirmed the importance of 1 positive reaction for emerging, not fully established, Compositae allergy. In conclusion, the overall prevalence of 4.7% in our study represents a basal SL mix detection rate of 3.4% reinforced and safely supplemented by testing with the dandelion extract.
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Esatbeyoglu, Tuba; Obermair, Betina; Dorn, Tabea; Siems, Karsten; Rimbach, Gerald; Birringer, Marc
2017-01-01
Taraxacum officinale, the common dandelion, is a plant of the Asteraceae family, which is used as a food and medical herb. Various secondary plant metabolites such as sesquiterpene lactones, triterpenoids, flavonoids, phenolic acids, coumarins, and steroids have been described to be present in T. officinale. Dandelion may exhibit various health benefits, including antioxidant, anti-inflammatory, and anticarcinogenic properties. We analyzed the leaves and roots of the common dandelion (T. officinale) using high-performance liquid chromatography/mass spectrometry to determine its sesquiterpene lactone composition. The main compound of the leaf extract taraxinic acid β-d-glucopyranosyl ester (1), a sesquiterpene lactone, was isolated and the structure elucidation was conducted by nuclear magnetic resonance spectrometry. The leaf extract and its main compound 1 activated the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in human hepatocytes more significantly than the root extract. Furthermore, the leaf extract induced the Nrf2 target gene heme oxygenase 1. Overall, present data suggest that compound 1 may be one of the active principles of T. officinale.
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Yuan, Xiaoyan; Yang, Qianxu
2017-04-01
A method of ultra high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry was developed for the simultaneous quantification of 11 sesquiterpene lactones in 11 Jerusalem artichoke leaf samples harvested in a number of areas at different periods. The optimal chromatographic conditions were achieved on a ZORBAX Eclipse Plus C 18 column (3.0 × 150 mm, 1.8 μm) with linear gradient elution of methanol and water in 8 min. Quantitative analysis was carried out under selective ion monitoring mode. All of the sesquiterpene lactones showed good linearity (R 2 ≥ 0.9949), repeatability (relative standard deviations < 4.66%), and intra- and interday precisions (relative standard deviations < 4.52%) with an accuracy of 95.24-104.84%. The recoveries measured at three concentration levels varied from 95.07 to 104.87% with relative standard deviations less than 4.9%. The limit of detection and limit of quantitation for this method were 0.89-5.05 and 1.12-44.33 ng/mL, respectively. The results showed that the contents of sesquiterpene lactones varied significantly in the Jerusalem artichoke leaf samples from different areas. Among them, the content of sesquiterpene lactones in the sample collected from Dalian, Liaoning province was the highest and the early flowering period was considered to be the optimal harvest time. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Paulsen, E; Søgaard, J; Andersen, K E
1998-03-01
The clinical part of the study aimed at describing epidemiological and diagnostic aspects of occupational Compositae dermatitis. Patch testing with the sesquiterpene lactone (SL) and Compositae mixes, feverfew extract and supplementary allergens in 250 selected gardeners showed Compositae allergy in 25, 17 females and 8 males. 24 were possibly occupationally sensitized. The mean age was lower and the preponderance of women higher compared to classical Compositae dermatitis, and the distribution and course of the dermatitis most often did not differ from other occupational plant dermatoses. The Compositae mix detected 2x as many as the SL mix, and the overall detection rate with both was 76%, making aimed patch testing necessary. Chrysanthemum (Dendranthema), marguerite daisy (Argyranthemum frutescens) and lettuce (Lactuca sativa) were frequent sensitizers. Occupational type I allergy to Compositae comprised sensitization to Gerbera, chrysanthemum, lettuce, Senecio cruentus and Aster. Among 1657 respondents in the questionnaire part of the study, 824 had worked with Compositae, and 160 (19%) reported occupational Compositae-related symptoms of skin and mucous membranes. Possible risk factors for the development of these were assessed in a stepwise logistic regression model and a history of childhood eczema, hay fever and duration of exposure were significantly associated with Compositae-related irritant and allergic symptoms in both sexes.
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Sesquiterpene lactones from neurolaena oaxacana
Passreiter; Sandoval-Ramirez; Wright
1999-08-01
Twelve sesquiterpene lactones, two new (1 and 2) and 10 known neurolenin-type germacranolides and furanoheliangolides (3-12) were isolated from Neurolaena oaxacana, and their structures were elucidated by NMR and GC-MS analysis. The chemotaxonomic importance of these findings is discussed. As N. lobata is used against dysenteries, neurolenin B (4) and a mixture of the neurolenins C (5) and D (6) were tested against Entamoeba histolytica and Giardia intestinalis.
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François, G; Passreiter, C M; Woerdenbag, H J; Van Looveren, M
1996-04-01
Aqueous and lipophilic extracts of Neurolaena lobata (Asteraceae), obtained from Guatemala, were tested against Plasmodium falciparum in vitro. Moreover, sesquiterpene lactones, of the germacranolide and furanoheliangolide type, isolated from N. lobata, were shown to be active against P. falciparum in vitro. In addition to their antiplasmodial activity, their cytotoxic effects on human carcinoma cell lines were evaluated. Structure-activity relationships are discussed.
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Mahesh, A; Jeyachandran, R; Cindrella, L; Thangadurai, D; Veerapur, V P; Muralidhara Rao, D
2010-06-01
The hepatocurative potential of ethanolic extract (ETO) and sesquiterpene lactones enriched fraction (SL) of Taraxacum officinale roots was evaluated against carbon tetrachloride (CCl 4 ) induced hepatotoxicity in mice. The diagnostic markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin contents were significantly elevated, whereas significant reduction in the level of reduced glutathione (GSH) and enhanced hepatic lipid peroxidation, liver weight and liver protein were observed in CCl 4 induced hepatotoxicity in mice. Post-treatment with ETO and SL significantly protected the hepatotoxicity as evident from the lower levels of hepatic enzyme markers, such as serum transaminase (ALT, AST), ALP and total bilirubin. Further, significant reduction in the liver weight and liver protein in drug-treated hepatotoxic mice and also reduced oxidative stress by increasing reduced glutathione content and decreasing lipid peroxidation level has been noticed. The histopathological evaluation of the liver also revealed that ETO and SL reduced the incidence of liver lesions induced by CCl 4 . The results indicate that sesquiterpene lactones have a protective effect against acute hepatotoxicity induced by the administration of CCl 4 in mice. Furthermore, observed activity of SL may be due to the synergistic action of two sesquiterpene lactones identified from enriched ethyl acetate fraction by HPLC method.
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Effect of different types of sesquiterpene lactones on the maturation of Rhinella arenarum oocytes.
Sánchez-Toranzo, G; Zapata-Martínez, J; Catalán, C; Bühler, M I
2015-06-01
The sesquiterpene lactones (STLs) are a large class of plant secondary metabolites that are generally found in the Asteraceae family and that have high diversity with respect to chemical structure as well as biological activity. STLs have been classified into different groups, such as guaianolides, germacranolides, and melampolides etc., based on their carboxylic skeleton. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under the stimulus of progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. The purpose of this work was to determine whether sesquiterpene lactones from the germacranolide and melampolide groups act as inhibitor agents on the meiosis of amphibian oocytes in vitro. Results for germacranolides indicated that the addition of deoxyelephantopins caused a high degree of inhibition and that minimolide showed a moderate inhibitory effect, whereas glaucolide A was inactive. Furthermore, the addition of melampolides (uvedalin, enhydrin, polymatin A and polymatin B) showed inhibitory effects. For enhydrin and uvedalin, inhibitory effects were observed at the higher concentrations assayed. The results of this study suggest that the inhibitory activity of the tested sesquiterpene lactones on the meiosis of Rhinella arenarum oocytes is not dependent on the group to which they belong, i.e. not on the carboxylic skeleton, but probably due to the arrangement and type of function groups present in the molecules. All assayed lactones in the germacranolide group showed low toxicity. In contrast, important differences in toxicity were observed for lactones from the melampolide group: enhydrin and uvedalin showed low toxicity, but polymatin A and B were highly toxic.
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Álvarez-Calero, José María; Ruiz, Enrique; López-Pérez, José Luis; Jaraíz, Martín; Rubio, José E; Jorge, Zacarías D; Suárez, Margarita; Massanet, Guillermo M
2018-05-18
A study on the electrophile-induced rearrangement of two 15-hydroxygermacranolides, salonitenolide and artemisiifolin, was carried out. These compounds underwent electrophilic intramolecular cyclizations or acid-mediated rearrangements to give sesquiterpene lactones with different skeletons such as eudesmanolides, guaianolides, amorphanolides, or other germacranolides. The cyclization that gives guaianolides can be considered a biomimetic route to this type of sesquiterpene lactones. The use of acetone as a solvent changes the reactivity of the two starting germacranolides to the acid catalysts, with a 4,15-diol acetonide being the main product obtained. The δ-amorphenolide obtained by intramolecular cyclization of this acetonide is a valuable intermediate for accessing the antimalarials artemisinin and its derivatives. Mechanistic proposals for the transformations are raised, and to provide support them, quantum chemical calculations [DFT B3LYP/6-31+G(d,p) level] were undertaken.
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Cala, Antonio; Molinillo, José M G; Fernández-Aparicio, Mónica; Ayuso, Jesús; Álvarez, José A; Rubiales, Diego; Macías, Francisco A
2017-08-09
Allelochemicals are safer, more selective and more active alternatives than synthetic agrochemicals for weed control. However, the low solubility of these compounds in aqueous media limits their use as agrochemicals. Herein, we propose the application of α-, β- and γ-cyclodextrins to improve the physicochemical properties and biological activities of three sesquiterpene lactones: dehydrocostuslactone, costunolide and (-)-α-santonin. Complexation was achieved by kneading and coprecipitation methods. Aqueous solubility was increased in the range 100-4600% and the solubility-phase diagrams suggested that complex formation had been successful. The results of the PM3 semiempirical calculations were consistent with the experimental results. The activities on etiolated wheat coleoptiles, Standard Target Species and parasitic weeds were improved. Cyclodextrins preserved or enhanced the activity of the three sesquiterpene lactones. Free cyclodextrins did not show significant activity and therefore the enhancement in activity was due to complexation. These results are promising for applications in agrochemical design.
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A new sesquiterpene and other constituents from Saussurea lappa root.
Duan, Jin-Ao; Hou, Pengfei; Tang, Yuping; Liu, Pei; Su, Shulan; Liu, Hanqing
2010-10-01
Five sesquiterpenes, dehydrocostus lactone (1), santamarine (5), beta-cyclocostunolide (6), 4alpha-hydroxy-4beta-methyldihydrocostol (7) and 10alpha-hydroxyl-artemisinic acid (9), along with four other compounds, beta-sitosterol (2), daucosterol (3), 5-hydroxymethyl-furaldehyde (4), and trans-syingin (8), were isolated and identified from the roots of Saussurea lappa (Compositae). Based on previous reports and our study, sesquiterpene derivatives are common and characteristic constituents of the genus Saussurea. Among the nine compounds obtained, 9 is a new sesquiterpene. It is an artemisinic acid derivative, whose structural skeleton has not been reported for Saussurea species before, but artemisinic acid is a common compound in another Compositae species, Artemisia annua. Dehydrocostus lactone (1) is present in high-content and is a possible bioprecursor of 10alpha-hydroxyartemisinic acid (9).
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Božičević, Alen; De Mieri, Maria; Nassenstein, Christina; Wiegand, Silke; Hamburger, Matthias
2017-11-22
Plant pollens are strong airborne elicitors of asthma. Their proteinaceous allergens have been studied intensively, but little is known about a possible contribution of pollen secondary metabolites to the nonallergic exacerbation of asthma. Pollen samples originating from 30 plant species were analyzed by HPLC coupled to PDA, ESIMS, and ELSD detectors and off-line NMR spectroscopy. Polyamine conjugates, flavonoids, and sesquiterpene lactones were identified. Polyamine conjugates were characteristic of all Asteraceae species. The presence of sesquiterpene lactones in Asteraceae pollen varied between species and pollen lots. All plant pollen, including those from non-Asteraceae species, contained to some extent electrophiles as determined by their reaction with N-acetyl-l-cysteine. Selected pollen extracts and pure compounds were tested in murine afferent neurons and in murine tracheal preparations. Tetrahydrofuran extracts of Ambrosia artemisiifolia and Ambrosia psilostachya pollen and a mixture of sesquiterpene lactones coronopilin/parthenin increased the intracellular Ca 2+ concentration in 15%, 32%, and 37% of cinnamaldehyde-responsive neurons, respectively. In organ bath experiments, only the sesquiterpene lactones tested induced a weak dilatation of naïve tracheas and strongly lowered the maximal methacholine-induced tracheal constriction. A tetrahydrofuran extract of A. psilostachya and coronopilin/parthenin led to a time-dependent relaxation of the methacholine-preconstricted trachea. These results provide the first evidence for a potential role of pollen secondary metabolites in the modulation of the tracheal tone.
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Epidemiological data on airborne contact dermatitis - results of the IVDK.
Breuer, Kristine; Uter, Wolfgang; Geier, Johannes
2015-10-01
Airborne contact dermatitis (AirbCD) is not uncommon, according to a large number of published case reports and review articles. Epidemiological data on AirbCD based on larger clinical samples have not yet been published. To investigate demographic characteristics and patch test reactivity in patients diagnosed with both occupational and non-occupational AirbCD. A retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 1994-2013, including 201 344 consecutively patch tested patients, was performed. One thousand two hundred and three patients (0.6%) were diagnosed with AirbCD, 421 (35.0%) of these with an occupational background. Occupational dermatitis and face involvement were more prevalent than in patients without AirbCD (n = 200 141). Sensitization to epoxy resin and sensitization to methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) were significantly associated with AirbCD, and there was a trend for sensitization to Compositae mix and/or sesquiterpene lactone mix to be associated with AirbCD. Adhesives, plastics, construction materials, paints and varnishes in occupational cases, and plants in non-occupational cases, were the most commonly documented culprit product categories. AirbCD is more common in patients with occupational dermatitis than in patients with non-occupational dermatitis. In our clinical sample, components of epoxy resin systems, MCI/MI and Compositae allergens were the most important contact allergens associated with AirbCD. Patch testing with additional allergens is important. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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de Kraker, Jan-Willem; Franssen, Maurice C.R.; Joerink, Maaike; de Groot, Aede; Bouwmeester, Harro J.
2002-01-01
Chicory (Cichorium intybus) is known to contain guaianolides, eudesmanolides, and germacranolides. These sesquiterpene lactones are postulated to originate from a common germacranolide, namely (+)-costunolide. Whereas a pathway for the formation of germacra-1(10),4,11(13)-trien-12-oic acid from farnesyl diphosphate had previously been established, we now report the isolation of an enzyme activity from chicory roots that converts the germacrene acid into (+)-costunolide. This (+)-costunolide synthase catalyzes the last step in the formation of the lactone ring present in sesquiterpene lactones and is dependent on NADPH and molecular oxygen. Incubation of the germacrene acid in the presence of 18O2 resulted in the incorporation of one atom of 18O into (+)-costunolide. The label was situated at the ring oxygen atom. Hence, formation of the lactone ring most likely occurs via C6-hydroxylation of the germacrene acid and subsequent attack of this hydroxyl group at the C12-atom of the carboxyl group. Blue light-reversible CO inhibition and experiments with cytochrome P450 inhibitors demonstrated that the (+)-costunolide synthase is a cytochrome P450 enzyme. In addition, enzymatic conversion of (+)-costunolide into 11(S),13-dihydrocostunolide and leucodin, a guaianolide, was detected. The first-mentioned reaction involves an enoate reductase, whereas the formation of leucodin from (+)-costunolide probably involves more than one enzyme, including a cytochrome P450 enzyme. PMID:12011356
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de Kraker, Jan-Willem; Franssen, Maurice C R; Joerink, Maaike; de Groot, Aede; Bouwmeester, Harro J
2002-05-01
Chicory (Cichorium intybus) is known to contain guaianolides, eudesmanolides, and germacranolides. These sesquiterpene lactones are postulated to originate from a common germacranolide, namely (+)-costunolide. Whereas a pathway for the formation of germacra-1(10),4,11(13)-trien-12-oic acid from farnesyl diphosphate had previously been established, we now report the isolation of an enzyme activity from chicory roots that converts the germacrene acid into (+)-costunolide. This (+)-costunolide synthase catalyzes the last step in the formation of the lactone ring present in sesquiterpene lactones and is dependent on NADPH and molecular oxygen. Incubation of the germacrene acid in the presence of 18O2 resulted in the incorporation of one atom of 18O into (+)-costunolide. The label was situated at the ring oxygen atom. Hence, formation of the lactone ring most likely occurs via C6-hydroxylation of the germacrene acid and subsequent attack of this hydroxyl group at the C12-atom of the carboxyl group. Blue light-reversible CO inhibition and experiments with cytochrome P450 inhibitors demonstrated that the (+)-costunolide synthase is a cytochrome P450 enzyme. In addition, enzymatic conversion of (+)-costunolide into 11(S),13-dihydrocostunolide and leucodin, a guaianolide, was detected. The first-mentioned reaction involves an enoate reductase, whereas the formation of leucodin from (+)-costunolide probably involves more than one enzyme, including a cytochrome P450 enzyme.
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Ramos, Patrícia A B; Guerra, Ângela R; Guerreiro, Olinda; Freire, Carmen S R; Silva, Artur M S; Duarte, Maria F; Silvestre, Armando J D
2013-09-04
Lipophilic extracts of Cynara cardunculus L. var. altilis (DC) from the south of Portugal (Baixo Alentejo) were studied by gas chromatography-mass spectrometry. One sesquiterpene lactone, four pentacyclic triterpenes, and four sterols were reported for the first time as cultivated cardoon components, namely, deacylcynaropicrin, β- and α-amyrin, lupenyl and ψ-taraxasteryl acetates, stigmasterol, 24-methylenecholesterol, campesterol, and Δ(5)-avenasterol. In addition, other new compounds were identified: ten fatty acids, eight long-chain aliphatic alcohols, and six aromatic compounds. Four triterpenyl fatty acid esters were also detected. Sesquiterpene lactones and pentacyclic triterpenes were the major lipophilic families, representing respectively 2-46% and 10-89% of the detected compounds. Cynaropicrin was the most abundant sesquiterpene lactone, while taraxasteryl acetate was the main pentacyclic triterpene. Fatty acids and sterols, mainly hexadecanoic acid and β-sitosterol, were present at lower amounts (1-20% and 1-11% of the detected compounds). Long-chain aliphatic alcohols and aromatic compounds were detected at reduced abundances (1-6% of the detected compounds).
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Developmental and Environmental Effects on Sesquiterpene Lactones in Cultivated Arnica montana L.
Todorova, Milka; Trendafilova, Antoaneta; Vitkova, Antonina; Petrova, Maria; Zayova, Ely; Antonova, Daniela
2016-08-01
The amount of sesquiterpene lactones and the lactone profile of Arnica montana L. in flowering and seed formation stages in vitro and in vivo propagated from seeds of German, Ukrainian, and Austrian origin and grown in two experimental fields were studied. It was found that in vitro propagated 2-year plants in full flowering stage accumulated higher amount of lactones in comparison to in vivo propagated 3-year plants and to the seed formation stage, respectively. Helenalins predominated in in vivo propagated 2-year or in vitro propagated 3-year plants. 2-Methylbutyrate (2MeBu) was the principal ester in the samples with prevalence of helenalins, while isobutyrate (iBu) was the major one in the samples with predominance of 11,13-dihydrohelenalins. The results revealed that the environmental conditions on Vitosha Mt. are more suitable for cultivation of A. montana giving higher content of lactones. © 2016 Wiley-VHCA AG, Zürich.
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Formisano, Carmen; Sanna, Cinzia; Ballero, Mauro; Chianese, Giuseppina; Sirignano, Carmina; Rigano, Daniela; Millán, Estrella; Muñoz, Eduardo; Taglialatela-Scafati, Orazio
2017-01-01
Onopordum illyricum L. is a medicinal plant used in the Mediterranean area as antipyretic for the treatment of respiratory and urinary inflammations and to treat skin ulcers. Repeated chromatographic purification of O. illyricum aerial parts led to the isolation of six known sesquiterpenes, which were evaluated for the inhibition of the pro-inflammatory transcription factors NF-κB and STAT3 and for the activation of the transcription factor Nrf2, which regulates the cellular antioxidant response. Structure-activity relationships were interpreted by the NMR-based cysteamine assay. The sesquiterpene lactone vernomelitensin significantly inhibited NF-κB and STAT3, showing also a significant Nrf2 activation. Accordingly, the cysteamine assay selected vernomelitensin as the most reactive of the isolated sesquiterpenes, identifying the α,β-unsaturated aldehyde moiety as responsible for the higher (re)activity. Copyright © 2016 Elsevier B.V. All rights reserved.
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Divergent synthesis and identification of the cellular targets of deoxyelephantopins
NASA Astrophysics Data System (ADS)
Lagoutte, Roman; Serba, Christelle; Abegg, Daniel; Hoch, Dominic G.; Adibekian, Alexander; Winssinger, Nicolas
2016-08-01
Herbal extracts containing sesquiterpene lactones have been extensively used in traditional medicine and are known to be rich in α,β-unsaturated functionalities that can covalently engage target proteins. Here we report synthetic methodologies to access analogues of deoxyelephantopin, a sesquiterpene lactone with anticancer properties. Using alkyne-tagged cellular probes and quantitative proteomics analysis, we identified several cellular targets of deoxyelephantopin. We further demonstrate that deoxyelephantopin antagonizes PPARγ activity in situ via covalent engagement of a cysteine residue in the zinc-finger motif of this nuclear receptor.
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Further amphoricarpolides from the surface extracts of Amphoricarpos complex from Montenegro.
Cvetković, Mirjana; Ethorđević, Iris; Jadranin, Milka; Vajs, Vlatka; Vučković, Ivan; Menković, Nebojša; Milosavljević, Slobodan; Tešević, Vele
2014-09-01
Analysis of composition of sesquiterpene lactone fraction of leaf cuticular neutral lipids of Amphoricarpos complex from two different localities in north Montenegro, i.e., canyon of river Tara (A. autariatus ssp. autariatus) and mountain Zeletin (A. autariatus ssp. bertisceus) afforded sesquiterpene lactones with guaianolide skeletons (17 compounds), so called amphoricarpolides, typical for this genus. Nine of them, 9-17, were new compounds, and their structures were elucidated by detailed analyses of IR, NMR, and MS data. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.
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Dendocarbin A: a sesquiterpene lactone from Drimys winteri.
Paz Robles, Cristian; Burgos, Viviana; Suarez, Sebastián; Baggio, Ricardo
2014-11-01
The natural compound dendocarbin A, C15H22O3, is a sesquiterpene lactone isolated for the first time from Drimys winteri for var chilensis. The compound crystallizes in the orthorhombic space group P2₁2₁2₁ and its X-ray crystal structure confirmed the S/R character of the chiral centres at C-5/C-10 and C-9/C-11, respectively. The α-OH group at C-11 was found to be involved in intermolecular hydrogen bonding, defining chains along the <100> 2₁ screw axis.
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McKinnon, R; Binder, M; Zupkó, I; Afonyushkin, T; Lajter, I; Vasas, A; de Martin, R; Unger, C; Dolznig, H; Diaz, R; Frisch, R; Passreiter, C M; Krupitza, G; Hohmann, J; Kopp, B; Bochkov, V N
2014-10-15
Neurolaena lobata is a Caribbean medicinal plant used for the treatment of several conditions including inflammation. Recent data regarding potent anti-inflammatory activity of the plant and isolated sesquiterpene lactones raised our interest in further pharmacological studies. The present work aimed at providing a mechanistic insight into the anti-inflammatory activity of N. lobata and eight isolated sesquiterpene lactones, as well as a structure-activity relationship and in vivo anti-inflammatory data. The effect of the extract and its compounds on the generation of pro-inflammatory proteins was assessed in vitro in endothelial and monocytic cells by enzyme-linked immunosorbent assay. Their potential to modulate the expression of inflammatory genes was further studied at the mRNA level. In vivo anti-inflammatory activity of the chemically characterized extract was evaluated using carrageenan-induced paw edema model in rats. The compounds and extract inhibited LPS- and TNF-α-induced upregulation of the pro-inflammatory molecules E-selectin and interleukin-8 in HUVECtert and THP-1 cells. LPS-induced elevation of mRNA encoding for E-selectin and interleukin-8 was also suppressed. Furthermore, the extract inhibited the development of acute inflammation in rats. Sesquiterpene lactones from N. lobata interfered with the induction of inflammatory cell adhesion molecules and chemokines in cells stimulated with bacterial products and cytokines. Structure-activity analysis revealed the importance of the double bond at C-4-C-5 and C-2-C-3 and the acetyl group at C-9 for the anti-inflammatory activity. The effect was confirmed in vivo, which raises further interest in the therapeutic potential of the compounds for the treatment of inflammatory diseases. Copyright © 2014 Elsevier GmbH. All rights reserved.
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Bivona, Augusto E.; Sánchez Alberti, Andrés; Giberti, Gustavo; Malchiodi, Emilio L.; Martino, Virginia S.; Catalan, Cesar A.; Alonso, María Rosario; Cazorla, Silvia I.
2017-01-01
Four sesquiterpene lactones, mikanolide, deoxymikanolide, dihydromikanolide and scandenolide, were isolated by a bioassay-guided fractionation of Mikania variifolia and Mikania micrantha dichloromethane extracts. Mikanolide and deoxymikanolide were the major compounds in both extracts (2.2% and 0.4% for Mikania variifolia and 21.0% and 6.4% for Mikania micrantha respectively, calculated on extract dry weight). Mikanolide, deoxymikanolide and dihydromikanolide were active against Trypanosoma cruzi epimastigotes (50% inhibitory concentrations of 0.7, 0.08 and 2.5 μg/mL, for each compound respectively). These sesquiterpene lactones were also active against the bloodstream trypomastigotes (50% inhibitory concentrations for each compound were 2.1, 1.5 and 0.3 μg/mL, respectively) and against amastigotes (50% inhibitory concentrations for each compound were 4.5, 6.3 and 8.5 μg/mL, respectively). By contrast, scandenolide was not active on Trypanosoma cruzi. Besides, mikanolide and deoxymikanolide were also active on Leishmania braziliensis promastigotes (50% inhibitory concentrations of 5.1 and 11.5 μg/mL, respectively). The four sesquiterpene lactones were tested for their cytotoxicity on THP 1 cells. Deoxymikanolide presented the highest selectivity index for trypomastigotes (SI = 54) and amastigotes (SI = 12.5). In an in vivo model of Trypanosoma cruzi infection, deoxymikanolide was able to decrease the parasitemia and the weight loss associated to the acute phase of the parasite infection. More importantly, while 100% of control mice died by day 22 after receiving a lethal T. cruzi infection, 70% of deoxymikanolide-treated mice survived. We also observed that this compound increased TNF-α and IL-12 production by macrophages, which could contribute to control T. cruzi infection. PMID:28945741
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[Two new sesquiterpene lactones from the pericarp of Illicium macranthum].
Ma, Hai-juan; Ma, Chang-hua; Huang, Jian-mei
2010-03-01
Silica gel column chromatography was used for the isolation and purification of the chemical constituents of the pericarp of Illicium macranthum. From dichloromethane-EtOAc (1:1) fraction and EtOAc fraction of the methanol extracts, eleven compounds were identified on the basis of chemical and spectral data. Two new compounds were elucidated to be 6-deoxyneomajucin (1) and 2-oxo-6-deoxyneomajucin (2), along with nine known compounds 6-deoxypseudoanisatin (3), pseudoanisatin (4), anisatin (5), pseudomajucin (6), protocatecheuic acid (7), shikimic acid (8), shikimic acid methylester (9), beta-sitosterol (10) and daucosterol (11). Compounds 1 and 2 are new majucin-type sesquiterpene lactones.
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Two novel sesquiterpene lactones, cytotoxic vernolide-A and -B, from Vernonia cinerea.
Kuo, Yao-Haur; Kuo, Yu-Jen; Yu, Ang-Su; Wu, Ming-Der; Ong, Chi-Wi; Yang Kuo, Li-Ming; Huang, Jo-Ti; Chen, Chieh-Fu; Li, Shyh-Yuan
2003-04-01
Bioassay-directed fractionation of an ethanolic extract of stems of Vernonia cinerea has resulted in the isolation of two novel sesquiterpene lactones, vernolide-A and -B. Their structures were elucidated on the basis of spectroscopic analysis. Biological evaluation showed that vernolide-A demonstrated potent cytotoxicity against human KB, DLD-1, NCI-661, and Hela tumor cell lines (ED(50)=0.02, 0.05, 0.53, 0.04 microg/ml for KB, DLD-1, NCI-661, and Hela, respectively); vernolide-B had marginal cytoxicity (ED(50)=3.78, 5.88, 6.42 microg/ml for KB, NCI-661, and Hela, respectively).
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Lundh, Kerstin; Gruvberger, Birgitta; Möller, Halvor; Persson, Lena; Hindsén, Monica; Zimerson, Erik; Svensson, Ake; Bruze, Magnus
2007-10-01
Patients with contact allergy to sesquiterpene lactones (SLs) are usually hypersensitive to Asteraceae plant products such as herbal teas. The objective of this study was to show sensitizers in chamomile tea by patch testing with thin-layer chromatograms. Tea made from German chamomile was separated by thin-layer chromatography. Strips of the thin-layer chromatograms were used for patch testing SL-positive patients. 15 (43%) of 35 patients tested positively to 1 or more spots on the thin-layer chromatogram, with many individual reaction patterns. Patch testing with thin-layer chromatograms of German chamomile tea showed the presence of several allergens.
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Walshe-Roussel, Brendan; Choueiri, Christine; Saleem, Ammar; Asim, Muhammd; Caal, Federico; Cal, Victor; Rojas, Marco Otarola; Pesek, Todd; Durst, Tony; Arnason, John Thor
2013-08-01
The widespread use of Neurolaena lobata (L.) R. Br. ex Cass. by Q'eqchi' Maya and indigenous healers throughout the Caribbean for inflammatory conditions prompted the study of the anti-inflammatory activity of this traditional medicine. The objectives of this study were to conduct a detailed ethnobotanical investigation of the uses of N. lobata by the Q'eqchi' Maya of Belize for a variety of inflammatory symptoms and to evaluate the in vitro anti-inflammatory activity of leaf extract and isolated sesquiterpene lactones. The crude 80% EtOH extract of N. lobata leaves administered at 100 μg/mL reduced LPS-stimulated TNF-α production in THP-1 monocytes by 72% relative to the stimulated vehicle control. Isolated sesquiterpene lactones, neurolenins B, C+D, lobatin B and 9α-hydroxy-8β-isovalerianyloxy-calyculatolide were more active (IC50=0.17-2.32 μM) than the positive control parthenolide (IC50=4.79 μM). The results provide a pharmacological and phytochemical basis for the traditional use of this leaf for inflammatory conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Reider, N; Komericki, P; Hausen, B M; Fritsch, P; Aberer, W
2001-11-01
Medical remedies of plant origin have gained increasing popularity in recent years. Both anaphylactic and eczematous allergic reactions are on the rise, accordingly. Arnica and marigold, both of the Compositae family, are in widespread use, but only limited data are available on their allergenic potential. We tested 443 consecutive patients, in addition to the European standard and other series, with Compositae mix, sesquiterpene lactone mix, arnica, marigold, and propolis. 5 subjects ( approximately 1.13%) reacted to arnica, 9 ( approximately 2.03%) to marigold. The Compositae mix was positive in 18 cases ( approximately 4.06%). Among them were 3 out of 5 individuals with a sensitization to arnica, and 4 out of 9 who reacted to marigold. Sensitization to arnica and marigold was often accompanied by reactions to nickel, Myroxylon Pereirae resin, fragrance mix, propolis, and colophonium. We conclude that Compositae allergy contributes significantly to the epidemiology of contact dermatitis and that sensitization to arnica and marigold cannot be assessed by testing with the Compositae or sesquiterpene mix alone. As extracts of these plants are frequently used in occupational and cosmetic products, patch testing with additional plant extracts or adjustment of the commercial Compositae mix to regional conditions is recommended.
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Further sesquiterpenoids and phenolics from Taraxacum officinale.
Kisiel, W; Barszcz, B
2000-06-01
Five germacrane- and guaiane-type sesquiterpene lactones, including two previously described taraxinic acid derivatives, were isolated from the roots of Taraxacum officinale, together with benzyl glucoside, dihydroconiferin, syringin and dihydrosyringin. The other three lactones were identified as 11beta, 13-dihydrolactucin, ixerin D and ainslioside. Moreover, the stereochemistry at C-11 in dihydrotaraxinic acid was assigned.
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Joel, Daniel M; Chaudhuri, Swapan K; Plakhine, Dina; Ziadna, Hammam; Steffens, John C
2011-05-01
The germination of the obligate root parasites of the Orobanchaceae depends on the perception of chemical stimuli from host roots. Several compounds, collectively termed strigolactones, stimulate the germination of the various Orobanche species, but do not significantly elicit germination of Orobanche cumana, a specific parasite of sunflower. Phosphate starvation markedly decreased the stimulatory activity of sunflower root exudates toward O. cumana, and fluridone - an inhibitor of the carotenoid biosynthesis pathway - did not inhibit the production of the germination stimulant in both shoots and roots of young sunflower plants, indicating that the stimulant is not a strigolactone. We identified the natural germination stimulant from sunflower root exudates by bioassay-driven purification. Its chemical structure was elucidated as the guaianolide sesquiterpene lactone dehydrocostus lactone (DCL). Low DCL concentrations effectively stimulate the germination of O. cumana seeds but not of Phelipanche aegyptiaca (syn. Orobanche aegyptiaca). DCL and other sesquiterpene lactones were found in various plant organs, but were previously not known to be exuded to the rhizosphere where they can interact with other organisms. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Ueno, Kotomi; Furumoto, Toshio; Umeda, Shuhei; Mizutani, Masaharu; Takikawa, Hirosato; Batchvarova, Rossitza; Sugimoto, Yukihiro
2014-12-01
Root exudates of sunflower (Helianthus annuus L.) line 2607A induced germination of seeds of root parasitic weeds Striga hermonthica, Orobanche cumana, Orobanche minor, Orobanche crenata, and Phelipanche aegyptiaca. Bioassay-guided purification led to the isolation of a germination stimulant designated as heliolactone. FT-MS analysis indicated a molecular formula of C20H24O6. Detailed NMR spectroscopic studies established a methylfuranone group, a common structural component of strigolactones connected to a methyl ester of a C14 carboxylic acid via an enol ether bridge. The cyclohexenone ring is identical to that of 3-oxo-α-ionol and the other part of the molecule corresponds to an oxidized carlactone at C-19. It is a carlactone-type molecule and functions as a germination stimulant for seeds of root parasitic weeds. Heliolactone induced seed germination of the above mentioned root parasitic weeds, while dehydrocostus lactone and costunolide, sesquiterpene lactones isolated from sunflower root exudates, were effective only on O. cumana and O. minor. Heliolactone production in aquacultures increased when sunflower seedlings were grown hydroponically in tap water and decreased on supplementation of the culture with either phosphorus or nitrogen. Costunolide, on the other hand, was detected at a higher concentration in well-nourished medium as opposed to nutrient-deficient media, thus suggesting a contrasting contribution of heliolactone and the sesquiterpene lactone to the germination of O. cumana under different soil fertility levels. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Phytotoxic properties of cnicin, a sesquiterpene lactone fromcentaurea maculosa (spotted knapweed).
Kelsey, R G; Locken, L J
1987-01-01
Water and solvent extracts from the aerial tissues ofCentaurea maculosa, spotted knapweed, inhibited the root growth of lettuce. Column chromatography and lettuce bioassay of a chloroform extract led to the isolation of cnicin, a sesquiterpene lactone. Pure cnicin was bioassayed at 0, 1, 2, 4, 6, 8, and 10 mg/5 ml water with lettuce, created wheatgrass, bluebunch wheatgrass, rough fescue, western larch, lodgepole pine, and spotted knapweed. Germination was inhibited at one or more concentrations for all species except lodgepole pine and spotted knapweed. Growth, particularly of the roots, was retarded between 1 and 4 mg of cnicin. Lettuce, bluebunch wheatgrass, and spotted knapweed were inhibited significantly at all concentrations tested.
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New sesquiterpene lactones from Ambrosia cumanensis Kunth.
Jimenez-Usuga, Nora Del Socorro; Malafronte, Nicola; Cotugno, Roberta; De Leo, Marinella; Osorio, Edison; De Tommasi, Nunziatina
2016-09-01
Eleven sesquiterpene lactones, including three new natural products (1-3), were isolated from the n-butanolic extract of Ambrosia cumanensis Kunth. aerial parts. The structure of all isolated compounds was elucidated by 1D- and 2D-NMR, and MS analyses. All compounds were tested for their antiproliferative activity on HeLa, Jurkat, and U937 cell lines. Compound 3, 2,3-dehydropsilostachyn C, showed cytotoxic activity with different potency in all cell lines. By means of flow cytometric studies, compound 3 was demonstrated to induce in Jurkat cells a G2/M cell cycle block, while in U937 elicited both cytostatic and cytotoxic responses. Copyright © 2016 Elsevier B.V. All rights reserved.
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Ekenäs, Catarina; Zebrowska, Anna; Schuler, Barbara; Vrede, Tobias; Andreasen, Katarina; Backlund, Anders; Merfort, Irmgard; Bohlin, Lars
2008-12-01
Several species in the genus Arnica have been used in traditional medicine to treat inflammatory-related disorders. Extracts of twelve Arnica species and two species closely related to arnica ( Layia hieracioides and Madia sativa) were investigated for inhibition of human neutrophil elastase release and inhibition of transcription factor NF-kappaB. Statistical analyses reveal significant differences in inhibitory capacities between extracts. Sesquiterpene lactones of the helenanolide type, of which some are known inhibitors of human neutrophil elastase release and NF-kappaB, are present in large amounts in the very active extracts of A. montana and A. chamissonis. Furthermore, A. longifolia, which has previously not been investigated, shows a high activity similar to that of A. montana and A. chamissonis in both bioassays. Sesquiterpene lactones of the xanthalongin type are present in large amounts in A. longifolia and other active extracts and would be interesting to evaluate further. COX-2:cyclooxygenase 2 EMSA:electrophoretic mobility shift assay fMLP: N-formyl-methionyl-leucyl-phenylalanine HaCaT:human keratinocyte HNE:human neutrophil elastase IkappaB:inhibitory subunit of kappaB iNOS:inducible nitric oxide synthase NF-kappaB:nuclear factor kappaB PAF:platelet activating factor STL:sesquiterpene lactone TNF-alpha:tumor necrosis factor alpha.
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Aschenbrenner, Anna-Katharina; Amrehn, Evelyn; Bechtel, Lisa; Spring, Otmar
2015-04-01
Sunflower trichomes fully develop on embryonic plumula within 3 days after start of germination. Toxic sesquiterpene lactones are produced immediately thereafter thus protecting the apical bud of the seedling against herbivory. Helianthus annuus harbors non-glandular and two different types of multicellular glandular trichomes, namely the biseriate capitate glandular trichomes and the uniseriate linear glandular trichomes. The development of capitate glandular trichomes is well known from anther tips on sunflower disk florets, but not from leaves and no information is yet available on the development of the linear glandular trichomes. Scanning electron microscopy of sunflower seedlings unravelled that within the first 40 h of seed germination all three types of trichomes started to emerge on primordia of the first true leaves. Within the following 20-30 h trichomes developed from trichoblasts to fully differentiated hairs. Gene expression studies showed that genes involved in the trichome-based sesquiterpene lactone formation were up-regulated between 72 and 96 h after start of germination. Metabolite profiling with HPLC confirmed the synthesis of sesquiterpene lactones which may contribute to protect the germinating seedlings from herbivory. The study has shown that sunflower leaf primordia can serve as a fast and easy to handle model system for the investigation of trichome development in Asteraceae.
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Permeation of bioactive constituents from Arnica montana preparations through human skin in-vitro.
Tekko, I A; Bonner, M C; Bowen, R D; Williams, A C
2006-09-01
This study investigated and characterised transdermal permeation of bioactive agents from a topically applied Arnica montana tincture. Permeation experiments conducted over 48 h used polydimethylsiloxane (silastic) and human epidermal membranes mounted in Franz-type diffusion cells with a methanol-water (50:50 v/v) receptor fluid. A commercially available tincture of A. montana L. derived from dried Spanish flower heads was a donor solution. Further donor solutions prepared from this stock tincture concentrated the tincture constituents 1, 2 and 10 fold and its sesquiterpene lactones 10 fold. Permeants were assayed using a high-performance liquid chromatography method. Five components permeated through silastic membranes providing peaks with relative retention factors to an internal standard (santonin) of 0.28, 1.18, 1.45, 1.98 and 2.76, respectively. No permeant was detected within 12 h of applying the Arnica tincture onto human epidermal membranes. However, after 12 h, the first two of these components were detected. These were shown by Zimmermann reagent reaction to be sesquiterpene lactones and liquid chromatography/diode array detection/mass spectrometry indicated that these two permeants were 11,13-dihydrohelenalin (DH) analogues (methacrylate and tiglate esters). The same two components were also detected within 3 h of topical application of the 10-fold concentrated tincture and the concentrated sesquiterpene lactone extract.
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Hegazy, Mohamed-Elamir F; Ibrahim, Abeer Y; Mohamed, Tarik A; Shahat, Abdelaaty A; El Halawany, Ali M; Abdel-Azim, Nahla S; Alsaid, Mansour S; Paré, Paul W
2016-01-01
Wild artichoke (Cynara cornigera), a thistle-like perennial belonging to the Asteraceae family, is native to the Mediterranean region, northwestern Africa, and the Canary Islands. While the pleasant, albeit bitter, taste of the leaves and flowers is attributed to the sesquiterpene lactones cynaropicrin and cynarin, a comprehensive phytochemical investigation still needs to be reported. In this study seven sesquiterpene lactones were isolated from an aqueous methanol plant extract, including a new halogenated metabolite (1), the naturally isolated compound sibthorpine (2), and five metabolites isolated for the first time from C. cornigera. Structures were established by spectroscopic methods, including HREIMS, (1 )H, (13 )C, DEPT, (1 )H-(1 )H COSY, HMQC, and HMBC-NMR experiments as well as by X-ray analysis. The isolated bioactive nutrients were analyzed for their antioxidant and metal chelating activity. Compound 1 exhibited a potent metal chelating activity as well as a high antioxidant capacity. Moreover, select compounds were effective as acetyl cholinesterase inhibitors presenting the possibility for such compounds to be examined for anti-neurodegenerative activity. A computational pharmacophore elucidation and docking study was performed to estimate the pharmacophoric features and binding conformation of isolated compounds in the acetyl cholinesterase active site. Georg Thieme Verlag KG Stuttgart · New York.
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Paulsen, Evy; Andersen, Klaus E
2016-02-01
Lettuce (Lactuca sativa L.) and its varieties are important vegetable crops worldwide. They are also well-known, rarely reported, causes of contact allergy. As lettuce allergens and extracts are not commercially available, the allergy may be underdiagnosed. The aims of this article are to present new data on lettuce contact allergy and review the literature. Lettuce is weakly allergenic, and occupational cases are mainly reported. Using aimed patch testing in Compositae-allergic patients, two recent Danish studies showed prevalence rates of positive lettuce reactions of 11% and 22%. The majority of cases are non-occupational, and may partly be caused by cross-reactivity. The sesquiterpene lactone mix seems to be a poor screening agent for lettuce contact allergy, as the prevalence of positive reactions is significantly higher in non-occupationally sensitized patients. Because of the easy degradability of lettuce allergens, it is recommended to patch test with freshly cut lettuce stem and supplement this with Compositae mix. As contact urticaria and protein contact dermatitis may present as dermatitis, it is important to perform prick-to-prick tests, and possibly scratch patch tests as well. Any person who is occupationally exposed to lettuce for longer periods, especially atopics, amateur gardeners, and persons keeping lettuce-eating pets, is potentially at risk of developing lettuce contact allergy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Ikezawa, Nobuhiro; Göpfert, Jens Christian; Nguyen, Don Trinh; Kim, Soo-Un; O'Maille, Paul E.; Spring, Otmar; Ro, Dae-Kyun
2011-01-01
Sesquiterpene lactones (STLs) are terpenoid natural products possessing the γ-lactone, well known for their diverse biological and medicinal activities. The occurrence of STLs is sporadic in nature, but most STLs have been isolated from plants in the Asteraceae family. Despite the implication of the γ-lactone group in many reported bioactivities of STLs, the biosynthetic origins of the γ-lactone ring remains elusive. Germacrene A acid (GAA) has been suggested as a central precursor of diverse STLs. The regioselective (C6 or C8) and stereoselective (α or β) hydroxylation on a carbon of GAA adjacent to its carboxylic acid at C12 is responsible for the γ-lactone formation. Here, we report two cytochrome P450 monooxygenases (P450s) capable of catalyzing 6α- and 8β-hydroxylation of GAA from lettuce and sunflower, respectively. To identify these P450s, sunflower trichomes were isolated to generate a trichome-specific transcript library, from which 10 P450 clones were retrieved. Expression of these clones in a yeast strain metabolically engineered to synthesize substrate GAA identified a P450 catalyzing 8β-hydroxylation of GAA, but the STL was not formed by spontaneous lactonization. Subsequently, we identified the closest homolog of the GAA 8β-hydroxylase from lettuce and discovered 6α-hydroxylation of GAA by the recombinant enzyme. The resulting 6α-hydroxy-GAA spontaneously undergoes a lactonization to yield the simplest form of STL, costunolide. Furthermore, we demonstrate the milligram per liter scale de novo synthesis of costunolide using the lettuce P450 in an engineered yeast strain, an important advance that will enable exploitation of STLs. Evolution and homology models of these two P450s are discussed. PMID:21515683
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Ordóñez, Paola E; Sharma, Krishan K; Bystrom, Laura M; Alas, Maria A; Enriquez, Raul G; Malagón, Omar; Jones, Darin E; Guzman, Monica L; Compadre, Cesar M
2016-04-22
The sesquiterpene lactones dehydroleucodine (1) and leucodine (2) were isolated from Gynoxys verrucosa, a species used in traditional medicine in southern Ecuador. The activity of these compounds was determined against eight acute myeloid leukemia (AML) cell lines and compared with their activity against normal peripheral blood mononuclear cells. Compound 1 showed cytotoxic activity against the tested cell lines, with LD50 values between 5.0 and 18.9 μM. Compound 2 was inactive against all of the tested cell lines, demonstrating that the exocyclic methylene in the lactone ring is required for cytotoxic activity. Importantly, compound 1 induced less toxicity to normal blood cells than to AML cell lines and was active against human AML cell samples from five patients, with an average LD50 of 9.4 μM. Mechanistic assays suggest that compound 1 has a similar mechanism of action to parthenolide (3). Although these compounds have significant structural differences, their lipophilic surface signatures show striking similarities.
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Bordignon, Annélise; Frédérich, Michel; Ledoux, Allison; Campos, Pierre-Eric; Clerc, Patricia; Hermann, Thomas; Quetin-Leclercq, Joëlle; Cieckiewicz, Ewa
2018-06-01
Due to the in vitro antiplasmodial activity of leaf extracts from Vernonia fimbrillifera Less. (Asteraceae), a bioactivity-guided fractionation was carried out. Three sesquiterpene lactones were isolated, namely 8-(4'-hydroxymethacrylate)-dehydromelitensin (1), onopordopicrin (2) and 8α-[4'-hydroxymethacryloyloxy]-4-epi-sonchucarpolide (3). Their structures were elucidated by spectroscopic methods (1D and 2D NMR and MS analyses) and by comparison with published data. The isolated compounds exhibited antiplasmodial activity with IC 50 values ≤ 5 μg/mL. Cytotoxicity of the compounds against a human cancer cell line (HeLa) and a mouse lung epithelial cell line (MLE12) was assessed to determine selectivity. Compound 3 displayed promising selective antiplasmodial activity (SI > 10).
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Antispasmodic activity of fractions and cynaropicrin from Cynara scolymus on guinea-pig ileum.
Emendörfer, Fernanda; Emendörfer, Fabiane; Bellato, Fernanda; Noldin, Vânia Floriani; Cechinel-Filho, Valdir; Yunes, Rosendo Augusto; Delle Monache, Franco; Cardozo, Alcíbia Maia
2005-05-01
This study describes the antispasmodic activity of some fractions and cynaropicrin, a sesquiterpene lactone from Cynara scolymus, cultivated in Brazil, against guinea-pig ileum contracted by acetylcholine. The dichloromethane fraction showed the most promising biological effects, with an IC(50) of 0.93 (0.49-1.77) mg/ml. Its main active component, the sesquiterpene lactone cynaropicrin, exhibited potent activity, with IC(50) of 0.065 (0.049-0.086) mg/ml, being about 14-fold more active than dichloromethane fraction and having similar potency to that of papaverine, a well-known antispasmodic agent. The results confirm the popular use of artichoke for the treatment of gastrointestinal disturbances, and encourage new studies on this compound, in order to obtain new antispasmodic agents.
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Bombo, A B; Appezzato-da-Glória, B; Aschenbrenner, A-K; Spring, O
2016-05-01
The capitate glandular trichome is the most common type described in Asteraceae species. It is known for its ability to produce various plant metabolites of ecological and economic importance, among which sesquiterpene lactones are predominant. In this paper, we applied microscopy, phytochemical and molecular genetics techniques to characterise the capitate glandular trichome in Aldama discolor, a native Brazilian species of Asteraceae, with pharmacological potential. It was found that formation of trichomes on leaf primordia of germinating seeds starts between 24 h and 48 h after radicle growth indicates germination. The start of metabolic activity of trichomes was indicated by separation of the cuticle from the cell wall of secretory cells at the trichome tip after 72 h. This coincided with the accumulation of budlein A, the major sesquiterpene lactone of A. discolor capitate glandular trichomes, in extracts of leaf primordia after 96 h. In the same timeframe of 72-96 h post-germination, gene expression studies showed up-regulation of the putative germacrene A synthase (pGAS2) and putative germacrene A oxidase (pGAO) of A. discolor in the transcriptome of these samples, indicating the start of sesquiterpene lactone biosynthesis. Sequencing of the two genes revealed high similarity to HaGAS and HaGAO from sunflower, which shows that key steps of this pathway are highly conserved. The processes of trichome differentiation, metabolic activity and genetic regulation in A. discolor and in sunflower appear to be typical for other species of the subtribe Helianthinae. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.
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Sesquiterpene lactones from Gynoxys verrucosa and their anti-MRSA activity.
Ordóñez, Paola E; Quave, Cassandra L; Reynolds, William F; Varughese, Kottayil I; Berry, Brian; Breen, Philip J; Malagón, Omar; Smeltzer, Mark S; Compadre, Cesar M
2011-09-02
Because of its virulence and antibiotic resistance, Staphylococcus aureus is a more formidable pathogen now than at any time since the pre-antibiotic era. In an effort to identify and develop novel antimicrobial agents with activity against this pathogen, we have examined Gynoxys verrucosa Wedd (Asteraceae), an herb used in traditional medicine in southern Ecuador for the treatment and healing of wounds. The sesquiterpene lactones leucodine (1) and dehydroleucodine (2) were extracted and purified from the aerial parts of Gynoxys verrucosa, and their structure was elucidated by spectroscopic methods and single-crystal X-ray analysis. The in vitro anti-microbial activity of Gynoxys verrucosa extracts and its purified constituents was determined against six clinical isolates including Staphylococcus aureus and Staphylococcus epidermidis strains with different drug-resistance profiles, using the microtiter broth method. Compound 1 has very low activity, while compound 2 has moderate activity with MIC(50)s between 49 and 195 μg/mL. The extract of Gynoxys verrucosa has weak activity with MIC(50)s between 908 and 3290 μg/mL. We are reporting the full assignment of the (1)H NMR and (13)C NMR of both compounds, and the crystal structure of compound 2, for the first time. Moreover, the fact that compound 2 has antimicrobial activity and compound 1 does not, demonstrates that the exocyclic conjugated methylene in the lactone ring is essential for the antimicrobial activity of these sesquiterpene lactones. However, the weak activity observed for the plant extracts, does not explain the use of Gynoxys verrucosa in traditional medicine for the treatment of wounds and skin infections. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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Sesquiterpene Lactones from Gynoxys verrucosa and their Anti-MRSA Activity
Ordóñez, Paola E.; Quave, Cassandra L.; Reynolds, William F.; Varughese, Kottayil I.; Berry, Brian; Breen, Philip J.; Malagón, Omar; Smeltzer, Mark S.; Compadre, Cesar M.
2011-01-01
Ethnopharmacological relevance Because of its virulence and antibiotic resistance, Staphylococcus aureus is a more formidable pathogen now than at any time since the pre-antibiotic era. In an effort to identify and develop novel antimicrobial agents with activity against this pathogen, we have examined Gynoxys verrucosa Wedd (Asteraceae), an herb used in traditional medicine in southern Ecuador for the treatment and healing of wounds. Materials and Methods The sesquiterpene lactones leucodine (1) and dehydroleucodine (2) were extracted and purified from the aerial parts of G. verrucosa, and their structure was elucidated by spectroscopic methods and single-crystal X-ray analysis. The in vitro anti-microbial activity of G. verrucosa extracts and its purified constituents was determined against six clinical isolates including S. aureus and Staphylococcus epidermidis strains with different drug-resistance profiles, using the microtiter broth method. Results Compound 1 has very low activity, while compound 2 has moderate activity with MIC50s between 49 and195 μg/mL. The extract of G. verrucosa has weak activity with MIC50s between 908 and 3290 μg/mL. Conclusions We are reporting the full assignment of the 1H-NMR and 13C-NMR of both compounds, and the crystal structure of compound 2, for the first time. Moreover, the fact that compound 2 has antimicrobial activity and compound 1 does not, demonstrates that the exocyclic conjugated methylene in the lactone ring is essential for the antimicrobial activity of these sesquiterpene lactones. However, the weak activity observed for the plants extracts, does not explain the use of G. verrucosa in traditional medicine for the treatment of wounds and skin infections. PMID:21782013
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Development and stability of semisolid preparations based on a supercritical CO2 Arnica extract.
Bilia, Anna Rita; Bergonzi, Maria Camilla; Mazzi, Giovanni; Vincieri, Franco Francesco
2006-05-03
Conventional herbal drug preparations (HDP) based on Arnica montana L. have a low content of the active principles, sesquiterpene lactones, which show poor stability and low physical compatibility in semisolid formulations. Recently, an innovative supercritical carbon dioxide (CO2) extract with high sesquiterpene content has been marketed. Development of six semisolid preparations (cetomacrogol, polysorbate 60, polawax, anphyphil, natrosol and sepigel) based on this innovative CO2 extract is discussed. Stability of these preparations was investigated according to ICH guidelines. The evaluation of in vitro release of active constituents was performed using the cell method reported in the European Pharmacopoeia. Preliminary data on in vivo permeation of three selected formulations is demonstrated using the "skin stripping" test, according to the FDA, in healthy subjects. Analysis of sesquiterpene lactones within the extract and in vitro and in vivo studies was performed by RP-HPLC-DAD-MS method. The cetomacrogol showed the best release profile in the in vitro test, while in the in vivo test the best preparation resulted polysorbate 60 and polawax.
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Sesquiterpenoids and phenolics from Taraxacum hondoense.
Kisiel, Wanda; Michalska, Klaudia
2005-09-01
Eleven sesquiterpene lactones, including the new guaianolide 11beta-hydroxydeacetylmatricarin-8-O-beta-glucopyranoside, along with four known phenolic glucosides were isolated from Taraxacum hondoense. The compounds were characterized by spectral methods.
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Baccharis pteronioides toxicity
USDA-ARS?s Scientific Manuscript database
Baccharis pteronioides DC. occasionally poisons livestock in the southwestern United States. Various toxins including diterpenic lactones, sesquiterpenes , flavonoids, saponins, tannins, phenolic compounds and essential oils have been isolated and described from several Baccharis species, but none...
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Phytotoxicity Study on Bidens sulphurea Sch. Bip. as a Preliminary Approach for Weed Control.
da Silva, Bruna P; Nepomuceno, Mariluce P; Varela, Rosa M; Torres, Ascensión; Molinillo, José M G; Alves, Pedro L C A; Macías, Francisco A
2017-06-28
Farmers of the Franca region in Brazil observed that Bidens sulphurea was able to eliminate the Panicum maximum weed, which infected coffee plantations, without affecting the crop. In an effort to determine if the inhibitory effects observed were due to the presence of phytotoxic compounds from leaves and roots, a biodirected isolation and spectroscopic characterization has been carried out. The leaf dichloromethane and root acetone extracts were the most active, and the former appeared to be more phytotoxic to the target species, including four weeds. A total of 26 compounds were isolated from leaves and roots, and four of them are described here for the first time. The major compounds in the leaf extract are the sesquiterpene lactones costunolide, reynosin, and santamarine, and these showed marked inhibition. Amaranthus viridis and Panicum maximum were the most sensitive species of the weeds tested. These three phytotoxic lactones were also evaluated on A. viridis and P. maximum under hydroponic conditions. A. viridis was the most affected species with the three lactones, and santamarine was the most phytotoxic compound on both. This is the first time that the phytotoxicity of sesquiterpene lactones has been evaluated on hydroponic culture. The work described here is a preliminary approach for the use of B. sulphurea for weed control in agriculture, both as a cover crop and by use of its components as natural herbicide leads.
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de Kraker, Jan-Willem; Franssen, Maurice C. R.; Dalm, Marcella C. F.; de Groot, Aede; Bouwmeester, Harro J.
2001-01-01
Sprouts of chicory (Cichorium intybus), a vegetable grown in the dark, have a slightly bitter taste associated with the presence of guaianolides, eudesmanolides, and germacranolides. The committed step in the biosynthesis of these compounds is catalyzed by a (+)-germacrene A synthase. Formation of the lactone ring is the postulated next step in biosynthesis of the germacrene-derived sesquiterpene lactones. The present study confirms this hypothesis by isolation of enzyme activities from chicory roots that introduce a carboxylic acid function in the germacrene A isopropenyl side chain, which is necessary for lactone ring formation. (+)-Germacrene A is hydroxylated to germacra-1(10),4,11(13)-trien-12-ol by a cytochrome P450 enzyme, and is subsequently oxidized to germacra-1(10),4,11(13)-trien-12-oic acid by NADP+-dependent dehydrogenase(s). Both oxidized germacrenes were detected as their Cope-rearrangement products elema-1,3,11(13)-trien-12-ol and elema-1,3,11(13)-trien-12-oic acid, respectively. The cyclization products of germacra-1(10),4,11(13)-trien-12-ol, i.e. costol, were also observed. The (+)-germacrene A hydroxylase is inhibited by carbon monoxide (blue-light reversible), has an optimum pH at 8.0, and hydroxylates β-elemene with a modest degree of enantioselectivity. PMID:11299372
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Kim, Young Sup; Kim, Jeoung Seob; Park, Sung-Hee; Choi, Sang-Un; Lee, Chong Ock; Kim, Seong-Kie; Kim, Young-Kyoon; Kim, Sung Hoon; Ryu, Shi Yong
2003-04-01
Two xanthanolide sesquiterpene lactones, 8- epi-xanthatin (1) and 8- epi-xanthatin epoxide (2), isolated from the leaves of Xanthium strumarium (Compositae), demonstrated a significant inhibition on the proliferation of cultured human tumor cells, i. e., A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nervous system) and HCT-15 (colon) in vitro. They were also found to inhibit the farnesylation process of human lamin-B by farnesyltransferase (FTase), in a dose-dependent manner in vitro (IC 50 value was calculated as 64 and 58 microM, respectively). Due to the relatively high concentrations of 1 and 2 required to obtain an FTase inhibition as compared with those necessary for a cytotoxic effect on tumor cells, it remains unclear whether a relationship between these two activities exists.
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Macías, Francisco A; Santana, Alejandro; Yamahata, Azusa; Varela, Rosa M; Fronczek, Frank R; Molinillo, José M G
2012-11-26
Commercially available santonin was used to synthesize seven sesquiterpene lactones using a facile strategy that involved a high-yielding photochemical reaction. Three natural products from Artemisia gorgonum were synthesized in good yields, and in the case of two compounds, absolute configurations were determined from X-ray quality crystals. The structures previously reported for these compounds were revised. Sesquiterpene lactones were tested using the etiolated wheat coleoptile bioassay, and the most active compounds were assayed in standard target species. seco-Guaianolide (4) showed higher phytotoxic activities than the known herbicide Logran. This high activity could be due to the presence of a cyclopentenedione ring. These results suggest that compound 4 should be involved in defense of A. gorgorum, displaying a wide range of activities that allow proposing them as new leads for development of a natural herbicide model with a seco-guaianolide skeleton.
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Bidirectional Secretions from Glandular Trichomes of Pyrethrum Enable Immunization of Seedlings[W
Ramirez, Aldana M.; Stoopen, Geert; Menzel, Tila R.; Gols, Rieta; Bouwmeester, Harro J.; Dicke, Marcel; Jongsma, Maarten A.
2012-01-01
Glandular trichomes are currently known only to store mono- and sesquiterpene compounds in the subcuticular cavity just above the apical cells of trichomes or emit them into the headspace. We demonstrate that basipetal secretions can also occur, by addressing the organization of the biosynthesis and storage of pyrethrins in pyrethrum (Tanacetum cinerariifolium) flowers. Pyrethrum produces a diverse array of pyrethrins and sesquiterpene lactones for plant defense. The highest concentrations accumulate in the flower achenes, which are densely covered by glandular trichomes. The trichomes of mature achenes contain sesquiterpene lactones and other secondary metabolites, but no pyrethrins. However, during achene maturation, the key pyrethrin biosynthetic pathway enzyme chrysanthemyl diphosphate synthase is expressed only in glandular trichomes. We show evidence that chrysanthemic acid is translocated from trichomes to pericarp, where it is esterified into pyrethrins that accumulate in intercellular spaces. During seed maturation, pyrethrins are then absorbed by the embryo, and during seed germination, the embryo-stored pyrethrins are recruited by seedling tissues, which, for lack of trichomes, cannot produce pyrethrins themselves. The findings demonstrate that plant glandular trichomes can selectively secrete in a basipetal direction monoterpenoids, which can reach distant tissues, participate in chemical conversions, and immunize seedlings against insects and fungi. PMID:23104830
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Potential ecological roles of Artemisinin produced by Artemisis annua L
USDA-ARS?s Scientific Manuscript database
Artemisia annua L. (annual wormwood, Asteraceae) and its secondary metabolite artemisinin, a unique sesquiterpene lactone with an endoperoxide bridge, has gained much attention due to its antimalarial properties. Artemisinin is a complex structure that is requires a significant amount of energy for ...
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Fraga, Braulio M; Terrero, David; Cabrera, Inmaculada; Reina, Matías
2018-06-01
The germacranolide 1-epi-tatridin B has been isolated from the aerial parts of Laurus novocanariensis. We have observed that the identification of this lactone and its epimer tetradin B in the scientific literature is confusing and contradictory. We have therefore studied this issue clarifying errors and contributing to the structural elucidation of other related products. Moreover, we have isolated from this plant a lactone with an 1,5-ether bridge, previously obtained from Austrolabium candidum. We have now named it austroliolide, reassigned its 13 C NMR spectrum and compared its structure with that of badgerin. In addition, we have also isolated from L. novocanariensis the known germacranolides artemorin, costunolide, tatridin A, tulirinol and verlotorin, the eudesmanolides β-cyclopyrethrosin, 1β-hydroxy-arbusculin A, magnoliaolide and reynosin, and the guaianolide dehydrocostus lactone. Copyright © 2018 Elsevier Ltd. All rights reserved.
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USDA-ARS?s Scientific Manuscript database
The anti-parasitic, anti-cancer, and anti-viral sesquiterpene lactone artemisinin, commercially extracted from Artemisia annua, is in high demand worldwide. However, limited information is available on how post-harvest drying procedures affect plant biochemistry leading to the biosynthesis of artem...
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Isolation, NMR studies, and biological activities of onopordopicrin from Centaurea sonchifolia.
Lonergan, G; Routsi, E; Georgiadis, T; Agelis, G; Hondrelis, J; Matsoukas, J; Larsen, L K; Caplan, F R
1992-02-01
A sesquiterpene lactone, onopordopicrin [1], has been isolated from Centaurea sonchifolia. Its structure was established by 2D nmr (1H-1H and 13C-1H correlations), and the conformation in CHCl3 was examined by nOe studies. Cytotoxic, antibacterial, and antifungal activities are reported.
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USDA-ARS?s Scientific Manuscript database
Capitate glandular trichomes (CGT), one type of glandular trichomes, are most common in Asteraceae species. Capitate glandular trichomes can produce various secondary metabolites such as sesquiterpene lactones (STLs) and provide durable resistance to insect pests. In sunflower, CGT-based host resist...
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USDA-ARS?s Scientific Manuscript database
Ginkgo biloba is one of the oldest living tree species and has been extensively investigated as a source of bioactive natural compounds, including flavonoids, diterpene lactones, terpenoids and polysaccharides which accumulate in leaf tissues. Relatively few genes associated with biosynthetic pathwa...
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Seemann, Andreas; Wallner, Teresa; Poschlod, Peter; Heilmann, Jörg
2010-05-01
In ten grassland or heathland sites along a geographic (north to south) and climatic gradient in Germany, flowerheads of Arnica montana were collected, and the total content of sesquiterpene lactones (SLs) as well as the content of the detected single compounds were determined. The ratios of helenalin (H)- and corresponding 11 alpha,13-dihydrohelenalin(DH)-type compounds were calculated. All habitats were characterised concerning the climatic and soil conditions, and the values obtained were correlated with SL contents according to univariate statistical analyses. All populations showed very similar and constant ratios of helenalin ( 1)/11 alpha,13-dihydrohelenalin ( 2) at around 1.5-2/1 irrespective of different ecological parameters. The ratio of helenalin/11 alpha,13-dihydrohelenalin esters was several fold higher in all samples, but it was nearly identical in every habitat among each other, except for the helenalin/11 alpha,13-dihydrohelenalin 2-methylbutyrate pair ( 5/ 11), which showed a constantly twofold higher H/DH ratio. However, the 6- O-isovalerylhelenalin content ( 6) showed highly significant correlations to climatic factors. Georg Thieme Verlag KG Stuttgart New York.
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Amrehn, Evelyn; Aschenbrenner, Anna-Katharina; Heller, Annerose; Spring, Otmar
2016-03-01
Capitate glandular trichomes (CGT) of sunflower, Helianthus annuus, synthesize bioactive sesquiterpene lactones (STLs) within a short period of only a few days during trichome development. In the current project, the subcellular localization of H. annuus germacrene A monooxygenase (HaGAO), a key enzyme of the STL biosynthesis in sunflower CGT, was investigated. A polyclonal antibody raised against this enzyme was used for immunolabelling. HaGAO was found in secretory and stalk cells of CGT. This correlated with the appearance of smooth endoplasmic reticulum in both cell types. Stalk cells and secretory cells differed in form, size and types of plastids, but both had structures necessary for secretion. No HaGAO-specific immunoreaction was found in sunflower leaf tissue outside of CGT or in developing CGT before the secretory phase had started. Our results indicated that not only secretory cells but also nearly all cells of the CGT were involved in the biosynthesis of STL and that this process was not linked to the presence or absence of a specific type of plastid.
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Mathema, Vivek Bhakta; Koh, Young-Sang; Thakuri, Balkrishna Chand; Sillanpää, Mika
2012-04-01
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-β). 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.
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Anti-inflammatory sesquiterpene lactones from the flower of Vernonia cinerea.
Youn, Ui Joung; Park, Eun-Jung; Kondratyuk, Tamara P; Simmons, Charles J; Borris, Robert P; Tanamatayarat, Patcharawan; Wongwiwatthananukit, Supakit; Toyama, Onoomar; Songsak, Thanapat; Pezzuto, John M; Chang, Leng Chee
2012-09-01
Bioassay-guided fractionation of the hexane extract from the flowers of Vernonia cinerea (Asteraceae) led to the isolation of a new sesquiterpene lactone, 8α-hydroxyhirsutinolide (2), and a new naturally occurring derivative, 8α-hydroxyl-1-O-methylhirsutinolide (3), along with seven known compounds (1 and 4-9). The structures of the new compounds were determined by 1D and 2D NMR experiments and by comparison with the structure of compound 1, whose relative stereochemistry was determined by X-ray analysis. The isolated compounds were evaluated for their cancer chemopreventive potential based on their ability to inhibit nitric oxide (NO) production and tumor necrosis factor alpha (TNF-α)-induced NF-κB activity. Compounds 1, 2, 4, 5, and 9 inhibited TNF-α-induced NF-κB activity with IC(50) values of 3.1, 1.9, 0.6, 5.2, and 1.6 μM, respectively; compounds 4 and 6-9 exhibited significant NO inhibitory activity with IC(50) values of 2.0, 1.5, 1.2, 2.7, and 2.4 μM, respectively. Published by Elsevier Ltd.
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Total synthesis of (±)-antroquinonol d.
Sulake, Rohidas S; Jiang, Yan-Feng; Lin, Hsiao-Han; Chen, Chinpiao
2014-11-21
Total synthesis of (±)-antroquinonol D, which is isolated from very expensive and rarely found Antrodia camphorata and which has potential anticancer properties, was achieved from 4-methoxyphenol. In addition, a Michael addition to dimethoxy cyclohexadienones was studied. The main step involved chelation and substrate-controlled diastereoselective reduction of cyclohexenone and lactonization. Lactone synthesis facilitated the diastereoselective reduction of ketone, which help control the desired stereochemistry at the crucial stereogenic center in the natural product. Other key reactions in the synthesis involved a Michael addition of dimethyl malonate on cyclohexadienone, dihydroxylation, and Wittig olefination. A sesquiterpene side chain was synthesized through coupling with geranyl phenyl sulfide and Bouveault-Blanc reduction.
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Ota, Koichiro; Yamazaki, Ikuma; Saigoku, Takahiro; Fukui, Mei; Miyata, Tomoki; Kamaike, Kazuo; Shirahata, Tatsuya; Mizuno, Fumi; Asada, Yoshihisa; Hirotani, Masao; Ino, Chieko; Yoshikawa, Takafumi; Kobayashi, Yoshinori; Miyaoka, Hiroaki
2017-12-01
A new cyclopropane-containing sesquiterpenoid, phellilane L (1), was isolated from the medicinal mushroom Phellinus linteus ("Meshimakobu" in Japanese), a member of the Hymenochaetaceae family and a well-known fungus that is widely used in East Asia. The planar structure of 1 was determined on the basis of spectroscopic analysis. The authors achieved the first total synthesis of 1. Our protecting group-free synthesis features a highly stereoselective one-pot synthesis involving an intermolecular alkylation/cyclization/lactonization strategy for construction of the key cyclopropane-γ-lactone intermediate. Additionally, our synthesis determined the absolute configuration of phellilane L (1).
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Guaianolides from two subspecies of Amphoricarpos neumayeri from Montenegro.
Djordjević, Iris; Vajs, Vlatka; Bulatović, Vanja; Menković, Nebojsa; Tesević, Vele; Macura, Slobodan; Janaćković, Pedja; Milosavljević, Slobodan
2004-08-01
Quantitative (1)H NMR measurements revealed delta(11(13)) sesquiterpene gamma-lactones as the main constituents ( >or= 1% per weight of dried plant material) in the crude extracts of the aerial parts of Amphoricarpos neumayeri ssp. neumayeri and ssp. murbeckii from mountains Orjen and Visitor (Montenegro), respectively. Preparative silica gel chromatography afforded thirteen guai-11(13)-en-12,6alpha-olides, named amphoricarpolides (1-13), with the same relative (1alphaH,4betaH,5alphaH,7betaH) configuration of the basic skeleton. The common structural feature of lactones 2-13 was 3beta,15-dioxygenation pattern. The only exception was 1 (3-deoxyamphoricarpolide), containing a single oxygen substituent (15-OH). Eight of them exhibited an additional oxygen substituent, 9beta-OH (5 and 6), 2alpha-OH (8-12), or 2alpha-OAc (13). Compound 7 was epoxydated at 10alpha(14)-position, whereas the remaining lactones contained a 10(14) double bond.
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Paulsen, Evy; Chistensen, Lars P; Andersen, Klaus E
2008-01-01
Compositae-sensitive patients are routinely warned against topical use of Compositae-containing cosmetics and herbal remedies. However, the risk of elicitation of dermatitis in presensitized persons is unknown. The main aim of this study was to assess the significance of direct plant allergen contact via Compositae-derived cosmetics and herbal remedies in Compositae-allergic patients with special reference to arnica (Arnica montana) and German chamomile (Chamomilla recutita). 8 of 12 chamomile-sensitive patients tested positive to chamomile-containing preparations, including tea, creams, ointments, and oil. 5 of 6 arnica-sensitive persons tested positive to arnica-based products. When the group was patch tested with cosmetic and/or herbal product ingredients, plant allergens elicited positive reactions most frequently, but fragrances, emulsifiers, and preservatives tested positive as well. Plant allergens were mainly derived from Compositae, but avocado oil, and Hamamelis virginiana tincture were unexpectedly detected as sensitizers too. Chemical analyses indicated that the Compositae allergens were both sesquiterpene lactones and other naturally occurring compounds. In conclusion, Compositae-allergic persons should be warned against topical use of Compositae-containing products, not only because of the plant allergens, but also because of allergenic cream constituents that may cause reactions in the group of patients who have multiple contact allergies beside the Compositae allergy.
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Total synthesis of (+)-antroquinonol and (+)-antroquinonol D.
Sulake, Rohidas S; Chen, Chinpiao
2015-03-06
The first total synthesis of (+)-antroquinonol and (+)-antroquinonol D, two structurally unique quinonols with a sesquiterpene side chain, is described. The route features an iridium-catalyzed olefin isomerization-Claisen rearrangement reaction (ICR), lactonization, and Grubbs olefin metathesis. The requisite α,β-unsaturation was achieved via the selenylation/oxidation protocol and elimination of β-methoxy group to provide two natural products from a common intermediate.
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Choi, Jung-Hye; Shin, Kyung-Min; Kim, Na-Young; Hong, Jung-Pyo; Lee, Yong Sup; Kim, Hyoung Ja; Park, Hee-Juhn; Lee, Kyung-Tae
2002-11-01
The present work was performed to elucidate the active moiety of a sesquiterpene lactone, taraxinic acid-1'-O-beta-D-glucopyranoside (1). from Taraxacum coreanum NAKAI on the cytotoxicity of various cancer cells. Based on enzymatic hydrolysis and MTT assay, the active moiety should be attributed to the aglycone taraxinic acid (1a). rather than the glycoside (1). Taraxinic acid exhibited potent antiproliferative activity against human leukemia-derived HL-60. In addition, this compound was found to be a potent inducer of HL-60 cell differentiation as assessed by a nitroblue tetrazolium reduction test, esterase activity assay, phagocytic activity assay, morphology change, and expression of CD 14 and CD 66 b surface antigens. These results suggest that taraxinic acid induces the differentiation of human leukemia cells to monocyte/macrophage lineage. Moreover, the expression level of c-myc was down-regulated during taraxinic acid-dependent HL-60 cell differentiation, whereas p21(CIP1) and p27(KIP1) were up-regulated. Taken together, our results suggest that taraxinic acid may have potential as a therapeutic agent in human leukemia.
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Aberham, Anita; Cicek, Serhat Sezai; Schneider, Peter; Stuppner, Hermann
2010-10-27
Today, the medicinal use of wormwood (Artemisia absinthium) is enjoying a resurgence of popularity. This study presents a specific and validated high-performance liquid chromatography (HPLC)-diode array detection method for the simultaneous determination and quantification of bioactive compounds in wormwood and commercial preparations thereof. Five sesquiterpene lactones, two lignans, and a polymethoxylated flavonoid were baseline separated on RP-18 material, using a solvent gradient consisting of 0.085% (v/v) o-phosphoric acid and acetonitrile. The flow rate was 1.0 mL/min, and chromatograms were recorded at 205 nm. The stability of absinthin was tested exposing samples to light, moisture, and different temperatures. Methanolic and aqueous solutions of absinthin were found to be stable for up to 6 months. This was also the case when the solid compound was kept in the refrigerator at -35 °C. In contrast, the colorless needles, when stored at room temperature, turned yellow. Three degradation compounds (anabsin, anabsinthin, and the new dimer 3'-hydroxyanabsinthin) were identified by HPLC-mass spectrometry and HPLC-solid-phase extraction-nuclear magnetic resonance and quantified by the established HPLC method.
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Salapovic, Helena; Geier, Johannes; Reznicek, Gottfried
2013-01-01
Sesquiterpene lactones (SLs), mainly those with an activated exocyclic methylene group, are important allergens in Asteraceae (Compositae) plants. As a screening tool, the Compositae mix, consisting of five Asteraceae plant extracts with allergenic potential (feverfew, tansy, arnica, yarrow, and German chamomile) is part of several national patch test baseline series. However, the SL content of the Compositae mix may vary due to the source material. Therefore, a simple spectrophotometric method for the quantitative measurement of SLs with the α-methylene-γ-butyrolactone moiety was developed, giving the percentage of allergenic compounds in plant extracts. The method has been validated and five Asteraceae extracts, namely feverfew (Tanacetum parthenium L.), tansy (Tanacetum vulgare L.), arnica (Arnica montana L.), yarrow (Achillea millefolium L.), and German chamomile (Chamomilla recutita L. Rauschert) that have been used in routine patch test screening were evaluated. A good correlation could be found between the results obtained using the proposed spectrophotometric method and the corresponding clinical results. Thus, the introduced method is a valuable tool for evaluating the allergenic potential and for the simple and efficient quality control of plant extracts with allergenic potential. PMID:24106675
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Bioactive sesquiterpene lactones and other compounds isolated from Vernonia cinerea
Youn, Ui Joung; Miklossy, Gabriella; Chai, Xingyun; Wongwiwatthananukit, Supakit; Toyama, Onoomar; Songsak, Thanapat; Turkson, James; Chang, Leng Chee
2014-01-01
Four new sesquiterpene lactones, 8α-(2′Z-tigloyloxy)-hirsutinolide (1), 8α-(2′Z-tigloyloxy)-hirsutinolide-13-O-acetate (2), 8α-(4-hydroxytigloyloxy)-hirsutinolide (3), and 8α-hydroxy-13-O-tigloyl-hirsutinolide (4), along with seven known derivatives (5–11), three norisoprenoids (12–14), a flavonoid (15), and a linoleic acid derivative (16), were isolated from the chloroform partition of a methanol extract from the combined leaves and stems of Vernonia cinerea. Their structures were established by 1D and 2D NMR, UV, and MS analyses. Compounds 1–16 were evaluated for their inhibitory effects against the viability of U251MG glioblastoma and MDA-MB-231 breast cancer cells that harbour aberrantly-active STAT3, compared to normal NIH3T3 mouse fibroblasts that show no evidence of activated STAT3. Among the isolates, compounds 2 and 7 inhibited the aberrant STAT3 activity in glioblastoma or breast cancer cells. Further, compounds 7 and 8 inhibited viability of all three cell lines, compounds 2, 4, and 9 predominantly inhibited the viability of the U251MG glioblastoma cell line. PMID:24370662
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Bioactive sesquiterpene lactones and other compounds isolated from Vernonia cinerea.
Youn, Ui Joung; Miklossy, Gabriella; Chai, Xingyun; Wongwiwatthananukit, Supakit; Toyama, Onoomar; Songsak, Thanapat; Turkson, James; Chang, Leng Chee
2014-03-01
Four new sesquiterpene lactones, 8α-(2'Z-tigloyloxy)-hirsutinolide (1), 8α-(2'Z-tigloyloxy)-hirsutinolide-13-O-acetate (2), 8α-(4-hydroxytigloyloxy)-hirsutinolide (3), and 8α-hydroxy-13-O-tigloyl-hirsutinolide (4), along with seven known derivatives (5-11), three norisoprenoids (12-14), a flavonoid (15), and a linoleic acid derivative (16), were isolated from the chloroform partition of a methanol extract from the combined leaves and stems of Vernonia cinerea. Their structures were established by 1D and 2D NMR, UV, and MS analyses. Compounds 1-16 were evaluated for their inhibitory effects against the viability of U251MG glioblastoma and MDA-MB-231 breast cancer cells that harbour aberrantly-active STAT3, compared to normal NIH3T3 mouse fibroblasts that show no evidence of activated STAT3. Among the isolates, compounds 2 and 7 inhibited the aberrant STAT3 activity in glioblastoma or breast cancer cells. Further, compounds 7 and 8 inhibited viability of all three cell lines, compounds 2, 4, and 9 predominantly inhibited the viability of the U251MG glioblastoma cell line. Copyright © 2014 Elsevier B.V. All rights reserved.
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Boonruang, Supattra; Prakobsri, Khanistha; Pouyfung, Phisit; Srisook, Ekaruth; Prasopthum, Aruna; Rongnoparut, Pornpimol; Sarapusit, Songklod
2017-12-01
The human liver cytochrome P450 (CYP) 2A6 and the respiratory CYP2A13 enzymes play role in nicotine metabolism and activation of tobacco-specific nitrosamine carcinogens. Inhibition of both enzymes could offer a strategy for smoking abstinence and decreased risks of respiratory diseases and lung cancer. In this study, activity-guided isolation identified four flavonoids 1-4 (apigenin, luteolin, chrysoeriol, quercetin) from Vernonia cinerea and Pluchea indica, four hirsutinolide-type sesquiterpene lactones 5-8 from V. cinerea, and acetylenic thiophenes 9-11 from P. indica that inhibited CYP2A6- and CYP2A13-mediated coumarin 7-hydroxylation. Flavonoids were most effective in inhibition against CYP2A6 and CYP2A13, followed by thiophenes, and hirsutinolides. Hirsutinolides and thiophenes exhibited mechanism-based inhibition and in irreversible mode against both enzymes. The inactivation kinetic K I values of hirsutinolides against CYP2A6 and CYP2A13 were 5.32-15.4 and 0.92-8.67 µM, respectively, while those of thiophenes were 0.11-1.01 and 0.67-0.97 µM, respectively.
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Vibrational and structural study of onopordopicrin based on the FTIR spectrum and DFT calculations.
Chain, Fernando E; Romano, Elida; Leyton, Patricio; Paipa, Carolina; Catalán, César A N; Fortuna, Mario; Brandán, Silvia Antonia
2015-01-01
In the present work, the structural and vibrational properties of the sesquiterpene lactone onopordopicrin (OP) were studied by using infrared spectroscopy and density functional theory (DFT) calculations together with the 6-31G(∗) basis set. The harmonic vibrational wavenumbers for the optimized geometry were calculated at the same level of theory. The complete assignment of the observed bands in the infrared spectrum was performed by combining the DFT calculations with Pulay's scaled quantum mechanical force field (SQMFF) methodology. The comparison between the theoretical and experimental infrared spectrum demonstrated good agreement. Then, the results were used to predict the Raman spectrum. Additionally, the structural properties of OP, such as atomic charges, bond orders, molecular electrostatic potentials, characteristics of electronic delocalization and topological properties of the electronic charge density were evaluated by natural bond orbital (NBO), atoms in molecules (AIM) and frontier orbitals studies. The calculated energy band gap and the chemical potential (μ), electronegativity (χ), global hardness (η), global softness (S) and global electrophilicity index (ω) descriptors predicted for OP low reactivity, higher stability and lower electrophilicity index as compared with the sesquiterpene lactone cnicin containing similar rings. Copyright © 2015 Elsevier B.V. All rights reserved.
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Dračínský, Martin; Buděšínský, Miloš; Warżajtis, Beata; Rychlewska, Urszula
2012-01-12
Selected guaianolide type sesquiterpene lactones were studied combining solution and solid-state NMR spectroscopy with theoretical calculations of the chemical shifts in both environments and with the X-ray data. The experimental (1)H and (13)C chemical shifts in solution were successfully reproduced by theoretical calculations (with the GIAO method and DFT B3LYP 6-31++G**) after geometry optimization (DFT B3LYP 6-31 G**) in vacuum. The GIPAW method was used for calculations of solid-state (13)C chemical shifts. The studied cases involved two polymorphs of helenalin, two pseudopolymorphs of 6α-hydroxydihydro-aromaticin and two cases of multiple asymmetric units in crystals: one in which the symmetry-independent molecules were connected by a series of hydrogen bonds (geigerinin) and the other in which the symmetry-independent molecules, deprived of any specific intermolecular interactions, differed in the conformation of the side chain (badkhysin). Geometrically different molecules present in the crystal lattices could be easily distinguished in the solid-state NMR spectra. Moreover, the experimental differences in the (13)C chemical shifts corresponding to nuclei in different polymorphs or in geometrically different molecules were nicely reproduced with the GIPAW calculations.
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Milutinović, Violeta; Niketić, Marjan; Krunić, Aleksej; Nikolić, Dejan; Petković, Miloš; Ušjak, Ljuboš; Petrović, Silvana
2018-06-20
Four sesquiterpene lactones (SLs), including three undescribed proline-SL conjugates, the guaianolides calophyllamine A and 8-epiixerisamine A, and the eudesmanolide calophyllamine B, were isolated from the methanol extract of Hieracium calophyllum R. Uechtr. (Compositae) flowering heads. Another known guaianolide, crepiside E, was detected in Hieracium L. species for the first time. Their structures were elucidated using extensive 1D and 2D NMR spectroscopy in combination with HRMS. The isolated SLs were used as external standards for qualitative and quantitative LC-MS analysis of the dry methanol extracts of the flowering aerial parts of 28 Hieracium species from the Balkan Peninsula. Guaianolides were the dominant SLs in 27 species studied. The chemosystematic significance of detected SLs was evaluated using multivariate statistics (PCA, nMDS and UPGMA). Differentiation between the main groups was well supported. All four compounds significantly and equally contributed to the differences between the species. In addition, the eudesmanolide calophyllamine B could be a significant chemosystematic marker for H. sect. Villosa (Griseb.) Gremli s.l. and Glauciformia (Freyn) Zahn-Italica (Fr.) Av. Touv. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Paz Robles, Cristian; Mercado, Darío; Suarez, Sebastián; Baggio, Ricardo
2014-12-01
A cocrystal, C15H22O3·C15H22O3, (I), obtained from Drimys winteri, is composed of two isomeric drimane sesquiterpene lactones, namely valdiviolide, (Ia), and 11-epivaldiviolide, (Ib), neither of which has been reported in the crystal form. Both diastereoisomers present three chiral centres at sites 5, 10 and 11, with an SSR sequence in (Ia) and an SSS sequence in (Ib). O-H···O hydrogen bonds bind molecules into chains running along [120] and the chains are in turn linked by π-π stacking interactions to define planar weakly interacting arrays parallel to (001).
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Sülsen, Valeria P.; Frank, Fernanda M.; Cazorla, Silvia I.; Anesini, Claudia A.; Malchiodi, Emilio L.; Freixa, Blanca; Vila, Roser; Muschietti, Liliana V.; Martino, Virginia S.
2008-01-01
Bioassay-guided fractionation of the organic extract of Ambrosia tenuifolia Sprengel (Asteraceae) led to the isolation of two bioactive sesquiterpene lactones with significant trypanocidal and leishmanicidal activities. By spectroscopic methods (1H- and 13C-nuclear magnetic resonance, distortionless enhancement by polarization transfer, correlated spectroscopy, heteronuclear multiple-quantum coherence, electron impact-mass spectrometry, and infrared spectroscopy), these compounds were identified as psilostachyin and peruvin. Both compounds showed a marked in vitro trypanocidal activity against Trypanosoma cruzi epimastigotes with 50% inhibitory concentration (IC50) values of less than 2 μg/ml. Psilostachyin exerted a significant in vitro activity against the trypomastigote forms of T. cruzi (IC50, 0.76 μg/ml) and was selected for in vivo testing. Psilostachyin-treated mice had a survival of 100% and lower parasitemia values than control mice. Both compounds were also tested on Leishmania sp. promastigotes: psilostachyin (IC50, 0.12 μg/ml) and peruvin (IC50, 0.39 μg/ml) exerted significant leishmanicidal activities. This is the first time that the trypanocidal and leishmanicidal activities of these compounds have been reported. The selectivity index (SI) was employed to evaluate the cytotoxic effect of lactones on T lymphocytes. Although the SIs of both compounds were high for T. cruzi epimastigotes, psilostachyin was more selective against trypomastigotes (SI, 33.8) while peruvin showed no specificity for this parasite. Both compounds presented high selectivity for Leishmania spp. The results shown herein suggest that psilostachyin and peruvin could be considered potential candidates for the development of new antiprotozoal agents against Chagas' disease and leishmaniasis. PMID:18443111
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Czechowski, Tomasz; Larson, Tony R; Catania, Theresa M; Harvey, David; Brown, Geoffrey D; Graham, Ian A
2016-12-27
Artemisinin, a sesquiterpene lactone produced by Artemisia annua glandular secretory trichomes, is the active ingredient in the most effective treatment for malaria currently available. We identified a mutation that disrupts the amorpha-4,11-diene C-12 oxidase (CYP71AV1) enzyme, responsible for a series of oxidation reactions in the artemisinin biosynthetic pathway. Detailed metabolic studies of cyp71av1-1 revealed that the consequence of blocking the artemisinin biosynthetic pathway is the redirection of sesquiterpene metabolism to a sesquiterpene epoxide, which we designate arteannuin X. This sesquiterpene approaches half the concentration observed for artemisinin in wild-type plants, demonstrating high-flux plasticity in A. annua glandular trichomes and their potential as factories for the production of novel alternate sesquiterpenes at commercially viable levels. Detailed metabolite profiling of leaf maturation time-series and precursor-feeding experiments revealed that nonenzymatic conversion steps are central to both artemisinin and arteannuin X biosynthesis. In particular, feeding studies using 13 C-labeled dihydroartemisinic acid (DHAA) provided strong evidence that the final steps in the synthesis of artemisinin are nonenzymatic in vivo. Our findings also suggest that the specialized subapical cavity of glandular secretory trichomes functions as a location for both the chemical conversion and the storage of phytotoxic compounds, including artemisinin. We conclude that metabolic engineering to produce high yields of novel secondary compounds such as sesquiterpenes is feasible in complex glandular trichomes. Such systems offer advantages over single-cell microbial hosts for production of toxic natural products.
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Sesquiterpene lactones in Arnica montana: helenalin and dihydrohelenalin chemotypes in Spain.
Perry, Nigel B; Burgess, Elaine J; Rodríguez Guitián, Manuel A; Romero Franco, Rosa; López Mosquera, Elvira; Smallfield, Bruce M; Joyce, Nigel I; Littlejohn, Roger P
2009-05-01
An analytical RPLC method for sesquiterpene lactones in Arnica montana has been extended to include quantitative analyses of dihydrohelenalin esters. LC-ESI-MS-MS distinguished the isomeric helenalin and dihydrohelenalin esters. The dihydrohelenalin esters have lower response factors for UV detection than do helenalin esters, which must be taken into account for quantitative analyses. Analyses of flowers from 16 different wild populations of A. montana in Spain showed differing proportions of helenalin and dihydrohelenalin esters. For the first time a chemotype with high levels of helenalin esters (total helenalins 5.2-10.3 mg/g dry weight) is reported in Spanish A. montana. These samples were from heath lands at high altitude (1330-1460 m), whereas samples from meadows and peat bogs at lower altitudes were the expected chemotype with high levels of dihydrohelenalin esters (total dihydrohelenalins 10.9-18.2 mg/g). The phenolic compounds, both flavonoid glycosides and caffeoylquinic acids, in Spanish A. montana are reported for the first time. The levels of several of these compounds differed significantly between samples from heath lands and samples from peat bogs or meadows, with the heath land samples being most similar to central European A. montana in their phenolic composition. Copyright Georg Thieme Verlag KG Stuttgart. New York.
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Kim, Seung Hyun; Kim, Tae Sung
2002-10-01
Many anti-inflammatory agents are known to significantly enhance the terminal differentiation of some cancer cells such as leukemia cells. In this study, the effect of yomogin, a eudesmane sesquiterpene lactone isolated from Artemisia princeps with anti-inflammatory activity, was investigated in human promyelocytic leukemia HL-60 cells. Yomogin by itself induced small increases in cell differentiation, with less than 19 % of the cells attaining a differentiated phenotype. Importantly, yomogin synergistically enhanced differentiation of HL-60 cells in a dose-dependent manner when combined with either 5 nM 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2) D(3)] or 50 nM all- trans retinoic acid (all- trans RA). Cytofluorometric analysis and morphologic studies indicated that the combinations of yomogin and 1,25-(OH)(2) D(3) stimulated differentiation to monocytes whereas the combinations of yomogin and all- trans RA stimulated differentiation to granulocytes. These results suggest that yomogin may be useful in combination with 1,25-(OH)(2) D(3) or all- trans-RA in the differentiation therapy for myeloid leukemias. Abbreviations. 1,25-(OH)(2) D(3) :1,25-dihydroxyvitamin D(3) FITC:fluorescein isothiocyanate NBT:nitroblue tetrazolium RA:retinoic acid PE:phytoerythrin
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Wang, Wei; Chen, Bin; Zou, Ruolan; Tu, Xiuying; Tan, Songlin; Lu, Hong; Liu, Zhaojie; Fu, Jianjiang
2014-11-01
Metastasis is the most insidious aspect of breast cancer, but effective strategies to control this malignant process are still lacking. In previous studies, we screened over 200 extracts from plants of genus Chloranthaceae by bioactivity-guided fractionation, and found that Codonolactone (CLT) exhibited potential antimetastatic properties in breast cancer cells. This sesquiterpene lactone was isolated from Chloranthus henryi Hemsl, and is also found in other medical herbs, such as Codonopsis pilosula, Atractylodes macrocephala Koidz and others. Here, we report that CLT inhibited the ability of invasion and migration in metastatic breast cancer cells. Furthermore, CLT exhibited significant suppression on formation of lung metastatic foci of breast cancer in vivo. We next investigated the mechanism of CLT-induced metastasis inhibitory effects in breast cancer cells. A significant inhibition on activity and expression of MMP-9 and MMP-13 was observed. Moreover, data from western blotting, Runx2 transcription factor assay and chromatin immunoprecipitation assay showed that binding ability of Runx2 to sequences of the mmp-13 promoter was inhibited by CLT. Collectively, these findings suggested that the antimetastatic properties of CLT in breast cancer were due to the inhibition of MMPs, which might be associated with a downregulation of Runx2 transcriptional activity.
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Butturini, Elena; Cavalieri, Elisabetta; Carcereri de Prati, Alessandra; Darra, Elena; Rigo, Antonella; Shoji, Kazuo; Murayama, Norie; Yamazaki, Hiroshi; Watanabe, Yasuo; Suzuki, Hisanori; Mariotto, Sofia
2011-01-01
The main purpose of the present study is to envisage the molecular mechanism of inhibitory action ofdehydrocostuslactone (DCE) andcostunolide (CS), two naturally occurring sesquiterpene lactones, towards the activation of signal transducer and activator of transcription 3 (STAT3). We report that, in human THP-1 cell line, they inhibit IL-6-elicited tyrosine phosphorylation of STAT3 and its DNA binding activity with EC50 of 10 µM with concomitantdown-regulation ofthe phosphorylation of the tyrosine Janus kinases JAK1, JAK2 and Tyk2. Furthermore, these compounds that contain an α-β-unsatured carbonyl moiety and function as potent Michael reaction acceptor, induce a rapid drop in intracellular glutathione (GSH) concentration by direct interaction with it, thereby triggering S-glutathionylation of STAT3. Dehydrocostunolide (HCS), the reduced form of CS lacking only the α-β-unsaturated carbonyl group, fails to exert any inhibitory action. Finally, the glutathione ethylene ester (GEE), the cell permeable GSH form, reverts the inhibitory action of DCE and CS on STAT3 tyrosine phosphorylation. We conclude that these two sesquiterpene lactones are able to induce redox-dependent post-translational modification of cysteine residues of STAT3 protein in order to regulate its function. PMID:21625597
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May, Bianca; Lange, B. Markus; Wüst, Matthias
2013-01-01
The participation of the mevalonic acid (MVA) and 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol-4-phosphate (DOXP/MEP) pathways in sesquiterpene biosynthesis of grape berries was investigated. There is an increasing interest in this class of terpenoids, since the oxygenated sesquiterpene rotundone was identified as the peppery aroma impact compound in Australian Shiraz wines. To investigate precursor supply pathway utilization, in vivo feeding experiments were performed with the deuterium labeled, pathway specific, precursors [5,5-2H2]-1-deoxy-D-xylulose and [5,5-2H2]-mevalonic acid lactone. Head Space-Solid Phase Micro Extraction-Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS) analysis of the generated volatile metabolites demonstrated that de novo sesquiterpene biosynthesis is mainly located in the grape berry exocarp (skin), with no detectable activity in the mesocarp (flesh) of the Lemberger variety. Interestingly, precursors from both the (primarily) cytosolic MVA and plastidial DOXP/MEP pathways were incorporated into grape sesquiterpenes in the varieties Lemberger, Gewürztraminer and Syrah. Our labeling data provide evidence for a homogenous, cytosolic pool of precursors for sesquiterpene biosynthesis, indicating that a transport of precursors occurs mostly from plastids to the cytosol. The labeling patterns of the sesquiterpene germacrene D were in agreement with a cyclization mechanism analogous to that of a previously cloned enantioselective (R)-germacrene D synthase from Solidago canadensis. This observation was subsequently confirmed by enantioselective GC-MS analysis demonstrating the exclusive presence of (R)-germacrene D, and not the (S)-enantiomer, in grape berries. PMID:23954075
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May, Bianca; Lange, B Markus; Wüst, Matthias
2013-11-01
The participation of the mevalonic acid (MVA) and 1-deoxy-d-xylulose 5-phosphate/2-C-methyl-d-erythritol-4-phosphate (DOXP/MEP) pathways in sesquiterpene biosynthesis of grape berries was investigated. There is an increasing interest in this class of terpenoids, since the oxygenated sesquiterpene rotundone was identified as the peppery aroma impact compound in Australian Shiraz wines. To investigate precursor supply pathway utilization, in vivo feeding experiments were performed with the deuterium labeled, pathway specific, precursors [5,5-(2)H2]-1-deoxy-d-xylulose and [5,5-(2)H2]-mevalonic acid lactone. Head Space-Solid Phase Micro Extraction-Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS) analysis of the generated volatile metabolites demonstrated that de novo sesquiterpene biosynthesis is mainly located in the grape berry exocarp (skin), with no detectable activity in the mesocarp (flesh) of the Lemberger variety. Interestingly, precursors from both the (primarily) cytosolic MVA and plastidial DOXP/MEP pathways were incorporated into grape sesquiterpenes in the varieties Lemberger, Gewürztraminer and Syrah. Our labeling data provide evidence for a homogenous, cytosolic pool of precursors for sesquiterpene biosynthesis, indicating that a transport of precursors occurs mostly from plastids to the cytosol. The labeling patterns of the sesquiterpene germacrene D were in agreement with a cyclization mechanism analogous to that of a previously cloned enantioselective (R)-germacrene D synthase from Solidago canadensis. This observation was subsequently confirmed by enantioselective GC-MS analysis demonstrating the exclusive presence of (R)-germacrene D, and not the (S)-enantiomer, in grape berries. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Czechowski, Tomasz; Larson, Tony R.; Catania, Theresa M.; Harvey, David; Brown, Geoffrey D.; Graham, Ian A.
2016-01-01
Artemisinin, a sesquiterpene lactone produced by Artemisia annua glandular secretory trichomes, is the active ingredient in the most effective treatment for malaria currently available. We identified a mutation that disrupts the amorpha-4,11-diene C-12 oxidase (CYP71AV1) enzyme, responsible for a series of oxidation reactions in the artemisinin biosynthetic pathway. Detailed metabolic studies of cyp71av1-1 revealed that the consequence of blocking the artemisinin biosynthetic pathway is the redirection of sesquiterpene metabolism to a sesquiterpene epoxide, which we designate arteannuin X. This sesquiterpene approaches half the concentration observed for artemisinin in wild-type plants, demonstrating high-flux plasticity in A. annua glandular trichomes and their potential as factories for the production of novel alternate sesquiterpenes at commercially viable levels. Detailed metabolite profiling of leaf maturation time-series and precursor-feeding experiments revealed that nonenzymatic conversion steps are central to both artemisinin and arteannuin X biosynthesis. In particular, feeding studies using 13C-labeled dihydroartemisinic acid (DHAA) provided strong evidence that the final steps in the synthesis of artemisinin are nonenzymatic in vivo. Our findings also suggest that the specialized subapical cavity of glandular secretory trichomes functions as a location for both the chemical conversion and the storage of phytotoxic compounds, including artemisinin. We conclude that metabolic engineering to produce high yields of novel secondary compounds such as sesquiterpenes is feasible in complex glandular trichomes. Such systems offer advantages over single-cell microbial hosts for production of toxic natural products. PMID:27930305
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Lass, Christian; Vocanson, Marc; Wagner, Steffen; Schempp, Christoph M; Nicolas, Jean-Francois; Merfort, Irmgard; Martin, Stefan F
2008-10-01
Sesquiterpene lactones (SL), secondary plant metabolites from flowerheads of Arnica, exert anti-inflammatory effects mainly by preventing nuclear factor (NF)-kappaB activation because of alkylation of the p65 subunit. Despite its known immunosuppressive action, Arnica has been classified as a plant with strong potency to induce allergic contact dermatitis. Here we examined the dual role of SL as anti-inflammatory compounds and contact allergens in vitro and in vivo. We tested the anti-inflammatory and allergenic potential of SL in the mouse contact hypersensitivity model. We also used dendritic cells to study the activation of NF-kappaB and the secretion of interleukin (IL)-12 in the presence of different doses of SL in vitro. Arnica tinctures and SL potently suppressed NF-kappaB activation and IL-12 production in dendritic cells at high concentrations, but had immunostimulatory effects at low concentrations. Contact hypersensitivity could not be induced in the mouse model, even when Arnica tinctures or SL were applied undiluted to inflamed skin. In contrast, Arnica tinctures suppressed contact hypersensitivity to the strong contact sensitizer trinitrochlorobenzene and activation of dendritic cells. However, contact hypersensitivity to Arnica tincture could be induced in acutely CD4-depleted MHC II knockout mice. These results suggest that induction of contact hypersensitivity by Arnica is prevented by its anti-inflammatory effect and immunosuppression as a result of immune regulation in immunocompetent mice.
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sarA as a Target for the Treatment and Prevention of Staphylococcal Biofilm-Associated Infection
2015-02-01
M.S., Compadre, C.M. 2011. Sesquiterpene lactons from Gynoxys verrucosa and their anti - MRSA activity. Journal of Ethnopharmacology, 137:1055-1059. 11...estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data...needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this
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Brentan Silva, Denise; Aschenbrenner, Anna-Katharina; Lopes, Norberto Peporine; Spring, Otmar
2017-05-10
Helianthus annuus (sunflower) displays non-glandular trichomes (NGT), capitate glandular trichomes (CGT), and linear glandular trichomes (LGT), which reveal different chemical compositions and locations in different plant tissues. With matrix-assisted laser desorption/ionization (MALDI) and laser desorption/ionization (LDI) mass spectrometry imaging (MSI) techniques, efficient methods were developed to analyze the tissue distribution of secondary metabolites (flavonoids and sesquiterpenes) and proteins inside of trichomes. Herein, we analyzed sesquiterpene lactones, present in CGT, from leaf transversal sections using the matrix 2,5-dihydroxybenzoic acid (DHB) and α-cyano-4-hydroxycinnamic acid (CHCA) (mixture 1:1) with sodium ions added to increase the ionization in positive ion mode. The results observed for sesquiterpenes and polymethoxylated flavones from LGT were similar. However, upon desiccation, LGT changed their shape in the ionization source, complicating analyses by MSI mainly after matrix application. An alternative method could be applied to LGT regions by employing LDI (without matrix) in negative ion mode. The polymethoxylated flavones were easily ionized by LDI, producing images with higher resolution, but the sesquiterpenes were not observed in spectra. Thus, the application and viability of MALDI imaging for the analyses of protein and secondary metabolites inside trichomes were confirmed, highlighting the importance of optimization parameters.
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Rolli, Enrico; Marieschi, Matteo; Maietti, Silvia; Guerrini, Alessandra; Grandini, Alessandro; Sacchetti, Gianni; Bruni, Renato
2016-01-01
The hydrodistilled oil of Cryptocarya massoy bark was characterized by GC-FID and GC/MS analyses, allowing the identification of unusual C10 massoia lactone (3, 56.2%), C12 massoia lactone (4, 16.5%), benzyl benzoate (1, 12.7%), C8 massoia lactone (3.4%), δ-decalactone (5, 1.5%), and benzyl salicylate (2, 1.8%) as main constituents. The phytotoxic activities of the oil, three enriched fractions (lactone-rich, ester-rich, and sesquiterpene-rich), and four constituents (compounds 1, 2, 5, and δ-dodecalactone (6)) against Lycopersicon esculentum and Cucumis sativus seeds and seedlings were screened. At a concentration of 1000 μl/l, the essential oil and the massoia lactone-rich fraction caused a complete inhibition of the germination of both seeds, and, when applied on tomato plantlets, they induced an 85 and 100% dieback, respectively. These performances exceeded those of the well-known phytotoxic essential oils of Syzygium aromaticum and Cymbopogon citratus, already used in commercial products for the weed and pest management. The same substances were also evaluated against four phytopathogenic bacteria and ten phytopathogenic fungi, providing EC50 values against the most susceptible strains in the 100-500 μl/l range for the essential oil and in the 10-50 μl/l range for compound 6 and the lactone-rich fraction. The phytotoxic behavior was related mainly to massoia lactones and benzyl esters, while a greater amount of 6 may infer a good activity against some phytopathogenic fungi. Further investigations of these secondary metabolites are warranted, to evaluate their use as natural herbicides. Copyright © 2016 Verlag Helvetica Chimica Acta AG, Zürich.
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Lee, Hyun-Kyung; Song, Ha Eun; Lee, Haeng-Byung; Kim, Cheol-Soo; Koketsu, Mamoru; Thi My Ngan, Luong; Ahn, Young-Joon
2014-01-01
Helicobacter pylori is associated with various diseases of the upper gastrointestinal tract, such as gastric inflammation and duodenal and gastric ulcers. The aim of the study was to assess anti-H. pylori effects of the sesquiterpene lactone dehydrocostus lactone (DCL) from Magnolia sieboldii leaves, compared to commercial pure DCL, two previously known sesquiterpene lactones (costunolide and parthenolide), (–)-epigallocatechin gallate, and four antibiotics. The antibacterial activity of natural DCL toward antibiotic-susceptible H. pylori ATCC 700392 and H. pylori ATCC 700824 strains (MIC, 4.9 and 4.4 mg/L) was similar to that of commercial DCL and was more effective than costunolide, parthenolide, and EGCG. The activity of DCL was slightly lower than that of metronidazole (MIC, 1.10 and 1.07 mg/L). The antibacterial activity of DCL was virtually identical toward susceptible and resistant strains, even though resistance to amoxicillin (MIC, 11.1 mg/L for PED 503G strain), clarithromycin (49.8 mg/L for PED 3582GA strain), metronidazole (21.6 mg/L for H. pylori ATCC 43504 strain; 71.1 mg/L for 221 strain), or tetracycline (14.2 mg/L for B strain) was observed. This finding indicates that DCL and the antibiotics do not share a common mode of action. The bactericidal activity of DCL toward H. pylori ATCC 43504 was not affected by pH values examined (4.0–7.0). DCL caused considerable conversion to coccoid form (94 versus 49% at 8 and 4 mg/L of DCL for 48 h). The Western blot analysis revealed that urease subunits (UreA and UreB) of H. pylori ATCC 43504 were not affected by 10 mM of DCL, whereas UreA monomer band completely disappeared at 0.1 mM of (–)-epigallocatechin gallate. Global efforts to reduce the level of antibiotics justify further studies on M. sieboldii leaf-derived materials containing DCL as potential antibacterial products or a lead molecule for the prevention or eradication of drug-resistant H. pylori. PMID:24747984
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Sesquiterpenoids and phenolics from roots of Taraxacum udum.
Michalska, Klaudia; Marciniuk, Jolanta; Kisiel, Wanda
2010-07-01
From roots of Taraxacum udum, two new and four known sesquiterpene lactones were isolated, together with five known phenolic compounds. The new compounds were characterized as 11beta, 13-dihydrotaraxinic acid and taraxinic acid 6-O-acetyl-beta-glucopyranosyl ester by spectroscopic methods, especially 1D and 2D NMR, and by comparison with structurally related compounds. The plant material was shown to be a good source of taraxinic acid derivatives. Copyright 2009 Elsevier B.V. All rights reserved.
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Antiprotozoal activity of Neurolaena lobata.
Berger, I; Passreiter, C M; Cáceres, A; Kubelka, W
2001-06-01
Extracts, fractions and sesquiterpene lactones from Neurolaena lobata (L.) R. Br. (Asteraceae), a traditional medicinal plant from Guatemala, were tested in vitro against Leishmania spp. promastigotes, Trypanosoma cruzi trypomastigotes and epimastigotes and Trichomonas vaginalis trophozoites. The ethanol extract inhibited the parasite growth of L. mexicana, T. cruzi and T. vaginalis significantly. The pure germacranolides 1 and a mixture of 2 and 3, isolated from the ethonal extract, were highly active against L. mexicana and T. cruzi. Copyright 2001 John Wiley & Sons, Ltd.
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Wagner, Steffen; Merfort, Irmgard
2007-01-04
Preparations of Arnica montana L. are widely used for the topical treatment of inflammatory diseases. The anti-inflammatory activity is mainly attributed to their sesquiterpene lactones (SLs) from the helenalin and 11alpha,13-dihydrohelenalin type. To study the penetration kinetics of SLs in Arnica preparations, a stripping method with adhesive tape and pig skin as a model was used. For the determination of SLs in the stripped layers of the stratum corneum (SC), a gas chromatography/mass spectrometry method was developed and validated. Thereby the amount of helenalin derivatives was calculated as helenalin isobutyrate, and 11alpha,13-dihydrohelenalin derivatives as 11alpha,13-dihydrohelenalin methacrylate. This GC-MSD method is suitable also to determine low amounts of SLs in Arnica preparations. The penetration behaviour of one gel preparation and two ointment preparations was investigated. The SLs of all preparations show a comparable penetration in and a permeation through the stratum corneum, the uppermost part of the skin. Interestingly, the gel preparation showed a decrease of the penetration rate over 4h, whereas the penetration rate of ointments kept constant over time. Moreover, we could demonstrate that the totally penetrated amount of SLs only depends on the kind of the formulation and of the SLs-content in the formulation but not on the SLs composition or on the used extraction agent.
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New sesquiterpene lactones from Arnica tincture prepared from fresh flowerheads of Arnica montana.
Kos, Olha; Lindenmeyer, Maja T; Tubaro, Aurelia; Sosa, Silvio; Merfort, Irmgard
2005-11-01
Investigation of an ethanolic extract prepared from fresh Arnica montana flowers afforded three new 1,5- trans-guaianolides, of which 11alpha,13-dihydro-2-O-tigloylflorilenalin and the respective 2-O-isovaleryl derivative are reported for the first time. Additionally, three new and one known 2beta-ethoxy-2,3-dihydrohelenalin esters were isolated. GC/MS studies of the extract after a two year storage at 4 degrees C demonstrated that the latter were artefacts that had been formed by addition of ethanol to the cyclopentenone structure of helenalin. Formation of these adducts gave compounds possessing an inhibitory activity comparable to that of 11alpha,13-dihydrohelenalin derivatives in the NF-kappaB EMSA and the IL-8 ELISA in vitro assays as well as in the in vivo croton oil-induced mouse ear edema test for one adduct, namely 2beta-ethoxy-6-O-acetyl-2,3-dihydrohelenalin. As expected, 6-O-(2-methylbutyryl)- and 6-O-methacryloyl-helenalin exhibited a stronger activity in the NF-kappaB EMSA and IL-8 ELISA. Sesquiterpene lactones seem to be the most important NF-kappaB inhibiting compounds in the Arnica extract. Bioguided fractionation using the luciferase reporter gene assay resulted in the isolation of only moderately active compounds, such as 6-acetoxy-2,2-dimethylchroman-4-one and 10-acetoxy-8,9-epoxythymol isobutyrate.
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Ważny, Rafał; Rozpądek, Piotr; Jędrzejczyk, Roman J; Śliwa, Marta; Stojakowska, Anna; Anielska, Teresa; Turnau, Katarzyna
2018-04-01
Phytoremediation of polluted sites can be improved by co-inoculation with mycorrhizal and endophytic fungi. In this study, the effects of single- and co-inoculation of Lactuca serriola with an arbuscular mycorrhizal (AM) fungus, Rhizoglomus intraradices, and endophytic fungi, Mucor sp. or Trichoderma asperellum, on plant growth, vitality, toxic metal accumulation, sesquiterpene lactone production and flavonoid concentration in the presence of toxic metals were evaluated. Inoculation with the AM fungus increased biomass yield of the plants grown on non-polluted and polluted substrate. Co-inoculation with the AM fungus and Mucor sp. resulted in increased biomass yield of plants cultivated on the polluted substrate, whereas co-inoculation with T. asperellum and the AM fungus increased plant biomass on the non-polluted substrate. In the presence of Mucor sp., mycorrhizal colonization and arbuscule richness were increased in the non-polluted substrate. Co-inoculation with the AM fungus and Mucor sp. increased Zn concentration in leaves and roots. The concentration of sesquiterpene lactones in plant leaves was decreased by AM fungus inoculation in both substrates. Despite enhanced host plant costs caused by maintaining symbiosis with numerous microorganisms, interaction of wild lettuce with both mycorrhizal and endophytic fungi was more beneficial than that with a single fungus. The study shows the potential of double inoculation in unfavourable environments, including agricultural areas and toxic metal-polluted areas.
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Hance, Philippe; Fertin, Anne; Voedts, Najia; Duhal, Nathalie; Goossens, Jean-François; Hilbert, Jean-Louis
2014-01-01
A method for the simultaneous determination of free chlorogenic acids (CGA) and sesquiterpene lactones (STL) in chicory root and its dried (flour) and roasted (grain) forms is described. The method uses one extraction and one analysis for all chicory root products. Various solvents with low to high polarity, such as methanol, chloroform, or n-hexane, were tested alone, in combination in different proportions or with acidified or neutral aqueous solvent. The water/chloroform/methanol (30/30/40, v/v/v) mixture generated the best extraction yield, 21% higher than alcohol mixtures. The profiling of CGA and STL content was performed through a conventional HPLC-DAD method using a PFP core shell column in a fast single run. Good retention time and area repeatability (RDD mean % 0.46 and 5.6, resp.) and linearity (R 2 ≥ 0.96) were obtained. The STL and chlorogenic acids levels determined were 254.7 and 100.2 μg/g of dry matter in the root, 792.5 and 1,547 μg/g in flour, and 160.4 and 822.5 μg/g in the roasted grains, respectively. With an average recovery of 106% and precision of 90%, this method is rapid, reproducible, and straightforward way to quantify the chlorogenic acids and STL in chicory raw material and end products. PMID:25548785
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Gobbo-Neto, Leonardo; Lopes, Norberto P
2008-02-27
Lychnophora ericoides Mart. (Asteraceae, Vernonieae) is a plant, endemic to Brazil, with occurrence restricted to the "cerrado" biome. Traditional medicine employs alcoholic and aqueous-alcoholic preparations of leaves from this species for the treatment of wounds, inflammation, and pain. Furthermore, leaves of L. ericoides are also widely used as flavorings for the Brazilian traditional spirit "cachaça". A method has been developed for the extraction and HPLC-DAD analysis of the secondary metabolites of L. ericoides leaves. This analytical method was validated with 11 secondary metabolites chosen to represent the different classes and polarities of secondary metabolites occurring in L. ericoides leaves, and good responses were obtained for each validation parameter analyzed. The same HPLC analytical method was also employed for online secondary metabolite identification by HPLC-DAD-MS and HPLC-DAD-MS/MS, leading to the identification of di- C-glucosylflavones, coumaroylglucosylflavonols, flavone, flavanones, flavonols, chalcones, goyazensolide, and eremantholide-type sesquiterpene lactones and positional isomeric series of chlorogenic acids possessing caffeic and/or ferulic moieties. Among the 52 chromatographic peaks observed, 36 were fully identified and 8 were attributed to compounds belonging to series of caffeoylferuloylquinic and diferuloylquinic acids that could not be individualized from each other.
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Kitai, Yurika; Zhang, Xia; Hayashida, Yushi; Kakehi, Yoshiyuki; Tamura, Hirotoshi
2017-07-01
Dimer sesquiterpene lactones (SLs), uvedafolin and enhydrofolin, against four monomer SLs isolated from yacon, Smallanthus sonchifolius, leaf were the most cytotoxic substances on HeLa cells (IC 50 values 2.96-3.17 μM at 24 hours). However, the cytotoxic mechanism of dimer SL has not been elucidated yet. Therefore, in this study, we clarified the in vitro cytotoxic mechanism of uvedafolin on the HeLa cells, and evaluated the cytotoxicity against NIH/3T3 cells which were used as normal cells. In consequence, the dimer SLs had low toxicity for the NIH/3T3 cells (IC 50 4.81-4.98 μM at 24 hours) and then the uvedafolin mediated cell cycle arrest at the G 2 /M phase and induced apoptosis on the HeLa cells evidenced by appearance of a subG1 peak. Uvedafolin induced apoptosis was attributed to caspase-9 and caspase-3/7 activities. An effectively induced apoptosis pathway was demonstrated from mitochondria membrane potential change and cytochrome c release to cytosol. These results reveal that uvedafolin induced apoptosis via the mitochondria pathway. The present results indicate the potential of uvedafolin as a leading compound of new anticancer agents. Copyright © 2016. Published by Elsevier B.V.
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Final report on the safety assessment of Arnica montana extract and Arnica montana.
2001-01-01
Arnica Montana Extract is an extract of dried flowerheads of the plant, Arnica montana. Arnica Montana is a generic term used to describe a plant material derived from the dried flowers, roots, or rhizomes of A. montana. Common names for A. montana include leopard's bane, mountain tobacco, mountain snuff, and wolf's bane. Two techniques for preparing Arnica Montana Extract are hydroalcoholic maceration and gentle disintegration in soybean oil. Propylene glycol and butylene glycol extractions were also reported. The composition of these extracts can include fatty acids, especially palmitic, linoleic, myristic, and linolenic acids, essential oil, triterpenic alcohols, sesquiterpene lactones, sugars, phytosterols, phenol acids, tannins, choline, inulin, phulin, arnicin, flavonoids, carotenoids, coumarins, and heavy metals. The components present in these extracts are dependent on where the plant is grown. Arnica Montana Extract was reported to be used in almost 100 cosmetic formulations across a wide range of product types, whereas Arnica Montana was reported only once. Extractions of Arnica Montana were tested and found not toxic in acute toxicity tests in rabbits, mice, and rats; they were not irritating, sensitizing, or phototoxic to mouse or guinea pig skin; and they did not produce significant ocular irritation. In an Ames test, an extract of A. montana was mutagenic, possibly related to the flavenoid content of the extract. No carcinogenicity or reproductive/developmental toxicity data were available. Clinical tests of extractions failed to elicit irritation or sensitization, yet Arnica dermatitis, a delayed type IV allergy, is reported in individuals who handle arnica flowers and may be caused by sesquiterpene lactones found in the flowers. Ingestion of A. montana-containing products has induced severe gastroenteritis, nervousness, accelerated heart rate, muscular weakness, and death. Absent any basis for concluding that data on one member of a botanical ingredient group can be extrapolated to another in the group, or to the same ingredient extracted differently, these data were not considered sufficient to assess the safety of these ingredients. Additional data needs include current concentration of use data; function in cosmetics; ultraviolet (UV) absorption data-if absorption occurs in the UVA or UVB range, photosensitization data are needed; gross pathology and histopathology in skin and other major organ systems associated with repeated dermal exposures; dermal reproductive/developmental toxicity data; inhalation toxicity data, especially addressing the concentration, amount delivered, and particle size; and genotoxicity testing in a mammalian system; if positive, a 2-year dermal carcinogenicity assay performed using National Toxicology Program (NTP) methods is needed. Until these data are available, it is concluded that the available data are insufficient to support the safety of these ingredients in cosmetic formulations.
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Cytotoxic sesquiterpene lactones from the leaves of Vernonia guineensis Benth. (Asteraceae)
Toyang, Ngeh J.; Wabo, Hippolyte K.; Ateh, Eugene N.; Davis, Harry; Tane, Pierre; Sondengam, Luc B.; Bryant, Joseph; Verpoorte, Rob
2015-01-01
Ethnopharmacological relevance Vernonia guineensis Benth. (Asteraceae) preparations are used in folk medicine in Cameroon to treat a number of ailments, including prostate cancer and malaria, and is used as an anthelmintic, adaptogen and antidote. The aim of this study was to continue the validation of the activity of Vernonia guineensis Benth. extracts and isolated molecules against cancer cell lines following the previous isolation of an anti-prostate cancer sugar ester from the root extract. Materials and methods Acetone extracts of Vernonia guineensis Benth. leaves were tested for activity against 10 cancer cell lines (Breast—MDA-MB-231, Breast—MCF-7, Colon—HCT-116, Leukemia—HL-60, Lung—A549, Melanoma—A375, Ovarian—OVCAR3, Pancreas—Mia-paca, Prostate—PC-3 and Prostate—DU-145). The acetone extract was subjected to bioactivity guided fractionation. Anti-proliferation and clonogenic activity of the isolated compounds were tested. The WST-1 assay was used for the anti-proliferation activity, while the standard clonogenic test was used to determine the clonogenic activity. Results The acetone extract of Vernonia guineensis Benth. demonstrated in vitro activity ranging from IC50 4–26 mg/mL against the 10 cell lines. Activity guided fractionation of this extract yielded two sesquiterpene lactones, isolated for the first time from the genus Vernonia. The compounds were characterized using spectroscopic experiments, including a combination of 1D and 2D NMR data. Vernopicrin (1) and Vernomelitensin (2) demonstrated in vitro activity against human cancer cell lines with IC50 ranging from 0.35–2.04 μM (P < 0.05) and 0.13–1.5 μM (P < 0.05), respectively, between the most and least sensitive cell lines for each compound. Vernopicrin was most active against the human melanoma (A375) cell line and least active against the lung cancer (A549) cell line, while Vernomelitensin was also most active against the human melanoma (A375) cell line and least active against the breast cancer (MCF-7) cell line. Both compounds also demonstrated anticlonogenic activity. Conclusion The cytotoxicity demonstrated by the crude extract and isolated sesquiterpenes against cancer cell lines highlights the medicinal potential of V. guineensis. The selective anti-proliferation and dose dependent anticlonogenic activities suggest that the identified sesquiterpenes could be potential antitumor agents.. PMID:23376285
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Skin penetration studies of Arnica preparations and of their sesquiterpene lactones.
Wagner, Steffen; Suter, Andreas; Merfort, Irmgard
2004-10-01
Alcoholic preparations of Arnica montana are widely used for the topical treatment of various inflammatory diseases. Sesquiterpene lactones (SLs) are mainly responsible for their anti-inflammatory activity. Here we have studied the penetration kinetics of Arnica tinctures prepared from dried Arnica flowers originating from different chemotypes as well as of their respective dominating SLs, helenalin isobutyrate and 11alpha,13-dihydrohelenalin acetate. Some alcoholic preparations of fresh Arnica flowers and an Arnica fresh plant gel were also included in the study. We used the stripping method with adhesive tape and pig skin as a model and determined the quantity of SLs in the stripped layers of the stratum corneum (SC). Thus, we observed the penetration into and permeation through this uppermost part of the skin. Whereas isolated SLs permeate through the SC only in a very small amount, permeation of SLs was much higher when they were present in the tinctures. Furthermore, differences of permeation were observed between helenalin and dihydrohelenalin derivatives. Permeation through the SC could be determined for the tested Arnica preparations of fresh Arnica flowers with two preparations showing the best penetration behaviour of all the tested substances. Moreover, the effects of incubation time as well as of repeated applications were investigated with one preparation. Altogether, this study shows that a sufficient amount of SLs might permeate the skin barrier by using Arnica preparations to exert anti-inflammatory effects and that the topical use of plant preparations may be advantageous compared to the isolated compounds.
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Landau, I; Müller-Schärer, H; Ward, P I
1994-04-01
The sesquiterpene lactone cnicin was extracted fromCentaurea maculosa andCentaurea vallesiaca. We examined its effects on the ovipositional response and larval development of generalist and specialist insect herbivores associated withC. maculosa. For the oviposition trials, three plant species (C. maculosa, Achillea millefolium, andCichorium intybus), half of which were sprayed with 3% of cnicin, were exposed to the specialist mothsStenodes straminea, Agapeta zoegana, andPterolonche inspersa in field cages. All three species significantly preferredC. maculosa to other plants andP. inspersa significantly preferred cnicin-sprayed plants to untreated plants for oviposition. Tested over all species, cnicin significantly increased the number of eggs laid on a given plant. A larval diet test examined the toxicity of cnicin for larvae of the generalist noctuid mothSpodoptera littoralis. Cnicin concentrations of 3% and 6% were lethal and 1% and 0.5% seriously inhibited growth and development. The larvae of theC. maculosa specialistStenodes straminea survived at 6% cnicin, but none of the pupae hatched.Agapeta zoegana was able to survive at 1% and 3% cnicin. Both specialists had difficulties with the artificial diet, but weight increase and survival was not further reduced when cnicin was present compared with on the control diet. In conclusion, cnicin influenced host recognition by the specialist species, and larvae of the generalist did not survive on natural levels of cnicin. Growth and survival of the specialist were not influenced by cnicin but were considerably hampered on artificial diet.
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Enhanced cytostatic activity of the sesquiterpene lactone eupatoriopicrin by glutathione depletion.
Woerdenbag, H. J.; Lemstra, W.; Malingré, T. M.; Konings, A. W.
1989-01-01
Eupatoriopicrin (EUP), a sesquiterpene lactone from Eupatorium cannabinum L., possesses cytostatic activity. This was demonstrated for FIO 26 cells in vitro with the aid of a clonogenic assay and in vivo by tumour growth delay in FIO 26 and Lewis lung tumour-bearing mice. In vitro the IC50 for 1 h exposure to EUP was 1.5 microgram ml-1 (4.1 nmol ml-1). This concentration depleted about 25% of its cellular GSH concentration. Pretreatment of FIO 26 cells with BSO, resulting in greater than 99%. GSH depletion, enhanced the cytotoxic effect of EUP. The dose-enhancement factor at the level of 10% cell survival was 2.3. Growth inhibition of the Lewis lung carcinoma and the FIO 26 fibrosarcoma, solidly growing in C57Bl mice, was found after i.v. injection of 20 or 40 mg kg-1 EUP, at a tumour volume of about 500 microliters. Pretreatment with BSO at a dose of 4 mmol kg-1 i.p., 6 h before EUP administration, resulted in a significantly stronger growth delay of both tumours compared with EUP only. At the time of EUP treatment, cellular GSH in the tumours was reduced by BSO treatment to about 60%. It is concluded that EUP possesses antitumour activity in vivo and that chemosensitisation of EUP may be accomplished by pretreatment with BSO, indicating that endogenous GSH protects against the cytostatic action of EUP. PMID:2757925
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Novel spirobicyclic artemisinin analogues (artemalogues): Synthesis and antitumor activities.
Liu, Gang; Song, Shanshan; Shu, Shiqi; Miao, Zehong; Zhang, Ao; Ding, Chunyong
2015-10-20
The sesquiterpene lactone framework of artemisinin was used as a drug repositioning prototype for the development of novel antitumor drugs. Several series of novel artemisinin analogues (artemalogues) were designed and synthesized through 1,3-dipolar cycloaddition of artemisitene with nitrile oxides or nitrones. The isoxazolidine-containing spirobicyclic artemalogue 11b turns out to be the most potent with low micromolar IC₅₀ values against all three tumor cells, which were at least 4- to 14-fold more potent than the parent artemisinin. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
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Yomogin, an inhibitor of nitric oxide production in LPS-activated macrophages.
Ryu, J H; Lee, H J; Jeong, Y S; Ryu, S Y; Han, Y N
1998-08-01
In activated macrophages the inducible form of nitric oxide synthase (i-NOS) generates high amounts of toxic mediator, nitric oxide (NO) which contributes to the circulatory failure associated with septic shock. A sesquiterpene lactone compound (yomogin) isolated from medicinal plant Artemisia princeps Pampan inhibited the production of NO in LPS-activated RAW 264.7 cells by suppressing i-NOS enzyme expression. Thus, yomogin may be a useful candidate for the development of new drugs to treat endotoxemia and inflammation accompanied by the overproduction of NO.
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Toxicity of Crepis lacera in grazing ruminants.
Russo, Rosario; Restucci, Brunella; Vassallo, Antonio; Cortese, Laura; D'Ambola, Massimiliano; Montagnaro, Serena; Ciarcia, Roberto; Florio, Salvatore; De Tommasi, Nunziatina; Severino, Lorella
2018-03-07
Crepis lacera is a plant from the Asteraceae family that is common in the Mediterranean region. Farmers believe that this plant may be deadly to small ruminants in areas of southern Italy. However, scientific evidence is lacking, and no proof exists that C. lacera is toxic to ruminants. Necropsies conducted on four sheep revealed lesions in their livers and kidneys. In the current study, we described sheep poisoning and isolated secondary metabolites from Crepis lacera to assess the metabolites' biological activity both in vitro and in vivo. Phytochemical study of the aerial portions of Crepis lacera led to the isolation of five sesquiterpene lactones and two phenolic compounds. Cellular viability was evaluated in cell cultures of the bovine kidney cell line Madin Darby Bovine Kidney (MDBK) after incubation with phytochemicals. Our results showed that three sesquiterpene lactones, 8-epidesacylcynaropicrin-3-O-β-glucopyranoside (2), 8-epigrosheimin (3), and 8-β-hydroxydehydrozaluzanin C (4), were cytotoxic after 48 h of incubation. In addition, in the in vivo study, animals that received 1 mg/kg body weight (bw) of Crepis lacera extract and were then sacrificed after 48 h showed significant lesions in their liver, lungs and kidneys. These lesions were also found in rats that received 2 mg/kg bw of the same extract and sacrificed after 24 and 48 h. These results validate the hypothesis that C. lacera is potentially dangerous when ingested in large quantities by grazing small domestic ruminants. Further studies are necessary to clarify the molecular mechanisms of Crepis spp. toxicity in animals.
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Biochemical Conservation and Evolution of Germacrene A Oxidase in Asteraceae*
Nguyen, Don Trinh; Göpfert, Jens Christian; Ikezawa, Nobuhiro; MacNevin, Gillian; Kathiresan, Meena; Conrad, Jürgen; Spring, Otmar; Ro, Dae-Kyun
2010-01-01
Sesquiterpene lactones are characteristic natural products in Asteraceae, which constitutes ∼8% of all plant species. Despite their physiological and pharmaceutical importance, the biochemistry and evolution of sesquiterpene lactones remain unexplored. Here we show that germacrene A oxidase (GAO), evolutionarily conserved in all major subfamilies of Asteraceae, catalyzes three consecutive oxidations of germacrene A to yield germacrene A acid. Furthermore, it is also capable of oxidizing non-natural substrate amorphadiene. Co-expression of lettuce GAO with germacrene synthase in engineered yeast synthesized aberrant products, costic acids and ilicic acid, in an acidic condition. However, cultivation in a neutral condition allowed the de novo synthesis of a single novel compound that was identified as germacrene A acid by gas and liquid chromatography and NMR analyses. To trace the evolutionary lineage of GAO in Asteraceae, homologous genes were further isolated from the representative species of three major subfamilies of Asteraceae (sunflower, chicory, and costus from Asteroideae, Cichorioideae, and Carduoideae, respectively) and also from the phylogenetically basal species, Barnadesia spinosa, from Barnadesioideae. The recombinant GAOs from these genes clearly showed germacrene A oxidase activities, suggesting that GAO activity is widely conserved in Asteraceae including the basal lineage. All GAOs could catalyze the three-step oxidation of non-natural substrate amorphadiene to artemisinic acid, whereas amorphadiene oxidase diverged from GAO displayed negligible activity for germacrene A oxidation. The observed amorphadiene oxidase activity in GAOs suggests that the catalytic plasticity is embedded in ancestral GAO enzymes that may contribute to the chemical and catalytic diversity in nature. PMID:20351109
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Mkenda, Prisila; Mwanauta, Regina; Stevenson, Philip C.; Ndakidemi, Patrick; Mtei, Kelvin; Belmain, Steven R.
2015-01-01
Plants with pesticidal properties have been investigated for decades as alternatives to synthetics, but most progress has been shown in the laboratory. Consequently, research on pesticidal plants is failing to address gaps in our knowledge that constrain their uptake. Some of these gaps are their evaluation of their efficacy under field conditions, their economic viability and impact on beneficial organisms. Extracts made from four abundant weed species found in northern Tanzania, Tithonia diversifolia, Tephrosia vogelii, Vernonia amygdalina and Lippia javanica offered effective control of key pest species on common bean plants (Phaseolus vulgaris) that was comparable to the pyrethroid synthetic, Karate. The plant pesticide treatments had significantly lower effects on natural enemies (lady beetles and spiders). Plant pesticide treatments were more cost effective to use than the synthetic pesticide where the marginal rate of return for the synthetic was no different from the untreated control, around 4USD/ha, compared to a rate of return of around 5.50USD/ha for plant pesticide treatments. Chemical analysis confirmed the presence of known insecticidal compounds in water extracts of T. vogelii (the rotenoid deguelin) and T. diversifolia (the sesquiterpene lactone tagitinin A). Sesquiterpene lactones and the saponin vernonioside C were also identified in organic extracts of V. amygdalina but only the saponin was recorded in water extracts which are similar to those used in the field trial. Pesticidal plants were better able to facilitate ecosystem services whilst effectively managing pests. The labour costs of collecting and processing abundant plants near farm land were less than the cost of purchasing synthetic pesticides. PMID:26599609
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Mkenda, Prisila; Mwanauta, Regina; Stevenson, Philip C; Ndakidemi, Patrick; Mtei, Kelvin; Belmain, Steven R
2015-01-01
Plants with pesticidal properties have been investigated for decades as alternatives to synthetics, but most progress has been shown in the laboratory. Consequently, research on pesticidal plants is failing to address gaps in our knowledge that constrain their uptake. Some of these gaps are their evaluation of their efficacy under field conditions, their economic viability and impact on beneficial organisms. Extracts made from four abundant weed species found in northern Tanzania, Tithonia diversifolia, Tephrosia vogelii, Vernonia amygdalina and Lippia javanica offered effective control of key pest species on common bean plants (Phaseolus vulgaris) that was comparable to the pyrethroid synthetic, Karate. The plant pesticide treatments had significantly lower effects on natural enemies (lady beetles and spiders). Plant pesticide treatments were more cost effective to use than the synthetic pesticide where the marginal rate of return for the synthetic was no different from the untreated control, around 4USD/ha, compared to a rate of return of around 5.50USD/ha for plant pesticide treatments. Chemical analysis confirmed the presence of known insecticidal compounds in water extracts of T. vogelii (the rotenoid deguelin) and T. diversifolia (the sesquiterpene lactone tagitinin A). Sesquiterpene lactones and the saponin vernonioside C were also identified in organic extracts of V. amygdalina but only the saponin was recorded in water extracts which are similar to those used in the field trial. Pesticidal plants were better able to facilitate ecosystem services whilst effectively managing pests. The labour costs of collecting and processing abundant plants near farm land were less than the cost of purchasing synthetic pesticides.
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Balaich, Jared N.; Mathias, Derrick K.; Torto, Baldwyn; Jackson, Bryan T.; Tao, Dingyin; Ebrahimi, Babak; Tarimo, Brian B.; Cheseto, Xavier; Foster, Woodbridge A.
2016-01-01
Parthenin and parthenolide are natural products that are closely related in structure to artemisinin, which is also a sesquiterpene lactone (SQL) and one of the most important antimalarial drugs available. Parthenin, like artemisinin, has an effect on Plasmodium blood stage development. We extended the evaluation of parthenin as a potential therapeutic for the transmissible stages of Plasmodium falciparum as it transitions between human and mosquito, with the aim of gaining potential mechanistic insight into the inhibitory activity of this compound. We posited that if parthenin targets different biological pathways in the parasite, this in turn could pave the way for the development of druggable compounds that could prevent the spread of artemisinin-resistant parasites. We examined parthenin's effect on male gamete activation and the ookinete-to-oocyst transition in the mosquito as well as on stage V gametocytes that are present in peripheral blood. Parthenin arrested parasite development for each of the stages tested. The broad inhibitory properties of parthenin on the evaluated parasite stages may suggest different mechanisms of action between parthenin and artemisinin. Parthenin's cytotoxicity notwithstanding, its demonstrated activity in this study suggests that structurally related SQLs with a better safety profile deserve further exploration. We used our battery of assays to test parthenolide, which has a more compelling safety profile. Parthenolide demonstrated activity nearly identical to that of parthenin against P. falciparum, highlighting its potential as a possible transmission-blocking drug scaffold. We discuss the context of the evidence with respect to the next steps toward expanding the current antimalarial arsenal. PMID:26787692
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Balaich, Jared N; Mathias, Derrick K; Torto, Baldwyn; Jackson, Bryan T; Tao, Dingyin; Ebrahimi, Babak; Tarimo, Brian B; Cheseto, Xavier; Foster, Woodbridge A; Dinglasan, Rhoel R
2016-04-01
Parthenin and parthenolide are natural products that are closely related in structure to artemisinin, which is also a sesquiterpene lactone (SQL) and one of the most important antimalarial drugs available. Parthenin, like artemisinin, has an effect onPlasmodiumblood stage development. We extended the evaluation of parthenin as a potential therapeutic for the transmissible stages ofPlasmodium falciparumas it transitions between human and mosquito, with the aim of gaining potential mechanistic insight into the inhibitory activity of this compound. We posited that if parthenin targets different biological pathways in the parasite, this in turn could pave the way for the development of druggable compounds that could prevent the spread of artemisinin-resistant parasites. We examined parthenin's effect on male gamete activation and the ookinete-to-oocyst transition in the mosquito as well as on stage V gametocytes that are present in peripheral blood. Parthenin arrested parasite development for each of the stages tested. The broad inhibitory properties of parthenin on the evaluated parasite stages may suggest different mechanisms of action between parthenin and artemisinin. Parthenin's cytotoxicity notwithstanding, its demonstrated activity in this study suggests that structurally related SQLs with a better safety profile deserve further exploration. We used our battery of assays to test parthenolide, which has a more compelling safety profile. Parthenolide demonstrated activity nearly identical to that of parthenin againstP. falciparum, highlighting its potential as a possible transmission-blocking drug scaffold. We discuss the context of the evidence with respect to the next steps toward expanding the current antimalarial arsenal. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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Jones, Michael D; Avula, Bharathi; Wang, Yan-Hong; Lu, Lu; Zhao, Jianping; Avonto, Cristina; Isaac, Giorgis; Meeker, Larry; Yu, Kate; Legido-Quigley, Cristina; Smith, Norman; Khan, Ikhlas A
2014-10-17
Roman and German chamomile are widely used throughout the world. Chamomiles contain a wide variety of active constituents including sesquiterpene lactones. Various extraction techniques were performed on these two types of chamomile. A packed-column supercritical fluid chromatography-mass spectrometry method was designed for the identification of sesquiterpenes and other constituents from chamomile extracts with no derivatization step prior to analysis. Mass spectrometry detection was achieved by using electrospray ionization. All of the compounds of interest were separated within 15 min. The chamomile extracts were analyzed and compared for similarities and distinct differences. Multivariate statistical analysis including principal component analysis and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to differentiate between the chamomile samples. German chamomile samples confirmed the presence of cis- and trans-tonghaosu, chrysosplenols, apigenin diglucoside whereas Roman chamomile samples confirmed the presence of apigenin, nobilin, 1,10-epioxynobilin, and hydroxyisonobilin. Copyright © 2014 Elsevier B.V. All rights reserved.
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Gonzalez Ibarra, Alan Alexander; Wrobel, Kazimierz; Yanez Barrientos, Eunice; Corrales Escobosa, Alma Rosa; Gutierrez Corona, J. Felix; Enciso Donis, Israel
2017-01-01
The application of capHPLC-ESI-QTOF-MS and MS/MS to study the impact of Cr(VI) on metabolites profile in Helianthus annuus is reported. Germinated seeds were grown hydroponically in the presence of Cr(VI) (25 mgCr/L) and root extracts of the exposed and control plants were analyzed by untargeted metabolomic approach. The main goal was to detect which metabolite groups were mostly affected by Cr(VI) stress; two data analysis tools (ProfileAnalysis, Bruker, and online XCMS) were used under criteria of intensity threshold 5 · 104 cps, fold change ≥ 5, and p ≤ 0.01, yielding precursor ions. Molecular formulas were assigned based on data processing with two computational tools (SIRIUS and MS-Finder); annotation of candidate structures was performed by database search using CSI:FingerID and MS-Finder. Even though ultimate identification has not been achieved, it was demonstrated that secondary metabolism became activated under Cr(VI) stress. Among 42 candidate compounds returned from database search for seven molecular formulas, ten structures corresponded to isocoumarin derivatives and eleven were sesquiterpenes or sesquiterpene lactones; three benzofurans and four glycoside or pyrane derivatives of phenolic compounds were also suggested. To gain further insight on the effect of Cr(VI) in sunflower, isocoumarins and sesquiterpenes were selected as the target compounds for future study. PMID:29359067
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Toyang, Ngeh J.; Krause, Michael A.; Fairhurst, Rick M.; Tane, Pierre; Bryant, Joseph; Verpoorte, Rob
2013-01-01
Ethnopharmacological relevance Aqueous preparations of Vernonia guineensis Benth. (Asteraceae) are used in Cameroonian folk medicine as a general stimulant and to treat various illnesses and conditions including malaria, bacterial infections and helminthic infestations. Materials and methods 10-g samples of the leaf and tuber powders of V. guineensis were extracted separately using dichloromethane, methanol and distilled water. The extracts were dried in vacuo and used in bioassays. These extracts and three compounds previously isolated from V. guineensis [vernopicrin (1), vernomelitensin (2) and pentaisovalerylsucrose (3)] were screened for antiplasmodial activity against chloroquine (CQ)-sensitive (Hb3) and CQ-resistant (Dd2) Plasmodium falciparum lines. Results Crude extracts and pure compounds from V. guineensis showed antiplasmodial activity against both Hb3 and Dd2. The IC50 values of extracts ranged from 1.64 – 27.2 μg/ml for Hb3 and 1.82 – 30.0 μg/ml for Dd2; those for compounds 1, 2 and 3 ranged from 0.47 – 1.62 μg/ml (1364 – 1774 nM) for Hb3 and 0.57 – 1.50 μg/ml (1644 – 2332 nM) for Dd2. None of the crude extracts or pure compounds was observed to exert toxic effects on the erythrocytes used to cultivate the P. falciparum lines. Conclusion In Cameroonian folk medicine, V. guineensis may be used to treat malaria in part due to the antiplasmodial activity of sesquiterpene lactones (1, 2), a sucrose ester (3) and perhaps other compounds present in crude plant extracts. Exploring the safety and antiplasmodial efficacy of these compounds in vivo requires further study. PMID:23542146
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Nguyen, Trinh-Don; Faraldos, Juan A; Vardakou, Maria; Salmon, Melissa; O'Maille, Paul E; Ro, Dae-Kyun
2016-10-28
The Andes-endemic Barnadesioideae lineage is the oldest surviving and phylogenetically basal subfamily of the Asteraceae (Compositae), a prolific group of flowering plants with world-wide distribution (∼24,000 species) marked by a rich diversity of sesquiterpene lactones (STLs). Intriguingly, there is no evidence that members of the Barnadesioideae produce STLs, specialized metabolites thought to have contributed to the adaptive success of the Asteraceae family outside South America. The biosynthesis of STLs requires the intimate expression and functional integration of germacrene A synthase (GAS) and germacrene A oxidase (GAO) to sequentially cyclize and oxidize farnesyl diphosphate into the advanced intermediate germacrene A acid leading to diverse STLs. Our previous discovery of GAO activity conserved across all major subfamilies of Asteraceae, including the phylogenetically basal lineage of Barnadesioideae, prompted further investigation of the presence of the gateway GAS in Barnadesioideae. Herein we isolated two terpene synthases (BsGAS1/BsGAS2) from the basal Barnadesia spinosa (Barnadesioideae) that displayed robust GAS activity when reconstituted in yeast and characterized in vitro. Despite the apparent lack of STLs in the Barnadesioideae, this work unambiguously confirms the presence of GAS in the basal genera of the Asteraceae. Phylogenetic analysis reveals that the two BsGASs fall into two distinct clades of the Asteraceae's GASs, and BsGAS1 clade is only retained in the evolutionary closer Cichorioideae subfamily, implicating BsGAS2 is likely the ancestral base of most GASs found in the lineages outside the Barnadesioideae. Taken together, these results show the enzymatic capacities of GAS and GAO emerged prior to the subsequent radiation of STL-producing Asteraceae subfamilies. Copyright © 2016 Elsevier Inc. All rights reserved.
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Scotti, Marcus T; Emerenciano, Vicente; Ferreira, Marcelo J P; Scotti, Luciana; Stefani, Ricardo; da Silva, Marcelo S; Mendonça Junior, Francisco Jaime B
2012-04-20
The Asteraceae, one of the largest families among angiosperms, is chemically characterised by the production of sesquiterpene lactones (SLs). A total of 1,111 SLs, which were extracted from 658 species, 161 genera, 63 subtribes and 15 tribes of Asteraceae, were represented and registered in two dimensions in the SISTEMATX, an in-house software system, and were associated with their botanical sources. The respective 11 block of descriptors: Constitutional, Functional groups, BCUT, Atom-centred, 2D autocorrelations, Topological, Geometrical, RDF, 3D-MoRSE, GETAWAY and WHIM were used as input data to separate the botanical occurrences through self-organising maps. Maps that were generated with each descriptor divided the Asteraceae tribes, with total index values between 66.7% and 83.6%. The analysis of the results shows evident similarities among the Heliantheae, Helenieae and Eupatorieae tribes as well as between the Anthemideae and Inuleae tribes. Those observations are in agreement with systematic classifications that were proposed by Bremer, which use mainly morphological and molecular data, therefore chemical markers partially corroborate with these classifications. The results demonstrate that the atom-centred and RDF descriptors can be used as a tool for taxonomic classification in low hierarchical levels, such as tribes. Descriptors obtained through fragments or by the two-dimensional representation of the SL structures were sufficient to obtain significant results, and better results were not achieved by using descriptors derived from three-dimensional representations of SLs. Such models based on physico-chemical properties can project new design SLs, similar structures from literature or even unreported structures in two-dimensional chemical space. Therefore, the generated SOMs can predict the most probable tribe where a biologically active molecule can be found according Bremer classification.
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Unger, Christine; Kiss, Izabella; Vasas, Andrea; Lajter, Ildikó; Kramer, Nina; Atanasov, Atanas Georgiev; Nguyen, Chi Huu; Chatuphonprasert, Waranya; Brenner, Stefan; Krieger, Sigurd; McKinnon, Ruxandra; Peschel, Andrea; Kain, Renate; Saiko, Philipp; Szekeres, Thomas; Kenner, Lukas; Hassler, Melanie R; Diaz, Rene; Frisch, Richard; Dirsch, Verena M; Jäger, Walter; de Martin, Rainer; Bochkov, Valery N; Passreiter, Claus M; Peter-Vörösmarty, Barbara; Mader, Robert M; Grusch, Michael; Dolznig, Helmut; Kopp, Brigitte; Zupko, Istvan; Hohmann, Judit; Krupitza, Georg
2015-08-15
The t(2;5)(p23;q35) chromosomal translocation results in the expression of the fusion protein NPM/ALK that when expressed in T-lymphocytes gives rise to anaplastic large cell lymphomas (ALCL). In search of new therapy options the dichloromethane extract of the ethnomedicinal plant Neurolaena lobata (L.) R.Br. ex Cass was shown to inhibit NPM/ALK expression. Therefore, we analysed whether the active principles that were recently isolated and found to inhibit inflammatory responses specifically inhibit growth of NPM/ALK+ ALCL, leukaemia and breast cancer cells, but not of normal cells, and the intravasation through the lymphendothelial barrier. ALCL, leukaemia and breast cancer cells, and normal peripheral blood mononuclear cells (PBMCs) were treated with isolated sesquiterpene lactones and analysed for cell cycle progression, proliferation, mitochondrial activity, apoptosis, protein and mRNA expression, NF-κB and cytochrome P450 activity, 12(S)-HETE production and lymphendothelial intravasation. In vitro treatment of ALCL by neurolenin B suppressed NPM/ALK, JunB and PDGF-Rβ expression, inhibited the growth of ALCL cells late in M phase, and induced apoptosis via caspase 3 without compromising mitochondrial activity (as a measure of general exogenic toxicity). Moreover, neurolenin B attenuated tumour spheroid intravasation probably through inhibition of NF-κB and CYP1A1. Neurolenin B specifically decreased pro-carcinogenic NPM/ALK expression in ALK+ ALCL cells and, via the inhibition of NF-kB signalling, attenuated tumour intra/extravasation into the lymphatics. Hence, neurolenin B may open new options to treat ALCL and to manage early metastatic processes to which no other therapies exist. Copyright © 2015 Elsevier GmbH. All rights reserved.
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Avula, Bharathi; Sagi, Satyanarayanaraju; Gafner, Stefan; Upton, Roy; Wang, Yan-Hong; Wang, Mei; Khan, Ikhlas A
2015-10-01
Ginkgo biloba is one of the most widely sold herbal supplements and medicines in the world. Its popularity stems from having a positive effect on memory and the circulatory system in clinical studies. As ginkgo popularity increased, non-proprietary extracts were introduced claiming to have a similar phytochemical profile as the clinically tested extracts. The standardized commercial extracts of G. biloba leaf used in ginkgo supplements contain not less than 6% sesquiterpene lactones and 24% flavonol glycosides. While sesquiterpene lactones are unique constituents of ginkgo leaf, the flavonol glycosides are found in many other botanical extracts. Being a high value botanical, low quality ginkgo extracts may be subjected to adulteration with flavonoids to meet the requirement of 24% flavonol glycosides. Chemical analysis by ultra high performance liquid chromatography-mass spectrometry revealed that adulteration of ginkgo leaf extracts in many of these products is common, the naturally flavonol glycoside-rich extract being spiked with pure flavonoids or extracts made from another flavonoid-rich material, such as the fruit/flower of Japanese sophora (Styphnolobium japonicum), which also contains the isoflavone genistein. Recently, genistein has been proposed as an analytical marker for the detection of adulteration of ginkgo extracts with S. japonicum. This study confirms that botanically authenticated G. biloba leaf and extracts made therefrom do not contain genistein, and the presence of which even in trace amounts is suggestive of adulteration. In addition to the mass spectrometric approach, a high performance thin layer chromatography method was developed as a fast and economic method for chemical fingerprint analysis of ginkgo samples.
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Abu-Reidah, I M; Contreras, M M; Arráez-Román, D; Segura-Carretero, A; Fernández-Gutiérrez, A
2013-10-25
Lettuce (Lactuca sativa), a leafy vegetal widely consumed worldwide, fresh cut or minimally processed, constitutes a major dietary source of natural antioxidants and bioactive compounds. In this study, reversed-phase ultra-high-performance liquid chromatography (RP-UHPLC) coupled to electrospray ionization-quadrupole-time-of-flight mass spectrometry (ESI-QTOF-MS) was applied for the comprehensive profiling of polar and semi-polar metabolites from three lettuce cultivars (baby, romaine, and iceberg). The UHPLC systems allowed the use of a small-particle-size C18 column (1.8 μm), with very fine resolution for the separation of up to seven isomers, and the QTOF mass analyzer enabled sensitive detection with high mass resolution and accuracy in full scan. Thus, a total of 171 compounds were tentatively identified by matching their accurate mass signals and suggested molecular formula with those previously reported in family Asteraceae. Afterwards, their structures were also corroborated by the MS/MS data provided by the QTOF analyzer. Well-known amino acids, organic acids, sesquiterpene lactones, phenolic acids and flavonoids were characterized, e.g. lactucin, lactucopicrin, caftaric acid, chlorogenic acid, caffeoylmalic acid, chicoric acid, isochlorogenic acid A, luteolin, and quercetin glycosides. For this plant species, this is the first available report of several isomeric forms of the latter polyphenols and other types of components such as nucleosides, peptides, and tryptophan-derived alkaloids. Remarkably, 10 novel structures formed by the conjugation of known amino acids and sesquiterpene lactones were also proposed. Thus, the methodology applied is a useful option to develop an exhaustive metabolic profiling of plants that helps to explain their potential biological activities and folk uses. Copyright © 2013 Elsevier B.V. All rights reserved.
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Bioherbicidal activity of a germacranolide sesquiterpene dilactone from Ambrosia artemisiifolia L.
Molinaro, Francesco; Monterumici, Chiara Mozzetti; Ferrero, Aldo; Tabasso, Silvia; Negre, Michèle
2016-12-01
Ambrosia artemisiifolia L. (common ragweed) is an invasive plant whose allelopathic properties have been suggested by its field behaviour and demonstrated through phytotoxicity bioassays. However, the nature of the molecules responsible for the allelopathic activity of common ragweed has not been explored. The main objective of this study was to identify the phytotoxic molecules produced by A. artemisiifolia. A preliminary investigation has indicated that a methanol extract of A. artemisiifolia completely inhibited the germination of cress and radish. Semi-preparative fractionation of the methanol extract allowed separating of phytotoxic fraction which contained a single compound. The structure of this compound was elucidated by liquid chromatography-mass spectrometry (LC-MS)/MS, high-resolution mass spectral, nuclear magnetic resonance, and Fourier transform infrared spectra as sesquiterpene lactone isabelin (C 15 H 16 O 4 ). The effect of pure isabelin was tested on four different weed species, confirming the inhibitory activity of molecule. The results indicate directions for the future studies about herbicidal specific activity of isabelin, as pure molecule or in the crude extract, as a potential candidate for biological weed control.
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Some wild-growing plant species from Serbia and Montenegro as the potential sources of drugs.
Aljancić, I S; Vajs, V E; Tesević, V V; Milosavljević, S M
2008-01-01
The results of phytochemical investigation, over the last decade, of some wild-growing plant species from Serbia and Montenegro belonging to the families Asteraceae, Guttiferae and Gentianaceae are reported. Most of the investigated species are endemites and the emphasis in this report is on those exhibiting biological activities that could be regarded as the potential sources of drugs. This review comprises 154 compounds, e.g. sesquiterpene lactones and flavonoids (Asteraceae), xanthones, secoiridoids and C-glucoflavonoids (Gentanaceae) and prenylated phloroglucinols (Guttiferae) as well as some other secondary metabolites, produced by the above families, which could be of pharmacological interest.
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Cho, J Y; Park, J; Kim, P S; Yoo, E S; Baik, K U; Park, M H
2001-02-01
Two lignans were isolated from the heartwood of Pterocarpus santalinus by activity-guided fractionation and investigated for their biological properties and molecular mechanism of action. On the basis of their spectroscopic data, these compounds were identified as savinin (1) and calocedrin (2), dibenzyl butyrolactone-type lignan compounds having an alpha-arylidene gamma-lactone structure. These lignans significantly inhibited tumor necrosis factor (TNF)-a production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and T cell proliferation elicited by concanavalin (Con A), without displaying cytotoxicity. The molecular inhibitory mechanism of compound 1 was confirmed to be mediated by the non-polar butyrolactone ring, according to a structure-relationship study with structurally related and unrelated compounds, such as arctigenin (a dibenzyl butyrolactone type lignan), eudesmin (a furofuran type lignan), isolariciresinol (a dibenzylbutane type lignan), and cynaropicrin (a sesquiterpene lactone). The results suggest that savinin may act as an active principle in the reported biological activities of P. santalinus, such as antiinflammatory effect, by mediation of the butyrolactone ring as a valuable pharmacophore.
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Effect of guaianolides in the meiosis reinitiation of amphibian oocytes.
Zapata-Martínez, J; Sánchez-Toranzo, G; Chaín, F; Catalán, C A N; Bühler, M I
2017-02-01
Sesquiterpene lactones (STLs) are a large and structurally diverse group of plant metabolites generally found in the Asteraceae family. STLs exhibit a wide spectrum of biological activities and it is generally accepted that their major mechanism of action is the alkylation of the thiol groups of biological molecules. The guaianolides is one of various groups of STLs. Anti-tumour and anti-migraine effects, an allergenic agent, an inhibitor of smooth muscle cells and of meristematic cell proliferation are only a few of the most commonly reported activities of STLs. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under stimulus with progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. There are previous records of the inhibitory effect of dehydroleucodin (DhL), a guaianolide lactone, on the progression of meiosis. It has been also shown that DhL and its 11,13-dihydroderivative (2H-DhL; a mixture of epimers at C-11) act as blockers of the resumption of meiosis in fully grown ovarian oocytes from the amphibian Rhinella arenarum (formerly classified as Bufo arenarum). The aim of this study was to analyze the effect of four closely related guaianolides, i.e., DhL, achillin, desacetoxymatricarin and estafietin as possible inhibitors of meiosis in oocytes of amphibians in vitro and discuss some structure-activity relationships. It was found that the inhibitory effect on meiosis resumption is greater when the lactone has two potentially reactive centres, either a α,β-α',β'-diunsaturated cyclopentanone moiety or an epoxide group plus an exo-methylene-γ-lactone function.
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Becker, John V W; van der Merwe, Marina M; van Brummelen, Anna C; Pillay, Pamisha; Crampton, Bridget G; Mmutlane, Edwin M; Parkinson, Chris; van Heerden, Fanie R; Crouch, Neil R; Smith, Peter J; Mancama, Dalu T; Maharaj, Vinesh J
2011-10-11
Anti-malarial drug resistance threatens to undermine efforts to eliminate this deadly disease. The resulting omnipresent requirement for drugs with novel modes of action prompted a national consortium initiative to discover new anti-plasmodial agents from South African medicinal plants. One of the plants selected for investigation was Dicoma anomala subsp. gerrardii, based on its ethnomedicinal profile. Standard phytochemical analysis techniques, including solvent-solvent extraction, thin-layer- and column chromatography, were used to isolate the main active constituent of Dicoma anomala subsp. gerrardii. The crystallized pure compound was identified using nuclear magnetic resonance spectroscopy, mass spectrometry and X-ray crystallography. The compound was tested in vitro on Plasmodium falciparum cultures using the parasite lactate dehydrogenase (pLDH) assay and was found to have anti-malarial activity. To determine the functional groups responsible for the activity, a small collection of synthetic analogues was generated - the aim being to vary features proposed as likely to be related to the anti-malarial activity and to quantify the effect of the modifications in vitro using the pLDH assay. The effects of the pure compound on the P. falciparum transcriptome were subsequently investigated by treating ring-stage parasites (alongside untreated controls), followed by oligonucleotide microarray- and data analysis. The main active constituent was identified as dehydrobrachylaenolide, a eudesmanolide-type sesquiterpene lactone. The compound demonstrated an in vitro IC50 of 1.865 μM against a chloroquine-sensitive strain (D10) of P. falciparum. Synthetic analogues of the compound confirmed an absolute requirement that the α-methylene lactone be present in the eudesmanolide before significant anti-malarial activity was observed. This feature is absent in the artemisinins and suggests a different mode of action. Microarray data analysis identified 572 unique genes that were differentially expressed as a result of the treatment and gene ontology analysis identified various biological processes and molecular functions that were significantly affected. Comparison of the dehydrobrachylaenolide treatment transcriptional dataset with a published artesunate (also a sesquiterpene lactone) dataset revealed little overlap. These results strengthen the notion that the isolated compound and the artemisinins have differentiated modes of action. The novel mode of action of dehydrobrachylaenolide, detected during these studies, will play an ongoing role in advancing anti-plasmodial drug discovery efforts.
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Prevalence of contact allergy in the general population in different European regions.
Diepgen, T L; Ofenloch, R F; Bruze, M; Bertuccio, P; Cazzaniga, S; Coenraads, P-J; Elsner, P; Goncalo, M; Svensson, Å; Naldi, L
2016-02-01
Population-based studies about contact allergy are scarce. To obtain reliable estimates of the prevalence of contact allergy in the general population in Europe. A cross-sectional study of a random sample from the general population, aged 18-74 years, in five different European countries (Sweden, the Netherlands, Germany, Italy and Portugal). In total, 12 377 subjects were interviewed and a random sample (n = 3119) patch tested to TRUE Test panels 1-3 and Fragrance Mix (FM) II, hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) and sesquiterpene lactone mix. A positive patch test reaction is considered as contact allergy. In total, 27·0% [95% confidence interval (CI) 25·5-28·5] had at least one positive reaction to an allergen of the European baseline series, with a significantly higher prevalence in women than in men. The highest age-standardized prevalences (≥ 1%) were found for nickel (14·5%, 95% CI 13·2-15·8), thiomersal (5·0%, 95% CI 4·2-5·8), cobalt (2·2%, 95% CI 1·7-2·7), FM II (1·9%, 95% CI 1·5-2·5), FM I (1·8%, 95% CI 1·4-2·3), HICC (1·4%, 95% CI 1·0-1·9), p-tert-butylphenol formaldehyde resin (1·3%, 95% CI 0·9-1·7) and para-phenylenediamine (1·0%, 95% CI 0·6-1·3). Only nickel and thiomersal showed a statistically significantly different prevalence for contact allergy among the different European populations. Subjects reporting contact dermatitis in their lifetime (age-standardized prevalence 15·1%, 95% CI 13·8-16·3) had an increased risk for contact allergy (odds ratio 1·9, 95% CI 1·5-2·5). The risk of having a contact allergy was not increased in those with atopic dermatitis (prevalence 7·6%, 95% CI 6·7-8·6; odds ratio 1·0, 95% CI 0·7-1·4). Contact allergy to at least one allergen of the European baseline series was diagnosed in more than one-quarter of the general European population. Therefore measures to improve the primary prevention of contact allergy have to be enforced. © 2015 British Association of Dermatologists.
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HPLC analysis and cytotoxic activity of Vernonia cinerea.
Khay, Mom; Toeng, Phirom; Mahiou-Leddet, Valérie; Mabrouki, Fathi; Sothea, Kim; Ollivier, Evelyne; Elias, Riad; Bun, Sok-Siya
2012-10-01
The extracts of five Cambodian medicinal plants (Aganosma marginata, Dracaena cambodiana, Harrisonia perforata, Hymenodictyon excelsum and Vernonia cinerea) were evaluated in vitro for their cytotoxic activity against HT29 colon adenocarcinoma cells and HepG2 hepatoma cells, using the MTT assay. Among these five plants, Vernonia cinerea displayed potent cytotoxicity. One main sesquiterpene lactone, 8alpha-tigloyloxy-hirsutinolide-13-O-acetate was isolated from the whole plant of V. cinerea. This compound was active against both cancer cell lines (IC50 = 3.50 microM for HT29 and IC50 = 4.27 microM for HepG2). To quantify this compound in the plant, an analytical high-performance liquid chromatography (HPLC) method was developed and validated.
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2012-01-01
Background Numerous studies have demonstrated that autophagy plays a vital role in maintaining cellular homeostasis. Interestingly, several anticancer agents were found to exert their anticancer effects by triggering autophagy. Emerging data suggest that autophagy represents a novel mechanism that can be exploited for therapeutic benefit. Pharmacologically active natural compounds such as those from marine, terrestrial plants and animals represent a promising resource for novel anticancer drugs. There are several prominent examples from the past proving the success of natural products and derivatives exhibiting anticancer activity. Helenalin, a sesquiterpene lactone has been demonstrated to have potent anti-inflammatory and antitumor activity. Albeit previous studies demonstrating helenalin’s multi modal action on cellular proliferative and apoptosis, the mechanisms underlying its action are largely unexplained. Methods To deduce the mechanistic action of helenalin, cancer cells were treated with the drug at various concentrations and time intervals. Using western blot, FACS analysis, overexpression and knockdown studies, cellular signaling pathways were interrogated focusing on apoptosis and autophagy markers. Results We show here that helenalin induces sub-G1 arrest, apoptosis, caspase cleavage and increases the levels of the autophagic markers. Suppression of caspase cleavage by the pan caspase inhibitor, Z-VAD-fmk, suppressed induction of LC3-B and Atg12 and reduced autophagic cell death, indicating caspase activity was essential for autophagic cell death induced by helenalin. Additionally, helenalin suppressed NF-κB p65 expression in a dose and time dependent manner. Exogenous overexpression of p65 was accompanied by reduced levels of cell death whereas siRNA mediated suppression led to augmented levels of caspase cleavage, autophagic cell death markers and increased cell death. Conclusions Taken together, these results show that helenalin mediated autophagic cell death entails inhibition of NF-κB p65, thus providing a promising approach for the treatment of cancers with aberrant activation of the NF-κB pathway. PMID:22784363
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Feng, Jia-Hua; Nakagawa-Goto, Kyoko; Lee, Kuo-Hsiung; Shyur, Lie-Fen
2016-06-01
Acquired resistance to vemurafenib develops through reactivation of RAF/MEK/ERK signaling or bypass mechanisms. Recent combination therapies such as a MEK inhibitor combined with vemurafenib show improvement in major clinical end points, but the percentage of patients with adverse toxic events is higher than with vemurafenib monotherapy and most patients ultimately relapse. Therefore, there is an urgent need to develop new antimelanoma drugs and/or adjuvant agents for vemurafenib therapy. In this study, we created a novel semiorganically modified derivative, DETD-35, from deoxyelephantopin (DET), a plant sesquiterpene lactone demonstrated as an anti-inflammatory and anti-mammary tumor agent. Our results show that DETD-35 inhibited proliferation of a panel of melanoma cell lines, including acquired vemurafenib resistance A375 cells (A375-R) established in this study, with superior activities to DET and no cytotoxicity to normal melanocytes. DETD-35 suppressed tumor growth and reduced tumor mass as effectively as vemurafenib in A375 xenograft study. Furthermore, DETD-35 also reduced tumor growth in both acquired (A375-R) and intrinsic (A2058) vemurafenib resistance xenograft models, where vemurafenib showed no antitumor activity. Notably, the combination of DETD-35 and vemurafenib exhibited the most significant effects in both in vitro and in vivo xenograft studies due to synergism of the compound and the drug. Mechanistic studies suggested that DETD-35 overcame acquired vemurafenib resistance at least in part through deregulating MEK-ERK, Akt, and STAT3 signaling pathways and promoting apoptosis of cancer cells. Overall, our results suggest that DETD-35 may be useful as a therapeutic or adjuvant agent against BRAF(V600E) mutant and acquired vemurafenib resistance melanoma. Mol Cancer Ther; 15(6); 1163-76. ©2016 AACR. ©2016 American Association for Cancer Research.
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Neutron Diffraction Structure of Melampodin: Its Role in the Reclassification of the Germacranolides
Watkins, Steven F.; Fischer, Nikolaus H.; Bernal, Ivan
1973-01-01
The precise crystal and molecular structure of melampodin, C21H24O9, was determined from three-dimensional neutron diffraction data collected by counter techniques and phases by direct statistical methods. Crystals are orthorhombic, P212121, a = 8,990(9), b = 14.352(14), c = 16.294(16) Å, V = 2102 Å3, d(calc.) = 1.328 g·cm-3, Z = 4 molecules per unit cell. The structural model was refined by full matrix least-squares of 2303 observed independent reflections, with all 54 atoms treated anisotropically, to R(F) = 5.0%. Hydrogen bonds link melampodin molecules together in the solid state. The conformation of the cyclodeca-1,5-diene ring is such that one intraannular hydrogen atom interacts strongly with one double bond, but there is little or no transannular interaction between double bonds. Strain in the ten-membered ring and in the trans-fused lactone ring is discussed, as are chemical implications of the unsymmetric epoxide in the epoxyangelic acid side chain. The previously suggested reclassification of germacranolide sesquiterpene lactones into four subgroups is supported, and a new convention for configurational representations of the four subgroups is proposed. PMID:16592106
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Pagán, Oné R; Baker, Debra; Deats, Sean; Montgomery, Erica; Tenaglia, Matthew; Randolph, Clinita; Kotturu, Dharini; Tallarida, Christopher; Bach, Daniel; Wilk, Galia; Rawls, Scott; Raffa, Robert B
2012-01-01
Planarians are traditional animal models in developmental and regeneration biology. Recently, these organisms are arising as vertebrate-relevant animal models in neuropharmacology. Using an adaptation of published behavioral protocols, we have described the alleviation of cocaine-induced planarian seizure-like movements (pSLM) by a naturally-occurring sesquiterpene lactone, parthenolide. Interestingly, parthenolide does not prevent the expression of pSLM induced by amphetamines; in vertebrates, amphetamines interact with the same protein target as cocaine. Parthenolide is also unable to prevent pSLM elicited by the cholinergic com-pounds nicotine and cytisine or by the glutamatergic agents L- or D- glutamic acid or NMDA. Thus, we conclude that parthenolide is a specific anti-cocaine agent in this experimental organism.
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Atrrog, Abubaker A B; Natić, Maja; Tosti, Tomislav; Milojković-Opsenica, Dusanka; Dordević, Iris; Tesević, Vele; Jadranin, Milka; Milosavljević, Slobodan; Lazić, Milan; Radulović, Sinisa; Tesić, Zivoslav
2009-03-01
In this study 10 guaianolide-type sesquiterpene gamma-lactones named amphoricarpolides, isolated from the aerial parts of two endemic subspecies of Amphoricarpos neumayeri (ssp. neumayeri and ssp. murbeckii Bosnjak), were investigated by means of reversed-phase thin-layer chromatography. Methanol-water and tetrahydrofuran-water binary mixtures were used as mobile phase in order to determine lipophilicity parameters R (0) (M) and C(0). Some of the investigated compounds were screened for their cytotoxic activity against HeLa and B16 cells. Chromatographically obtained lipophilicity parameters were correlated with calculated logP values and IC(50) values. Principal component analysis identified the dominant pattern in the chromatographically obtained data. 2008 John Wiley & Sons, Ltd.
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Irmisch, Sandra; Krause, Sandra T; Kunert, Grit; Gershenzon, Jonathan; Degenhardt, Jörg; Köllner, Tobias G
2012-06-08
The essential oil of chamomile, one of the oldest and agronomically most important medicinal plant species in Europe, has significant antiphlogistic, spasmolytic and antimicrobial activities. It is rich in chamazulene, a pharmaceutically active compound spontaneously formed during steam distillation from the sesquiterpene lactone matricine. Chamomile oil also contains sesquiterpene alcohols and hydrocarbons which are produced by the action of terpene synthases (TPS), the key enzymes in constructing terpene carbon skeletons. Here, we present the identification and characterization of five TPS enzymes contributing to terpene biosynthesis in chamomile (Matricaria recutita). Four of these enzymes were exclusively expressed in above-ground organs and produced the common terpene hydrocarbons (-)-(E)-β-caryophyllene (MrTPS1), (+)-germacrene A (MrTPS3), (E)-β-ocimene (MrTPS4) and (-)-germacrene D (MrTPS5). A fifth TPS, the multiproduct enzyme MrTPS2, was mainly expressed in roots and formed several Asteraceae-specific tricyclic sesquiterpenes with (-)-α-isocomene being the major product. The TPS transcript accumulation patterns in different organs of chamomile were consistent with the abundance of the corresponding TPS products isolated from these organs suggesting that the spatial regulation of TPS gene expression qualitatively contribute to terpene composition. The terpene synthases characterized in this study are involved in the organ-specific formation of essential oils in chamomile. While the products of MrTPS1, MrTPS2, MrTPS4 and MrTPS5 accumulate in the oils without further chemical alterations, (+)-germacrene A produced by MrTPS3 accumulates only in trace amounts, indicating that it is converted into another compound like matricine. Thus, MrTPS3, but also the other TPS genes, are good markers for further breeding of chamomile cultivars rich in pharmaceutically active essential oils.
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Sánchez Toranzo, G; López, L A; Martínez, J Zapata; Bühler, M C Gramajo; Bühler, M I
2010-02-01
Dehydroleucodine (DhL), a sesquiterpenic lactone, was isolated and purified from aerial parts of Artemisia douglasiana Besser, a medicinal herb used in Argentina. DhL is an alpha-methylene butyro-gamma-lactone ring connected to a seven-membered ring fused to an exocyclic alpha,beta-unsaturated cyclopentenone ring. It has been previously shown that DhL selectively induces a dose-dependent transient arrest in G2 of both meristematic cells and vascular smooth muscle cells. Treatment with DhL induces an inhibition of spontaneous and progesterone-induced maturation in a dose-dependent manner in Bufo arenarum fully grown oocytes arrested at G2, at the beginning of meiosis I. However, the nature of the mechanisms involved in the process is still unknown. The aim of this work was to analyse whether DhL's alpha-methylene-gamma-lactone function is responsible for the inhibition effect on meiosis reinitiation of Bufo arenarum oocytes as well as some of the transduction pathways that could be involved in this effect using a derivative of DhL inactivated for alpha-methylenelactone, the 11,13-dihydro-dehydroleucodine (2H-DhL). The use of 2H-DhL in the maturation promoting factor (MPF) amplification experiments by injection of both cytoplasm with active MPF and of germinal vesicle content showed results similar to the ones obtained with DhL, suggesting that the hydrogenated derivative would act in a similar way to DhL. Pretreatment with DhL or 2H-DhL did not affect the percentage of germinal vesicle breakdown (GVBD) induced by H89, a protein kinase A (PKA) inhibitor, which suggests that these lactones would act on another step of the signalling pathway that induces MPF activation. The fact that both DhL and 2H-Dhl inhibit GVBD induced by okadaic acid microinjection suggests that they could act on the activity of the Myt1 kinase. This idea is supported by the experiments of injection of GV contents in which an inhibitory effect of these lactones on GVBD was also observed. Our results indicate that the inhibitory effect on meiosis progression of DhL does not depend only on the activity of the alpha-methylenelactone function, as its hydrogenated derivative, 2H-DhL, in which this function has been inactivated, causes similar effects on amphibian oocytes. However, 2H-DhL was less active than DhL as higher doses were required to obtain a significant inhibition. On the other hand, the analysis of the participation of certain mediators in some of the signalling pathways leading to MPF activation suggests that the Myt1 kinase could be a target of these lactones, while cdc25 phosphatase would not be affected. Besides, the PKA inhibition assays indicate that these lactones would act earlier in the signalling pathways.
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Diepgen, T L; Ofenloch, R; Bruze, M; Cazzaniga, S; Coenraads, P J; Elsner, P; Goncalo, M; Svensson, Å; Naldi, L
2015-12-01
Contact allergy to fragrances is assessed mostly in clinical populations of patients. Studies in the general population are scarce and vary in their methodology across countries. To determine the prevalence of fragrance contact allergy in the European general population and to assess the clinical relevance of positive patch test reactions to different fragrances. In five European countries (Germany, Italy, the Netherlands, Portugal and Sweden) a random sample from the general population aged 18-74 years was drawn. In total, 12 377 subjects were interviewed in this cross-sectional study and a random sample (n = 3119) was patch tested using the TRUE Test and Finn Chamber techniques. Patch test procedures were harmonized by mandatory training before the study and monitoring during the study. The highest prevalence for contact allergy of 2·6% [95% confidence interval (CI) 2·1-3·2] was found for fragrance mix (FM) I in petrolatum, with a high content of atranol and chloratranol, followed by 1·9% (95% CI 1·5-2·4) for FM II in petrolatum. The conservatively estimated prevalence of fragrance contact allergy was 1·9% (95% CI 1·5-2·5). This is defined as the existence of a positive patch test to FM I or FM II; any of their individual materials; Myroxylon pereirae; sesquiterpene lactones or 3- and 4-hydroxyisohexyl 3-cyclohexene carboxaldehyde that show clinical relevance, defined conservatively as lifetime avoidance of scented products and an itchy skin rash lasting > 3 days in a lifetime. Using the reported lifetime prevalence of any contact dermatitis instead of the lifetime prevalence of any itchy skin rash, the prevalence is 0·8% (95% CI 0·5-1·2). The prevalence rates of contact allergy to fragrances in women are about twice those in men. This study helps to identify targets for prevention of fragrance allergy. © 2015 British Association of Dermatologists.
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Crook, Damon J; Francese, Joseph A; Rietz, Michael L; Lance, David R; Hull-Sanders, Helen M; Mastro, Victor C; Silk, Peter J; Ryall, Krista L
2014-08-01
The emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), is a serious invasive pest of North American ash (Fraxinus spp.) that has caused devastating mortality since it was first identified in North America in 2002. In 2012, we conducted field trapping assays that tested the efficacy of purple prism and fluon-coated green multifunnel (Lindgren funnel) traps. Traps were baited with combinations of several lures that were previously shown to be attractive to A. planipennis: manuka oil--a sesquiterpene-rich oil, (3Z)-hexenol--a green leaf volatile, or (3Z)-dodecen-12-olide [= (3Z)-lactone], a sex pheromone. Eighty-nine blocks (trap lines) were tested throughout nine states along the outer edges of the currently known A. planipennis infestation in North America. Trap catch was highest on fluon-coated green multifunnel traps, and trap detections at sites with low A. planipennis population density ranged from 72 to 76% for all trap and lure types tested. (3Z)-hexenol and (3Z)-lactone baited traps functioned as well as (3Z)-hexenol and manuka oil-baited traps. Independent of the lure used, detection rates on green fluon-coated multifunnel traps were comparable with glued purple prism traps in areas with low A. planipennis population densities.
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Mousa, Walaa Kamel; Schwan, Adrian L; Raizada, Manish N
2016-09-03
Finger millet is an ancient African-Indian crop that is resistant to many pathogens including the fungus, Fusarium graminearum. We previously reported the first isolation of putative fungal endophytes from finger millet and showed that the crude extracts of four strains had anti-Fusarium activity. However, active compounds were isolated from only one strain. The objectives of this study were to confirm the endophytic lifestyle of the three remaining anti-Fusarium isolates, to identify the major underlying antifungal compounds, and to initially characterize the mode(s) of action of each compound. Results of confocal microscopy and a plant disease assay were consistent with the three fungal strains behaving as endophytes. Using bio-assay guided fractionation and spectroscopic structural elucidation, three anti-Fusarium secondary metabolites were purified and characterized. These molecules were not previously reported to derive from fungi nor have antifungal activity. The purified antifungal compounds were: 5-hydroxy 2(3H)-benzofuranone, dehydrocostus lactone (guaianolide sesquiterpene lactone), and harpagoside (an iridoide glycoside). Light microscopy and vitality staining were used to visualize the in vitro interactions between each compound and Fusarium; the results suggested a mixed fungicidal/fungistatic mode of action. We conclude that finger millet possesses fungal endophytes that can synthesize anti-fungal compounds not previously reported as bio-fungicides against F. graminearum.
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Screening and HPLC-Based Activity Profiling for New Antiprotozoal Leads from European Plants.
Zimmermann, Stefanie; Thomi, Semira; Kaiser, Marcel; Hamburger, Matthias; Adams, Michael
2012-01-01
Based on a survey of remedies used in Renaissance Europe to treat malaria, we prepared and screened a library of 254 extracts from 61 plants for antiplasmodial activity in vitro. HPLC-based activity profiling was performed for targeted identification of active constituents in extracts. One of the most remarkable results was the identification of onopordopicrin, a germacranolide sesquiterpene lactone isolated from Arctium nemorosum as a potent inhibitor of P. falciparum with an IC(50) of 6.9 μM. It was tested similarly against Trypanosoma brucei rhodesiense, the parasite which causes African sleeping sickness. With an IC(50) of 0.37 μM, onopordopicrin was one of the most potent natural products reported so far. Cytotoxicity was determined against rat myoblast L6 cells (IC(50): 3.06).
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Screening and HPLC-Based Activity Profiling for New Antiprotozoal Leads from European Plants
Zimmermann, Stefanie; Thomi, Semira; Kaiser, Marcel; Hamburger, Matthias; Adams, Michael
2012-01-01
Based on a survey of remedies used in Renaissance Europe to treat malaria, we prepared and screened a library of 254 extracts from 61 plants for antiplasmodial activity in vitro. HPLC-based activity profiling was performed for targeted identification of active constituents in extracts. One of the most remarkable results was the identification of onopordopicrin, a germacranolide sesquiterpene lactone isolated from Arctium nemorosum as a potent inhibitor of P. falciparum with an IC50 of 6.9 μM. It was tested similarly against Trypanosoma brucei rhodesiense, the parasite which causes African sleeping sickness. With an IC50 of 0.37 μM, onopordopicrin was one of the most potent natural products reported so far. Cytotoxicity was determined against rat myoblast L6 cells (IC50: 3.06). PMID:22396915
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Chemometrics-based Approach in Analysis of Arnicae flos
Zheleva-Dimitrova, Dimitrina Zh.; Balabanova, Vessela; Gevrenova, Reneta; Doichinova, Irini; Vitkova, Antonina
2015-01-01
Introduction: Arnica montana flowers have a long history as herbal medicines for external use on injuries and rheumatic complaints. Objective: To investigate Arnicae flos of cultivated accessions from Bulgaria, Poland, Germany, Finland, and Pharmacy store for phenolic derivatives and sesquiterpene lactones (STLs). Materials and Methods: Samples of Arnica from nine origins were prepared by ultrasound-assisted extraction with 80% methanol for phenolic compounds analysis. Subsequent reverse-phase high-performance liquid chromatography (HPLC) separation of the analytes was performed using gradient elution and ultraviolet detection at 280 and 310 nm (phenolic acids), and 360 nm (flavonoids). Total STLs were determined in chloroform extracts by solid-phase extraction-HPLC at 225 nm. The HPLC generated chromatographic data were analyzed using principal component analysis (PCA) and hierarchical clustering (HC). Results: The highest total amount of phenolic acids was found in the sample from Botanical Garden at Joensuu University, Finland (2.36 mg/g dw). Astragalin, isoquercitrin, and isorhamnetin 3-glucoside were the main flavonol glycosides being present up to 3.37 mg/g (astragalin). Three well-defined clusters were distinguished by PCA and HC. Cluster C1 comprised of the German and Finnish accessions characterized by the highest content of flavonols. Cluster C2 included the Bulgarian and Polish samples presenting a low content of flavonoids. Cluster C3 consisted only of one sample from a pharmacy store. Conclusion: A validated HPLC method for simultaneous determination of phenolic acids, flavonoid glycosides, and aglycones in A. montana flowers was developed. The PCA loading plot showed that quercetin, kaempferol, and isorhamnetin can be used to distinguish different Arnica accessions. SUMMARY A principal component analysis (PCA) on 13 phenolic compounds and total amount of sesquiterpene lactones in Arnicae flos collection tended to cluster the studied 9 accessions into three main groups. The profiles obtained demonstrated that the samples from Germany and Finland are characterized by greater amounts of phenolic derivatives than the Bulgarian and Polish ones. The PCA loading plot showed that quercetin, kaemferol and isorhamnetin can be used to distinguish different arnica accessions. PMID:27013791
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Ulloa, Jerónimo L; Spina, Renata; Casasco, Agustina; Petray, Patricia B; Martino, Virginia; Sosa, Miguel A; Frank, Fernanda M; Muschietti, Liliana V
2017-11-13
Leishmaniasis and Chagas disease are life-threatening illnesses caused by the protozoan parasites Leishmania spp. and Trypanosoma cruzi, respectively. They are known as "neglected diseases" due to the lack of effective drug treatments and the scarcity of research work devoted to them. Therefore, the development of novel and effective drugs is an important and urgent need. Natural products are an important source of bioactive molecules for the development of new drugs. In this study, we evaluated the activity of enhydrin, uvedalin and polymatin B, three sesquiterpene lactones (STLs) isolated from Smallanthus sonchifolius, on Leishmania mexicana (MNYC/BZ/62/M) and Trypanosoma cruzi (Dm28c). In addition, the in vivo trypanocidal activity of enhydrin and uvedalin and the effects of these STLs on parasites' ultrastructure were evaluated. The inhibitory effect of the three STLs on the growth of L. mexicana amastigotes and promastigotes as well as T. cruzi epimastigotes was evaluated in vitro. The changes produced by the STLs on the ultrastructure of parasites were examined by transmission electron microscopy (TEM). Enhydrin and uvedalin were also studied in a murine model of acute T. cruzi infection (RA strain). Serum activities of the hepatic enzymes alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were used as biochemical markers of hepatotoxicity. The three compounds exhibited leishmanicidal activity on both parasite forms with IC 50 values of 0.42-0.54 μg/ml for promastigotes and 0.85-1.64 μg/ml for intracellular amastigotes. Similar results were observed on T. cruzi epimastigotes (IC 50 0.35-0.60 μg/ml). The TEM evaluation showed marked ultrastructural alterations, such as an intense vacuolization and mitochondrial swelling in both L. mexicana promastigotes and T. cruzi epimastigotes exposed to the STLs. In the in vivo study, enhydrin and uvedalin displayed a significant decrease in circulating parasites (50-71%) and no signs of hepatotoxicity were detected. Enhydrin, uvedalin and polymatin B possess significant leishmanicidal and trypanocidal activity on different parasite stages. These results show that these compounds may provide valuable leads for the development of new drugs against these neglected parasitic diseases.
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Isolation and Characterization of Three New Monoterpene Synthases from Artemisia annua
Ruan, Ju-Xin; Li, Jian-Xu; Fang, Xin; Wang, Ling-Jian; Hu, Wen-Li; Chen, Xiao-Ya; Yang, Chang-Qing
2016-01-01
Artemisia annua, an annual herb used in traditional Chinese medicine, produces a wealth of monoterpenes and sesquiterpenes, including the well-known sesquiterpene lactone artemisinin, an active ingredient in the treatment for malaria. Here we report three new monoterpene synthases of A. annua. From a glandular trichome cDNA library, monoterpene synthases of AaTPS2, AaTPS5, and AaTPS6, were isolated and characterized. The recombinant proteins of AaTPS5 and AaTPS6 produced multiple products with camphene and 1,8-cineole as major products, respectively, and AaTPS2 produced a single product, β-myrcene. Although both Mg2+ and Mn2+ were able to support their catalytic activities, altered product spectrum was observed in the presence of Mn2+ for AaTPS2 and AaTPS5. Analysis of extracts of aerial tissues and root of A. annua with gas chromatography–mass spectrometry detected more than 20 monoterpenes, of which the three enzymes constituted more than 1/3 of the total. Mechanical wounding induced the expression of all three monoterpene synthase genes, and transcript levels of AaTPS5 and AaTPS6 were also elevated after treatments with phytohormones of methyl jasmonate, salicylic acid, and gibberellin, suggesting a role of these monoterpene synthases in plant–environment interactions. The three new monoterpene synthases reported here further our understanding of molecular basis of monoterpene biosynthesis and regulation in plant. PMID:27242840
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Arnica montana L. - a plant of healing: review.
Kriplani, Priyanka; Guarve, Kumar; Baghael, Uttam S
2017-08-01
Arnica montana is a widely used therapeutic plant used traditionally to treat various ailments. The objective of this study was to evaluate the botany, phytochemistry and ethnopharmacology along with special emphasis given on pharmacological activity of plant A. montana. The plant extracts have been reported to possess antibacterial, antitumor, antioxidant, anti-inflammatory, antifungal and immunomodulatory activity. A wide range of chemical compounds including sesquiterpene lactones and their short-chain carbonic acid esters, flavonoids, carotenoids, essential oils, diterpenes, arnidiol, pyrrolizidine alkaloids, coumarins, phenolic acids, lignans and oligosaccharides, etc., are found in different parts of the plant. It has been scrutinized that extensive research has been carried out to explore the therapeutic potential of flowers of the plant. Therefore, investigations should be carried out to explore the therapeutic potential of other parts of the plant for better therapeutic utilization. © 2017 Royal Pharmaceutical Society.
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Lim, Hye-Sun; Ha, Hyekyung; Shin, Hyeun-Kyoo; Jeong, Soo-Jin
2015-09-01
Saussurea lappa has been reported to possess anti-atopic properties. In this study, we have confirmed the S. lappa's anti-atopic properties in Nc/Nga mice and investigated the candidate gene related with its properties using microarray. We determined the target gene using real time PCR in in vitro experiment. S. lappa showed the significant reduction in atopic dermatitis (AD) score and immunoglobulin E compared with the AD induced Nc/Nga mice. In the results of microarray using back skin obtained from animals, we found that S. lappa's properties are closely associated with cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway. Consistent with the microarray data, real-time RT-PCR confirmed these modulation at the mRNA level in skin tissues from S. lappa-treated mice. Among these genes, PI3Kca and IL20Rβ were significantly downregulated by S. lappa treatment in Nc/Nga mouse model. In in vitro experiment using HaCaT cells, we found that the S. lappa components, including alantolactone, caryophyllene, costic acid, costunolide and dehydrocostus lactone significantly decreased the expression of PI3Kca but not IL20Rβ in vitro. Therefore, our study suggests that PI3Kca-related signaling is closely related with the protective effects of S. lappa against the development of atopic-dermatitis.
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2012-01-01
Background The essential oil of chamomile, one of the oldest and agronomically most important medicinal plant species in Europe, has significant antiphlogistic, spasmolytic and antimicrobial activities. It is rich in chamazulene, a pharmaceutically active compound spontaneously formed during steam distillation from the sesquiterpene lactone matricine. Chamomile oil also contains sesquiterpene alcohols and hydrocarbons which are produced by the action of terpene synthases (TPS), the key enzymes in constructing terpene carbon skeletons. Results Here, we present the identification and characterization of five TPS enzymes contributing to terpene biosynthesis in chamomile (Matricaria recutita). Four of these enzymes were exclusively expressed in above-ground organs and produced the common terpene hydrocarbons (−)-(E)-β-caryophyllene (MrTPS1), (+)-germacrene A (MrTPS3), (E)-β-ocimene (MrTPS4) and (−)-germacrene D (MrTPS5). A fifth TPS, the multiproduct enzyme MrTPS2, was mainly expressed in roots and formed several Asteraceae-specific tricyclic sesquiterpenes with (−)-α-isocomene being the major product. The TPS transcript accumulation patterns in different organs of chamomile were consistent with the abundance of the corresponding TPS products isolated from these organs suggesting that the spatial regulation of TPS gene expression qualitatively contribute to terpene composition. Conclusions The terpene synthases characterized in this study are involved in the organ-specific formation of essential oils in chamomile. While the products of MrTPS1, MrTPS2, MrTPS4 and MrTPS5 accumulate in the oils without further chemical alterations, (+)-germacrene A produced by MrTPS3 accumulates only in trace amounts, indicating that it is converted into another compound like matricine. Thus, MrTPS3, but also the other TPS genes, are good markers for further breeding of chamomile cultivars rich in pharmaceutically active essential oils. PMID:22682202
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Tao, Li; Fan, Fangtian; Liu, Yuping; Li, Weidong; Zhang, Lei; Ruan, Junshan; Shen, Cunsi; Sheng, Xiaobo; Zhu, Zhijie; Wang, Aiyun; Chen, Wenxing; Huang, Shile; Lu, Yin
2013-01-01
Xanthatin, a sesquiterpene lactone purified from Xanthium strumarium L., possesses prominent anticancer activity. We found that disruption of GSK3β activity was essential for xanthatin to exert its anticancer properties in non-small cell lung cancer (NSCLC), concurrent with preferable suppression of constitutive activation of STAT3. Interestingly, inactivation of the two signals are two mutually exclusive events in xanthatin-induced cell death. Moreover, we surprisingly found that exposure of xanthatin failed to trigger the presumable side effect of canonical Wnt/β-Catenin followed by GSK3β inactivation. We further observed that the downregulation of STAT3 was required for xanthatin to fine-tune the risk. Thus, the discovery of xanthatin, which has ability to simultaneously orchestrate two independent signaling cascades, may have important implications for screening promising drugs in cancer therapies.
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A below-ground herbivore shapes root defensive chemistry in natural plant populations
Huber, Meret; Bont, Zoe; Fricke, Julia; Brillatz, Théo; Aziz, Zohra; Gershenzon, Jonathan; Erb, Matthias
2016-01-01
Plants display extensive intraspecific variation in secondary metabolites. However, the selective forces shaping this diversity remain often unknown, especially below ground. Using Taraxacum officinale and its major native insect root herbivore Melolontha melolontha, we tested whether below-ground herbivores drive intraspecific variation in root secondary metabolites. We found that high M. melolontha infestation levels over recent decades are associated with high concentrations of major root latex secondary metabolites across 21 central European T. officinale field populations. By cultivating offspring of these populations, we show that both heritable variation and phenotypic plasticity contribute to the observed differences. Furthermore, we demonstrate that the production of the sesquiterpene lactone taraxinic acid β-d-glucopyranosyl ester (TA-G) is costly in the absence, but beneficial in the presence of M. melolontha, resulting in divergent selection of TA-G. Our results highlight the role of soil-dwelling insects for the evolution of plant defences in nature. PMID:27009228
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Tao, Li; Fan, Fangtian; Liu, Yuping; Li, Weidong; Zhang, Lei; Ruan, Junshan; Shen, Cunsi; Sheng, Xiaobo; Zhu, Zhijie; Wang, Aiyun; Chen, Wenxing; Huang, Shile; Lu, Yin
2013-01-01
Xanthatin, a sesquiterpene lactone purified from Xanthium strumarium L., possesses prominent anticancer activity. We found that disruption of GSK3β activity was essential for xanthatin to exert its anticancer properties in non-small cell lung cancer (NSCLC), concurrent with preferable suppression of constitutive activation of STAT3. Interestingly, inactivation of the two signals are two mutually exclusive events in xanthatin-induced cell death. Moreover, we surprisingly found that exposure of xanthatin failed to trigger the presumable side effect of canonical Wnt/β-Catenin followed by GSK3β inactivation. We further observed that the downregulation of STAT3 was required for xanthatin to fine-tune the risk. Thus, the discovery of xanthatin, which has ability to simultaneously orchestrate two independent signaling cascades, may have important implications for screening promising drugs in cancer therapies. PMID:24312384
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Lethal effect of dehydroleucodine (DhL) on amphibian Bufo arenarum embryos.
Moreno, Liliana Elizabeth; Juárez, Américo Osvaldo; Pelzer, Lilian Eugenia
2012-03-01
The dehydroleucodine is a sesquiterpene lactone isolated from Artemisia douglasiana Besser which is used in popular medicine. Toxicity tests using embryos of amphibian have been widely used in order to predict toxic effects of different compounds. However, to our knowledge, there are not studies focussed on the toxic effects of dehydroleucodine on Bufo arenarum, which is an anuran widely distributed in South America. The effect of dehydroleucodine on the survival of embryos was evaluated in an acute test during the early life stage of B. arenarum embryos. Lethality and the degree of adverse effects were dehydroleucodine dose-dependent. Overall, amphibian early life stages appeared to be more susceptible to the embryotoxicity associated with exposure to dehydroleucodine, especially at concentration greater that 3mM. This increased susceptibility may result from the relatively high rate of cellular differentiation and morphogenesis that occurs at this early stage of development. Copyright © 2012 Elsevier Ltd. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lincoln, D.E.
Preliminary analysis of two populations of Artemisia tridentata compared leaf chemical and physiological characteristics which influence herbivores. The proportion of sixteen of the volatile compounds differed significantly between the two populations; however, total yield of volatiles did not. This initial survey established the reliability of the procedure to quantitatively monitor plant responses to CO/sub 2/ enrichment and suggests that test samples be restricted to a single population. Four sesquiterpene lactones have been selected for the experimental quantitative HPLC analysis; all peaks have been assigned identities and have demonstrated high degree of reproducibility. Growth of Artemisia under high and low lightmore » at three CO/sub 2/ levels demonstrated that this species also undergoes a ''dilution'' of the leaf carbon content and is useful as test species for herbivory response to CO/sub 2/ induced effects. The initial experiment also showed that high irradiance is a necessary growth condition. 10 refs.« less
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Relative stability of radicals derived from artemisinin: A semiempirical and DFT study
NASA Astrophysics Data System (ADS)
Arantes, C.; de Araujo, M. T.; Taranto, A. G.; de M. Carneiro, J. W.
The semiempirical AM1 and PM3 methods, as well as the density functional (DFT/B3LYP) approach using the 6-31g(d) basis set, were employed to calculate the relative stability of intermediate radicals derived from artemisinin, a sesquiterpene lactone having an endoperoxide bridge that is essential for its antimalarial activity. The compounds studied have their nonperoxidic oxygen atom of the trioxane ring and/or the carbonyl group replaced by a CH2 unit. Relative stabilities were calculated by means of isodesmic equations using artemisinin as reference. It was found that replacement of oxygen atoms decreases the relative stability of the anionic radical intermediates. In contrast, for compounds with inverted stereochemistry the intermediate radicals were found to be more stable than those with the artemisinin-like stereochemistry. These relative stabilities may modulate the antimalarial potency. Radicals centered on carbon are always more stable than the corresponding radicals centered on oxygen.
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Parveen, Iffat; Wang, Mei; Zhao, Jianping; Chittiboyina, Amar G; Tabanca, Nurhayat; Ali, Abbas; Baerson, Scott R; Techen, Natascha; Chappell, Joe; Khan, Ikhlas A; Pan, Zhiqiang
2015-11-01
Ginkgo biloba is one of the oldest living tree species and has been extensively investigated as a source of bioactive natural compounds, including bioactive flavonoids, diterpene lactones, terpenoids and polysaccharides which accumulate in foliar tissues. Despite this chemical diversity, relatively few enzymes associated with any biosynthetic pathway from ginkgo have been characterized to date. In the present work, predicted transcripts potentially encoding enzymes associated with the biosynthesis of diterpenoid and terpenoid compounds, including putative terpene synthases, were first identified by mining publicly-available G. biloba RNA-seq data sets. Recombinant enzyme studies with two of the TPS-like sequences led to the identification of GbTPS1 and GbTPS2, encoding farnesol and bisabolene synthases, respectively. Additionally, the phylogenetic analysis revealed the two terpene synthase genes as primitive genes that might have evolved from an ancestral diterpene synthase.
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Phytotoxicity of cardoon (Cynara cardunculus) allelochemicals on standard target species and weeds.
Rial, Carlos; Novaes, Paula; Varela, Rosa M; Molinillo, José M G; Macias, Francisco A
2014-07-16
Cardoon (Cynara cardunculus L.) is a native plant to the Iberian Peninsula and the European Atlantic coast and invasive in American environments. Different solvents were used to perform cardoon extracts that were tested in phytotoxic bioassays. The ethyl acetate extract had the highest inhibitory activity so this was tested on the germination and growth of standard target species (lettuce, watercress, tomato, and onion) and weeds (barnyardgrass and brachiaria). The ethyl acetate extract was very active on root growth in both standard target species and weeds and it was therefore fractionated by chromatography. The spectroscopic data showed that the major compounds were sesquiterpene lactones. Aguerin B, grosheimin, and cynaropicrin were very active on etiolated wheat coleoptile, standard target species, and weed growth. The presence of these compounds explains the bioactivity of the ethyl acetate extract. The strong phytotoxicity of these compounds on important weeds shows the potential of these compounds as natural herbicide models.
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Global characterization of Artemisia annua glandular trichome transcriptome using 454 pyrosequencing
Wang, Wei; Wang, Yejun; Zhang, Qing; Qi, Yan; Guo, Dianjing
2009-01-01
Background Glandular trichomes produce a wide variety of commercially important secondary metabolites in many plant species. The most prominent anti-malarial drug artemisinin, a sesquiterpene lactone, is produced in glandular trichomes of Artemisia annua. However, only limited genomic information is currently available in this non-model plant species. Results We present a global characterization of A. annua glandular trichome transcriptome using 454 pyrosequencing. Sequencing runs using two normalized cDNA collections from glandular trichomes yielded 406,044 expressed sequence tags (average length = 210 nucleotides), which assembled into 42,678 contigs and 147,699 singletons. Performing a second sequencing run only increased the number of genes identified by ~30%, indicating that massively parallel pyrosequencing provides deep coverage of the A. annua trichome transcriptome. By BLAST search against the NCBI non-redundant protein database, putative functions were assigned to over 28,573 unigenes, including previously undescribed enzymes likely involved in sesquiterpene biosynthesis. Comparison with ESTs derived from trichome collections of other plant species revealed expressed genes in common functional categories across different plant species. RT-PCR analysis confirmed the expression of selected unigenes and novel transcripts in A. annua glandular trichomes. Conclusion The presence of contigs corresponding to enzymes for terpenoids and flavonoids biosynthesis suggests important metabolic activity in A. annua glandular trichomes. Our comprehensive survey of genes expressed in glandular trichome will facilitate new gene discovery and shed light on the regulatory mechanism of artemisinin metabolism and trichome function in A. annua. PMID:19818120
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Abiri, Rambod; Silva, Abraão Lincoln Macedo; de Mesquita, Ludmilla Santos Silva; de Mesquita, José Wilson Carvalho; Atabaki, Narges; de Almeida, Eduardo Bezerra; Shaharuddin, Noor Azmi; Malik, Sonia
2018-07-01
Artemisia vulgaris is one of the important medicinal plant species of the genus Artemisia, which is usually known for its volatile oils. The genus Artemisia has become the subject of great interest due to its chemical and biological diversity as well as the discovery and isolation of promising anti-malarial drug artemisinin. A. vulgaris has a long history in treatment of human ailments by medicinal plants in various parts of the world. This medicinal plant possesses a broad spectrum of therapeutic properties including: anti-malarial, anti-inflammatory, anti-hypertensive, anti-oxidant, anti-tumoral, immunomodulatory, hepatoprotective, anti-spasmodic and anti-septic. These activities are mainly attributed to the presence of various classes of secondary metabolites, including flavonoids, sesquiterpene lactones, coumarins, acetylenes, phenolic acids, organic acids, mono- and sesquiterpenes. Studies related to A. vulgaris morphology, anatomy and phytochemistry has gained a significant interest for better understanding of production and accumulation of therapeutic compounds in this species. Recently, phytochemical and pharmacological investigations have corroborated the therapeutic potential of bioactive compounds of A. vulgaris. These findings provided further evidence for gaining deeper insight into the identification and isolation of novel compounds, which act as alternative sources of anti-malarial drugs in a cost-effective manner. Considering the rising demand and various medical applications of A. vulgaris, this review highlights the recent reports on the chemistry, biological activities and biotechnological interventions for controlled and continuous production of bioactive compounds from this plant species. Copyright © 2018 Elsevier Ltd. All rights reserved.
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de Almeida, Ana Beatriz Albino; Luiz-Ferreira, Anderson; Cola, Maíra; Di Pietro Magri, Luciana; Batista, Leonia Maria; de Paiva, Joseilson Alves; Trigo, José Roberto; Souza-Brito, Alba R M
2012-04-01
Arctium lappa L. has been used in folk medicine as a diuretic, depurative, and digestive stimulant and in dermatological conditions. The mechanisms involved in the anti-ulcerogenic activity of the sesquiterpene onopordopicrin (ONP)-enriched fraction (termed the ONP fraction), obtained from A. lappa leaves, were studied. The gastroprotective mechanism of the ONP fraction was evaluated in experimental in vivo models in rodents, mimicking this disease in humans. ONP fraction (50 mg/kg, p.o.) significantly inhibited the mucosal injury induced by ethanol/HCl solution (75%), indomethacin/bethanecol (68.9%), and stress (58.3%). When the ONP fraction was investigated in pylorus ligature, it did not induce alteration in the gastric volume but did modify the pH and total acid concentration of gastric juice. ONP fraction significantly increased serum somatostatin levels (82.1±4.1 vs. control group 12.7±4 pmol/L) and decreased serum gastrin levels (62.6±6.04 vs. control group 361.5±8.2 μU/mL). Mucus production was not significantly altered by the ONP fraction. Gastroprotection by the ONP fraction was completely inhibited by N-ethylmaleimide treatment and did not modify the effect in the animals pretreated with l-N(G)-nitroarginine methyl ester. These results suggest an antisecretory mechanism involved with the antiulcerogenic effect of the ONP fraction. However, only endogenous sulfhydryls play an important role in gastroprotection of the ONP fraction.
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Sagebrush and grasshopper responses to atmospheric carbon dioxide concentration.
Johnson, R H; Lincoln, D E
1990-08-01
Seed- and clonally-propagated plants of Big Sagebrush (Artemisia tridentata var.tridentata) were grown under atmospheric carbon dioxide regimes of 270, 350 and 650 μl l -1 and fed toMelanoplus differentialis andM. sanguinipes grasshoppers. Total shrub biomass significantly increased as carbon dioxide levels increased, as did the weight and area of individual leaves. Plants grown from seed collected in a single population exhibited a 3-5 fold variation in the concentration of leaf volatile mono- and sesquiterpenes, guaianolide sesquiterpene lactones, coumarins and flavones within each CO 2 treatment. The concentration of leaf allelochemicals did not differ significantly among CO 2 treatments for these seed-propagated plants. Further, when genotypic variation was controlled by vegetative propagation, allelochemical concentrations also did not differ among carbon dioxide treatments. On the other hand, overall leaf nitrogen concentration declined significantly with elevated CO 2 . Carbon accumulation was seen to dilute leaf nitrogen as the balance of leaf carbon versus nitrogen progressively increased as CO 2 growth concentration increased. Grasshopper feeding was highest on sagebrush leaves grown under 270 and 650 μl l -1 CO 2 , but varied widely within treatments. Leaf nitrogen concentration was an important positive factor in grasshopper relative growth but had no overall effect on consumption. Potential compensatory consumption by these generalist grasshoppers was apparently limited by the sagebrush allelochemicals. Insects with a greater ability to feed on chemically defended host plants under carbon dioxide enrichment may ultimately consume leaves with a lower nitrogen concentration but the same concentration of allelochemicals. Compensatory feeding may potentially increase the amount of dietary allelochemicals ingested for each unit of nitrogen consumed.
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Jäger, Christoph; Hrenn, Andrea; Zwingmann, Jörn; Suter, Andreas; Merfort, Irmgard
2009-10-01
Arnica preparations have long been used for the symptomatic treatment of rheumatic complaints and recent clinical trials have demonstrated the beneficial effects of Arnica preparations in the treatment of osteoarthritis (OA). The efficacy of Arnica is presumed to be mainly due to its anti-inflammatory properties and inhibition of the transcription factor NF-kappaB. Here we provide further insights into its molecular mode of action. Arnica preparations suppress MMP1 and MMP13 mRNA levels in bovine and human articular chondrocytes in a concentration-dependent manner and in a low concentration range. This suppression may be due to inhibition of DNA binding of the transcription factors AP-1 and NF-kappaB. Interestingly, sesquiterpene lactones present in the preparations were always more active than the pure compounds, demonstrating the advantage of using plant preparations. Georg Thieme Verlag KG Stuttgart, New York.
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A below-ground herbivore shapes root defensive chemistry in natural plant populations.
Huber, Meret; Bont, Zoe; Fricke, Julia; Brillatz, Théo; Aziz, Zohra; Gershenzon, Jonathan; Erb, Matthias
2016-03-30
Plants display extensive intraspecific variation in secondary metabolites. However, the selective forces shaping this diversity remain often unknown, especially below ground. Using Taraxacum officinale and its major native insect root herbivore Melolontha melolontha, we tested whether below-ground herbivores drive intraspecific variation in root secondary metabolites. We found that high M. melolontha infestation levels over recent decades are associated with high concentrations of major root latex secondary metabolites across 21 central European T. officinale field populations. By cultivating offspring of these populations, we show that both heritable variation and phenotypic plasticity contribute to the observed differences. Furthermore, we demonstrate that the production of the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G) is costly in the absence, but beneficial in the presence of M. melolontha, resulting in divergent selection of TA-G. Our results highlight the role of soil-dwelling insects for the evolution of plant defences in nature. © 2016 The Author(s).
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Investigation of Glandular Trichome Proteins in Artemisia annua L. Using Comparative Proteomics
Wu, Ting; Wang, Yejun; Guo, Dianjing
2012-01-01
Glandular secreting trichomes (GSTs) are called biofactories because they are active in synthesizing, storing and secreting various types of plant secondary metabolites. As the most effective drug against malaria, artemisinin, a sesquiterpene lactone is derived from GSTs of Artemisia annua. However, low artemisinin content (0.001%∼1.54% of dry weight) has hindered its wide application. We investigate the GST-expressed proteins in Artemisia annua using a comparative proteomics approach, aiming for a better understanding of the trichome proteome and arteminisin metabolism. 2D-electrophoresis was employed to compare the protein profiles of GSTs and leaves. More than 700 spots were resolved for GSTs, of which ∼93 non-redundant proteins were confidently identified by searching NCBI and Artemisia EST databases. Over 70% of these proteins were highly expressed in GTSs. Functional classification of these GSTs enriched proteins revealed that many of them participate in major plant metabolic processes such as electron transport, transcription and translation. PMID:22905110
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El Marsni, Zouhir; Torres, Ascension; Varela, Rosa M; Molinillo, José M G; Casas, Lourdes; Mantell, Casimiro; Martinez de la Ossa, Enrique J; Macias, Francisco A
2015-07-22
The work described herein is a continuation of our initial studies on the supercritical fluid extraction (SFE) with CO2 of bioactive substances from Helianthus annuus L. var. Arianna. The selected SFE extract showed high activity in the wheat coleoptile bioassay, in Petri dish phytotoxicity bioassays, and in the hydroponic culture of tomato seeds. Chromatographic fractionations of the extracts and a spectroscopic analysis of the isolated compounds showed 52 substances belonging to 10 different chemical classes, which were mainly sesquiterpene lactones, diterpenes, and flavonoids. Heliannuol M (31), helivypolides K and L (36, 37), and helieudesmanolide B (38) are described for the first time in the literature. Metabolites have been tested in the etiolated wheat coleoptile bioassay with good results in a noteworthy effect on germination. The most active compounds were also tested on tomato seeds, heliannuol A (30) and leptocarpin (45) being the most active, with values similar to those of the commercial herbicide.
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Glutathione metabolism as a determinant of therapeutic efficacy: a review.
Arrick, B A; Nathan, C F
1984-10-01
Glutathione, as the chief nonprotein intracellular sulfhydryl, affects the efficacy and interactions of a variety of antineoplastic interventions, mainly through nucleophilic thioether formation or oxidation-reduction reactions. Thus, glutathione plays a role in the detoxification and repair of cellular injury by such diverse agents as mechlorethamine, melphalan, cyclophosphamide, nitrosoureas, 6-thiopurine, 4'-(9-acridinylamino)methanesulfon-m-anisidide, the quinone antibiotics (including Adriamycin, daunorubicin, and mitomycin C), the sesquiterpene lactones (such as vernolepin), and other sulfhydryl-reactive diterpenes (like jatrophone). Glutathione may play a similar role in host and tumor cell responses to radiation, hyperthermia, and the reactive reduction products of oxygen secreted by inflammatory cells. Further, glutathione participates in the formation of toxic metabolites of such chemotherapeutics as azathioprine and bleomycin and may affect the cellular uptake of other agents, such as methotrexate. It seems likely that alterations in glutathione metabolism of tumor or host as a result of one therapeutic intervention may affect the outcome of concurrent treatments. Knowledge of these interactions may be useful in designing combination therapy for neoplastic disease.
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Móricz, Ágnes M; Krüzselyi, Dániel; Alberti, Ágnes; Darcsi, András; Horváth, Györgyi; Csontos, Péter; Béni, Szabolcs; Ott, Péter G
2017-11-17
The antibacterial profiling of Onopordum acanthium L. leaf extract and subsequent targeted identification of active compounds is demonstrated. Thin-layer chromatography (TLC) and off-line overpressured layer chromatography (OPLC) coupled with direct bioautography were utilized for investigation of the extract against eight bacterial strains including two plant and three human pathogens and a soil, a marine and a probiotic human gut bacteria. Antibacterial fractions obtaining infusion-transfusion OPLC were transferred to HPLC-MS/MS analysis that resulted in the characterization of three active compounds and two of them were identified as, linoleic and linolenic acid. OPLC method was adopted to preparative-scale flash chromatography for the isolation of the third active compound, which was identified after a further semi-preparative HPLC purification as the germacranolide sesquiterpene lactone onopordopicrin. Pure onopordopicrin exhibited antibacterial activity that was specified as minimal inhibitory concentration in the liquid phase as well. Copyright © 2017 Elsevier B.V. All rights reserved.
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Chen, Zhengxu; Zhang, Dan; Li, Man; Wang, Baolong
2018-06-12
Lipoteichoic acid (LTA)-induced acute lung injury (ALI) is an experimental model for mimicking Gram-positive bacteria-induced pneumonia that is a refractory disease with lack of effective medicines. Here, we reported that costunolide, a sesquiterpene lactone, ameliorated LTA-induced ALI. Costunolide treatment reduced LTA-induced neutrophil lung infiltration, cytokine and chemokine production (TNF-α, IL-6 and KC), and pulmonary edema. In response to LTA challenge, treatment with costunolide resulted less iNOS expression and produced less inflammatory cytokines in bone marrow derived macrophages (BMDMs). Pretreatment with costunolide also attenuated the LTA-induced the phosphorylation of p38 MAPK and ERK in BMDMs. Furthermore, costunolide treatment reduced the phosphorylation of TAK1 and inhibited the interaction of TAK1 with Tab1. In conclusion, we have demonstrated that costunolide protects against LTA-induced ALI via inhibiting TAK1-mediated MAPK signaling pathway, and our studies suggest that costunolide is a promising agent for treatment of Gram-positive bacteria-mediated pneumonia. Copyright © 2018 Elsevier B.V. All rights reserved.
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Shale, Karabo
2017-01-01
Chicory is a perennial plant grown in different parts of the world, used as forage for livestock, as folklore remedies, or as a vegetable addition in human diets. There are several varieties of the chicory plant, known differently globally due to its numerous medicinal, culinary, and nutritional qualities. Most parts of the plant contain a potpourri of nutrients ranging within carbohydrates, proteins, vitamins, minerals, soluble fiber, trace elements, and bioactive phenolic compounds, which are responsible for the various nutritive, prophylactic, and therapeutic qualities of chicory. Inulin, coumarins, tannins, monomeric flavonoids, and sesquiterpene lactones are some of the major phytocompounds mostly found in chicory plants. The health-promoting activities attributed to chicory comprise, among others, anti-inflammatory, anticarcinogenic, antiviral, antibacterial, antimutagenic, antifungal, anthelmintic, immune-stimulating, and antihepatotoxic and its antioxidative qualities. As a versatile plant, chicory's chemical composition and use as a suitable livestock feed supplement or as an alternative feed ingredient (AFI) are thus reviewed. PMID:29387778
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Steingass, Christof Björn; Carle, Reinhold; Schmarr, Hans-Georg
2015-03-01
Qualitative ripening-dependent changes of pineapple volatiles were studied via headspace solid-phase microextraction and analyzed by comprehensive two-dimensional gas chromatography quadrupole mass spectrometry (HS-SPME-GC×GC-qMS). Early green-ripe stage, post-harvest ripened, and green-ripe fruits at the end of their commercial shelf-life were compared to air-freighted pineapples harvested at full maturity. In total, more than 290 volatiles could be identified by mass spectrometry and their linear retention indices. The majority of compounds comprise esters (methyl and ethyl esters of saturated and unsaturated fatty acids, acetates), terpenes, alcohols, aldehydes, 2-ketones, free fatty acids, and miscellaneous γ- and δ-lactones. The structured separation space obtained by GC×GC allowed revealing various homologous series of compound classes as well as clustering of sesquiterpenes. Post-harvest ripening increased the diversity of the volatile profile compared to both early green-ripe maturity stages and on-plant ripened fruits.
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Trendafilova, Antoaneta; Jadranin, Milka; Gorgorov, Rossen; Stanilova, Marina
2015-06-01
In vitro cultures were initiated from a single seed of Centaurea davidovii. Whole plantlets were regenerated and cultivated for several months on agar-solidified nutrient media differing by their composition: basal MS medium, MS medium supplemented with plant growth regulators, and liquid MS medium. Plantlets were ex vitro adapted and successfully acclimated to open-air conditions; flowering was observed in some individuals in the first summer, and mass flowering during the second summer. The contents of the total flavonoids and the total phenolic compounds were determined spectrophotometrically in the leaves of the in vitro plantlets cultured on different media, and then compared with those in the leaves of the wild plants and in the leaves of the acclimated plants of the field plot. The sesquiterpene lactone 8α-(5'-hydroxyangeloyl)-salonitenolide was determined by HPLC in leaf samples of C. davidovii wild plants, in vitro obtained plantlets and ex vitro acclimated plants in the greenhouse and on the experimental field plot. The composition of the nutrient medium influenced the contents of all studied bioactive substances. The highest concentrations of all tested secondary metabolites were detected in the leaves of the acclimated plants during mass flowering, the content of the lactone reaching 56.2 mg/g DW, which was several times more than in the other leaf samples. The obtained results revealed both the effectiveness of biotechnological methods for propagation and conservation of rare and endangered plant species, and the possibility to use C. davidovii plants ex vitro acclimated to field conditions as a source of secondary metabolites with potential biological activity.
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Gönenç, Tuba Mert; Akkol, Esra Küpeli; Süntar, Ipek; Erdoğan, Tuğçe Fafal; Kıvçak, Bijen
2014-01-01
Background: Anthemis species have been used for the treatment of gastrointestinal disorders, hemorrhoid, stomachache and inflammatory diseases in Turkish folk medicine. Anthemis wiedemanniana Fisch. And Mey. is an endemic plant used as painkiller, antispasmodic, sedative and for the treatment of urinary inflammations. Objective: The objective of the present study is to evaluate the anti-inflamatory activity of the extracts of A. wiedemanniana by using in vivo methods. Materials and Methods: Carrageenan-, PGE2- and serotonin-induced hind paw edema, 12-O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema and acetic acid-induced increase in capillary permeability models were used for the anti-inflammatory activity assessment. Moreover, the fatty acid composition of A. wiedemanniana was investigated by gas chromatography (GC). Results: n-Hexane, diethyl ether and total sesquiterpene lactone extracts exhibited significant inhibition in carrageenan-induced hind paw edema and acetic acid-induced increase in capillary permeability model. n-Hexane and total sesquiterperne lactone extracts showed anti-inflammatory activity in PGE2- and serotonin-induced hind paw edema model. However none of the extracts displayed significant activity in TPA-induced ear edema model in mice. C4:0 (Buthyric acid), C20:0 (Arachidic acid) and C16:1 (Palmitoleik acid) were found to be the major fatty acids in these species. Saturated fatty acids (SFA) were found in higher amounts than monounsaturated fatty acids and polyunsaturated fatty acids. SFAs were determined as 63.17%, UFAs as 20.89% and PuFAs as 15.95%. Conclusion: This study confirms the traditional usage of A. wiedemanniana for inflammatory diseases. PMID:24696546
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Girardi, Cynthia; Fabre, Nicolas; Paloque, Lucie; Ramadani, Arba Pramundita; Benoit-Vical, Françoise; González-Aspajo, German; Haddad, Mohamed; Rengifo, Elsa; Jullian, Valérie
2015-07-21
Pseudelephantopus spiralis (Less.) Cronquist is distributed in the Caribbean, Mesoamerica and Latin America. Preparations of the plant are traditionally used in Latin America for the treatment of various diseases including fever, malaria, and spleen or liver inflammations. Aerial parts of P. spiralis were extracted with either ethanol or distilled water. Seven hirsutinolide-type sesquiterpenoids were isolated: 8-acetyl-13-ethoxypiptocarphol (1), diacetylpiptocarphol (2), piptocarphins A (3), F (4) and D (5), (1S(*),4R(*),8S(*),10R(*))-1,4-epoxy-13-ethoxy-1,8,10-trihydroxygermacra-5E,7(11)-dien-6,12-olide (6), and piptocarphol (7). Extracts and isolated compounds (2, 3, 5-7) were screened for their in vitro antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum strain FcM29-Cameroon and antileishmanial activity against three stages of Leishmania infantum. Their cytotoxicities were also evaluated against healthy VERO cell lines and J774A.1 macrophages, the host cells of the Leishmania parasites in humans. Aqueous extracts showed a greater inhibitory effect than alcoholic extracts, with IC50 on P. falciparum of 3.0µg/mL versus 21.1µg/mL, and on L. infantum of 13.4µg/mL versus >50µg/mL. Both extracts were found to be cytotoxic to VERO cells (CC50<3µg/mL). Sesquiterpene lactones 2 and 3 showed the best activity against both parasites but failed in selectivity. Carbon 8 hydroxylated hirsutinolides 5-7 presented the particularity of exhibiting two conformers observed in solution during extensive NMR analyses in CD3OD and UHPLC-MS. The presence of a hydroxyl function at C-8 decreased the activity of 5-7 on the two parasites and also on VERO cells. The antiplasmodial activity displayed by the aqueous extract explains the traditional use of P. spiralis in the treatment of malaria. This activity seems to be attributable to the presence of sesquiterpene lactones 2 and 3, the most active against P. falciparum. Aqueous extract and compounds 2, 3 and 6 were also active against L. infantum but lacked in selectivity due to their cytotoxicity towards macrophages. Exploring the safety and antiplasmodial efficacy of this traditional remedy will require further toxicological and in vivo studies in the light of the cytotoxicity towards healthy cell lines displayed by the aqueous extract and compounds 2 and 3. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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Chagas-Paula, Daniela Aparecida; Oliveira, Rejane Barbosa de; da Silva, Vanessa Cristina; Gobbo-Neto, Leonardo; Gasparoto, Thaís Helena; Campanelli, Ana Paula; Faccioli, Lúcia Helena; Da Costa, Fernando Batista
2011-06-22
T. diversifolia (Hemsl.) A. Gray (Asteraceae) has been used in the traditional medicine in several countries as anti-inflammatory and against other illnesses. It is important to evaluate the anti-inflammatory activity of extracts from the leaves of this species, including an infusion, to identify the main constituents of the extracts, observe their effects and correlate them with the anti-inflammatory activity. An infusion, a leaf rinse extract (LRE) and a polar extract from the rinsed leaves (PE) were obtained and analysed by HPLC-UV-DAD and infrared spectroscopy. The major compounds of these extracts were quantified. The three obtained extracts were evaluated for their anti-inflammatory activities using the paw oedema and croton oil ear oedema assays in mice. Furthermore, neutrophil migration was measured by evaluating myeloperoxidase activity. The PE consists primarily of chlorogenic acids (CAs) and lacks sesquiterpene lactones (STLs). The LRE is rich in STLs and includes a few flavonoids. The infusion is chemically similar to the PE but also contains very low amounts of STLs. The PE and LRE have better mechanisms of action than non-steroidal anti-inflammatory drugs (NSAIDs). Unlike NSAIDs, both the PE and LRE inhibit oedema and neutrophil migration. The pool of CAs from the PE of T. diversifolia has an additional mechanism of action, and its anti-inflammatory effect was greater than what is described in the literature for this class of compounds using the same evaluation models. The similar chemical compositions observed for the infusion and the PE, contrasted with the different activities observed, suggests the presence of antagonist compounds produced during the extraction procedure (infusion); the infusion did not inhibit oedema, however it inhibited neutrophil migration. It suggests that although the great majority of plants present CAs, the category of anti-inflammatory effect of their extracts depends on a suitable pool of compounds and an absence of antagonists, among other factors. CAs from T. diversifolia comprise a good pool of anti-inflammatory compounds with better activity mechanisms than NSAIDs, other active compounds from the leaf extracts (STLs and flavonoids) and CAs from other plant sources. Thus, the PE of T. diversifolia has high potential for the development of new anti-inflammatory phytomedicines. The infusion probably contains antagonists, and therefore it can be useful to treat inflammation processes where neutrophil recruitment is involved and oedema is not. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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Spitaler, Renate; Schlorhaufer, P Daniel; Ellmerer, Ernst P; Merfort, Irmgard; Bortenschlager, Sigmar; Stuppner, Hermann; Zidorn, Christian
2006-02-01
The altitudinal variation on the contents of secondary metabolites in flowering heads of Arnica montana was assessed. Plants of A. montana cultivar ARBO were grown in nine experimental plots at altitudes between 590 and 2230m at Mount Patscherkofel near Innsbruck/Austria. The total contents of sesquiterpene lactones and flavonoids were not positively correlated with the altitude of the growing site. However, the proportion of flavonoids with vicinal free hydroxy groups in ring B to flavonoids lacking this feature significantly increased with elevation. Additionally, the level of caffeic acid derivatives also positively correlated with the altitude of the growing site. In particular amounts of 1-methoxyoxaloyl-3,5-dicaffeoylquinic acid significantly increased in higher sites and samples from the summit region contained 85% more of this compound than samples from valley sites. These results are discussed with regards to chemosystematic studies comparing samples collected in different altitudes as well as in the light of a UV-B protective and radical scavenging function of phenolics and their significance for plant life in environments with elevated UV-B radiation.
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Costunolide inhibits proinflammatory cytokines and iNOS in activated murine BV2 microglia.
Rayan, Nirmala Arul; Baby, Nimmi; Pitchai, Daisy; Indraswari, Fransisca; Ling, Eng-Ang; Lu, Jia; Dheen, Thameem
2011-06-01
Costunolide, a sesquiterpene lactone present in Costus speciosus root exerts a variety of pharmacological activity but its effects on neuroinflammation have not been studied. Microglia, the resident phagocytic cells in the central nervous system respond to neuroinflammation and their overwhelming response in turn aggravate brain damage during infection, ischemia and neurodegenerative diseases. In this study, we report the effect of Costunolide on the production of proinflammatory mediators and mechanisms involved in BV2 microglial cells stimulated with LPS. Costunolide attenuated the expression of tumour necrosis factor-alpha, interleukin-1,6, inducible nitric oxide synthase, monocyte chemotactic protein 1 and cyclooxygenase 2 in activated microglia. This Costunolide-mediated inhibition was correspondent with the inhibition of NFkappaB activation. It has been further shown that Costunolide suppressed MAPK pathway activation by inducing MKP-1 production. Collectively our results suggest that Costunolide shows an ability to inhibit expression of multiple neuroinflammatory mediators and this is attributable to the compounds inhibition of NFkappaB and MAPK activation. This novel role of Costunolide upon investigation may aid in developing better therapeutic strategies for treatment of neuroinflammatory diseases.
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Rocha, Danilo D; Dantas, Ivana N F; Albuquerque, Maria Rose Jane R; Montenegro, Raquel C; Pessoa, Cláudia; de Moraes, Manoel Odorico; Pessoa, Otília Deusdênia L; Silveira, Edilberto R; Costa-Lotufo, Letícia V
2007-12-01
A detailed study on the cytotoxic effects of five known constituents isolated from the flowers and roots of Eupatorium betonicaeforme is reported, including 2,2-dimethyl-6-vinylchroman-4-one (1), 2-senecioyl-4-vinylphenol (2), 6-acetyl-2,2-dimethylchroman-4-one (3), (4E)-8beta-angeloyloxy-9beta,10beta-dihydroxy-1-oxogermacra-4,11(13)-dien-12,6alpha-olide (4), and 3beta-hydroxyicosan-1,5beta-olide (5). The sesquiterpene lactone 4 exhibited the highest cytotoxicity, with IC50 values ranging from 3.9 to 9.9 microM, showing some degree of cell selectivity. The antiproliferative activity of 4 was examined towards HL-60 cells, and found to diminish cell viability in a dose-dependent manner. Moreover, at all concentrations tested, there was a decrease in the number of cells capable of incorporating 5-bromo-2'-deoxyuridine (BrdU), indicating disruption of DNA synthesis. The morphological changes induced by 4 were compatible with apoptotic cell death. This work, thus, corroborates the anticancer potential of Eupatorium secondary metabolites.
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Sohn, Sang-Hyun; Yun, Bong-Sik; Kim, So-Young; Choi, Wahn-Soo; Jeon, Hyun-Soo; Yoo, Jun-Sik; Kim, Si-Kwan
2013-01-01
We isolated a sesquiterpene lactone from the methanol extract of the roots of Cosmos bipinnatus, namely, MDI (a mixture of dihydrocallitrisin and isohelenin). The anti-inflammatory activity of MDI was evaluated using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. MDI significantly inhibited the expression of inducible nitric oxide synthase and cyclooxygenase-2. Consistent with these results, the production of NO and prostaglandin E2 (PGE2) was suggested to be suppressed by MDI in a concentration-dependent manner (IC50 value was 0.94 and 2.88 µg mL(-1) for NO and PGE2, respectively). In addition, MDI significantly inhibited the expressions of pro-inflammatory cytokines such as IL-1β, IL-6, IFN-γ and TNF-α. Furthermore, MDI attenuated DNA-binding activity of NF-κB by inhibiting the phosphorylation of IκB. These results indicate that MDI isolated from the roots of C. bipinnatus shows anti-inflammatory activity in LPS-stimulated murine macrophages by modulating the NF-κB pathway.
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Temperature dependencies of Henry’s law constants for different plant sesquiterpenes
Copolovici, Lucian; Niinemets, Ülo
2018-01-01
Sesquiterpenes are plant-produced hydrocarbons with important ecological functions in plant-to-plant and plant-to-insect communication, but due to their high reactivity they can also play a significant role in atmospheric chemistry. So far, there is little information of gas/liquid phase partition coefficients (Henry’s law constants) and their temperature dependencies for sesquiterpenes, but this information is needed for quantitative simulation of the release of sesquiterpenes from plants and modeling atmospheric reactions in different phases. In this study, we estimated Henry’s law constants (Hpc) and their temperature responses for 12 key plant sesquiterpenes with varying structure (aliphatic, mono-, bi- and tricyclic sesquiterpenes). At 25 °C, Henry’s law constants varied 1.4-fold among different sesquiterpenes, and the values were within the range previously observed for monocyclic monoterpenes. Hpc of sesquiterpenes exhibited a high rate of increase, on average ca. 1.5-fold with a 10 °C increase in temperature (Q10). The values of Q10 varied 1.2-fold among different sesquiterpenes. Overall, these data demonstrate moderately high variation in Hpc values and Hpc temperature responses among different sesquiterpenes. We argue that these variations can importantly alter the emission kinetics of sesquiterpenes from plants. PMID:26291755
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Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis.
Want, Muzamil Y; Islammudin, Mohammad; Chouhan, Garima; Ozbak, Hani A; Hemeg, Hassan A; Chattopadhyay, Asoke P; Afrin, Farhat
2017-01-01
Visceral leishmaniasis (VL) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania . Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA) was prepared by thin-film hydration method and optimized using Box-Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of -27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of Leishmania donovani amastigotes and the number of infected macrophages ex vivo with an IC 50 of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a percentage inhibition of 82.4%±3.8% in the liver and 77.6%±5.5% in spleen at the highest dose of 20 mg/kg body weight with modulation of cell-mediated immunity towards protective Th1 type. This study is the first report on the use of a liposomal drug delivery system for artemisinin as a promising alternative intervention against VL.
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Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis
Want, Muzamil Y; Islammudin, Mohammad; Chouhan, Garima; Ozbak, Hani A; Hemeg, Hassan A; Chattopadhyay, Asoke P; Afrin, Farhat
2017-01-01
Visceral leishmaniasis (VL) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania. Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA) was prepared by thin-film hydration method and optimized using Box–Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of −27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of Leishmania donovani amastigotes and the number of infected macrophages ex vivo with an IC50 of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a percentage inhibition of 82.4%±3.8% in the liver and 77.6%±5.5% in spleen at the highest dose of 20 mg/kg body weight with modulation of cell-mediated immunity towards protective Th1 type. This study is the first report on the use of a liposomal drug delivery system for artemisinin as a promising alternative intervention against VL. PMID:28356736
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Changes in volatile compound composition of Antrodia camphorata during solid state fermentation.
Xia, Yongjun; Zhang, Baorong; Li, Weijiang; Xu, Ganrong
2011-10-01
Although the volatiles present in mushrooms and fungi have been investigated by many researchers, including Antrodia camphorata in submerged fermentation, there are few data available regarding changes in volatile compounds during fermentation. Our research has revealed that solid state fermentation of A. camphorata is highly odiferous compared with submerged cultures and the odor changed with increasing culture time. Therefore the aim of this study was to investigate the changes in volatile compound composition of A. camphorata during solid state fermentation. Altogether, 124 major volatile compounds were identified. The volatile compounds produced by A. camphorata during growth in solid state fermentation were quite different. Oct-1-en-3-ol, octan-3-one and methyl 2-phenylacetate were predominant in exponential growth phase production, while the dominant volatiles produced in stationary phase were octan-3-one and methyl 2-phenylacetate. In stationary phase, lactone compounds in A. camphorata, such as 5-butyloxolan-2-one, 5-heptyloxolan-2-one, 6-heptyloxan-2-one, contributed greatly to peach and fruit-like flavor. Terpene and terpene alcohol compounds, such as 1-terpineol, L-linalool, T-cadinol, (E, E)-farnesol, β-elemene, cis-α-bisabolene and α-muurolene, made different contributions to herbal fresh aroma in A. camphorata. Nineteen volatile sesquiterpenes were detected from solid state fermentation of A. camphorata. The compounds 5-n-butyl-5H-furan-2-one, β-ionone, (-)-caryophyllene oxide, aromadendrene oxide, diepi-α-cedrene epoxide, β-elemene, α-selinene, α-muurolene, azulene, germacrene D, γ-cadinene and 2-methylpyrazine have not hitherto been reported in A. camphorata. The preliminary results suggest that the aroma-active compounds produced by A camphorata in solid state fermentation might serve as an important source of natural aroma compounds for the food and cosmetic industries or antibiotic activity compounds. The sesquiterpenes could be identified as possible taxonomic markers for A. camphorata. Copyright © 2011 Society of Chemical Industry.
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Pratheeshkumar, P; Kuttan, Girija
2011-09-01
One of the major reasons for the rapid progression of cancers is the ability of tumor cells to escape from the immune surveillance mechanism of the body. Modulation of immune responses is highly relevant in tumor cell destruction. Effect of vernolide-A on the cell-mediated immune (CMI) response in metastatic condition was studied using C57BL/6 mice model. Administration of vernolide-A enhanced natural killer (NK) cell activity, antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent complement-mediated cytotoxicity (ACC) and the activity was observed in treated group much earlier compared with the metastatic tumor-bearing control. Administration of vernolide-A significantly enhanced the production of interleukin (IL)-2 and interferon-gamma (IFN-γ) in metastatic tumor-bearing animals. In addition, vernolide-A significantly down-regulated the serum levels of proinflammatory cytokines such as IL-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) during metastasis. All these results demonstrate that vernolide-A could enhance the immune response against metastatic progression of B16F-10 melanoma cells in mice.
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Phytotoxic potential of Onopordum acanthium L. (Asteraceae).
Watanabe, Yusuke; Novaes, Paula; Varela, Rosa M; Molinillo, José M G; Kato-Noguchi, Hisashi; Macías, Francisco A
2014-08-01
Onopordum acanthium L. (Asteraceae) is a plant native to southern Europe and southwestern Asia, but it is invasive in disturbed areas and agricultural fields around the world, causing many agronomic problems by interfering with crops or preventing animals from grazing on pastures. Allelopathy could be one of the reasons that this plant has spread over different continents. The aim of the present study was to bioprospect O. acanthium leaf extracts through the isolation and purification of allelopathic secondary metabolites with phytotoxicity to explain their invasive behavior. Phytotoxic activity was tested using etiolated wheat coleoptiles. The most active extract was selected to perform a bioassay-guided isolation of two flavonoids, pectolarigenin (1) and scutellarein 4'-methyl ether (2), and two sesquiterpene lactones, elemanolide 11(13)-dehydromelitensin β-hydroxyisobutyrate (3) and acanthiolide (4). All compounds were isolated for the first time from O. acanthium, and acanthiolide (4) is described for the first time. Compound 3 strongly inhibited the growth of wheat coleoptiles and 1 showed an intermediate effect. The results indicate that these compounds could contribute to the invasion of O. acanthium in ecological systems and agricultural fields. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.
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Li, Changlong; Wu, Hezhen; Yang, Yanfang; Liu, Jianwen; Chen, Zhenwen
2018-06-01
Multidrug resistance (MDR) is a major obstacle to cancer chemotherapy efficacy. In the present study, 6-O-angeloylplenolin repressed the overexpression of ATP binding cassette subfamily B member 1 ( MDR1 ) and increasing the intracellular concentration of anticancer drugs. A reduction in P-glycoprotein expression (encoded by MDR1 ) was observed in parallel with a decline in mRNA expression in vincristine-resistant HCT (HCT-8/VCR) cells treated with 6-O-angeloylplenolin. In addition, 6-O-angeloylplenolin suppressed the activity of the MDR1 gene promoter. Treatment with 6-O-angeloylplenolin also decreased the amount of the specific protein complex that interacted with the MDR1 gene promoter in HCT-8/VCR cells, potentially leading to the suppression of MDR1 expression. Treatment with 6-O-angeloylplenolin inhibited the nuclear translocation of Y-box binding protein-1 in HCT-8/VCR cells treated with 6-O-angeloylplenolin, contributing to the negative regulation of MDR1 . Finally, 6-O-angeloylplenolin reversed VCR resistance in an HCT/VCR xenograft model. In conclusion, 6-O-angeloylplenolin exhibited a MDR-reversing effect by downregulating MDR1 expression and could represent a novel adjuvant agent for chemotherapy.
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NASA Astrophysics Data System (ADS)
Hussain, Naseer; Abbasi, Tasneem; Abbasi, S. A.
2016-06-01
In a first study of its kind, the composition of vermicompost derived solely from the toxic and allelopathic weed lantana has been investigated using UV-visible and Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric (TG) and differential scanning calorimetry (DSC), gas chromatography-mass spectometry (GC-MS), and scanning electron microscopy (SEM). The studies reveal that a sharp reduction in humification index, substantial mineralization of organic matter and degradation of complex aromatics such as lignin and polyphenols into simpler carbohydrates and lipids occur in the course of vermicomposting. GC-MS analysis shows significant fragmentation, bio-oxidation and molecular rearrangements of chemical compounds in vermicompost in comparison to those in lantana. SEM micrographs of vermicompost reflect strong disaggregation of material compared to the much better formed lantana matrices. The phenols and sesquiterpene lactones which are specifically responsible for the toxicity and allelopathy of lantana are seen to get significantly degraded in the course of vermicomposting - turning it into a plant-friendly organic fertilizer. The study leads to the possibility that the millions of tons of phytomass that is generated annually by lantana can be gainfully utilized in producing organic fertilizer via vermicomposting.
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Within-canopy sesquiterpene ozonolysis in Amazonia
NASA Astrophysics Data System (ADS)
Jardine, K.; YañEz Serrano, A.; Arneth, A.; Abrell, L.; Jardine, A.; van Haren, J.; Artaxo, P.; Rizzo, L. V.; Ishida, F. Y.; Karl, T.; Kesselmeier, J.; Saleska, S.; Huxman, T.
2011-10-01
Through rapid reactions with ozone, which can initiate the formation of secondary organic aerosols, the emission of sesquiterpenes from vegetation in Amazonia may have significant impacts on tropospheric chemistry and climate. Little is known, however, about sesquiterpene emissions, transport, and chemistry within plant canopies owing to analytical difficulties stemming from very low ambient concentrations, high reactivities, and sampling losses. Here, we present ambient sesquiterpene concentration measurements obtained during the 2010 dry season within and above a primary tropical forest canopy in Amazonia. We show that by peaking at night instead of during the day, and near the ground instead of within the canopy, sesquiterpene concentrations followed a pattern different from that of monoterpenes, suggesting that unlike monoterpene emissions, which are mainly light dependent, sesquiterpene emissions are mainly temperature dependent. In addition, we observed that sesquiterpene concentrations were inversely related with ozone (with respect to time of day and vertical concentration), suggesting that ambient concentrations are highly sensitive to ozone. These conclusions are supported by experiments in a tropical rain forest mesocosm, where little atmospheric oxidation occurs and sesquiterpene and monoterpene concentrations followed similar diurnal patterns. We estimate that the daytime dry season ozone flux of -0.6 to -1.5 nmol m-2 s-1 due to in-canopy sesquiterpene reactivity could account for 7%-28% of the net ozone flux. Our study provides experimental evidence that a large fraction of total plant sesquiterpene emissions (46%-61% by mass) undergo within-canopy ozonolysis, which may benefit plants by reducing ozone uptake and its associated oxidative damage.
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Discovery of new lactones in sweet cream butter oil.
Sarrazin, Elise; Frerot, Eric; Bagnoud, Alain; Aeberhardt, Kasia; Rubin, Mark
2011-06-22
Sweet cream butter oil was analyzed to identify new volatile compounds that may contribute to its flavor, with an emphasis on lactones. The volatile part of butter oil was obtained by using short-path distillation. As some previously unknown lactones were detected in this first extract, it was fractionated further. The fatty acids were removed, and the extract was fractionated by flash chromatography. Three lactonic fractions possessing a creamy, buttery, and fatty character were investigated in depth by gas chromatography (GC) and mass spectrometry (MS) (EI and CI) and high-resolution GC-time-of-flight MS. Many lactones were identified by their mass fragmentation and by comparison with reference materials synthesized during this work. Six γ-lactones, five δ-lactones, and one ε-lactone were identified for the first time in butter oil, seven of them for the first time in a natural product. The possible contribution of these new lactones to the aroma of butter oil is briefly discussed.
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Hirsutane-type sesquiterpenes with uncommon modifications from three basidiomycetes.
Liermann, Johannes C; Schüffler, Anja; Wollinsky, Beate; Birnbacher, Judith; Kolshorn, Heinz; Anke, Timm; Opatz, Till
2010-05-07
From three basidiomycetes, Xeromphalina sp., Stereum sp., and Pleurocybella porrigens, six triquinane sesquiterpenes with unprecendented modifications and a rearranged sesquiterpene related to coriolin C have been isolated. Their isolation, structure elucidation, and biological evaluation are described.
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Jones, Christopher G; Ghisalberti, Emilio L; Plummer, Julie A; Barbour, Elizabeth L
2006-11-01
A chemotaxonomic approach was used to investigate biosynthetic relationships between heartwood sesquiterpenes in Indian sandalwood, Santalum album L. Strong, linear relationships exist between four structural classes of sesquiterpenes; alpha- and beta-santalenes and bergamotene; gamma- and beta-curcumene; beta-bisabolene and alpha-bisabolol and four unidentified sesquiterpenes. All samples within the heartwood yielded the same co-occurrence patterns, however wood from young trees tended to be more variable. It is proposed that the biosynthesis of each structural class of sesquiterpene in sandalwood oil is linked through common carbocation intermediates. Lack of co-occurrence between each structural class suggests that four separate cyclase enzymes may be operative. The biosynthesis of sandalwood oil sesquiterpenes is discussed with respect to these co-occurrence patterns. Extractable oil yield was correlated to heartwood content of each wood core and the oil composition did not vary significantly throughout the tree.
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21 CFR 184.1318 - Glucono delta-lactone.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Glucono delta-lactone. 184.1318 Section 184.1318... Listing of Specific Substances Affirmed as GRAS § 184.1318 Glucono delta-lactone. (a) Glucono delta-lactone (C6H10O6, CAS Reg. No. 90-80-2), also called D-gluconic acid delta-lactone or D-glucono-1,5...
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21 CFR 184.1318 - Glucono delta-lactone.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glucono delta-lactone. 184.1318 Section 184.1318... Listing of Specific Substances Affirmed as GRAS § 184.1318 Glucono delta-lactone. (a) Glucono delta-lactone (C6H10O6, CAS Reg. No. 90-80-2), also called D-gluconic acid delta-lactone or D-glucono-1,5...
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New sesquiterpenes from Euonymus europaeus (Celastraceae).
Descoins, Charles; Bazzocchi, Isabel López; Ravelo, Angel Gutiérrez
2002-02-01
A new sesquiterpene evoninate alkaloid (1), and two sesquiterpenes (2, 3) with a dihydro-beta-agarofuran skeleton, along with three known sesquiterpenes (4-6), were isolated from the seeds of Euonymus europaeus. Their structures were elucidated by high resolution mass analysis, and one- and two-dimensional (1D and 2D) NMR spectroscopy, including homonuclear and heteronuclear correlation [correlation spectroscopy (COSY), rotating frame Overhauser enhancement spectroscopy (ROESY), heteronuclear single quantum coherence (HSQC), and heteronuclear multiple bond correlation (HMBC)] experiments.
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Hassane, Duane C.; Guzman, Monica L.; Corbett, Cheryl; Li, Xiaojie; Abboud, Ramzi; Young, Fay; Liesveld, Jane L.; Carroll, Martin
2008-01-01
Increasing evidence indicates that malignant stem cells are important for the pathogenesis of acute myelogenous leukemia (AML) and represent a reservoir of cells that drive the development of AML and relapse. Therefore, new treatment regimens are necessary to prevent relapse and improve therapeutic outcomes. Previous studies have shown that the sesquiterpene lactone, parthenolide (PTL), ablates bulk, progenitor, and stem AML cells while causing no appreciable toxicity to normal hematopoietic cells. Thus, PTL must evoke cellular responses capable of mediating AML selective cell death. Given recent advances in chemical genomics such as gene expression-based high-throughput screening (GE-HTS) and the Connectivity Map, we hypothesized that the gene expression signature resulting from treatment of primary AML with PTL could be used to search for similar signatures in publicly available gene expression profiles deposited into the Gene Expression Omnibus (GEO). We therefore devised a broad in silico screen of the GEO database using the PTL gene expression signature as a template and discovered 2 new agents, celastrol and 4-hydroxy-2-nonenal, that effectively eradicate AML at the bulk, progenitor, and stem cell level. These findings suggest the use of multicenter collections of high-throughput data to facilitate discovery of leukemia drugs and drug targets. PMID:18305216
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Deshpande, Ashish B; Anamika, Krishanpal; Jha, Vineet; Chidley, Hemangi G; Oak, Pranjali S; Kadoo, Narendra Y; Pujari, Keshav H; Giri, Ashok P; Gupta, Vidya S
2017-08-18
Alphonso is known as the "King of mangos" due to its unique flavor, attractive color, low fiber pulp and long shelf life. We analyzed the transcriptome of Alphonso mango through Illumina sequencing from seven stages of fruit development and ripening as well as flower. Total transcriptome data from these stages ranged between 65 and 143 Mb. Importantly, 20,755 unique transcripts were annotated and 4,611 were assigned enzyme commission numbers, which encoded 142 biological pathways. These included ethylene and flavor related secondary metabolite biosynthesis pathways, as well as those involved in metabolism of starch, sucrose, amino acids and fatty acids. Differential regulation (p-value ≤ 0.05) of thousands of transcripts was evident in various stages of fruit development and ripening. Novel transcripts for biosynthesis of mono-terpenes, sesqui-terpenes, di-terpenes, lactones and furanones involved in flavor formation were identified. Large number of transcripts encoding cell wall modifying enzymes was found to be steady in their expression, while few were differentially regulated through these stages. Novel 79 transcripts of inhibitors of cell wall modifying enzymes were simultaneously detected throughout Alphonso fruit development and ripening, suggesting controlled activity of these enzymes involved in fruit softening.
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NASA Astrophysics Data System (ADS)
Sampaio, Bruno Leite; Edrada-Ebel, Ruangelie; da Costa, Fernando Batista
2016-07-01
Tithonia diversifolia is an invasive weed commonly found in tropical ecosystems. In this work, we investigate the influence of different abiotic environmental factors on the plant’s metabolite profile by multivariate statistical analyses of spectral data deduced by UHPLC-DAD-ESI-HRMS and NMR methods. Different plant part samples of T. diversifolia which included leaves, stems, roots, and inflorescences were collected from two Brazilian states throughout a 24-month period, along with the corresponding monthly environmental data. A metabolomic approach employing concatenated LC-MS and NMR data was utilised for the first time to study the relationships between environment and plant metabolism. A seasonal pattern was observed for the occurrence of metabolites that included sugars, sesquiterpenes lactones and phenolics in the leaf and stem parts, which can be correlated to the amount of rainfall and changes in temperature. The distribution of the metabolites in the inflorescence and root parts were mainly affected by variation of some soil nutrients such as Ca, Mg, P, K and Cu. We highlight the environment-metabolism relationship for T. diversifolia and the combined analytical approach to obtain reliable data that contributed to a holistic understanding of the influence of abiotic environmental factors on the production of metabolites in various plant parts.
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Belz, Regina G
2007-09-30
Parthenium hysterophorus L. is an invasive weed that biosynthesizes several phytochemicals. The sesquiterpene lactone parthenin receives most attention regarding allelopathy of the plant or potential herbicidal properties. Since parthenin exhibits dose-dependent phytotoxicity with low dose stimulation, this study investigated the occurrence and temporal features of parthenin hormesis in Sinapis arvensis L. sprayed with parthenin under semi-natural conditions. Dose/response studies showed that the occurrence and the magnitude of hormesis depended on climatic conditions and the parameter measured. Within the tested dose range, stimulatory responses were only observed under less-stressful conditions and were most pronounced for leaf area growth [138 % of control; 13 days after treatment (DAT)]. Temporal assessment of leaf area development showed that doses causing a stimulatory response at the end of the experiment (< 0.42 +/- 0.04 kg/ha; 13 DAT) were initially inhibitory up to ED(50) values (2 DAT). This clearly demonstrated an over-compensatory response. Inhibition of leaf area at 13 DAT reached ED(50) values on average at 0.62 +/-0.12 kg/ha, and S. arvensis was completely inhibited at doses exceeding 1.81 +/-0.56 kg/ha (ED(90)). Based on these findings, implications of parthenin hormesis are discussed with respect to allelopathy of P. hysterophorus and exploitation of growth stimulatory responses in agriculture.
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Sampaio, Bruno Leite; Edrada-Ebel, RuAngelie; Da Costa, Fernando Batista
2016-01-01
Tithonia diversifolia is an invasive weed commonly found in tropical ecosystems. In this work, we investigate the influence of different abiotic environmental factors on the plant’s metabolite profile by multivariate statistical analyses of spectral data deduced by UHPLC-DAD-ESI-HRMS and NMR methods. Different plant part samples of T. diversifolia which included leaves, stems, roots, and inflorescences were collected from two Brazilian states throughout a 24-month period, along with the corresponding monthly environmental data. A metabolomic approach employing concatenated LC-MS and NMR data was utilised for the first time to study the relationships between environment and plant metabolism. A seasonal pattern was observed for the occurrence of metabolites that included sugars, sesquiterpenes lactones and phenolics in the leaf and stem parts, which can be correlated to the amount of rainfall and changes in temperature. The distribution of the metabolites in the inflorescence and root parts were mainly affected by variation of some soil nutrients such as Ca, Mg, P, K and Cu. We highlight the environment-metabolism relationship for T. diversifolia and the combined analytical approach to obtain reliable data that contributed to a holistic understanding of the influence of abiotic environmental factors on the production of metabolites in various plant parts. PMID:27383265
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Matusova, Radoslava; Rani, Kumkum; Verstappen, Francel W.A.; Franssen, Maurice C.R.; Beale, Michael H.; Bouwmeester, Harro J.
2005-01-01
The seeds of parasitic plants of the genera Striga and Orobanche will only germinate after induction by a chemical signal exuded from the roots of their host. Up to now, several of these germination stimulants have been isolated and identified in the root exudates of a series of host plants of both Orobanche and Striga spp. In most cases, the compounds were shown to be isoprenoid and belong to one chemical class, collectively called the strigolactones, and suggested by many authors to be sesquiterpene lactones. However, this classification was never proven; hence, the biosynthetic pathways of the germination stimulants are unknown. We have used carotenoid mutants of maize (Zea mays) and inhibitors of isoprenoid pathways on maize, cowpea (Vigna unguiculata), and sorghum (Sorghum bicolor) and assessed the effects on the root exudate-induced germination of Striga hermonthica and Orobanche crenata. Here, we show that for these three host and two parasitic plant species, the strigolactone germination stimulants are derived from the carotenoid pathway. Furthermore, we hypothesize how the germination stimulants are formed. We also discuss this finding as an explanation for some phenomena that have been observed for the host-parasitic plant interaction, such as the effect of mycorrhiza on S. hermonthica infestation. PMID:16183851
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Tanaka, Yuka Tsuda; Tanaka, Kiyotaka; Kojima, Hiroyuki; Hamada, Tomoji; Masutani, Teruaki; Tsuboi, Makoto; Akao, Yukihiro
2013-01-15
Aging of skin is characterized by skin wrinkling, laxity, and pigmentation induced by several environmental stress factors. Histological changes during the photoaging of skin include hyperproliferation of keratinocytes and melanocytes causing skin wrinkles and pigmentation. Nuclear factor kappa B (NF-κB) is one of the representative transcription factors active in conjunction with inflammation. NF-κB is activated by stimulation such as ultraviolet rays and inflammatory cytokines and induces the expression of various genes such as those of basic fibroblast growth factor (bFGF) and matrix metalloprotease-1 (MMP-1). We screened several plant extracts for their possible inhibitory effect on the transcriptional activity of NF-κB. One of them, an extract from Cynara scolymus L., showed a greatest effect on the suppression of NF-κB transactivation. As a result, we found that cynaropicrin, which is a sesquiterpene lactone, inhibited the NF-κB-mediated transactivation of bFGF and MMP-1. Furthermore, it was confirmed that in an in vivo mouse model cynaropicrin prevented skin photoaging processes leading to the hyperproliferation of keratinocytes and melanocytes. These findings taken together indicate that cynaropicrin is an effective antiphotoaging agent that acts by inhibiting NF-κB-mediated transactivation. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Antioxidant Properties of Artemisia annua Extracts in Model Food Emulsions
Skowyra, Monika; Gallego, Maria Gabriela; Segovia, Francisco; Almajano, Maria Pilar
2014-01-01
Artemisia annua is currently the only commercial source of the sesquiterpene lactone artemisinin. Although artemisinin is a major bioactive component present in this Chinese herb, leaf flavonoids have shown a variety of biological activities. The polyphenolic profile of extract from leaves of A. annua was assessed as a source of natural antioxidants. Total phenolic content and total flavonoid content were established and three assays were used to measure the antioxidant capacity of the plant extract. The measurement of scavenging capacity against the 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical cation, the oxygen radical absorbance capacity (ORAC) and the ferric reducing antioxidant power (FRAP) were 314.99 µM Trolox equivalents (TE)/g DW, 736.26 µM TE/g DW and 212.18 µM TE/g DW, respectively. A. annua extracts also showed good antioxidant properties in 10% sunflower oil-in-water emulsions during prolonged storage (45 days) at 32 °C. Artemisia extract at 2 g/L was as effective as butylated hydroxyanisole (BHA) at 0.02 g/L in slowing down the formation of hydroperoxides as measured by peroxide value and thiobarbituric acid reactive substances. The results of this study indicate that extract of A. annua may be suitable for use in the food matrix as substitutes for synthetic antioxidants. PMID:26784667
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Sampaio, Bruno Leite; Edrada-Ebel, RuAngelie; Da Costa, Fernando Batista
2016-07-07
Tithonia diversifolia is an invasive weed commonly found in tropical ecosystems. In this work, we investigate the influence of different abiotic environmental factors on the plant's metabolite profile by multivariate statistical analyses of spectral data deduced by UHPLC-DAD-ESI-HRMS and NMR methods. Different plant part samples of T. diversifolia which included leaves, stems, roots, and inflorescences were collected from two Brazilian states throughout a 24-month period, along with the corresponding monthly environmental data. A metabolomic approach employing concatenated LC-MS and NMR data was utilised for the first time to study the relationships between environment and plant metabolism. A seasonal pattern was observed for the occurrence of metabolites that included sugars, sesquiterpenes lactones and phenolics in the leaf and stem parts, which can be correlated to the amount of rainfall and changes in temperature. The distribution of the metabolites in the inflorescence and root parts were mainly affected by variation of some soil nutrients such as Ca, Mg, P, K and Cu. We highlight the environment-metabolism relationship for T. diversifolia and the combined analytical approach to obtain reliable data that contributed to a holistic understanding of the influence of abiotic environmental factors on the production of metabolites in various plant parts.
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Phytoceuticals in Acute Pancreatitis: Targeting the Balance between Apoptosis and Necrosis
Gaman, Laura; Robu, Georgiana Catalina; Radoi, Mugurel Petrinel; Stroica, Laura; Badea, Mihaela
2018-01-01
Despite recent advances in understanding the complex pathogenesis of pancreatitis, the management of the disease remains suboptimal. The use of phytoceuticals (plant-derived pleiotropic multitarget molecules) represents a new research trend in pancreatology. The purpose of this review is to discuss the phytoceuticals with pancreatoprotective potential in acute pancreatitis and whose efficacy is based, at least in part, on their capacity to modulate the acinar cell death. The phytochemicals selected, belonging to such diverse classes as polyphenols, flavonoids, lignans, anthraquinones, sesquiterpene lactones, nitriles, and alkaloids, target the balance between apoptosis and necrosis. Activation of apoptosis via various mechanisms (e.g., inhibition of X-linked inhibitor of apoptosis proteins by embelin, upregulation of FasL gene expression by resveratrol) and/or inhibition of necrosis seem to represent the essential key for decreasing the severity of the disease. Apart from targeting the apoptosis/necrosis balance, the phytochemicals displayed other specific protective activities: inhibition of inflammasome (e.g., rutin), suppression of neutrophil infiltration (e.g., ligustrazine, resveratrol), and antioxidant activity. Even though many of the selected phytoceuticals represent a promising therapeutic alternative, there is a shortage of human evidence, and further studies are required to provide solid basis to justify their use in the treatment of pancreatitis. PMID:29686719
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Johansson, Eva; Prade, Thomas; Angelidaki, Irini; Svensson, Sven-Erik; Newson, William R.; Gunnarsson, Ingólfur Bragi; Persson Hovmalm, Helena
2015-01-01
Biorefinery applications are receiving growing interest due to climatic and waste disposal issues and lack of petroleum resources. Jerusalem artichoke (Helianthus tuberosus L.) is suitable for biorefinery applications due to high biomass production and limited cultivation requirements. This paper focuses on the potential of Jerusalem artichoke as a biorefinery crop and the most viable products in such a case. The carbohydrates in the tubers were found to have potential for production of platform chemicals, e.g., succinic acid. However, economic analysis showed that production of platform chemicals as a single product was too expensive to be competitive with petrochemically produced sugars. Therefore, production of several products from the same crop is a must. Additional products are protein based ones from tubers and leaves and biogas from residues, although both are of low value and amount. High bioactive activity was found in the young leaves of the crop, and the sesquiterpene lactones are of specific interest, as other compounds from this group have shown inhibitory effects on several human diseases. Thus, future focus should be on understanding the usefulness of small molecules, to develop methods for their extraction and purification and to further develop sustainable and viable methods for the production of platform chemicals. PMID:25913379
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Inhibition of Nod2 Signaling and Target Gene Expression by Curcumin
Huang, Shurong; Zhao, Ling; Kim, Kihoon; Lee, Dong Seok; Hwang, Daniel H.
2008-01-01
Nod2 is an intracellular pattern recognition receptor that detects a conserved moiety of bacterial peptidoglycan and subsequently activates proinflammatory signaling pathways. Mutations in Nod2 have been implicated to be linked to inflammatory granulomatous disorders, such as Crohn's disease and Blau syndrome. Many phytochemicals possess anti-inflammatory properties. However, it is not known whether any of these phytochemicals might modulate Nod2-mediated immune responses and thus might be of therapeutic value for the intervention of these inflammatory diseases. In this report, we demonstrate that curcumin, a polyphenol found in the plant Curcuma longa, and parthenolide, a sesquiterpene lactone, suppress both ligand-induced and lauric acid-induced Nod2 signaling, leading to the suppression of nuclear factor-κB activation and target gene interleukin-8 expression. We provide molecular and biochemical evidence that the suppression is mediated through the inhibition of Nod2 oligomerization and subsequent inhibition of downstream signaling. These results demonstrate for the first time that curcumin and parthenolide can directly inhibit Nod2-mediated signaling pathways at the receptor level and suggest that Nod2-mediated inflammatory responses can be modulated by these phytochemicals. It remains to be determined whether these phytochemicals possess protective or therapeutic efficacy against Nod2-mediated inflammatory disorders. PMID:18413660
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Sesquiterpenes from the Formosan stolonifer Tubipora musica.
Duh, C Y; Chen, K J; El-Gamal, A A; Dai, C F
2001-11-01
Eight new sesquiterpenes, tubipolides A-G (1-7) and tubiporone (8) (novel carbon skeleton), and a known sesquiterpene, spirotubipolide, have been isolated from the Formosan stolonifer Tubipora musica. The structures of compounds 1-8 were determined by 1D and 2D NMR spectral analysis.
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Male-specific sesquiterpenes from Phyllotreta flea beetles
USDA-ARS?s Scientific Manuscript database
Flea beetles in several genera are known to possess male-specific sesquiterpenes, at least some of which serve as aggregation pheromones that attract both sexes. In continuing research on the chemical ecology of Phyllotreta flea beetles, six new male-specific sesquiterpenes were identified, one fro...
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Silk, Peter J; Ryall, Krista; Mayo, Peter; Lemay, Matthew A; Grant, Gary; Crook, Damon; Cossé, Allard; Fraser, Ivich; Sweeney, Jon D; Lyons, D Barry; Pitt, Doug; Scarr, Taylor; Magee, David
2011-08-01
Analysis by gas chromatography/mass spectrometry (GC/MS) of volatiles from virgin female emerald ash borer, Agrilus planipennis Fairmaire confirmed the emission of (3Z)-lactone [(3Z)-dodecen-12-olide] but not its geometric isomer, (3E)-lactone [(3E)-dodecen-12-olide]. Gas chromatographic/electroantennographic (GC/EAD) analysis of synthetic (3Z)-lactone, which contained 10% (3E)-lactone, showed a strong response of male and female antennae to both isomers. EAG analysis with 0.01- to 100-μg dosages showed a positive dose response, with females giving significantly higher responses than males. In field experiments with sticky purple prism traps, neither lactone isomer affected catches when combined with ash foliar or cortical volatiles (green leaf volatiles or Phoebe oil, respectively). However, on green prism traps, the (3Z)-lactone significantly increased capture of male A. planipennis when traps were deployed in the canopy. Captures of males on traps with both (3E)-lactone and (3Z)-hexenol or with (3Z)-lactone and (3Z)-hexenol were increased by 45-100%, respectively, compared with traps baited with just (3Z)-hexenol. In olfactometer bioassays, males were significantly attracted to (3E)-lactone, but not the (3Z)-lactone or a 60:40 (3E):(3Z) blend. The combination of either (3E)- or (3Z)-lactone with Phoebe oil was not significantly attractive to males. Males were highly attracted to (3Z)-hexenol and the (3Z)-lactone + (3Z)-hexenol combination, providing support for the field trapping results. These data are the first to demonstrate increased attraction with a combination of a pheromone and a green leaf volatile in a Buprestid species.
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Kraehenbuehl, Karin; Page-Zoerkler, Nicole; Mauroux, Olivier; Gartenmann, Karin; Blank, Imre; Bel-Rhlid, Rachid
2017-03-01
Chlorogenic acid lactones have been identified as key contributors to coffee bitterness. These compounds are formed during roasting by dehydration and cyclization of their precursors, the chlorogenic acids (CGAs). In the present study, we investigated an approach to decompose these lactones in a selective way without affecting the positive coffee attributes developed during roasting. A model system composed of (3-caffeoylquinic acid lactone (3-CQAL), 4- caffeoyl quinic acid lactone (4-CQAL), and 4-feruloylquinic acid lactone (4-FQAL)) was used for the screening of enzymes before treatment of the coffee extracts. Hog liver esterase (HLE) hydrolyzed chlorogenic acid lactones (CQALs, FQALs) selectively, while chlorogenate esterase hydrolyzed all chlorogenic acids (CQAs, FQAs) and their corresponding lactones (CQALs, FQALs) in a non-selective way. Enzymatically treated coffee samples were evaluated for their bitterness by a trained sensory panel and were found significantly less bitter than the untreated samples. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Fragrance material review on 16-hydroxy-7-hexadecenoic acid lactone.
McGinty, D; Letizia, C S; Api, A M
2011-12-01
A toxicologic and dermatologic review of 16-hydroxy-7-hexadecenoic acid lactone when used as a fragrance ingredient is presented. 16-Hydroxy-7-hexadecenoic acid lactone is a member of the fragrance structural group macrocyclic lactone and lactide derivatives. The fragrance ingredient described herein is one of 12 structurally diverse C14, C15 and C16 compounds that include (1) saturated mono-and (2) saturated di-ester lactones and (3) unsaturated lactones. For the latter, the double bond is not adjacent to (in conjugation with) the ester group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to 16-hydroxy-7-hexadecenoic acid lactone and is not intended as a stand-alone document. Available data were evaluated, then summarized, and include physical properties data. A safety assessment of the entire macrocyclic lactone and lactide derivatives will be published simultaneously with this document. Please refer to Belsito et al., 2011 for an overall assessment of the safe use of this material and all macrocyclic lactone and lactide derivatives in fragrances. Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Hanifin, J.H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2011. A toxicologic and dermatologic assessment of macrocylic lactones and lactide derivatives when used as fragrance ingredients. Copyright © 2011. Published by Elsevier Ltd.
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Honda, Sari; Miura, Yukari; Masuda, Akiko; Masuda, Toshiya
2014-01-01
Xanthine oxidase (XO) inhibitory activity has been found in boiling water extracts from roasted coffee beans. Therefore, assay-guided purification of the extracts was performed using size-exclusion column chromatography, and subsequently with reversed phase HPLC to afford lactone derivatives of chlorogenic acids. Among the tested lactones, crypto- and neochlorogenic lactones showed potent XO inhibitory activities compared with three major chlorogenic acids found in coffee beans. These XO inhibitory lactones may ameliorate gout and hyperuricemia in humans who drink coffee.
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Mass spectrometry analysis of terpene lactones in Ginkgo biloba.
Ding, Shujing; Dudley, Ed; Song, Qingbao; Plummer, Sue; Tang, Jiandong; Newton, Russell P; Brenton, A Gareth
2008-01-01
Terpene lactones are a family of compounds with unique chemical structures, first recognised in an extract of Ginkgo biloba. The discovery of terpene lactone derivatives has recently been reported in more and more plant extracts and even food products. In this study, mass spectrometric characteristics of the standard terpene lactones in Ginkgo biloba were comprehensively studied using both an ion trap and a quadrupole time-of-flight (QTOF) mass spectrometer. The mass spectral fragmentation data from both techniques was compared to obtain the mass spectrometric fragmentation pathways of the terpene lactones with high confidence. The data obtained will facilitate the analysis and identification of terpene lactones in future plant research via the fragmentation knowledge reported here.
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Secondary organic aerosol from sesquiterpene and monoterpene emissions in the United States.
Sakulyanontvittaya, Tanarit; Guenther, Alex; Helmig, Detlev; Milford, Jana; Wiedinmyer, Christine
2008-12-01
Emissions of volatile organic compounds (VOC) from vegetation are believed to be a major source of secondary organic aerosol (SOA), which in turn comprises a large fraction of fine particulate matter in many areas. Sesquiterpenes are a class of biogenic VOC with high chemical reactivity and SOA yields. Sesquiterpenes have only recently been quantified in emissions from a wide variety of plants. In this study, a new sesquiterpene emission inventory is used to provide input to the Models-3 Community Multiscale Air Quality (CMAQ) model. CMAQ is used to estimate the contribution of sesquiterpenes and monoterpenes to SOA concentrations over the contiguous United States. The gas-particle partitioning module of CMAQ was modified to include condensable products of sesquiterpene oxidation and to update values of the enthalpy of vaporization. The resulting model predicts July monthly average surface concentrations of total SOA in the eastern U.S. ranging from about 0.2-0.8 microg m(-3). This is roughly double the amount of SOA produced in this region when sesquiterpenes are not included. Even with sesquiterpenes included, however, the model significantly underpredicts surface concentrations of particle-phase organic matter compared to observed values. Treating all SOA as capable of undergoing polymerization increases predicted monthly average surface concentrations in July to 0.4-1.2 microg m(-3), in closer agreement with observations. Using the original enthalpy of vaporization value in CMAQ in place of the values estimated from the recent literature results in predicted SOA concentrations of about 0.3-1.3 microg m(-3).
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ERIC Educational Resources Information Center
Sales, Eric S.; Silveira, Gustavo P.
2015-01-01
Lactone-size identification of [subscript D]-ribonolactone derivatives has been debated for four decades due to complex lactone-ring rearrangements and acetal migration. This laboratory experiment for an upper-division undergraduate organic chemistry laboratory course describes a fast and reliable assignment of lactone-size derivatives from…
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Voevodina, Irina; Scandola, Mariastella; Zhang, Junwei; Jiang, Zhaozhong
2014-01-01
Polymers bearing amino functional groups are an important class of materials capable of serving as non-viral carriers for DNA delivery to living cells. In this work biodegradable poly(amine- co -ester) terpolymers were synthesized via ring-opening and polycondensation copolymerization of lactone (ε-caprolactone (CL), ω-dodecalactone, ω-pentadecalactone (PDL), and ω-hexadecalactone) with diethyl sebacate (DES) and N-methyldiethanolamine (MDEA) in diphenyl ether, catalyzed by Candida antarctica lipase B (CALB). All lactone-DES-MDEA terpolymers had random distributions of lactone, sebacate, MDEA repeat units in the polymer chains. PDL-DES-MDEA terpolymers were studied in the composition range from 21 mol% to 90 mol% PDL whereas the terpolymers with other lactones were investigated at a single composition (80 mol% lactone). DSC and WAXS analyses showed that all investigated terpolymers crystallize in their respective homopolylactone crystal lattice. Terpolymers with large lactones and a high lactone content melt well above room temperature and are hard solids, whereas terpolymers with small lactones (e.g. CL) or with a low lactone content melt below/around ambient temperature and are waxy/gluey materials. Given the importance of hydrophobicity in influencing gene delivery, water contact angle measurements were carried out on lactone-DES-MDEA terpolymers showing that it is possible to tune the hydrophilic-to-hydrophobic balance by varying polymer composition and size of lactone units. To demonstrate the feasibility of using solid terpolymers as nanocarriers for DNA delivery, PDL-DES-MDEA copolymers with 65-90% PDL were successfully transformed into free-standing nanoparticles with average particle size ranging from 163 to 175 nm. Our preliminary results showed that LucDNA-loaded nanoparticles of the terpolymer with 65% PDL were effective for luciferase gene transfection of HEK293 cells.
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Voevodina, Irina; Scandola, Mariastella; Zhang, Junwei; Jiang, Zhaozhong
2014-01-01
Polymers bearing amino functional groups are an important class of materials capable of serving as non-viral carriers for DNA delivery to living cells. In this work biodegradable poly(amine-co-ester) terpolymers were synthesized via ring-opening and polycondensation copolymerization of lactone (ε-caprolactone (CL), ω-dodecalactone, ω-pentadecalactone (PDL), and ω-hexadecalactone) with diethyl sebacate (DES) and N-methyldiethanolamine (MDEA) in diphenyl ether, catalyzed by Candida antarctica lipase B (CALB). All lactone-DES-MDEA terpolymers had random distributions of lactone, sebacate, MDEA repeat units in the polymer chains. PDL-DES-MDEA terpolymers were studied in the composition range from 21 mol% to 90 mol% PDL whereas the terpolymers with other lactones were investigated at a single composition (80 mol% lactone). DSC and WAXS analyses showed that all investigated terpolymers crystallize in their respective homopolylactone crystal lattice. Terpolymers with large lactones and a high lactone content melt well above room temperature and are hard solids, whereas terpolymers with small lactones (e.g. CL) or with a low lactone content melt below/around ambient temperature and are waxy/gluey materials. Given the importance of hydrophobicity in influencing gene delivery, water contact angle measurements were carried out on lactone-DES-MDEA terpolymers showing that it is possible to tune the hydrophilic-to-hydrophobic balance by varying polymer composition and size of lactone units. To demonstrate the feasibility of using solid terpolymers as nanocarriers for DNA delivery, PDL-DES-MDEA copolymers with 65–90% PDL were successfully transformed into free-standing nanoparticles with average particle size ranging from 163 to 175 nm. Our preliminary results showed that LucDNA-loaded nanoparticles of the terpolymer with 65% PDL were effective for luciferase gene transfection of HEK293 cells. PMID:24683469
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Xia, Guiyang; Zhou, Li; Ma, Jianghao; Wang, Ying; Ding, Liqin; Zhao, Feng; Chen, Lixia; Qiu, Feng
2015-06-01
Three new sesquiterpenes including a new elemane-type sesquiterpene, 5βH-elem-1,3,7,8-tetraen-8,12-olide (1), and two new carabrane-type sesquiterpenes, 7α,11-epoxy-6α-methoxy-carabrane-4,8-dione (2) and 8,11-epidioxy-8-hydroxy-4-oxo-6-carabren (3), together with eight known sesquiterpenes (4-11) were isolated from Curcuma wenyujin Y. H. Chen et C. Ling. Their structures were elucidated based on extensive spectroscopic analyses. A possible biogenetic scheme for the related compounds was postulated. All of the isolated compounds were tested for inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages. Meanwhile, preliminary structure-activity relationships for these compounds are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.
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USDA-ARS?s Scientific Manuscript database
Dendrobium nobile is one of the fundamental herbs in traditional Chinese medicine (TCM). Sesquiterpene alkaloids are the main active components in this plant. Due to weak ultraviolet absorption and low content in D. nobile, these sesquiterpene alkaloids have not been extensively studied using chroma...
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Green, Sol; Baker, Edward N; Laing, William
2011-06-23
Plant sesquiterpene and hemiterpene synthases in the monoterpene synthase dominated TPS-b subgroup are thought to have evolved independently from a monoterpene synthase ancestor. A TPS-b sesquiterpene synthase from apple (MdAFS1), which predominantly produces α-farnesene, can also synthesize the monoterpene (E)-β-ocimene. The dual activity offered a functional link to an ancestral MdAFS1 enzyme and a rational basis for investigation of the evolution of TPS-b sesquiterpene enzymes. Protein modelling and mutagenesis analysis of the MdAFS1 active site identified a non-synonymous nucleotide substitution that could account for the requisite shift in substrate specificity necessary for the emergence of its sesquiterpene activity during the evolution of the TPS-b enzymes. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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Two new aliphatic lactones from the fruits of Coriandrum sativum L.
2012-01-01
Background The present paper describes the isolation and characterization of two new aliphatic δ-lactones along with three glycerides and n-nonadecanyl cetoleate from the fruits of Coriandrum sativum L. (Apiaceae). The structures of all the isolated phytoconstituents have been established on the basis of spectral data analysis and chemical reactions. Results Phytochemical investigation of the methanolic extract of C. sativum L. (Apiaceae) fruits resulted in the isolation of two new aliphatic δ-lactones characterized as 2α-n-heptatriacont-(Z)-3-en-1,5-olide (1) (coriander lactone) and 2α-n-tetracont-(Z,Z)-3,26-dien-18α-ol-1,5-olide (2) (hydroxy coriander lactone) together with glyceryl-1,2-dioctadec-9,12-dienoate-3-octadec-9-enoate (3); glyceryl-1,2,3-trioctadecanoate (4); n-nonadecanyl-n-docos-11-enoate (5) and oleiyl glucoside (6). Conclusions Phytochemical investigation of the methanolic extract of C. sativum gave coriander lactone and hydroxy coriander lactone as the new phytoconstituents. PMID:22800677
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Yoshikawa, M; Shimada, H; Matsuda, H; Yamahara, J; Murakami, N
1996-09-01
Two new sesquiterpene ketones, moxartenone and moxartenolide, and three octadecadienoic acids were isolated from Chinese moxa, the processed leaves of Artemisia argyi LEVL. et VANT., together with two sesquiterpenes, five triterpenes, two phenyl propanoids and three polyoxyflavones. The chemical structures of new sesquiterpenes, moxartenone, moxartenolide, and octadecadienoic acids were determined on the basis of chemical and physiochemical evidence. Moxartenolide was found to inhibit the contractions induced by a high concentration of K+, by norepinephrine, and by serotonin in isolated aortic strips of rat, while moxartenone showed little activity.
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The inside cover picture shows the molecular structure of a DAG lactone derivative on top of the inner leaflet of a DMPC bilayer. The confocal microscopy image illustrates DAG-lactone-stimulated membrane localization of PKCδ-ECFP in living cells, while the space-filling model shows the surface of the C1B domain of PKCδ, the target of the lactone.
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Schmarr, Hans-Georg; Mathes, Maximilian; Wall, Kristina; Metzner, Frank; Fraefel, Marius
2017-09-22
The chiral lactone 5-butyl-4-methyloxolan-2-one or 5-butyl-4-methyldihydro-2(3H)-furanone, often named whisky lactone, is found in oak wood, then contributing to the appreciated flavor of beverages stored in such wooden barrels. Its next higher homologue is named cognac lactone (5-pentyl-4-methyloxolan-2-one or 5-pentyl-4-methyldihydro-2(3H)-furanone), however is much less known, probably due to its minor concentration level. In order to study the direct enantioseparation of both lactones by gas chromatography on chiral stationary phases, individual enantiomers, particularly for cognac lactone were made available. This was achieved by baker's yeast reduction of synthesized ethyl 3-methyl-4-oxononanoate or, after hydrolysis, of the corresponding 4-ketoacid, that gave access to individual enantiomers of cognac lactone. Good enantioseparation was achieved for both whisky and cognac lactone with high values for the chiral resolution with 6-O-tert. butyl dimethylsilyl-2,3-dialkylated or 6-O-tert. butyl dimethylsilyl-2,3-diacylated cyclodextrin derivatives as chiral selectors. The influence of the nature and position of derivatization of the cyclodextrin moiety revealed a strong impact on the chiral recognition mechanism, as the investigated alkylated derivatives heptakis-(2,6-di-O-iso-pentyl-3-O-allyl)-β-cyclodextrin and octakis-(2,3-di-O-pentyl-6-O-methyl)-γ-cyclodextrin did not provide any or only minor chiral selectivity for the two lactones. Copyright © 2017 Elsevier B.V. All rights reserved.
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Buck, Suzanne B; Hardouin, Christophe; Ichikawa, Satoshi; Soenen, Danielle R; Gauss, C-M; Hwang, Inkyu; Swingle, Mark R; Bonness, Kathy M; Honkanen, Richard E; Boger, Dale L
2003-12-24
Key derivatives and analogues of fostriecin were prepared and examined that revealed a fundamental role for the unsaturated lactone and confirmed the essential nature of the phosphate monoester. Thus, an identical 200-fold reduction in protein phosphatase 2A (PP2A) inhibition is observed with either the saturated lactone (7) or with an analogue that lacks the entire lactone (15). This 200-fold increase in PP2A inhibition attributable to the unsaturated lactone potentially may be due to reversible C269 alkylation within the PP beta12-beta13 active site loop accounting for PP2A/4 potency and selectivity.
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Grabarczyk, Małgorzata
2012-08-14
Bicyclic chloro-, bromo- and iodo-γ-lactones with dimethylcyclohexane rings were used as substrates for bioconversion by several fungal strains (Fusarium, Botrytis and Beauveria). Most of the selected microorganisms transformed these lactones by hydrolytic dehalogenation into the new compound cis-2-hydroxy-4,6-dimethyl-9-oxabicyclo[4.3.0]- nonan-8-one, mainly the (-)-isomer. When iodo-γ-lactone was used as the substrate, two products were observed: a hydroxy-γ-lactone and an unsaturated lactone. The structures of all substrates and products were established on the basis of their spectral data. The mechanism of dehalogenation of three halolactones was also studied.
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Xu, Fang-Fang; Shi, Wei; Zhang, Hui; Guo, Qing-Ming; Wang Zhen-Zhong; Bi, Yu-An; Wang, Zhi-Min; Xiao, Wei
2015-01-01
In this study, hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata were prepared and the in vitro release behavior were also evaluated. The optimal prescription was achieved by studying the main factor of the type and amount of hydroxypropyl methylcellulose (HPMC) using single factor test and evaluating through cumulative release of three lactones. No burst drug release from the obtained matrix tablets was observed. Drug release sustained to 14 h. The release mechanism of three lactones from A. paniculata was accessed by zero-order, first-order, Higuchi and Peppas equation. The release behavior of total lactones from A. paniculata was better agreed with Higuchi model and the drug release from the tablets was controlled by degradation of the matrix. The preparation of hydrophilic matrix sustained release tablets of total lactones from A. paniculata with good performance of drug release was simple.
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Zeng, Lanting; Zhou, Ying; Fu, Xiumin; Liao, Yinyin; Yuan, Yunfei; Jia, Yongxia; Dong, Fang; Yang, Ziyin
2018-04-18
Jasmine lactone has a potent odor that contributes to the fruity, sweet floral aroma of tea ( Camellia sinensis). Our previous study demonstrated that jasmine lactone was mostly accumulated at the turnover stage of the oolong tea manufacturing process. This study investigates the previously unknown mechanism of formation of jasmine lactone in tea leaves exposed to multiple stresses occurring during the growth and manufacturing processes. Both continuous mechanical damage and the dual stress of low temperature and mechanical damage enhanced jasmine lactone accumulation in tea leaves. In addition, only one pathway, via hydroperoxy fatty acids from unsaturated fatty acid, including linoleic acid and α-linolenic acid, under the action of lipoxygenases (LOXs), especially CsLOX1, was significantly affected by these stresses. This is the first evidence of the mechanism of jasmine lactone formation in tea leaves and is a characteristic example of plant volatile formation in response to dual stress.
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Agarofuran sesquiterpenes from Schaefferia argentinensis.
García, Manuela E; Motrich, Rubén D; Caputto, Beatriz L; Sánchez, Marianela; Palermo, Jorge A; Estévez-Braun, Ana; Ravelo, Angel G; Nicotra, Viviana E
2013-10-01
Sixteen dihydro-β-agarofuran sesquiterpenes were isolated from the aerial parts of Schaefferia argentinensis Speg. Their structures were determined by a combination of 1D and 2D NMR and MS techniques. The in vitro antiproliferative activity of the major sesquiterpenes was examined in T47D, MCF7, and MDA-MB231 human cancer cell lines, but was found to be marginal. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Bisabolane-type sesquiterpenes from the aerial parts of Lippia dulcis.
Ono, Masateru; Tsuru, Tsuyoshi; Abe, Hiroaki; Eto, Masashi; Okawa, Masafumi; Abe, Fumiko; Kinjo, Junei; Ikeda, Tsuyoshi; Nohara, Toshihiro
2006-10-01
Six new bisabolane-type sesquiterpenes, peroxylippidulcines A-C (3-5), peroxyepilippidulcine B (6), and epilippidulcines B (7) and C (8), have been isolated from the aerial parts of Lippia dulcis, along with two known bisabolane-type sesquiterpenes, seven known flavonoids, and a known triterpenoid. The structures of 3-8 were characterized on the basis of NMR, MS, specific rotation, and X-ray crystallographic analysis data and chemical evidence.
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Wardecki, Tina; Brötz, Elke; De Ford, Christian; von Loewenich, Friederike D; Rebets, Yuriy; Tokovenko, Bogdan; Luzhetskyy, Andriy; Merfort, Irmgard
2015-08-01
Arnica montana L. is a medical plant of the Asteraceae family and grows preferably on nutrient poor soils in mountainous environments. Such surroundings are known to make plants dependent on symbiosis with other organisms. Up to now only arbuscular mycorrhizal fungi were found to act as endophytic symbiosis partners for A. montana. Here we identified five Streptomyces strains, microorganisms also known to occur as endophytes in plants and to produce a huge variety of active secondary metabolites, as inhabitants of A. montana. The secondary metabolite spectrum of these strains does not contain sesquiterpene lactones, but consists of the glutarimide antibiotics cycloheximide and actiphenol as well as the diketopiperazines cyclo-prolyl-valyl, cyclo-prolyl-isoleucyl, cyclo-prolyl-leucyl and cyclo-prolyl-phenylalanyl. Notably, genome analysis of one strain was performed and indicated a huge genome size with a high number of natural products gene clusters among which genes for cycloheximide production were detected. Only weak activity against the Gram-positive bacterium Staphylococcus aureus was revealed, but the extracts showed a marked cytotoxic activity as well as an antifungal activity against Candida parapsilosis and Fusarium verticillioides. Altogether, our results provide evidence that A. montana and its endophytic Streptomyces benefit from each other by completing their protection against competitors and pathogens and by exchanging plant growth promoting signals with nutrients.
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Testone, Giulio; Mele, Giovanni; Di Giacomo, Elisabetta; Gonnella, Maria; Renna, Massimiliano; Tenore, Gian Carlo; Nicolodi, Chiara; Frugis, Giovanna; Iannelli, Maria Adelaide; Arnesi, Giuseppe; Schiappa, Alessandro; Giannino, Donato
2016-01-01
Stem-chicory of the “Catalogna” group is a vegetable consumed for bitter-flavored stems. Type and levels of bitter sesquiterpene lactones (STLs) participate in conferring bitterness in vegetables. The content of lactucin—and lactucopocrin-like STLs was higher in “Molfettese” than “Galatina” landrace stalks, regardless of the cultivation sites, consistently with bitterness scores and gustative differences. The “Galatina” transcriptome assembly resulted in 58,872 unigenes, 77% of which were annotated, paving the way to molecular investigation of the STL pathway. Comparative transcriptome analysis allowed the identification of 69,352 SNPs and of 1640 differentially expressed genes that maintained the pattern independently of the site. Enrichment analyses revealed that 4 out of 29 unigenes were up-regulated in “Molfettese” vs “Galatina” within the sesquiterpenoid pathway. The expression of two germacrene A -synthase (GAS) and one -oxidase (GAO) genes of the costunolide branch correlated positively with the contents of lactucin-like molecules, supporting that STL biosynthesis regulation occurs at the transcriptional level. Finally, 46 genes encoding transcription factors (TFs) maintained a differential expression pattern between the two varieties regardless of the growth site; correlation analyses among TFs, GAS, GAO gene expressions and STLs contents suggest that one MYB and one bHLH may act in the pathway. PMID:27877190
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Belz, Regina G.
2008-01-01
Parthenium hysterophorus L. is an invasive weed that biosynthesizes several phytochemi-cals. The sesquiterpene lactone parthenin receives most attention regarding allelopathy of the plant or potential herbicidal properties. Since parthenin exhibits dose-dependent phy-totoxicity with low dose stimulation, this study investigated the occurrence and temporal features of parthenin hormesis in Sinapis arvensis L. sprayed with parthenin under semi-natural conditions. Dose/response studies showed that the occurrence and the magnitude of hormesis depended on climatic conditions and the parameter measured. Within the tested dose range, stimulatory responses were only observed under less-stressful conditions and were most pronounced for leaf area growth [138 % of control; 13 days after treatment (DAT)]. Temporal assessment of leaf area development showed that doses causing a stimulatory response at the end of the experiment (< 0.42 ± 0.04 kg/ha; 13 DAT) were initially inhibitory up to ED50 values (2 DAT). This clearly demonstrated an over-compensatory response. Inhibition of leaf area at 13 DAT reached ED50 values on average at 0.62 ±0.12 kg/ha, and S. arvensis was completely inhibited at doses exceeding 1.81 ±0.56 kg/ha (ED90). Based on these findings, implications of parthenin hormesis are discussed with respect to allelopathy of P. hysterophorus and exploitation of growth stimulatory responses in agriculture. PMID:18648571
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Gao, Qing-Ming; Kane, Nolan C.; Hulke, Brent S.; Reinert, Stephan; Pogoda, Cloe S.; Tittes, Silas; Prasifka, Jarrad R.
2018-01-01
Capitate glandular trichomes (CGT), one type of glandular trichomes, are most common in Asteraceae species. CGT can produce various secondary metabolites such as sesquiterpene lactones (STLs) and provide durable resistance to insect pests. In sunflower, CGT-based host resistance is effective to combat the specialist pest, sunflower moth. However, the genetic basis of CGT density is not well understood in sunflower. In this study, we identified two major QTL controlling CGT density in sunflower florets by using a F4 mapping population derived from the cross HA 300 × RHA 464 with a genetic linkage map constructed from genotyping-by-sequencing data and composed of 2121 SNP markers. One major QTL is located on chromosome 5, which explained 11.61% of the observed phenotypic variation, and the second QTL is located on chromosome 6, which explained 14.06% of the observed phenotypic variation. The QTL effects and the association between CGT density and QTL support interval were confirmed in a validation population which included 39 sunflower inbred lines with diverse genetic backgrounds. We also identified two strong candidate genes in the QTL support intervals, and the functions of their orthologs in other plant species suggested their potential roles in regulating capitate glandular trichome density in sunflower. Our results provide valuable information to sunflower breeding community for developing host resistance to sunflower insect pests. PMID:29375602
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Medicinal plants and their isolated compounds showing anti-Trichomonas vaginalis- activity.
Mehriardestani, Mozhgan; Aliahmadi, Atousa; Toliat, Tayebeh; Rahimi, Roja
2017-04-01
Trichomonas vaginalis is a major of non-viral sexually-transmitted infection and an important cause of serious obstetrical and gynecological complications. Treatment options for trichomoniasis are limited to nitroimidazole compounds. The increasing resistance and allergic reactions to nitroimidazole and recurrent trichomoniasis make it essential to identify and develop new drugs against trichomoniasis. Medicinal plants are an important source for discovery of new medications. This review discusses the anti-trichomonas effects of medicinal plants and their chemical constituents to find better options against this pathogenic protozoon. Electronic databases were searched to collect all data from the year 2000 through September 2015 for in vitro, in vivo and clinical studies on the effect of medicinal plants on T. vaginalis. A total of 95 in vitro and clinical studies were identified. Only four human studies were found in this review. The Asteracea, Lamiaceae and Myrtaceae families contained the greatest number of plants with anti-trichomonas activity. Persea americana, Ocimum basilicum and Verbascum thapsus were the most efficacious against T. vaginalis. Plant metabolites containing alkaloids, isoflavonoid glucosides, essential oils, lipids, saponins and sesquiterpene lactones were found to possess anti-trichomonas properties. Assessing the structure-activity of highly-potent anti-trichomonas phytochemicals is suggested for finding natural, semisynthetic and synthetic anti-trichomonas compounds. Further clinical studies are necessary for confirmation of natural anti-trichomonas substances and completion of their safety profiles. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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Bailon-Moscoso, Natalia; González-Arévalo, Gabriela; Velásquez-Rojas, Gabriela; Malagon, Omar; Vidari, Giovanni; Zentella-Dehesa, Alejandro; Ratovitski, Edward A; Ostrosky-Wegman, Patricia
2015-01-01
Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites) may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL), a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment.
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Bailon-Moscoso, Natalia; González-Arévalo, Gabriela; Velásquez-Rojas, Gabriela; Malagon, Omar; Vidari, Giovanni; Zentella-Dehesa, Alejandro; Ratovitski, Edward A.; Ostrosky-Wegman, Patricia
2015-01-01
Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites) may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL), a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment. PMID:26309132
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Cho, S-H; Na, Y-E; Ahn, Y-J
2003-01-01
The present work aimed at isolating antibacterial constituents from the whole plant of Artemisia princeps var. orientalis active towards nine human intestinal bacteria. The growth-inhibiting activities of materials derived from the Artemisia whole plant towards test bacteria were examined using an impregnated paper disc method. The biologically active constituents of the Artemisia whole plant were characterized as the sesquiterpene lactones seco-tanapartholides A and B by spectroscopic analysis. In a test using 1 mg per disc, seco-tanapartholides A and B produced a clear inhibitory effect against Clostridium perfringens, Bacteroides fragilis and Staphylococcus aureus. These compounds did not affect the growth of test lactic acid-producing bacteria (Bifidobacterium adolescentis, Bif. breve, Lactobacillus acidophilus and Lact. casei) and Escherichia coli, whereas weak growth inhibition towards Bif. bifidum was observed. At 0.5 mg per disc, seco-tanapartholides A and B exhibited moderate growth inhibition towards Cl. perfringens but weak growth inhibition towards Bact. fragilis and Staph. aureus. Inhibitory action of seco-tanapartholides A and B towards specific bacteria without any adverse effects on lactic acid-producing bacteria may be an indication of at least one of the pharmacological actions of A. princeps var. orientalis whole plant. These naturally occurring Artemisia whole plant-derived materials could be useful as a new preventive agent against various diseases caused by harmful intestinal bacteria such as clostridia.
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Eljounaidi, K; Comino, C; Moglia, A; Cankar, K; Genre, A; Hehn, A; Bourgaud, F; Beekwilder, J; Lanteri, S
2015-10-01
Globe artichoke (Cynara cardunculus var. scolymus) belongs to the Asteraceae family, in which one of the most biologically significant class of secondary metabolites are sesquiterpene lactones (STLs). In globe artichoke the principal STL is the cynaropicrin, which contributes to approximately 80% of its characteristic bitter taste. Cynaropicrin content was assessed in globe artichoke tissues and was observed to accumulate in leaves of different developmental stages. In the receptacle, a progressive decrease was observed during inflorescence development, while the STL could not be detected in the inflorescence bracts. Almost undetectable amounts were found in the roots and inflorescence stems at the commercial stage. Cynaropicrin content was found to correlate with expression of genes encoding CcGAS, CcGAO and CcCOS, which are involved in the STL biosynthesis. A more detailed study of leaf material revealed that cynaropicrin predominantly accumulates in the trichomes, and not in the apoplastic cavity fluids. Analysis of the promoter regions of CcGAO and CcCOS revealed the presence of L1-box motifs, which confers trichome-specific expression in Arabidopsis, suggesting that cynaropicrin is not only stored but also synthesized in trichomes. A transient expression of GFP fusion proteins was performed in Nicotiana benthamiana plants: the CcGAS fluorescence signal was located in the cytoplasm while the CcGAO and CcCOS localized to the endoplasmatic reticulum. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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Caldeira, Tamires G; Saúde-Guimarães, Dênia A; Dezani, André B; Serra, Cristina Helena Dos Reis; de Souza, Jacqueline
2017-11-01
Analysis of the biopharmaceutical properties of eremantholide C, sesquiterpene lactone with proven pharmacological activity and low toxicity, is required to evaluate its potential to become a drug. Preliminary analysis of the physicochemical characteristics of eremantholide C was performed in silico. Equilibrium solubility was evaluated using the shake-flask method, at 37.0 °C, 100 rpm during 72 h in biorelevant media. The permeability was analysed using parallel artificial membrane permeability assay, at 37.0 °C, 50 rpm for 5 h. The donor compartment was composed of an eremantholide C solution in intestinal fluid simulated without enzymes, while the acceptor compartment consisted of phosphate buffer. Physicochemical characteristics predicted in silico indicated that eremantholide C has a low solubility and high permeability. In-vitro data of eremantholide C showed low solubility, with values for the dose/solubility ratio (ml): 9448.82, 10 389.61 e 15 000.00 for buffers acetate (pH 4.5), intestinal fluid simulated without enzymes (pH 6.8) and phosphate (pH 7.4), respectively. Also, it showed high permeability, with effective permeability of 30.4 × 10 -6 cm/s, a higher result compared with propranolol hydrochloride (9.23 × 10 -6 cm/s). The high permeability combined with its solubility, pharmacological activity and low toxicity demonstrate the importance of eremantholide C as a potential drug candidate. © 2017 Royal Pharmaceutical Society.
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Lachi-Silva, Larissa; Sy, Sherwin K B; Voelkner, Alexander; de Sousa, João Paulo Barreto; Lopes, João Luis C; Silva, Denise B; Lopes, Norberto P; Kimura, Elza; Derendorf, Hartmut; Diniz, Andrea
2015-08-01
The pharmacokinetic properties of a new molecular entity are important aspects in evaluating the viability of the compound as a pharmacological agent. The sesquiterpene lactone lychnopholide exhibits important biological activities. The objective of this study was to characterize the pharmacokinetics of lychnopholide after intravenous administration of 1.65 mg/kg (n = 5) and oral administration of 3.3 mg/kg (n = 3) lychnopholide in rats (0.2 ± 0.02 kg in weight) through nonlinear mixed effects modeling and non-compartmental pharmacokinetic analysis. A highly sensitive analytical method was used to quantify the plasma lychnopholide concentrations in rats. Plasma protein binding of this compound was over 99 % as determined by a filtration method. A two-compartment body model plus three transit compartments to characterize the absorption process best described the disposition of lychnopholide after both routes of administration. The oral bioavailability was approximately 68 %. The clearance was 0.131 l/min and intercompartmental clearance was 0.171 l/min; steady-state volume of distribution was 4.83 l. The mean transit time for the absorption process was 9.15 minutes. No flip-flop phenomenon was observed after oral administration. The pharmacokinetic properties are favorable for further development of lychnopholide as a potential oral pharmacological agent. Georg Thieme Verlag KG Stuttgart · New York.
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Lee, Kuo-Hsiung
2010-01-01
Medicinal plants have long been an excellent source of pharmaceutical agents. Accordingly, the long term objectives of the author's research program are to discover and design new chemotherapeutic agents based on plant-derived compound leads by using a medicinal chemistry approach, which is a combination of chemistry and biology. Different examples of promising bioactive natural products and their synthetic analogs, including sesquiterpene lactones, quassinoids, naphthoquinones, phenylquinolones, dithiophenediones, neo-tanshinlactone, tylophorine, suksdorfin, DCK, and DCP, will be presented with respect to their discovery and preclinical development as potential clinical trial candidates. Research approaches include bioactivity- or mechanism of action-directed isolation and characterization of active compounds, rational drug design-based modification and analog synthesis, as well as structure-activity relationship and mechanism of action studies. Current clinical trials agents discovered by the Natural Products Research Laboratories, University of North Carolina, include bevirimat (dimethyl succinyl betulinic acid), which is now in Phase IIb trials for treating AIDS. Bevirimat is also the first in a new class of HIV drug candidates called “maturation inhibitors”. In addition, an etoposide analog, GL-331, progressed to anticancer Phase II clinical trials, and the curcumin analog JC-9 is in Phase II clinical trials for treating acne and in development for trials against prostate cancer. The discovery and development of these clinical trials candidates will also be discussed. PMID:20187635
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Patch tests with fragrance mix II and its components.
Pónyai, Györgyi; Németh, Ilona; Altmayer, Anita; Nagy, Gabriella; Irinyi, Beatrix; Battyáni, Zita; Temesvári, Erzsébet
2012-01-01
Fragrance mix II (FM II) was initiated to detect contact hypersenstitivity (CH) to fragrances that could not have been identified previously. The aim of this multicenter study was to map the frequency of CH to FM II and its components in Hungary. Six centers participated in the survey from 2009 to 2010. A total off 565 patients (434 women and 131 men) with former skin symptoms provoked by scented products were patch tested. The tests were performed with Brial GmbH D-Greven allergens. In the environmental patch test series, FM II, FM I, Myroxylon pereirae, colophonium, wood-tar mix, propolis, and sesquiterpene lactone mix were tested as fragrance allergens. The FM II components (citral, farnesol, coumarin, citronellol, α-hexyl-cinnamaldehyde, and hydroxy-isohexyl-3-cyclohexene-carboxaldehyde [Lyral]) were also tested. Contact hypersenstitivity to any fragrances was detected in 28.8%, to FM II in 17.2% of the patients. Contact hypersenstitivity to hydroxy-isohexyl-3-cyclohexene-carboxaldehyde was observed in 7.3%, to coumarin in 5.1%, to α-hexyl-cinnamaldehyde in 3.5%, to citral in 3.4%, to farnesol in 2.5%, and to citronellol in 1.2%. Of the FM II-positive cases, 48.4% showed isolated CH reaction. The frequency of CH to FM II is 17.2% in the tested, selected Hungarian population. The CH to FM II and its components could not have been revealed without the present test materials.
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White, J M L; McFadden, J P; White, I R
2008-03-01
Active patch test sensitization is an uncommon phenomenon which may have undesirable consequences for those undergoing this gold-standard investigation for contact allergy. To perform a retrospective analysis of the results of 241 subjects who were patch tested twice in a monocentre evaluating approximately 1500 subjects per year. Positivity to 11 common allergens in the recommended Baseline Series of contact allergens (European) was analysed: nickel sulphate; Myroxylon pereirae; fragrance mix I; para-phenylenediamine; colophonium; epoxy resin; neomycin; quaternium-15; thiuram mix; sesquiterpene lactone mix; and para-tert-butylphenol resin. Only fragrance mix I gave a statistically significant, increased rate of positivity on the second reading compared with the first (P=0.011). This trend was maintained when separately analysing a subgroup of 42 subjects who had been repeat patch tested within 1 year; this analysis was done to minimize the potential confounding factor of increased usage of fragrances with a wide interval between both tests. To reduce the confounding effect of age on our data, we calculated expected frequencies of positivity to fragrance mix I based on previously published data from our centre. This showed a marked excess of observed cases over predicted ones, particularly in women in the age range 40-60 years. We suspect that active sensitization to fragrance mix I may occur. Similar published analysis from another large group using standard methodology supports our data.
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Muñoz-Martínez, Francisco; Lu, Peihua; Cortés-Selva, Fernando; Pérez-Victoria, José María; Jiménez, Ignacio A; Ravelo, Angel G; Sharom, Frances J; Gamarro, Francisco; Castanys, Santiago
2004-10-01
Overexpression of ABCB1 (MDR1) P-glycoprotein, a multidrug efflux pump, is one mechanism by which tumor cells may develop multidrug resistance (MDR), preventing the successful chemotherapeutic treatment of cancer. Sesquiterpenes from Celastraceae family are natural compounds shown previously to reverse MDR in several human cancer cell lines and Leishmania strains. However, their molecular mechanism of reversion has not been characterized. In the present work, we have studied the ability of 28 dihydro-beta-agarofuran sesquiterpenes to reverse the P-glycoprotein-dependent MDR phenotype and elucidated their molecular mechanism of action. Cytotoxicity assays using human MDR1-transfected NIH-3T3 cells allowed us to select the most potent sesquiterpenes reversing the in vitro resistance to daunomycin and vinblastine. Flow cytometry experiments showed that the above active compounds specifically inhibited drug transport activity of P-glycoprotein in a saturable, concentration-dependent manner (K(i) down to 0.24 +/- 0.01 micromol/L) but not that of ABCC1 (multidrug resistance protein 1; MRP1), ABCC2 (MRP2), and ABCG2 (breast cancer resistance protein; BCRP) transporters. Moreover, sesquiterpenes inhibited at submicromolar concentrations the P-glycoprotein-mediated transport of [(3)H]colchicine and tetramethylrosamine in plasma membrane from CH(R)B30 cells and P-glycoprotein-enriched proteoliposomes, supporting that P-glycoprotein is their molecular target. Photoaffinity labeling in plasma membrane and fluorescence spectroscopy experiments with purified protein suggested that sesquiterpenes interact with transmembrane domains of P-glycoprotein. Finally, sesquiterpenes modulated P-glycoprotein ATPase-activity in a biphasic, concentration-dependent manner: they stimulated at very low concentrations but inhibited ATPase activity as noncompetitive inhibitors at higher concentrations. Sesquiterpenes from Celastraceae are promising P-glycoprotein modulators with potential applications in cancer chemotherapy because of their MDR reversal potency and specificity for P-glycoprotein.
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Sesquiterpenes and a phenylpropanoid from Cordia trichotoma.
de Menezes, Jane Eire S A; Machado, Francisca Elane A; Lemos, Telma Leda G; Silveira, Edilberto R; Braz Filho, Raimundo; Pessoa, Otília Deusdênia L
2004-01-01
Two new secondary metabolites, the phenylpropanoid 3-(2',4',5'-trimethoxyphenyl)propanoic acid (1) and the sesquiterpene (+)-1beta,4beta,6alpha-trihydroxyeudesmane (2) were isolated from the heartwood of Cordia trichotoma Vell., along with the known sesquiterpenes (-)-1beta,4beta,7alpha-trihydroxyeudesmane (3) and (+)-1beta,4beta,11-trihydroxyoppositane (4). Their structures were elucidated by means of spectroscopic data interpretation, mainly 1D and 2D NMR and mass spectrometry.
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Tagen, Michael; Zhuang, Yanli; Zhang, Fan; Harstead, K. Elaine; Shen, Jun; Schaiquevich, Paula; Fraga, Charles H.; Panetta, John C.; Waters, Christopher M.; Stewart, Clinton F.
2015-01-01
The ATP-binding cassette transporters P-glycoprotein (ABCB1, MDR1) and multidrug resistance protein 4 (MRP4) efflux irinotecan and its active metabolite SN-38 in vitro, and thus may contribute to system clearance of these compounds. Mdr1a/b−/−, Mrp4−/−, and wild-type mice were administered 20 or 40 mg/kg irinotecan, and plasma samples were collected for 6 hours. Irinotecan and SN-38 lactone and carboxylate were quantitated and data were analyzed with nonlinear mixed-effects modeling. Mdr1a/b genotype was a significant covariate for the clearance of both irinotecan lactone and SN-38 lactone. Exposures to irinotecan lactone and SN-38 lactone after a 40 mg/kg dose were 1.6-fold higher in Mdr1a/b−/− mice compared to wild-type mice. Plasma concentrations of irinotecan lactone, irinotecan carboxylate, and SN-38 lactone in Mrp4−/− mice were similar to the wild-type controls. These results suggest that P-gp plays a role in irinotecan and SN-38 elimination, but Mrp4 does not affect irinotecan or SN-38 plasma pharmacokinetics. PMID:20583968
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N-acyl-homoserine lactone-mediated quorum-sensing in Azospirillum: an exception rather than a rule.
Vial, Ludovic; Cuny, Caroline; Gluchoff-Fiasson, Katia; Comte, Gilles; Oger, Phil M; Faure, Denis; Dessaux, Yves; Bally, René; Wisniewski-Dyé, Florence
2006-11-01
Forty Azospirillum strains were tested for their ability to synthesize N-acyl-homoserine lactones (AHLs). AHL production was detected for four strains belonging to the lipoferum species and isolated from a rice rhizosphere. AHL molecules were structurally identified for two strains: Azospirillum lipoferum TVV3 produces 3O,C(8)-HSL (N-3-oxo-octanoyl-homoserine-lactone), C(8)-HSL (N-3-octanoyl-homoserine-lactone), 3O,C(10)-HSL (N-3-oxo-decanoyl-homoserine-lactone), 3OH,C(10)-HSL (N-3-hydroxy-decanoyl-homoserine-lactone) and C(10)-HSL (N-3-decanoyl-homoserine-lactone), whereas A. lipoferum B518 produced 3O,C(6)-HSL (N-3-oxo-hexanoyl-homoserine-lactone), C(6)-HSL (N-3-hexanoyl-homoserine-lactone), 3O,C(8)-HSL, 3OH,C(8)-HSL and C(8)-HSL. Genes involved in AHL production were characterized for A. lipoferum TVV3 by generating a genomic library and complementing an AHL-deficient strain with sensor capabilities. Those genes, designated alpI and alpR, were found to belong to the luxI and luxR families, respectively. When cloned in a suitable heterologous host, alpI and alpR could direct the synthesis of the five cognate AHLs present in A. lipoferum TVV3. These two adjacent genes were found to be located on a 85 kb plasmid. Southern hybridization experiments with probes alpI/R indicated that genes involved in AHL production in the three other AHL-producing strains were not closely related to alpI and alpR. This study demonstrates that AHL-based quorum-sensing is not widespread among the genus Azospirillum and could be found only in some A. lipoferum strains.
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de Albuquerque Ugoline, Bruno César; de Souza, Jacqueline; Ferrari, Fernanda Cristina; Ferraz-Filha, Zilma Schimith; Coelho, Grazielle Brandão; Saúde-Guimarães, Dênia Antunes
2017-02-23
Lychnophora passerina (Mart ex DC) Gardn (Asteraceae), popularly known as Brazilian arnica, is used in Brazilian folk medicine to treat pain, rheumatism, bruises, inflammatory diseases and insect bites. Investigate the influence of the seasons on the anti-inflammatory and anti-hyperuricemic activities of ethanolic extract of L. passerina and the ratio of the goyazensolide content, main chemical constituent of the ethanolic extract, with these activities. Ethanolic extracts of aerial parts of L. passerina were obtained from seasons: summer (ES), autumn (EA), winter (EW) and spring (EP). The sesquiterpene lactone goyazensolide, major metabolite, was quantified in ES, EA, EW and EP by a developed and validated HPLC-DAD method. The in vivo anti-hyperuricemic and anti-inflammatory effects of the ethanolic extracts from L. passerina and goyazensolide were assayed on experimental model of oxonate-induced hyperuricemia in mice, liver xanthine oxidase (XOD) inhibition and on carrageenan-induced paw edema in mice. HPLC method using aqueous solution of acetic acid 0.01% (v/v) and acetonitrile with acetic acid 0.01% (v/v) as a mobile phase in a gradient system, with coumarin as an internal standard and DAD detection at 270nm was developed. The validation parameters showed linearity in a range within 10.0-150.0µg/ml, with intraday and interday precisions a range of 0.61-3.82. The accuracy values of intraday and interday analysis within 87.58-100.95%. EA showed the highest goyazensolide content. From the third to the sixth hour after injection of carrageenan, treatments with all extracts at the dose of 125mg/kg were able to reduce edema. Goyazensolide (10mg/kg) showed significant reduction of paw swelling from the second hour assay. This sesquiterpene lactone was more active than extracts and presented similar effect to indomethacin. Treatments with ES, EA and EP (125mg/kg) and goyazensolide (10mg/kg) reduced serum urate levels compared to hyperuricemic control group and were able to inhibit liver XOD activity. One of the mechanisms by which ES, EA, EP and goyazensolide exercise their anti-hyperuricemic effect is by the inhibition of liver XOD activity. Goyazensolide was identified as the main compound present in ES, EA, EW and EP and it is shown to be one of the chemical constituents responsible for the anti-inflammatory and anti-hyperuricemic effects of the ethanolic extracts. The anti-inflammatory and anti-hyperuricemic activities of the ethanolic extracts from L. passerina were not proportionally influenced by the variation of goyazensolide content throughout the seasons. The involvement of goyazensolide on in vivo anti-inflammatory and anti-hyperuricemic activities of L.passerina extracts was confirmed, as well as the possibility of participation of other constituents on these effects. This study demonstrated that the aerial parts of L. passerina may be collected in any season for use as anti-inflammatory agent. For use in hyperuricemia, the best seasons for the collection are summer, autumn and spring. The ethanolic extract of L. passerina and goyazensolide can be considered promising agents in the therapeutic of inflammation, hyperuricemia and gout. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.
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Besser, Katrin; Harper, Andrea; Welsby, Nicholas; Schauvinhold, Ines; Slocombe, Stephen; Li, Yi; Dixon, Richard A.; Broun, Pierre
2009-01-01
The diversification of chemical production in glandular trichomes is important in the development of resistance against pathogens and pests in two species of tomato. We have used genetic and genomic approaches to uncover some of the biochemical and molecular mechanisms that underlie the divergence in trichome metabolism between the wild species Solanum habrochaites LA1777 and its cultivated relative, Solanum lycopersicum. LA1777 produces high amounts of insecticidal sesquiterpene carboxylic acids (SCAs), whereas cultivated tomatoes lack SCAs and are more susceptible to pests. We show that trichomes of the two species have nearly opposite terpenoid profiles, consisting mainly of monoterpenes and low levels of sesquiterpenes in S. lycopersicum and mainly of SCAs and very low monoterpene levels in LA1777. The accumulation patterns of these terpenoids are different during development, in contrast to the developmental expression profiles of terpenoid pathway genes, which are similar in the two species, but they do not correlate in either case with terpenoid accumulation. However, our data suggest that the accumulation of monoterpenes in S. lycopersicum and major sesquiterpenes in LA1777 are linked both genetically and biochemically. Metabolite analyses after targeted gene silencing, inhibitor treatments, and precursor feeding all show that sesquiterpene biosynthesis relies mainly on products from the plastidic 2-C-methyl-d-erythritol-4-phosphate pathway in LA1777 but less so in the cultivated species. Furthermore, two classes of sesquiterpenes produced by the wild species may be synthesized from distinct pools of precursors via cytosolic and plastidial cyclases. However, highly trichome-expressed sesquiterpene cyclase-like enzymes were ruled out as being involved in the production of major LA1777 sesquiterpenes. PMID:18997116
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Sesquiterpenes from the east African sandalwood Osyris tenuifolia.
Kreipl, Andreas Th; König, Wilfried A
2004-07-01
The essential oil of the east African sandalwood Osyris tenuifolia was investigated by chromatographic and spectroscopic methods. Beside several already known sesquiterpenes four new compounds could be isolated by preparative gas chromatography and their structures investigated by mass spectroscopy and NMR techniques. Two of the new compounds--tenuifolene (17) and ar-tenuifolene (15)--show a new sesquiterpene backbone. 2,(7Z,10Z)-Bisabolatrien-13-ol (23) and the cyclic ether lanceoloxide (21) belong to the bisabolanes.
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Wang, Su-Rui; Zhang, Ling; Chen, He-Ping; Li, Zheng-Hui; Dong, Ze-Jun; Wei, Kun; Liu, Ji-Kai
2015-09-01
Four new spiroaxane sesquiterpenes, tramspiroins A-D (1-4), one new rosenonolactone 15,16-acetonide (5), and the known drimane sesquiterpenes isodrimenediol (6) and funatrol D (7) have been isolated from the cultures of Basidiomycete Trametes versicolor. The structures of new compounds were elucidated by means of spectroscopic methods. Compounds 1-7 were investigated for their cytotoxicities against five human cancer cell lines. Copyright © 2015 Elsevier B.V. All rights reserved.
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Zhang, Yan; Li, Zhi-Xia; Yu, Xiu-Dao; Fan, Jia; Pickett, John A; Jones, Huw D; Zhou, Jing-Jiang; Birkett, Michael A; Caulfield, John; Napier, Johnathan A; Zhao, Guang-Yao; Cheng, Xian-Guo; Shi, Yi; Bruce, Toby J A; Xia, Lan-Qin
2015-05-01
Aphids are important pests of wheat (Triticum aestivum) that affect crop production globally. Herbivore-induced emission of sesquiterpenes can repel pests, and farnesyl pyrophosphate synthase (FPS) is a key enzyme involved in sesquiterpene biosynthesis. However, fps orthologues in wheat and their functional roles in sesquiterpene synthesis and defence against aphid infestation are unknown. Here, two fps isoforms, Tafps1 and Tafps2, were identified in wheat. Quantitative real-time polymerase chain reaction (qRT-PCR) and in vitro catalytic activity analyses were conducted to investigate expression patterns and activity. Heterologous expression of these isoforms in Arabidopsis thaliana, virus-induced gene silencing (VIGS) in wheat and aphid behavioural assays were performed to understand the functional roles of these two isoforms. We demonstrated that Tafps1 and Tafps2 played different roles in induced responses to aphid infestation and in sesquiterpene synthesis. Heterologous expression in A. thaliana resulted in repulsion of the peach aphid (Myzus persicae). Wheat plants with these two isoforms transiently silenced were significantly attractive to grain aphid (Sitobion avenae). Our results provide new insights into induced defence against aphid herbivory in wheat, in particular, the different roles of the two Tafps isoforms in both sesquiterpene biosynthesis and defence against aphid infestation. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.
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Functional Characterization of Novel Sesquiterpene Synthases from Indian Sandalwood, Santalum album
Srivastava, Prabhakar Lal; Daramwar, Pankaj P.; Krithika, Ramakrishnan; Pandreka, Avinash; Shankar, S. Shiva; Thulasiram, Hirekodathakallu V.
2015-01-01
Indian Sandalwood, Santalum album L. is highly valued for its fragrant heartwood oil and is dominated by a blend of sesquiterpenes. Sesquiterpenes are formed through cyclization of farnesyl diphosphate (FPP), catalyzed by metal dependent terpene cyclases. This report describes the cloning and functional characterization of five genes, which encode two sesquisabinene synthases (SaSQS1, SaSQS2), bisabolene synthase (SaBS), santalene synthase (SaSS) and farnesyl diphosphate synthase (SaFDS) using the transcriptome sequencing of S. album. Using Illumina next generation sequencing, 33.32 million high quality raw reads were generated, which were assembled into 84,094 unigenes with an average length of 494.17 bp. Based on the transcriptome sequencing, five sesquiterpene synthases SaFDS, SaSQS1, SaSQS2, SaBS and SaSS involved in the biosynthesis of FPP, sesquisabinene, β-bisabolene and santalenes, respectively, were cloned and functionally characterized. Novel sesquiterpene synthases (SaSQS1 and SaSQS2) were characterized as isoforms of sesquisabinene synthase with varying kinetic parameters and expression levels. Furthermore, the feasibility of microbial production of sesquisabinene from both the unigenes, SaSQS1 and SaSQS2 in non-optimized bacterial cell for the preparative scale production of sesquisabinene has been demonstrated. These results may pave the way for in vivo production of sandalwood sesquiterpenes in genetically tractable heterologous systems. PMID:25976282
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Functional Characterization of Novel Sesquiterpene Synthases from Indian Sandalwood, Santalum album.
Srivastava, Prabhakar Lal; Daramwar, Pankaj P; Krithika, Ramakrishnan; Pandreka, Avinash; Shankar, S Shiva; Thulasiram, Hirekodathakallu V
2015-05-15
Indian Sandalwood, Santalum album L. is highly valued for its fragrant heartwood oil and is dominated by a blend of sesquiterpenes. Sesquiterpenes are formed through cyclization of farnesyl diphosphate (FPP), catalyzed by metal dependent terpene cyclases. This report describes the cloning and functional characterization of five genes, which encode two sesquisabinene synthases (SaSQS1, SaSQS2), bisabolene synthase (SaBS), santalene synthase (SaSS) and farnesyl diphosphate synthase (SaFDS) using the transcriptome sequencing of S. album. Using Illumina next generation sequencing, 33.32 million high quality raw reads were generated, which were assembled into 84,094 unigenes with an average length of 494.17 bp. Based on the transcriptome sequencing, five sesquiterpene synthases SaFDS, SaSQS1, SaSQS2, SaBS and SaSS involved in the biosynthesis of FPP, sesquisabinene, β-bisabolene and santalenes, respectively, were cloned and functionally characterized. Novel sesquiterpene synthases (SaSQS1 and SaSQS2) were characterized as isoforms of sesquisabinene synthase with varying kinetic parameters and expression levels. Furthermore, the feasibility of microbial production of sesquisabinene from both the unigenes, SaSQS1 and SaSQS2 in non-optimized bacterial cell for the preparative scale production of sesquisabinene has been demonstrated. These results may pave the way for in vivo production of sandalwood sesquiterpenes in genetically tractable heterologous systems.
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Pereira, Flaviane G; Marquete, Ronaldo; Domingos, Levy T; Rocha, Marco E N; Ferreira-Pereira, Antonio; Mansur, Elisabeth; Moreira, Davyson L
2017-01-01
Casearia genus (Salicaceae) is found in sub-tropical and tropical regions of the world and comprises about 160-200 species. It is a medicinal plant used in South America, also known as "guaçatonga", "erva-de-tiú", "cafezinho-do-mato". In Brazil, there are about 48 species and 12 are registered in the State of Rio de Janeiro, including Casearia sylvestris Sw. There are many studies related to the chemical profile and cytotoxic activities of extracts from these plants, although few studies about the antifungal potential of the essential oil have been reported. In this work, we have studied the antifungal properties of the essential oil of C. sylvestris leaves, as well as of their fractions, against four yeasts (Saccharomyces cerevisae, Candida albicans, C. glabrata and C. krusei) for the first time. The chemical analysis of the essential oil revealed a very diversified (n = 21 compounds) volatile fraction composed mainly of non-oxygenated sesquiterpenes (72.1%). These sesquiterpenes included α-humulene (17.8%) and α-copaene (8.5%) and the oxygenated sesquiterpene spathulenol (11.8%) were also identified. Monoterpenes were not identified. The fractions are mainly composed of oxygenated sesquiterpenes, and the most active fraction is rich in the sesquiterpene 14-hydroxy -9-epi-β-caryophyllene. This fraction was the most effective in inhibiting the growth of three yeast strains.
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Palmer-Young, Evan C.; Veit, Daniel; Gershenzon, Jonathan; Schuman, Meredith C.
2015-01-01
Among the terpenes, isoprene (C5) and monoterpene hydrocarbons (C10) have been shown to ameliorate abiotic stress in a number of plant species via two proposed mechanisms: membrane stabilization and direct antioxidant effects. Sesquiterpene hydrocarbons (C15) not only share the structural properties thought to lend protective qualities to isoprene and monoterpene hydrocarbons, but also react rapidly with ozone, suggesting that sesquiterpenes may similarly enhance tolerance of abiotic stresses. To test whether sesquiterpenes protect plants against ozone, UVB light, or drought, we used transgenic lines of the wild tobacco Nicotiana attenuata. The transgenic plants expressed a maize terpene synthase gene (ZmTPS10) which produced a blend of (E)-ß-farnesene and (E)-α-bergamotene, or a point mutant of the same gene (ZmTPS10M) which produced (E)-ß-farnesene alone,. (E)-ß-farnesene exerted a local, external, and transient ozone-quenching effect in ozone-fumigated chambers, but we found no evidence that enhanced sesquiterpene production by the plant inhibited oxidative damage, or maintained photosynthetic function or plant fitness under acute or chronic stress. Although the sesquiterpenes (E)-ß-farnesene and (E)-α-bergamotene might confer benefits under intermittent heat stress, which was not tested, any roles in relieving abiotic stress may be secondary to their previously demonstrated functions in biotic interactions. PMID:26030663
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Ma, Jianghao; Wang, Ying; Liu, Yue; Gao, Suyu; Ding, Liqin; Zhao, Feng; Chen, Lixia; Qiu, Feng
2015-06-01
Four new cadinane-type sesquiterpenes named phacadinanes A-D (1-4) were isolated from the rhizomes of Curcuma phaeocaulis. Their structures were elucidated by 1D and 2D NMR, as well as accurate mass measurements. Compound 4 was the first example of a rare 4,5-seco-cadinane sesquiterpene isolated from the Zingiberaceae family. Furthermore, inhibitory effects of the isolated compounds on nitric oxide production in LPS-activated macrophages were evaluated. Compounds 1 and 2 showed strong inhibitory activities on NO production with IC50 values of 3.88±0.58 and 2.25±0.71 μM, respectively. A possible biogenetic pathway for 4,5-seco-cadinane sesquiterpene (4) was postulated. Copyright © 2015 Elsevier B.V. All rights reserved.
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Producing biofuels using polyketide synthases
Katz, Leonard; Fortman, Jeffrey L; Keasling, Jay D
2013-04-16
The present invention provides for a non-naturally occurring polyketide synthase (PKS) capable of synthesizing a carboxylic acid or a lactone, and a composition such that a carboxylic acid or lactone is included. The carboxylic acid or lactone, or derivative thereof, is useful as a biofuel. The present invention also provides for a recombinant nucleic acid or vector that encodes such a PKS, and host cells which also have such a recombinant nucleic acid or vector. The present invention also provides for a method of producing such carboxylic acids or lactones using such a PKS.
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Characteristic gamma-lactone odor production of the genus Pityrosporum.
Labows, J N; McGinley, K J; Leyden, J J; Webster, G F
1979-01-01
Mass spectrometric-gas chromatographic analysis of culture headspaces revealed that members of the genous Pityrosporum produce volatile gamma-lactones during growth on lipid-containing media. Representative members of other yeast genera found on humans failed to produce these compounds. Addition of lecithin, oleic acids, triolein, or human sebum to the culture media stimulated gamma-lactone production by Pityrosporum species. All yeasts tested produced isopentanol and phenylethanol. Production of gamma-lactones may serve as a valuable characteristic in the identification of organisms of the genus Pityrosporum. PMID:533274
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Yin, Wai-Fong; Purmal, Kathiravan; Chin, Shenyang; Chan, Xin-Yue; Chan, Kok-Gan
2012-01-01
We report the isolation of N-acyl homoserine lactone-producing Enterobacter sp. isolate T1-1 from the posterior dorsal surfaces of the tongue of a healthy individual. Spent supernatants extract from Enterobacter sp. isolate T1-1 activated the biosensor Agrobacterium tumefaciens NTL4(pZLR4), suggesting production of long chain AHLs by these isolates. High resolution mass spectrometry analysis of these extracts confirmed that Enterobacter sp. isolate T1-1 produced a long chain N-acyl homoserine lactone, namely N-dodecanoyl-homoserine lactone (C12-HSL). To the best of our knowledge, this is the first isolation of Enterobacter sp., strain T1-1 from the posterior dorsal surface of the human tongue and N-acyl homoserine lactones production by this bacterium. PMID:23202161
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A synthetic review of notoedres species mites and mange
Foley, Janet E.; Serieys, L.E.; Stephenson, N.; Riley, S.; Foley, C.; Jennings, M.; Wengert, G.; Vickers, W.; Boydston, Erin E.; Lyren, Lisa L.; Moriarty, J.; Clifford, D.L.
2016-01-01
Notoedric mange, caused by obligately parasitic sarcoptiform Notoedres mites, is associated with potentially fatal dermatitis with secondary systemic disease in small mammals, felids and procyonids among others, as well as an occasional zoonosis. We describe clinical spectra in non-chiropteran hosts, review risk factors and summarize ecological and epidemiological studies. The genus is disproportionately represented on rodents. Disease in felids and procyonids ranges from very mild to death. Knowledge of the geographical distribution of the mites is highly inadequate, with focal hot spots known for Notoedres cati in domestic cats and bobcats. Predisposing genetic and immunological factors are not known, except that co-infection with other parasites and anticoagulant rodenticide toxicoses may contribute to severe disease. Treatment of individual animals is typically successful with macrocytic lactones such as selamectin, but herd or wildlife population treatment has not been undertaken. Transmission requires close contact and typically is within a host species. Notoedric mange can kill half all individuals in a population and regulate host population below non-diseased density for decades, consistent with frequency-dependent transmission or spillover from other hosts. Epidemics are increasingly identified in various hosts, suggesting global change in suitable environmental conditions or increased reporting bias.
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Hata, H; Shimizu, S; Hattori, S; Yamada, H
1989-02-24
Ketopantoyl-lactone reductase (2-dehydropantoyl-lactone reductase, EC 1.1.1.168) was purified and crystallized from cells of Candida parapsilosis IFO 0708. The enzyme was found to be homogeneous on ultracentrifugation, high-performance gel-permeation liquid chromatography and SDS-polyacrylamide gel electrophoresis. The relative molecular mass of the native and SDS-treated enzyme is approximately 40,000. The isoelectric point of the enzyme is 6.3. The enzyme was found to catalyze specifically the reduction of a variety of natural and unnatural polyketones and quinones other than ketopantoyl lactone in the presence of NADPH. Isatin and 5-methylisatin are rapidly reduced by the enzyme, the Km and Vmax values for isatin being 14 microM and 306 mumol/min per mg protein, respectively. Ketopantoyl lactone is also a good substrate (Km = 333 microM and Vmax = 481 mumol/min per mg protein). Reverse reaction was not detected with pantoyl lactone and NADP+. The enzyme is inhibited by quercetin, several polyketones and SH-reagents. 3,4-Dihydroxy-3-cyclobutene-1,2-dione, cyclohexenediol-1,2,3,4-tetraone and parabanic acid are uncompetitive inhibitors for the enzyme, the Ki values being 1.4, 0.2 and 3140 microM, respectively, with isatin as substrate. Comparison of the enzyme with the conjugated polyketone reductase of Mucor ambiguus (S. Shimizu, H. Hattori, H. Hata and H. Yamada (1988) Eur. J. Biochem. 174, 37-44) and ketopantoyl-lactone reductase of Saccharomyces cerevisiae suggested that ketopantoyl-lactone reductase is a kind of conjugated polyketone reductase.
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USDA-ARS?s Scientific Manuscript database
Bioassay-guided fractionation of a fungus Neocosmospora sp. (UM-031509) resulted in the isolation of three new resorcyclic acid lactones, neocosmosin A (2), neocosmosin B (3) and neocosmosin C (4). Three known resorcylic acid lactones, monocillin IV (1), monocillin II (5) and monorden (6) were also ...
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Yeo, Yun-Soo; Nybo, S. Eric; Chittiboyina, Amar G.; Weerasooriya, Aruna D.; Wang, Yan-Hong; Góngora-Castillo, Elsa; Vaillancourt, Brieanne; Buell, C. Robin; DellaPenna, Dean; Celiz, Mary Dawn; Jones, A. Daniel; Wurtele, Eve Syrkin; Ransom, Nick; Dudareva, Natalia; Shaaban, Khaled A.; Tibrewal, Nidhi; Chandra, Suman; Smillie, Troy; Khan, Ikhlas A.; Coates, Robert M.; Watt, David S.; Chappell, Joe
2013-01-01
Valerian is an herbal preparation from the roots of Valeriana officinalis used as an anxiolytic and sedative and in the treatment of insomnia. The biological activities of valerian are attributed to valerenic acid and its putative biosynthetic precursor valerenadiene, sesquiterpenes, found in V. officinalis roots. These sesquiterpenes retain an isobutenyl side chain whose origin has been long recognized as enigmatic because a chemical rationalization for their biosynthesis has not been obvious. Using recently developed metabolomic and transcriptomic resources, we identified seven V. officinalis terpene synthase genes (VoTPSs), two that were functionally characterized as monoterpene synthases and three that preferred farnesyl diphosphate, the substrate for sesquiterpene synthases. The reaction products for two of the sesquiterpene synthases exhibiting root-specific expression were characterized by a combination of GC-MS and NMR in comparison to the terpenes accumulating in planta. VoTPS7 encodes for a synthase that biosynthesizes predominately germacrene C, whereas VoTPS1 catalyzes the conversion of farnesyl diphosphate to valerena-1,10-diene. Using a yeast expression system, specific labeled [13C]acetate, and NMR, we investigated the catalytic mechanism for VoTPS1 and provide evidence for the involvement of a caryophyllenyl carbocation, a cyclobutyl intermediate, in the biosynthesis of valerena-1,10-diene. We suggest a similar mechanism for the biosynthesis of several other biologically related isobutenyl-containing sesquiterpenes. PMID:23243312
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Yeo, Yun-Soo; Nybo, S Eric; Chittiboyina, Amar G; Weerasooriya, Aruna D; Wang, Yan-Hong; Góngora-Castillo, Elsa; Vaillancourt, Brieanne; Buell, C Robin; DellaPenna, Dean; Celiz, Mary Dawn; Jones, A Daniel; Wurtele, Eve Syrkin; Ransom, Nick; Dudareva, Natalia; Shaaban, Khaled A; Tibrewal, Nidhi; Chandra, Suman; Smillie, Troy; Khan, Ikhlas A; Coates, Robert M; Watt, David S; Chappell, Joe
2013-02-01
Valerian is an herbal preparation from the roots of Valeriana officinalis used as an anxiolytic and sedative and in the treatment of insomnia. The biological activities of valerian are attributed to valerenic acid and its putative biosynthetic precursor valerenadiene, sesquiterpenes, found in V. officinalis roots. These sesquiterpenes retain an isobutenyl side chain whose origin has been long recognized as enigmatic because a chemical rationalization for their biosynthesis has not been obvious. Using recently developed metabolomic and transcriptomic resources, we identified seven V. officinalis terpene synthase genes (VoTPSs), two that were functionally characterized as monoterpene synthases and three that preferred farnesyl diphosphate, the substrate for sesquiterpene synthases. The reaction products for two of the sesquiterpene synthases exhibiting root-specific expression were characterized by a combination of GC-MS and NMR in comparison to the terpenes accumulating in planta. VoTPS7 encodes for a synthase that biosynthesizes predominately germacrene C, whereas VoTPS1 catalyzes the conversion of farnesyl diphosphate to valerena-1,10-diene. Using a yeast expression system, specific labeled [(13)C]acetate, and NMR, we investigated the catalytic mechanism for VoTPS1 and provide evidence for the involvement of a caryophyllenyl carbocation, a cyclobutyl intermediate, in the biosynthesis of valerena-1,10-diene. We suggest a similar mechanism for the biosynthesis of several other biologically related isobutenyl-containing sesquiterpenes.
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Herbicidal and Fungicidal Activities of Lactones in Kava (Piper methysticum).
Xuan, T D; Elzaawely, A A; Fukuta, M; Tawata, S
2006-02-08
This is the first report showing that kava lactones are plant and plant fungus growth inhibitors. Aqueous extract of kava roots showed high allelopathic potential and strongly suppressed germination and growth of lettuce, radish, barnyardgrass, and monochoria. Nine kava lactones were detected using GC-MS including desmethoxyyagonin, kavain, 7,8-dihydrokavain, hydroxykavain, yagonin, 5,6,7,8-tetrahydroxyyagonin, methysticin, dihydromethysticin, and 11-hydroxy-12-methoxydihydrokavain. Quantities of desmethoxyyagonin, kavain, 7,8-dihydrokavain, yagonin, methysticin, and dihydromethysticin detected were 4.3, 6.9, 18.6, 5.7, 1.4, and 5.4 mg/g of dry weight, respectively. These six major lactones in kava roots showed great herbicidal and antifungal activities. Growth of lettuce and barnyardgrass were significantly inhibited at 1-10 ppm, and four plant fungi including Colletotrichum gloeosporides, Fusarium solani, Fusarium oxysporum, and Trichoderma viride were significantly inhibited at 10-50 ppm. The biological activities of kava lactones were characterized by different double-bond linkage patterns in positions 5,6 and 7,8. The findings of this study suggest that kava lactones may be useful for the development of bioactive herbicides and fungicides.
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Kaur, Mandeep; Kumar, Rakesh; Upendrabhai, Deep Patel; Singh, Inder Pal; Kaur, Sanehdeep
2017-05-01
The use of botanical pesticides for protecting crops from insect pests has assumed greater importance all over the world owing to growing awareness of harmful effects of indiscriminate use of synthetic pesticides. Inula racemosa Hook. f. (Asteraceae), a medicinally important perennial herb, is rich in sesquiterpenes with many biological activities. The present studies were conducted with the objective to evaluate the sesquiterpenes isolated from I. racemosa for insecticidal activity against Spodoptera litura (F.). Alantolactone and isoalantolactone isolated from I. racemosa exerted growth inhibitory effects on S. litura. Addition of both the sesquiterpenes to larval diet extended the development period and reduced pupation as well as adult emergence. The dietary utilisation experiments on third-instar larvae of S. litura revealed reduction in consumption and growth rates of larvae as well as efficiency of conversion of ingested and digested food owing to alantolactone and isoalantolactone. The root extract of I. racemosa, which is rich in two sesquiterpenes, i.e. alantolactone and isoalantolactone, has the potential for management of S. litura. However, there is a need to understand the specific mechanism of action of these compounds. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.
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He, Haibing; Ma, Zhongjun; Wang, Qianqian; Liu, Yu; Xu, Hualin
2016-07-01
A new eremophilane sesquiterpene, capnodiumone (1), along with five known eremophilane sesquiterpenes (2-6) and eight other compounds (7-14), have been isolated from a mangrove-associated fungus Capnodium sp. SZ-F22. The chemical structures were elucidated on the basis of extensive spectroscopic analysis. The broth extract of the fungus exhibited a good inhibitory effect on the mycelium growth against Fusarium graminearum at 100 μg/mL, however, all the 14 compounds showed no expected antifungal activity. The probable reasons were discussed.
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Wu, Guangwei; Lin, Aiqun; Gu, Qianqun; Zhu, Tianjiao; Li, Dehai
2013-01-01
A new chloro-trinoreremophilane sesquiterpene 1, three new chlorinated eremophilane sesquiterpenes 2–4, together with a known compound, eremofortine C (5), were isolated from an Antarctic deep-sea derived fungus, Penicillium sp. PR19N-1. Structures were established using IR, HRMS, 1D and 2D NMR techniques. In addition, the plausible metabolic network of these isolated products is proposed. Compound 1 showed moderate cytotoxic activity against HL-60 and A549 cancer cell lines. PMID:23612371
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Strong inhibitory effect of furanoses and sugar lactones on beta-galactosidase Escherichia coli.
Huber, R E; Brockbank, R L
1987-03-24
Various sugars and their lactones were tested for their inhibition of beta-galactosidase (Escherichia coli). L-Ribose, which in the furanose form has a hydroxyl configuration similar to that of D-galactose at positions equivalent to the 3- and 4-positions of D-galactose, was a very strong inhibitor, and D-lyxose, which in the furanose form also resembles D-galactose, was a much better inhibitor than expected. Structural comparisons prelude the pyranose forms of these sugars from being significant contributors to the inhibition, and inhibition at different temperatures (at which there are different furanose concentrations) strongly supported the conclusion that the furanose form is inhibitory. Studies with sugar derivatives that can only be in the furanose form also supported the conclusion. This is the first report of the inhibitory effect of furanose on beta-galactosidase. Lactones were also inhibitory. Every lactone tested was much more inhibitory than was its parent sugar. D-Galactonolactone was especially good. Experiments indicated that it was D-galactono-1,5-lactone rather than D-galactono-1,4-lactone which was inhibitory. Inhibition of beta-galactosidases from mammalian sources by lactones has been reported previously, but this is the first report of the effect of beta-galactosidase from E. coli. Since furanoses in the envelope form are analogous (in some ways) to half-chair or sofa conformations and since lactones with six-membered rings probably have half-chair or sofa conformations, the results indicate that beta-galactosidase probably destabilizes its substrate into a planar conformation of some type and that the galactose in the transition state may, therefore, also be quite planar.(ABSTRACT TRUNCATED AT 250 WORDS)
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Nell, Monika; Wawrosch, Christoph; Steinkellner, Siegrid; Vierheilig, Horst; Kopp, Brigitte; Lössl, Andreas; Franz, Chlodwig; Novak, Johannes; Zitterl-Eglseer, Karin
2010-03-01
In some medicinal plants a specific plant-fungus association, known as arbuscular mycorrhizal (AM) symbiosis, increases the levels of secondary plant metabolites and/or plant growth. In this study, the effects of three different AM treatments on biomass and sesquiterpenic acid concentrations in two IN VITRO propagated genotypes of valerian ( VALERIANA OFFICINALIS L., Valerianaceae) were investigated. Valerenic, acetoxyvalerenic and hydroxyvalerenic acid levels were analyzed in the rhizome and in two root fractions. Two of the AM treatments significantly increased the levels of sesquiterpenic acids in the underground parts of valerian. These treatments, however, influenced the biomass of rhizomes and roots negatively. Therefore this observed increase was not accompanied by an increase in yield of sesquiterpenic acids per plant. Furthermore, one of the two genotypes had remarkably high hydroxyvalerenic acid contents and can be regarded as a hydroxyvalerenic acid chemotype. Copyright Georg Thieme Verlag KG Stuttgart New York.
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Ham, Ahrom; Kim, Dong-Woo; Kim, Kyeong Ho; Lee, Sung-Jin; Oh, Ki-Bong; Shin, Jongheon; Mar, Woongchon
2013-08-02
Aggregation of α-synuclein (ASYN) is considered a major determinant of neuronal loss in Parkinson's disease (PD). E6-associated protein (E6-AP), an E3 ubiquitin protein ligase, has been known to promote the degradation of α-synuclein. The aim of this study was to assess the effects of the sesquiterpene lactone reynosin on dopamine (DA)-induced neuronal toxicity and regulation of E6-associated protein and α-synuclein proteins in both in vitro and in vivo models of Parkinson's disease. Usi"ng flow cytometry and western blot analysis, we determined that reynosin significantly protected both against cell death from dopamine-induced toxicity in human neuroblastoma SH-SY5Y cells and against the loss of tyrosine hydroxylase (TH)-positive cells in 6-hydroxydopamine (6-OHDA)-lesioned rats (a rodent Parkinson's disease model system). In addition, reynosin made up-regulation of E6-associated protein expression and down-regulation of the over-expression of α-synuclein protein in both dopamine-treated SH-SY5Y cells and 6-hydroxydopamine-lesioned rats. These results suggest that the protective effect of reynosin against dopamine-induced neuronal cell death may be due to the reciprocal up-regulation of E6-associated protein and down-regulation of α-synuclein protein expression. Copyright © 2013 Elsevier B.V. All rights reserved.
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Huber, Meret; Triebwasser-Freese, Daniella; Reichelt, Michael; Heiling, Sven; Paetz, Christian; Chandran, Jima N; Bartram, Stefan; Schneider, Bernd; Gershenzon, Jonathan; Erb, Matthias
2015-07-01
The secondary metabolites in the roots, leaves and flowers of the common dandelion (Taraxacum officinale agg.) have been studied in detail. However, little is known about the specific constituents of the plant's highly specialized laticifer cells. Using a combination of liquid and gas chromatography, mass spectrometry and nuclear magnetic resonance spectrometry, we identified and quantified the major secondary metabolites in the latex of different organs across different growth stages in three genotypes, and tested the activity of the metabolites against the generalist root herbivore Diabrotica balteata. We found that common dandelion latex is dominated by three classes of secondary metabolites: phenolic inositol esters (PIEs), triterpene acetates (TritAc) and the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G). Purification and absolute quantification revealed concentrations in the upper mgg(-1) range for all compound classes with up to 6% PIEs, 5% TritAc and 7% TA-G per gram latex fresh weight. Contrary to typical secondary metabolite patterns, concentrations of all three classes increased with plant age. The highest concentrations were measured in the main root. PIE profiles differed both quantitatively and qualitatively between plant genotypes, whereas TritAc and TA-G differed only quantitatively. Metabolite concentrations were positively correlated within and between the different compound classes, indicating tight biosynthetic co-regulation. Latex metabolite extracts strongly repelled D. balteata larvae, suggesting that the latex constituents are biologically active. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Amrehn, Evelyn; Heller, Annerose; Spring, Otmar
2014-01-01
Previous studies have shown that capitate glandular trichomes (CGT) of the common sunflower, Helianthus annuus, produce sesquiterpene lactones (STL) and flavonoids, which are sequestered and accumulated between the apical cuticle and the wall of the tip cells. To explore the cellular structures required and putatively involved in the STL biosynthesis and secretion, the present study was focused on the development of CGT and the comparison of the ultrastructure of its different cell types. Gradual maturation of flowers in the capitulum of the sunflower provided the possibility to study the simultaneous differentiation from the primordial to the secretory stage of CGT located by light microscopy (bright field, differential interference contrast and fluorescence) as well as transmission electron microscopy. It was shown that the CGT of sunflower anthers had a biseriate structure with up to 14 cell pairs. In mature trichomes, the apical cells called secretory cells were covered entirely by a large cuticle globe, which enclosed the resinous terpenoids and was specialised in thickness and structure. The secretory cells lacked chloroplasts and contained mainly smooth endoplasmic reticulum (sER). Conspicuous cell wall protuberances and an accumulation of mitochondria nearby occurred in the horizontally oriented cell walls. The cytological differences between stalk cells and secretory cells indicate a different function. The dominance of sER suggests its involvement in STL biosynthesis and cell wall protuberances enlarge the surface of the plasmamembrane of secretory cells and may be involved in the secretion processes of STL into the subcuticular space.
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Pratheeshkumar, Poyil; Kuttan, Girija
2011-07-01
In this study, we investigated the effect of vernolide-A on the induction of apoptosis as well as its regulatory effect on the activation of transcription factors in B16F-10 melanoma cells. Treatment of B16F-10 cells with nontoxic concentrations of vernolide-A showed the presence of apoptotic bodies and induced DNA fragmentation in a dose-dependent manner. Cell-cycle analysis and TUNEL assays also confirmed the observation. The proapoptotic genes, p53, Bax, caspase-9, and caspase-3, were upregulated in vernolide-A-treated cells, whereas the antiapoptotic gene, Bcl-2, was downregulated. vernolide-A treatment also showed a downregulation of cyclin D1 expression and upregulated p21 and p27 gene expression in B16F-10 melanoma cells. The study also reveals that vernolide-A treatment could alter the production and expression of proinflammatory cytokines and could inhibit the activation and nuclear translocation of p65, p50, and c-Rel subunits of nuclear factor-κB and other transcription factors, such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response-element-binding protein in B16F-10 melanoma cells. These results suggest that vernolide-A induces apoptosis via activation of p53-induced, caspase-3-mediated proapoptotic signaling and suppression of NF-κB-induced, bcl-2-mediated survival signaling.
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Chen, Fangfang; Hao, Fuhua; Li, Changfu; Gou, Junbo; Lu, Dayan; Gong, Fujun; Tang, Huiru; Zhang, Yansheng
2013-01-01
Xanthanolides, as the sesquiterpene lactones, are reportedly the major components for the pharmacological properties of X. strumarium L. species. Phytochemical studies indicated that the glandular structures on the surface of plant tissues would form the primary sites for the accumulation of this class of the compounds. As the interface between plants and their natural enemies, glandular trichomes may vary with respect to which of their chemicals are sequestered against different herbivores in different ecologies. However, to date, no data are available on the chemical characterisation of X. strumarium glandular cells. In this study, the trichome secretions of the X. strumarium species originating from nineteen unique areas across eleven provinces in China, were analysed by HPLC, LC-ESI-MS and NMR. For the first time three distinct chemotypes of X. strumarium glandular trichomes were discovered along with the qualitative and quantitative evaluations of their presence of xanthanolides; these were designated glandular cell Types I, II, and III, respectively. The main xanthanolides in Type I cells were 8-epi-xanthatin and xanthumin while no xanthatin was detected. Xanthatin, 8-epi-xanthatin, and xanthumin dominated in Type II cells with comparable levels of each being present. For Type III cells, significantly higher concentrations of 8-epi-xanthatin or xanthinosin (relative to xanthatin) were detected with xanthinosin only being observed in this type. Further research will focus on understanding the ecological and molecular mechanism causing these chemotype differences in X. strumarium glandular structures.
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Gou, Junbo; Lu, Dayan; Gong, Fujun; Tang, Huiru; Zhang, Yansheng
2013-01-01
Xanthanolides, as the sesquiterpene lactones, are reportedly the major components for the pharmacological properties of X. strumarium L. species. Phytochemical studies indicated that the glandular structures on the surface of plant tissues would form the primary sites for the accumulation of this class of the compounds. As the interface between plants and their natural enemies, glandular trichomes may vary with respect to which of their chemicals are sequestered against different herbivores in different ecologies. However, to date, no data are available on the chemical characterisation of X. strumarium glandular cells. In this study, the trichome secretions of the X. strumarium species originating from nineteen unique areas across eleven provinces in China, were analysed by HPLC, LC-ESI-MS and NMR. For the first time three distinct chemotypes of X. strumarium glandular trichomes were discovered along with the qualitative and quantitative evaluations of their presence of xanthanolides; these were designated glandular cell Types I, II, and III, respectively. The main xanthanolides in Type I cells were 8-epi-xanthatin and xanthumin while no xanthatin was detected. Xanthatin, 8-epi-xanthatin, and xanthumin dominated in Type II cells with comparable levels of each being present. For Type III cells, significantly higher concentrations of 8-epi-xanthatin or xanthinosin (relative to xanthatin) were detected with xanthinosin only being observed in this type. Further research will focus on understanding the ecological and molecular mechanism causing these chemotype differences in X. strumarium glandular structures. PMID:24098541
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Xanthatin and xanthinosin from the burs of Xanthium strumarium L. as potential anticancer agents.
Ramírez-Erosa, Irving; Huang, Yaoge; Hickie, Robert A; Sutherland, Ronald G; Barl, Branka
2007-11-01
Xanthatin and xanthinosin, 2 sesquiterpene lactones isolated from the burs of Xanthiun strumarium L. (cocklebur), showed moderate to high in vitro cytotoxic activity in the human cancer cell lines WiDr ATCC (colon), MDA-MB-231 ATCC (breast), and NCI-417 (lung). Xanthatin and xanthinosin were purified as the result of a multi-screening bioassay-guided study of wild plant species of the family Asteraceae, collected from various sites in Saskatchewan, Canada. Seventy-five extracts at a single concentration of 100 microg/mL were evaluated for in vitro cytotoxicity to the human cancer cell lines used. The chloroform extract of Carduus nutans L. (nodding thistle) aerial parts (IC50, 9.3 microg/mL) and the hexane extract of Echinacea angustifolia DC. (narrow-leaved purple coneflower) root (IC50, 4.0 microg/mL) were moderately to highly cytotoxic to the lung cancer cell line. The chloroform extracts of X. strumarium L. burs and Tanacetum vulgare L. (tansy) aerial parts exhibited the highest cytotoxicity for all cell lines tested; their IC50 values, obtained from multidose testing, ranged from 0.1 to 6.2 microg/mL (X. strumarium) and from 2.4 to 9.1 microg/mL (T. vulgare). Further purification of the chloroform fraction of X. strumarium yielded xanthatin and xanthinosin in high yields. This is the first time that these compounds have been reported in the burs of X. strumarium. Their IC50 values are also reported herein.
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Li, Yuanjun; Gou, Junbo; Chen, Fangfang; Li, Changfu; Zhang, Yansheng
2016-01-01
Xanthium strumarium L. is a traditional Chinese herb belonging to the Asteraceae family. The major bioactive components of this plant are sesquiterpene lactones (STLs), which include the xanthanolides. To date, the biogenesis of xanthanolides, especially their downstream pathway, remains largely unknown. In X. strumarium, xanthanolides primarily accumulate in its glandular trichomes. To identify putative gene candidates involved in the biosynthesis of xanthanolides, three X. strumarium transcriptomes, which were derived from the young leaves of two different cultivars and the purified glandular trichomes from one of the cultivars, were constructed in this study. In total, 157 million clean reads were generated and assembled into 91,861 unigenes, of which 59,858 unigenes were successfully annotated. All the genes coding for known enzymes in the upstream pathway to the biosynthesis of xanthanolides were present in the X. strumarium transcriptomes. From a comparative analysis of the X. strumarium transcriptomes, this study identified a number of gene candidates that are putatively involved in the downstream pathway to the synthesis of xanthanolides, such as four unigenes encoding CYP71 P450s, 50 unigenes for dehydrogenases, and 27 genes for acetyltransferases. The possible functions of these four CYP71 candidates are extensively discussed. In addition, 116 transcription factors that are highly expressed in X. strumarium glandular trichomes were also identified. Their possible regulatory roles in the biosynthesis of STLs are discussed. The global transcriptomic data for X. strumarium should provide a valuable resource for further research into the biosynthesis of xanthanolides.
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Potential ecological roles of artemisinin produced by Artemisia annua L.
Knudsmark Jessing, Karina; Duke, Stephen O; Cedergreeen, Nina
2014-02-01
Artemisia annua L. (annual wormwood, Asteraceae) and its secondary metabolite artemisinin, a unique sesquiterpene lactone with an endoperoxide bridge, has gained much attention due to its antimalarial properties. Artemisinin has a complex structure that requires a significant amount of energy for the plant to synthesize. So, what are the benefits to A. annua of producing this unique compound, and what is the ecological role of artemisinin? This review addresses these questions, discussing evidence of the potential utility of artemisinin in protecting the plant from insects and other herbivores, as well as pathogens and competing plant species. Abiotic factors affecting the artemisinin production, as well as mechanisms of artemisinin release to the surroundings also are discussed, and new data are provided on the toxicity of artemisinin towards soil and aquatic organisms. The antifungal and antibacterial effects reported are not very pronounced. Several studies have reported that extracts of A. annua have insecticidal effects, though few studies have proven that artemisinin could be the single compound responsible for the observed effects. However, the pathogen(s) or insect(s) that may have provided the selection pressure for the evolution of artemisinin synthesis may not have been represented in the research thus far conducted. The relatively high level of phytotoxicity of artemisinin in soil indicates that plant/plant allelopathy could be a beneficial function of artemisinin to the producing plant. The release routes of artemisinin (movement from roots and wash off from leaf surfaces) from A. annua to the soil support the rationale for allelopathy.
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Anti-Helicobacter pylori Potential of Artemisinin and Its Derivatives
Goswami, Suchandra; Chinniah, Annalakshmi; Pal, Anirban; Kar, Sudip K.
2012-01-01
The antimalarial drug artemisinin from Artemisia annua demonstrated remarkably strong activity against Helicobacter pylori, the pathogen responsible for peptic ulcer diseases. In an effort to develop a novel antimicrobial chemotherapeutic agent containing such a sesquiterpene lactone endoperoxide, a series of analogues (2 natural and 15 semisynthetic molecules), including eight newly synthesized compounds, were investigated against clinical and standard strains of H. pylori. The antimicrobial spectrum against 10 H. pylori strains and a few other bacterial and fungal strains indicated specificity against the ulcer causing organism. Of five promising molecules, a newly synthesized ether derivative β-artecyclopropylmether was found to be the most potent compound, which exhibited MIC range, MIC90, and minimum bactericidal concentration range values of 0.25 to 1.0 μg/ml, 1.0 μg/ml, and 1 to 16 μg/ml, respectively, against both resistant and sensitive strains of H. pylori. The molecule demonstrated strong bactericidal kinetics with extensive morphological degeneration, retained functional efficacy at stomach acidic pH unlike clarithromycin, did not elicit drug resistance unlike metronidazole, and imparted sensitivity to resistant strains. It is not cytotoxic and exhibits in vivo potentiality to reduce the H. pylori burden in a chronic infection model. Thus, β-artecyclopropylmether could be a lead candidate for anti-H. pylori therapeutics. Since the recurrence of gastroduodenal ulcers is believed to be mainly due to antibiotic resistance of the commensal organism H. pylori, development of a candidate drug from this finding is warranted. PMID:22687518
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Hussain, N; Abbasi, Tasneem; Abbasi, S A
2015-11-15
In evidently the first study of its kind, vermicompost derived solely from a weed known to possess plant and animal toxicity was used to assess its impact on the germination and early growth of several plant species. No pre-composting or supplementation of animal manure was done to generate the vermicompost in order to ensure that the impact is clearly attributable to the weed. Whereas the weed used in this study, Lantana (Lantana camara), is known to possess strong negative allelopathy, besides plant/animal toxicity in other forms, its vermicompost was seen to be a good organic fertilizer as it increased germination success and encouraged growth of all the three botanical species explored by the authors - green gram (Vigna radiata), ladies finger (Abelmoschus esculentus) and cucumber (Cucumis sativus). In terms of several physical, chemical and biochemical attributes that were studied, the vermicompost appeared plant-friendly, giving best results in general when employed at concentrations of 1.5% in soil (w/w). Fourier transform infrared spectrometry revealed that the phenols and the sesquiterpene lactones that are responsible for the allelopathic impact of Lantana were largely destroyed in the course of vermicomposting. There is also an indication that lignin content of Lantana was reduced during its vermicomposting. The findings open up the possibility that the billions of tons of phytomass that is generated annually by Lantana and other invasives can be gainfully utilized in generating organic fertilizer via vermicomposting. Copyright © 2015 Elsevier B.V. All rights reserved.
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Abd-Alla, Howaida I; Shalaby, Nagwa M M; Hamed, Manal A; El-Rigal, Nagy Saba; Al-Ghamdi, Samira N; Bouajila, Jalloul
2016-01-01
Three sesquiterpene lactones [two germacranolides (micranthin and sintenin) and one guaianolide (4β,10α-dihydroxy-5β,7β,8βH-guaia-1,11(13)dien-12,8α-olide)] and four derivatives of 3-methoxy flavones (santin, quercetagetin-3,6,3'-trimethyl ether, quercetagetin-3,6-dimethyl ether, and 5,7 dihydroxy 3,3',4'-trimethoxy flavone) were isolated from the ethyl acetate extract (EAE) of the aerial parts of Achillea biebersteinii Afan. (Asteraceae). Evaluation of protective and therapeutic effects of EAE against ethanol-induced gastric ulcer in rats was carried. Antiulcer activity evaluation was done through measuring ulcer indices, stomach acidity, gastric volume and lesion counts. Oxidative stress markers; malondialdehyde, glutathione and superoxide dismutase were also estimated. The work was extended to determine the histopathological assessment of the stomach. Gastric ulcer exhibited a significant elevation of the ulcer index and oxidative stress markers. The extract attenuated these increments and recorded protective and therapeutic effects against gastric ulcer. Hyperglycaemia increases the mucosal susceptibility to ulcerogenic stimuli and predisposes gastric ulceration. In vitro α-amylase inhibitory assay was applied to evaluate the post prandial antihyperglycaemia activity. The result showing that the EAE has the ability to reduce starch-induced postprandial glycaemic excursions by virtue of potent intestinal α-amylase inhibitory activity. These findings demonstrated the remarkable potential of A. biebersteinii as valuable source of antiulcer agent with post prandial hyperglycaemia lowering effect.
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Treatment of MDR1 Mutant Dogs with Macrocyclic Lactones
Geyer, Joachim; Janko, Christina
2012-01-01
P-glycoprotein, encoded by the multidrug resistance gene MDR1, is an ATP-driven drug efflux pump which is highly expressed at the blood-brain barrier of vertebrates. Drug efflux of macrocyclic lactones by P-glycoprotein is highly relevant for the therapeutic safety of macrocyclic lactones, as thereby GABA-gated chloride channels, which are confined to the central nervous system in vertebrates, are protected from high drug concentrations that otherwise would induce neurological toxicity. A 4-bp deletion mutation exists in the MDR1 gene of many dog breeds such as the Collie and the Australian Shepherd, which results in the expression of a non-functional P-glycoprotein and is associated with multiple drug sensitivity. Accordingly, dogs with homozygous MDR1 mutation are in general prone to neurotoxicity by macrocyclic lactones due to their increased brain penetration. Nevertheless, treatment of these dogs with macrocyclic lactones does not inevitably result in neurological symptoms, since, the safety of treatment highly depends on the treatment indication, dosage, route of application, and the individual compound used as outlined in this review. Whereas all available macrocyclic lactones can safely be administered to MDR1 mutant dogs at doses usually used for heartworm prevention, these dogs will experience neurological toxicity following a high dose regimen which is common for mange treatment in dogs. Here, we review and discuss the neurotoxicological potential of different macrocyclic lactones as well as their treatment options in MDR1 mutant dogs. PMID:22039792
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Rai, R; Katzenellenbogen, J A
1992-11-13
Previously, we have reported that some guanidino-substituted alpha- and beta-aryl enol lactones I and II behaved as selective, mechanism-based inhibitors of some trypsin-like proteases (Rai, R.; Katzenellenbogen, J.A. J. Med. Chem., submitted). In this study, we describe the synthesis and kinetic evaluation of some related, guanidino-substituted enol lactones having greater conformational mobility and affording additional hydrogen-bonding sites at the active site. The alpha-aryl-substituted lactones 1 and 2, which have greater conformational mobility in the guanidinoaryl linkage than I, selectively inhibited the trypsin-like enzymes, and they were relatively poor inactivators of alpha-chymotrypsin and human neutrophil elastase (HNE). The iodo enol lactone 2 permanently inactivated trypsin, urokinase, tissue plasminogen activator, and plasmin, showing exceptionally high specificity in its interaction with trypsin and urokinase. The selectivity pattern exhibited by the closely related, conformationally less mobile alpha-aryl-substituted iodo lactone Ib, which was previously shown to be a selective suicide substrate of urokinase and plasmin, provides an interesting comparison. The alpha-benzamido-substituted lactones 3 and 4, which afford an additional site for active-site hydrogen bonding, were found to be very potent alternate substrate inhibitors of trypsin and urokinase. In addition, the iodo lactone 4 permanently inactivated alpha-chymotrypsin. The importance of secondary interactions in increasing the specificities in the case of alpha-chymotrypsin is discussed.
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Underestimation of terpene exposure in the Nordic wood industry.
Granström, Karin M
2010-03-01
This study determined that emission of sesquiterpenes from processed wood warrants attention in the work environment. Currently, only the monoterpenes in the terpene group are monitored in occupational hygiene studies. Terpene emissions are a work environment issue for industries that process wood, as they are known to cause respiratory difficulties and mucous membrane irritation. Fresh sawdust of the most common boreal conifers, Norway spruce (Picea abies) and Scots pine (Pinus sylvestris), was subjected to processing (drying), and the emissions were analyzed with a gas chromatograph-mass spectrometer. The data indicate that workers are exposed to significant amounts of sesquiterpenes, an observation that has not been recorded previously at wood processing plants. On average, the proportion of sesquiterpenes to monoterpenes was 21 +/- 5% (STD, n = 11) for spruce and 15 +/- 5% (STD, n = 13) for pine. The composition of terpenes emitted in air from spruce wood differs from the composition in resin. The sum of monoterpenes and sesquiterpenes can exceed the occupational exposure limit for turpentine for processes where monoterpene concentrations are already close to the occupational exposure limit, and for processes involving the processing of bark. Findings suggest that future studies of health effects from terpenes in air should measure monoterpenes and sesquiterpenes to assess whether the current OELs are appropriate.
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Weikl, Fabian; Ghirardo, Andrea; Schnitzler, Jörg-Peter; Pritsch, Karin
2016-01-01
Alternaria alternata is one of the most studied fungi to date because of its impact on human life – from plant pathogenicity to allergenicity. However, its sesquiterpene emissions have not been systematically explored. Alternaria regularly co-occurs with Fusarium fungi, which are common plant pathogens, on withering plants. We analyzed the diversity and determined the absolute quantities of volatile organic compounds (VOCs) in the headspace above mycelial cultures of A. alternata and Fusarium oxysporum under different conditions (nutrient rich and poor, single cultures and co-cultivation) and at different mycelial ages. Using stir bar sorptive extraction and gas chromatography–mass spectrometry, we observed A. alternata to strongly emit sesquiterpenes, particularly during the early growth stages, while emissions from F. oxysporum consistently remained comparatively low. The emission profile characterizing A. alternata comprised over 20 sesquiterpenes with few effects from nutrient quality and age on the overall emission profile. Co-cultivation with F. oxysporum resulted in reduced amounts of VOCs emitted from A. alternata although its profile remained similar. Both fungi showed distinct emission profiles, rendering them suitable biomarkers for growth-detection of their phylotype in ambient air. The study highlights the importance of thorough and quantitative evaluations of fungal emissions of volatile infochemicals such as sesquiterpenes. PMID:26915756
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Diterpene lactones with labdane, halimane and clerodane frameworks.
Silva, Lúcia; Gomes, Arlindo C; Rodilla, Jesus M L
2011-04-01
The labdane, halimane and clerodane type diterpenoids are compounds that have been isolated in plants of several families. These molecules and their derivatives with a lactone group on the side chain or on the decaline system, have a great interest because of their biological properties as insect antifeedant, antiviral, cytotoxic and trypanocidal. The scope of this review is lactones diterpenoids with labdane, halimane and clerodane frameworks.
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Lipase-catalyzed ring-opening polymerization of lactones to polyesters and its mechanistic aspects.
Namekawa, S; Suda, S; Uyama, H; Kobayashi, S
1999-01-01
Lipase catalysis induced a ring-opening polymerization of lactones with different ring-sizes. Small-size (four-membered) and medium-size lactones (six- and seven-membered) as well as macrolides (12-, 13-, 16-, and 17-membered) were subjected to lipase-catalyzed polymerization. The polymerization behaviors depended primarily on the lipase origin and the monomer structure. The macrolides showing much lower anionic polymerizability were enzymatically polymerized faster than epsilon-caprolactone. The granular immobilized lipase derived from Candida antartica showed extremely efficient catalysis in the polymerization of epsilon-caprolactone. Single-step terminal functionalization of the polyester was achieved by initiator and terminator methods. The enzymatic polymerizability of lactones was quantitatively evaluated by Michaelis-Menten kinetics.
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Arthropod deterrents from Artemisia pallens (Davana oil) components
USDA-ARS?s Scientific Manuscript database
Davanone, a key sesquiterpene component of davana oil, has been synthesized in five convenient steps. Oxygenated sesquiterpenes have been linked to insect deterrent properties. Based on initial screening of davana oil, davanone and its hydroxy precursors have been generated and are being evaluated...
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Wang, Hongzhen; Han, Junli; Kanagarajan, Selvaraju; Lundgren, Anneli; Brodelius, Peter E.
2013-01-01
In order to better understand the influence of sesquiterpene synthases on artemisinin yield in Artemisia annua, the expression of some sesquiterpene synthases has been studied using transgenic plants expressing promoter-GUS fusions. The cloned promoter sequences were 923, 1182 and 1510 bp for β-caryophyllene (CPS), epi-cedrol (ECS) and β-farnesene (FS) synthase, respectively. Prediction of cis-acting regulatory elements showed that the promoters are involved in complex regulation of expression. Transgenic A. annua plants carrying promoter-GUS fusions were studied to elucidate the expression pattern of the three sesquiterpene synthases and compared to the previously studied promoter of amorpha-4,11-diene synthase (ADS), a key enzyme of artemisinin biosynthesis. The CPS and ECS promoters were active in T-shaped trichomes of leaves and stems, basal bracts of flower buds and also in some florets cells but not in glandular secretory trichome while FS promoter activity was only observed in leaf cells and trichomes of transgenic shoots. ADS, CPS, ECS and FS transcripts were induced by wounding in a time depended manner. The four sesquiterpene synthases may be involved in responsiveness of A. annua to herbivory. Methyl jasmonate treatment triggered activation of the promoters of all four sesquiterpene synthases in a time depended manner. Southern blot result showed that the GUS gene was inserted into genomic DNA of transgenic lines as a single copy or two copies. The relative amounts of CPS and ECS as well as germacrene A synthase (GAS) transcripts are much lower than that of ADS transcript. Consequently, down-regulation of the expression of the CPS, ECS or GAS gene may not improve artemsinin yield. However, blocking the expression of FS may have effects on artemisinin production. PMID:24278301
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Beran, Franziska; Rahfeld, Peter; Luck, Katrin; Nagel, Raimund; Vogel, Heiko; Wielsch, Natalie; Irmisch, Sandra; Ramasamy, Srinivasan; Gershenzon, Jonathan; Heckel, David G.; Köllner, Tobias G.
2016-01-01
Sesquiterpenes play important roles in insect communication, for example as pheromones. However, no sesquiterpene synthases, the enzymes involved in construction of the basic carbon skeleton, have been identified in insects to date. We investigated the biosynthesis of the sesquiterpene (6R,7S)-himachala-9,11-diene in the crucifer flea beetle Phyllotreta striolata, a compound previously identified as a male-produced aggregation pheromone in several Phyllotreta species. A (6R,7S)-himachala-9,11-diene–producing sesquiterpene synthase activity was detected in crude beetle protein extracts, but only when (Z,E)-farnesyl diphosphate [(Z,E)-FPP] was offered as a substrate. No sequences resembling sesquiterpene synthases from plants, fungi, or bacteria were found in the P. striolata transcriptome, but we identified nine divergent putative trans-isoprenyl diphosphate synthase (trans-IDS) transcripts. Four of these putative trans-IDSs exhibited terpene synthase (TPS) activity when heterologously expressed. Recombinant PsTPS1 converted (Z,E)-FPP to (6R,7S)-himachala-9,11-diene and other sesquiterpenes observed in beetle extracts. RNAi-mediated knockdown of PsTPS1 mRNA in P. striolata males led to reduced emission of aggregation pheromone, confirming a significant role of PsTPS1 in pheromone biosynthesis. Two expressed enzymes showed genuine IDS activity, with PsIDS1 synthesizing (E,E)-FPP, whereas PsIDS3 produced neryl diphosphate, (Z,Z)-FPP, and (Z,E)-FPP. In a phylogenetic analysis, the PsTPS enzymes and PsIDS3 were clearly separated from a clade of known coleopteran trans-IDS enzymes including PsIDS1 and PsIDS2. However, the exon–intron structures of IDS and TPS genes in P. striolata are conserved, suggesting that this TPS gene family evolved from trans-IDS ancestors. PMID:26936952
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2013-01-01
Background Agarwood is an expensive resinous heartwood derived from Aquilaria plants that is widely used in traditional medicines, incense and perfume. Only wounded trees can produce agarwood, and the huge demand for the agarwood products has led all Aquilaria spp. being endangered and listed in the Appendix II of the CITES (http://www.cites.org). The major components of agarwood are sesquiterpenes and phenylethyl chromones. Owing to a lack of genomic information, the molecular basis of wound-induced sesquiterpenes biosynthesis and agarwood formation remains unknown. Results To identify the primary genes that maybe related to agarwood formation, we sequenced 2 cDNA libraries generated from healthy and wounded A. sinensis (Lour.) Gilg. A total of 89,137 unigenes with an average length of 678.65 bp were obtained, and they were annotated in detail at bioinformatics levels. Of those associated with agarwood formation, 30 putatively encoded enzymes in the sesquiterpene biosynthesis pathway, and a handful of transcription factors and protein kinases were related to wound signal transduction. Three full-length cDNAs of sesquiterpene synthases (ASS1-3) were cloned and expressed in Escherichia coli, and enzyme assays revealed that they are active enzymes, with the major products being δ-guaiene. A methyl jasmonate (MJ) induction experiment revealed that the expression of ASS was significantly induced by MJ, and the production of sesquiterpenes was elevated accordingly. The expression of some transcription factors and protein kinases, especially MYB4, WRKY4, MPKK2 and MAPK2, was also induced by MJ and coordinated with ASS expression, suggesting they maybe positive regulators of ASS. Conclusions This study provides extensive transcriptome information for Aquilaria spp. and valuable clues for elucidating the mechanism of wound-induced agarwood sesquiterpenes biosynthesis and their regulation. PMID:23565705
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Schuman, Meredith C.; Palmer-Young, Evan C.; Schmidt, Axel; Gershenzon, Jonathan; Baldwin, Ian T.
2014-01-01
Sesquiterpenoids, with approximately 5,000 structures, are the most diverse class of plant volatiles with manifold hypothesized functions in defense, stress tolerance, and signaling between and within plants. These hypotheses have often been tested by transforming plants with sesquiterpene synthases expressed behind the constitutively active 35S promoter, which may have physiological costs measured as inhibited growth and reduced reproduction or may require augmentation of substrate pools to achieve enhanced emission, complicating the interpretation of data from affected transgenic lines. Here, we expressed maize (Zea mays) terpene synthase10 (ZmTPS10), which produces (E)-α-bergamotene and (E)-β-farnesene, or a point mutant ZmTPS10M, which produces primarily (E)-β-farnesene, under control of the 35S promoter in the ecological model plant Nicotiana attenuata. Transgenic N. attenuata plants had specifically enhanced emission of target sesquiterpene(s) with no changes detected in their emission of any other volatiles. Treatment with herbivore or jasmonate elicitors induces emission of (E)-α-bergamotene in wild-type plants and also tended to increase emission of (E)-α-bergamotene and (E)-β-farnesene in transgenics. However, transgenics did not differ from the wild type in defense signaling or chemistry and did not alter defense chemistry in neighboring wild-type plants. These data are inconsistent with within-plant and between-plant signaling functions of (E)-β-farnesene and (E)-α-bergamotene in N. attenuata. Ectopic sesquiterpene emission was apparently not costly for transgenics, which were similar to wild-type plants in their growth and reproduction, even when forced to compete for common resources. These transgenics would be well suited for field experiments to investigate indirect ecological effects of sesquiterpenes for a wild plant in its native habitat. PMID:25187528
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Flexural eczema versus atopic dermatitis.
Jacob, Sharon E; Goldenberg, Alina; Nedorost, Susan; Thyssen, Jacob P; Fonacier, Luz; Spiewak, Radoslaw
2015-01-01
Flexural eczema and atopic dermatitis are frequently synonymized. As respiratory atopy is rarely tested for and found in these patients, systematically equating a flexural distribution of dermatitis with atopic dermatitis may too frequently result in misclassified diagnoses and potentially missed opportunity for intervention toward improving patients' symptoms and quality of life. We present a critical review of the available evidence for the atopic dermatitis diagnosis and discuss the similarities between atopic dermatitis and allergic contact dermatitis. Because neither flexural predilection nor atopy is specific for atopic dermatitis, we conclude that the term atopic dermatitis is a misnomer and propose an etymologic reclassification of atopic dermatitis to "atopy-related" dermatitis. Allergic contact dermatitis can induce an atopic dermatitis-like phenotype, and thus, flexural dermatitis cannot be assumed as atopic without further testing. Patch testing should at least be considered in cases of chronic or recurrent eczema regardless of the working diagnosis.
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Detecting and characterizing N-acyl-homoserine lactone signal molecules by thin-layer chromatography
Shaw, Paul D.; Ping, Gao; Daly, Sean L.; Cha, Chung; Cronan, John E.; Rinehart, Kenneth L.; Farrand, Stephen K.
1997-01-01
Many Gram-negative bacteria regulate gene expression in response to their population size by sensing the level of acyl-homoserine lactone signal molecules which they produce and liberate to the environment. We have developed an assay for these signals that couples separation by thin-layer chromatography with detection using Agrobacterium tumefaciens harboring lacZ fused to a gene that is regulated by autoinduction. With the exception of N-butanoyl-l-homoserine lactone, the reporter detected acyl-homoserine lactones with 3-oxo-, 3-hydroxy-, and 3-unsubstituted side chains of all lengths tested. The intensity of the response was proportional to the amount of the signal molecule chromatographed. Each of the 3-oxo- and the 3-unsubstituted derivatives migrated with a unique mobility. Using the assay, we showed that some bacteria produce as many as five detectable signal molecules. Structures could be assigned tentatively on the basis of mobility and spot shape. The dominant species produced by Pseudomonas syringae pv. tabaci chromatographed with the properties of N-(3-oxohexanoyl)-l-homoserine lactone, a structure that was confirmed by mass spectrometry. An isolate of Pseudomonas fluorescens produced five detectable species, three of which had novel chromatographic properties. These were identified as the 3-hydroxy- forms of N-hexanoyl-, N-octanoyl-, and N-decanoyl-l-homoserine lactone. The assay can be used to screen cultures of bacteria for acyl-homoserine lactones, for quantifying the amounts of these molecules produced, and as an analytical and preparative aid in determining the structures of these signal molecules. PMID:9177164
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Okutsu, Noriya; Morohoshi, Tomohiro; Xie, Xiaonan; Kato, Norihiro; Ikeda, Tsukasa
2015-12-30
The cooling water systems are used to remove heat generated in the various industries. Biofouling of the cooling water systems causes blocking of condenser pipes and the heat exchanger tubes. In many Gram-negative bacteria, N-acylhomoserine lactone (AHL) are used as quorum-sensing signal molecule and associated with biofilm formation. To investigate the relationship between quorum sensing and biofouling in the cooling water system, we isolated a total of 192 bacterial strains from the five cooling water systems, and screened for AHL production. Seven isolates stimulated AHL-mediated purple pigment production in AHL reporter strain Chromobacterium violaceum CV026 or VIR07. Based on their 16S rRNA gene sequences, AHL-producing isolates were assigned to Aeromonas hydrophila, Lysobacter sp., Methylobacterium oryzae, and Bosea massiliensis. To the best of our knowledge, B. massiliensis and Lysobacter sp. have not been reported as AHL-producing species in the previous researches. AHLs extracted from the culture supernatants of B. massiliensis and Lysobacter sp. were identified by liquid chromatography-mass spectrometry. AHLs produced by B. massiliensis were assigned as N-hexanoyl-L-homoserine lactone (C6-HSL), N-(3-oxohexanoyl)-L-homoserine lactone (3-oxo-C6-HSL), and N-(3-oxooctanoyl)-L-homoserine lactone (3-oxo-C8-HSL). AHLs produced by Lysobacter sp. were assigned as N-decanoyl-L-homoserine lactone (C10-HSL) and N-(3-oxodecanoyl)-L-homoserine lactone (3-oxo-C10-HSL). This is the first report of identification of AHLs produced by B. massiliensis and Lysobacter sp. isolated from the cooling water system.
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Unusual features of a recombinant apple alpha-farnesene synthase.
Green, Sol; Friel, Ellen N; Matich, Adam; Beuning, Lesley L; Cooney, Janine M; Rowan, Daryl D; MacRae, Elspeth
2007-01-01
A recombinant alpha-farnesene synthase from apple (Malus x domestica), expressed in Escherichia coli, showed features not previously reported. Activity was enhanced 5-fold by K(+) and all four isomers of alpha-farnesene, as well as beta-farnesene, were produced from an isomeric mixture of farnesyl diphosphate (FDP). Monoterpenes, linalool, (Z)- and (E)-beta-ocimene and beta-myrcene, were synthesised from geranyl diphosphate (GDP), but at 18% of the optimised rate for alpha-farnesene synthesis from FDP. Addition of K(+) reduced monoterpene synthase activity. The enzyme also produced alpha-farnesene by a reaction involving coupling of GDP and isoprenyl diphosphate but at <1% of the rate with FDP. Mutagenesis of active site aspartate residues removed sesquiterpene, monoterpene and prenyltransferase activities suggesting catalysis through the same active site. Phylogenetic analysis clusters this enzyme with isoprene synthases rather than with other sesquiterpene synthases, suggesting that it has evolved differently from other plant sesquiterpene synthases. This is the first demonstration of a sesquiterpene synthase possessing prenyltransferase activity.
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Lin, Aiqun; Wu, Guangwei; Gu, Qianqun; Zhu, Tianjiao; Li, Dehai
2014-07-01
Chemical investigation of an Antarctic deepsea derived fungus Penicillium sp. PR19 N-1 yielded five new eremophilane-type sesquiterpenes 1–5 and a new rare lactam-type eremophilane 6, together with three known compounds 7–9. The structures of these diverse sesquiterpenes were determined by extensive NMR and mass spectroscopic analyses. Compounds 1, 2, 4–6, 8 and 9 were evaluated for their cytotoxities against HL-60 and A-549 human cancer cell lines, and 5 was the most active one with IC50 value of 5.2 lM against the A-549 cells.
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Isogermacrene A, a proposed intermediate in sesquiterpene biosynthesis.
Hackl, Thomas; König, Wilfried A; Muhle, Hermann
2004-08-01
In the essential oil of the liverwort Saccogyna viticulosa, collected on the island of Madeira, the new sesquiterpene hydrocarbons isogermacrene A (5) and its Cope rearrangement product iso-beta-elemene (6) were identified. 5 is proposed to act as the biogenetic precursor of several new sesquiterpenes identified in the volatiles of S. viticulosa. These include iso-alpha-humulene, alpha-gorgonene, gorgona-1,4(15), 11-triene and gorgon- 11-en-4-ol. In addition, the Cope product of zierene, isozierene, allo-aromadendra-4(15),10(14)-diene, aromadendra-4(15),10(14)-dien-1-ol and a prenylguaiane diterpene alcohol, named viticulol, were identified as new natural products.
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Ermophilane sesquiterpenes from Hawaiian endophytic fungus Chaetoconis sp.FT087
USDA-ARS?s Scientific Manuscript database
Seven sesquiterpene derivatives, including chaetopenoids A–F and dendryphiellin A1, and 6-methyl-(2E,4E, 6S) octadienoic acid were isolated from the culture broth of Chaetoconis sp. FT087. Their structures were determined through the analysis of HRMS and NMR spectroscopic data. The absolute configur...
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Puupehanol, a Sesquiterpene-Dihydroquinone Derivative from the Marine Sponge Hyrtios sp
USDA-ARS?s Scientific Manuscript database
Puupehanol (1), a new sesquiterpene-dihydroquinone derivative, was isolated from the marine sponge Hyrtios sp., along with the known compounds puupehenone (2) and chloropuupehenone (3). The structure of 1 was established as (20R,21R)-21-hydroxy-20,21-dihydropuupehenone by interpretation of spectros...
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Relationship between Menthiafolic Acid and Wine Lactone in Wine.
Giaccio, Joanne; Curtin, Chris D; Sefton, Mark A; Taylor, Dennis K
2015-09-23
Menthiafolic acid (6-hydroxy-2,6-dimethylocta-2,7-dienoic acid, 2a) was quantified by GC-MS in 28 white wines, 4 Shiraz wines, and for the first time in 6 white grape juice samples. Menthiafolic acid was detected in all but one of the wine samples at concentrations ranging from 26 to 342 μg/L and in the juice samples from 16 to 236 μg/L. Various model fermentation experiments showed that some menthiafolic acid in wine could be generated from the grape-derived menthiafolic acid glucose ester (2b) during alcoholic and malolactic fermentation. Samples containing high concentrations of menthiafolic acid were also analyzed by enantioselective GC-MS and were shown to contain this compound in predominantly the (S)-configuration. Enantioselective analysis of wine lactone (1) in one of these samples, a four-year-old Chardonnay wine showed, for the first time, the presence of the 3R,3aR,7aS isomer of wine lactone (1b), which is the enantiomer of the form previously reported as the sole isomer present in young wine samples. The weakly odorous 3R,3aR,7aS 1b form comprised 69% of the total wine lactone in the sample. On the basis of the enantioselectivity of the hydrolytic conversion of menthiafolic acid to wine lactone at pH 3.0 determined previously and the relative proportions of (R)- and (S)-menthiafolic acid in the Chardonnay wine, the predicted ratio of wine lactone enantiomers that would be formed from hydrolysis at ambient temperature of the menthiafolic acid present in this wine was close to the ratio measured, which was consistent with menthiafolic acid being the major or sole precursor to wine lactone in this sample.
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Shivali, Garg; Praful, Lahorkar; Vijay, Gadgil
2012-01-01
Fourier transform infrared (FT-IR) spectroscopy is a technique widely used for detection and quantification of various chemical moieties. This paper describes the use of the FT-IR spectroscopy technique for the quantification of total lactones present in Inula racemosa and Andrographis paniculata. To validate the FT-IR spectroscopy method for quantification of total lactones in I. racemosa and A. paniculata. Dried and powdered I. racemosa roots and A. paniculata plant were extracted with ethanol and dried to remove ethanol completely. The ethanol extract was analysed in a KBr pellet by FT-IR spectroscopy. The FT-IR spectroscopy method was validated and compared with a known spectrophotometric method for quantification of lactones in A. paniculata. By FT-IR spectroscopy, the amount of total lactones was found to be 2.12 ± 0.47% (n = 3) in I. racemosa and 8.65 ± 0.51% (n = 3) in A. paniculata. The method showed comparable results with a known spectrophotometric method used for quantification of such lactones: 8.42 ± 0.36% (n = 3) in A. paniculata. Limits of detection and quantification for isoallantolactone were 1 µg and 10 µg respectively; for andrographolide they were 1.5 µg and 15 µg respectively. Recoveries were over 98%, with good intra- and interday repeatability: RSD ≤ 2%. The FT-IR spectroscopy method proved linear, accurate, precise and specific, with low limits of detection and quantification, for estimation of total lactones, and is less tedious than the UV spectrophotometric method for the compounds tested. This validated FT-IR spectroscopy method is readily applicable for the quality control of I. racemosa and A. paniculata. Copyright © 2011 John Wiley & Sons, Ltd.
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Classification and possible bacterial infection in outpatients with eczema and dermatitis in China
Wang, Xin; Shi, Xiao-Dong; Li, Lin-Feng; Zhou, Ping; Shen, Yi-Wei
2017-01-01
Abstract Little is known about the classification and bacterial infection in outpatients with eczema and dermatitis in China. To investigate the prevalence of eczema and dermatitis in outpatients of dermatology clinics in China, examine classification and proportion of common types of dermatitis and the possible bacterial infection, and analyze the possible related factors. Outpatients with eczema or dermatitis from 39 tertiary hospitals of 15 provinces in mainland China from July 1 to September 30, 2014, were enrolled in this cross-sectional and multicenter study. Among 9393 enrolled outpatients, 636 patients (6.7%) were excluded because of incomplete information. The leading subtypes of dermatitis were unclassified eczema (35.5%), atopic dermatitis (13.4%), irritant dermatitis (9.2%), and widespread eczema (8.7%). Total bacterial infection rate was 52.3%, with widespread eczema, stasis dermatitis, and atopic dermatitis being the leading three (65.7%, 61.8%, and 61.4%, respectively). Clinically very likely bacterial infection has a significant positive correlation with disease duration, history of allergic disease, history of flexion dermatitis, and severe itching. Atopic dermatitis has become a common subtype of dermatitis in China. Secondary bacterial infection is common in all patients with dermatitis, and more attentions should be paid on this issue in other type of dermatitis apart from atopic dermatitis. PMID:28858126
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Wang, Xin; Shi, Xiao-Dong; Li, Lin-Feng; Zhou, Ping; Shen, Yi-Wei
2017-09-01
Little is known about the classification and bacterial infection in outpatients with eczema and dermatitis in China.To investigate the prevalence of eczema and dermatitis in outpatients of dermatology clinics in China, examine classification and proportion of common types of dermatitis and the possible bacterial infection, and analyze the possible related factors.Outpatients with eczema or dermatitis from 39 tertiary hospitals of 15 provinces in mainland China from July 1 to September 30, 2014, were enrolled in this cross-sectional and multicenter study. Among 9393 enrolled outpatients, 636 patients (6.7%) were excluded because of incomplete information.The leading subtypes of dermatitis were unclassified eczema (35.5%), atopic dermatitis (13.4%), irritant dermatitis (9.2%), and widespread eczema (8.7%). Total bacterial infection rate was 52.3%, with widespread eczema, stasis dermatitis, and atopic dermatitis being the leading three (65.7%, 61.8%, and 61.4%, respectively). Clinically very likely bacterial infection has a significant positive correlation with disease duration, history of allergic disease, history of flexion dermatitis, and severe itching.Atopic dermatitis has become a common subtype of dermatitis in China. Secondary bacterial infection is common in all patients with dermatitis, and more attentions should be paid on this issue in other type of dermatitis apart from atopic dermatitis.
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Deshpande, Ashish B; Chidley, Hemangi G; Oak, Pranjali S; Pujari, Keshav H; Giri, Ashok P; Gupta, Vidya S
2017-06-01
Uniqueness and diversity of mango flavour across various cultivars are well known. Among various flavour metabolites lactones form an important class of aroma volatiles in certain mango varieties due to their ripening specific appearance and lower odour detection threshold. In spite of their biological and biochemical importance, lactone biosynthetic pathway in plants remains elusive. Present study encompasses quantitative real-time analysis of 9-lipoxygenase (Mi9LOX), epoxide hydrolase 2 (MiEH2), peroxygenase, hydroperoxide lyase and acyl-CoA-oxidase genes during various developmental and ripening stages in fruit of Alphonso, Pairi and Kent cultivars with high, low and no lactone content and explains their variable lactone content. Study also covers isolation, recombinant protein characterization and transient over-expression of Mi9LOX and MiEH2 genes in mango fruits. Recombinant Mi9LOX utilized linoleic and linolenic acids, while MiEH2 utilized aromatic and fatty acid epoxides as their respective substrates depicting their role in fatty acid metabolism. Significant increase in concentration of δ-valerolactone and δ-decalactone upon Mi9LOX over-expression and that of δ-valerolactone, γ-hexalactone and δ-hexalactone upon MiEH2 over-expression further suggested probable involvement of these genes in lactone biosynthesis in mango. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Quorum sensing activity of Citrobacter amalonaticus L8A, a bacterium isolated from dental plaque.
Goh, Share-Yuan; Khan, Saad Ahmed; Tee, Kok Keng; Abu Kasim, Noor Hayaty; Yin, Wai-Fong; Chan, Kok-Gan
2016-02-10
Cell-cell communication is also known as quorum sensing (QS) that happens in the bacterial cells with the aim to regulate their genes expression in response to increased cell density. In this study, a bacterium (L8A) isolated from dental plaque biofilm was identified as Citrobacter amalonaticus by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Its N-acylhomoserine-lactone (AHL) production was screened by using two types of AHL biosensors namely Chromobacterium violaceum CV026 and Escherichia coli [pSB401]. Citrobacter amalonaticus strain L8A was identified and confirmed producing numerous types of AHL namely N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L-homoserine lactone (C8-HSL) and N-hexadecanoyl-L-homoserine lactone (C16-HSL). We performed the whole genome sequence analysis of this oral isolate where its genome sequence reveals the presence of QS signal synthase gene and our work will pave the ways to study the function of the related QS genes in this bacterium.
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Quorum sensing activity of Citrobacter amalonaticus L8A, a bacterium isolated from dental plaque
Goh, Share-Yuan; Khan, Saad Ahmed; Tee, Kok Keng; Abu Kasim, Noor Hayaty; Yin, Wai-Fong; Chan, Kok-Gan
2016-01-01
Cell-cell communication is also known as quorum sensing (QS) that happens in the bacterial cells with the aim to regulate their genes expression in response to increased cell density. In this study, a bacterium (L8A) isolated from dental plaque biofilm was identified as Citrobacter amalonaticus by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Its N-acylhomoserine-lactone (AHL) production was screened by using two types of AHL biosensors namely Chromobacterium violaceum CV026 and Escherichia coli [pSB401]. Citrobacter amalonaticus strain L8A was identified and confirmed producing numerous types of AHL namely N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L-homoserine lactone (C8-HSL) and N-hexadecanoyl-L-homoserine lactone (C16-HSL). We performed the whole genome sequence analysis of this oral isolate where its genome sequence reveals the presence of QS signal synthase gene and our work will pave the ways to study the function of the related QS genes in this bacterium. PMID:26860259
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Statin Lactonization by Uridine 5'-Diphospho-glucuronosyltransferases (UGTs).
Schirris, Tom J J; Ritschel, Tina; Bilos, Albert; Smeitink, Jan A M; Russel, Frans G M
2015-11-02
Statins are cholesterol-lowering drugs that have proven to be effective in lowering the risk of major cardiovascular events. Although well tolerated, statin-induced myopathies are the most common side effects. Compared to their pharmacologically active acid form, statin lactones are more potent inducers of toxicity. They can be formed by glucuronidation mediated by uridine 5'-diphospho-glucuronosyltransferases (UGTs), but a systematic characterization of subtype specificity and kinetics of lactonization is lacking. Here, we demonstrate for six clinically relevant statins that only UGT1A1, 1A3, and 2B7 contribute significantly to their lactonization. UGT1A3 appeared to have the highest lactonization capacity with marked differences in statin conversion rates: pitavastatin ≫ atorvastatin > cerivastatin > lovastatin > rosuvastatin (simvastatin not converted). Using in silico modeling we could identify a probable statin interaction region in the UGT binding pocket. Polymorphisms in these regions of UGT1A1, 1A3, and 2B7 may be a contributing factor in statin-induced myopathies, which could be used in personalization of statin therapy with improved safety.
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Abhijith, B L; Mohan, Moolya; Joseph, David; Haleema, Simimole; Aboul-Enein, Hassan Y; Ibnusaud, Ibrahim
2017-08-01
A simple capillary zone electrophoresis method with direct ultraviolet detection has been developed for the analysis of naturally occurring diastereomeric 2-hydroxycitric acid lactones. Using 50 mM sodium phosphate buffer of pH 7, a baseline resolution R s > 3.0 was observed for all organic acids selected for the present study. This method was employed for the quantitative determination of title acids present in the plant sources namely Garcinia cambogia fruit rinds and Hibiscus sabdariffa calyx. Conversion of 2-hydroxycitric acids to their lactones on heating the above plant sources is deliberated. The Hydrolysis of hydroxycitric acid lactones in aqueous solution is reported for the first time. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Chemoselective synthesis of sialic acid 1,7-lactones.
Allevi, Pietro; Rota, Paola; Scaringi, Raffaella; Colombo, Raffaele; Anastasia, Mario
2010-08-20
The chemoselective synthesis of the 1,7-lactones of N-acetylneuraminic acid, N-glycolylneuraminic acid, and 3-deoxy-d-glycero-d-galacto-nononic acid is accomplished in two steps: a simple treatment of the corresponding free sialic acid with benzyloxycarbonyl chloride and a successive hydrogenolysis of the formed 2-benzyloxycarbonyl 1,7-lactone. The instability of the 1,7-lactones to protic solvents has been also evidenced together with the rationalization of the mechanism of their formation under acylation conditions. The results permit to dispose of authentic 1,7-sialolactones to be used as reference standards and of a procedure useful for the preparation of their isotopologues to be used as inner standards in improved analytical procedures for the gas liquid chromatography-mass spectrometry (GLC-MS) analysis of 1,7-sialolactones in biological media.
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Souillart, Laetitia; Cramer, Nicolai
2014-09-01
The lactone motif is ubiquitous in natural products and pharmaceuticals. The Tishchenko disproportionation of two aldehydes, a carbonyl hydroacylation, is an efficient and atom-economic access to lactones. However, these reaction types are limited to the transfer of a hydride to the accepting carbonyl group. The transfer of alkyl groups enabling the formation of CC bonds during the ester formation would be of significant interest. Reported herein is such asymmetric carbonyl carboacylation of aldehydes and ketones, thus affording complex bicyclic lactones in excellent enantioselectivities. The rhodium(I)-catalyzed transformation is induced by an enantiotopic CC bond activation of a cyclobutanone and the formed rhodacyclic intermediate reacts with aldehyde or ketone groups to give highly functionalized lactones. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Gao, Suyu; Xia, Guiyang; Wang, Liqing; Zhou, Li; Zhao, Feng; Huang, Jian; Chen, Lixia
2017-03-01
One new sesquiterpene, 7α,11-epoxy-6α-hydroxy-carabrane-4,8-dione, along with 10 known ones were isolated from the essential oil of Curcuma wenyujin Y.H. Chen et C. Ling. Their structures were established based on extensive spectroscopic analysis. The absolute configuration of compound 1 was determined by the CD analysis of the insitu formed [Rh 2 (OCOCF 3 ) 4 ] complex, and the CD data analysis based on the octane rule of cyclohexanone. The inhibitory effects of these sesquiterpenes on nitric oxide production in lipopolysaccharide-activated macrophages were also evaluated. Furthermore, the biosynthesis pathway of the isolated compounds was proposed.
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NASA Astrophysics Data System (ADS)
Omar, Aimi Farehah; Ismail, Ismanizan
2016-11-01
Sesquiterpene synthase (SS) catalyzes the formation of sesquiterpenes from farnesyl diphosphate (FDP) via carbocation intermediates. In this study, the promoter region of sesquiterpene synthase was isolated from Persicaria minor to identify possible cis-acting elements in the promoter. The full-length PmSS promoter of P. minor is 1824-bp sequences. The sequence was analyzed and several putative cis-acting regulatory elements were identified. Three cis-acting regulatory elements were selected for deletion analysis which are cis-acting element involved in wound responsiveness (WUN), cis - acting element involved in defense and stress responsiveness (TC) and cis-acting element involved in ABA responsiveness (ABRE). Series of deletions were conducted to assess the promoter activity producing three truncated fragments promoter; Prom 2 1606-bp, Prom 3 1144- bp, and Prom 4 921-bp. The full-length promoter and its deletion series were cloned into the pBGWFS7 vector which contain β-glucuronidase (GUS) gene and green fluorescent protein (GFP) as the reporter gene. All constructs were successfully transformed into Arabidopsis thaliana based on PCR of positive BASTA resistance plants.
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Tippmann, Stefan; Scalcinati, Gionata; Siewers, Verena; Nielsen, Jens
2016-01-01
Terpenes have various applications as fragrances, cosmetics and fuels. One of the most prominent examples is the sesquiterpene farnesene, which can be used as diesel substitute in its hydrogenated form farnesane. Recent metabolic engineering efforts have enabled efficient production of several terpenes in Saccharomyces cerevisiae and Escherichia coli. Plant terpene synthases take on an essential function for sesquiterpene production as they catalyze the specific conversion of the universal precursor farnesyl diphosphate (FPP) to the sesquiterpene of interest and thereby impose limitations on the overall productivity. Using farnesene as a case study, we chose three terpene synthases with distinct plant origins and compared their applicability for farnesene production in the yeast S. cerevisiae. Differences regarding the efficiency of these enzymes were observed in shake flask cultivation with maximal final titers of 4 mg/L using α-farnesene synthase from Malus domestica. By employing two existing platform strains optimized for sesquiterpene production, final titers could be raised up 170 mg/L in fed-batch fermentations with RQ-controlled exponential feeding. Based on these experiments, the difference between the selected synthases was not significant. Lastly, the same fermentation setup was used to compare these results to production of the fragrance sesquiterpene santalene, and almost equivalent titers were obtained with 163 mg/L, using the highest producing strain expressing a santalene synthase from Clausena lansium. However, a reduction of the product yield on biomass by 50% could indicate a higher catalytic efficiency of the farnesene synthase. © 2015 Wiley Periodicals, Inc.
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Usui, Keiko; Ikeda, Tsuyoshi; Horibe, Yuumi; Nakao, Mitsuyoshi; Hoshino, Tatsuya; Mizushima, Tohru
2015-04-01
The expression of heat shock proteins (HSPs), particularly HSP70, is receiving considerable attention in the field of cosmetics, particularly given our recent report that ultraviolet-induced melanin production, skin damage and wrinkle formation were all suppressed in transgenic mice expressing HSP70. In the present study, we searched for HSP70-inducers from a library of herbal extracts that have already been approved as quasi-pharmaceutical products in Japan. We selected an ethanol extract of Arnica montana (A. montana), based on its high HSP70-inducing activity and low cytotoxicity. Cell viability was determined by MTT method and expression of HPS70 was monitored by immunoblotting analysis. From the extract, we purified and identified eight sesquiterpene lactones (AM1-8) as HSP70-inducers, among which AM-2 (helenalin 2-methylbutyrate) was selected due to its good HSP70-inducing properties and low cytotoxicity. Treatment of cultured mouse melanoma cells with AM-2 or A. montana extract up-regulated the expression of HSP70 in a dose-dependent manner. This treatment also activated heat shock factor-1, a transcription factor for hsp genes. Furthermore, pre-treatment of cells with AM-2 or A. montana extract decreased melanin production and expression and activity of tyrosinase. These results suggest that AM-2 and A. montana extract could be beneficial for use in hypopigmenting cosmetics as a consequence of their stimulatory effects on HSP70 expression. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
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GLANDULAR TRICHOME-SPECIFIC WRKY 1 promotes artemisinin biosynthesis in Artemisia annua.
Chen, Minghui; Yan, Tingxiang; Shen, Qian; Lu, Xu; Pan, Qifang; Huang, Youran; Tang, Yueli; Fu, Xueqing; Liu, Meng; Jiang, Weimin; Lv, Zongyou; Shi, Pu; Ma, Ya-Nan; Hao, Xiaolong; Zhang, Lida; Li, Ling; Tang, Kexuan
2017-04-01
Artemisinin is a type of sesquiterpene lactone well known as an antimalarial drug, and is specifically produced in glandular trichomes of Artemisia annua. However, the regulatory network for the artemisinin biosynthetic pathway remains poorly understood. Exploration of trichome-specific transcription factors would facilitate the elucidation of regulatory mechanism of artemisinin biosynthesis. The WRKY transcription factor GLANDULAR TRICHOME-SPECIFIC WRKY 1 (AaGSW1) was cloned and analysed in A. annua. AaGSW1 exhibited similar expression patterns to the trichome-specific genes of the artemisinin biosynthetic pathway and AP2/ERF transcription factor AaORA. A β-glucuronidase (GUS) staining assay further demonstrated that AaGSW1 is a glandular trichome-specific transcription factor. AaGSW1 positively regulates CYP71AV1 and AaORA expression by directly binding to the W-box motifs in their promoters. Overexpression of AaGSW1 in A. annua significantly improves artemisinin and dihydroartemisinic acid contents; moreover, AaGSW1 can be directly regulated by AaMYC2 and AabZIP1, which are positive regulators of jasmonate (JA)- and abscisic acid (ABA)-mediated artemisinin biosynthetic pathways, respectively. These results demonstrate that AaGSW1 is a glandular trichome-specific WRKY transcription factor and a positive regulator in the artemisinin biosynthetic pathway. Moreover, we propose that two trifurcate feed-forward pathways involving AaGSW1, CYP71AV1 and AaMYC2/AabZIP1 function in the JA/ABA response in A. annua. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.
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Chen, Xiao-Wen; Liu, Wen-Ting; Wang, Yu-Xian; Chen, Wen-Jing; Li, Hong-Yu; Chen, Yi-Hua; Du, Xiao-Yan; Peng, Fen-Fen; Zhou, Wei-Dong; Xu, Zhao-Zhong; Long, Hai-Bo
2016-07-01
The aim of this research was to investigate the effects of cyclopropanyldehydrocostunolide (also named LJ), a derivative of sesquiterpene lactones (SLs), on high glucose (HG)-induced podocyte injury and the associated molecular mechanisms. Differentiated mouse podocytes were incubated in different treatments. The migration and albumin filtration of podocytes were examined by Transwell filters. The protein and mRNA levels of MCP-1 were measured using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (q-PCR). Protein expression and phosphorylation were detected by western blot, and the nuclear translocation of NF-κB was performed with a confocal microscope. The gene expression of the receptor activator for NF-κB (RANK) was silenced by small interfering RNA (siRNA). Our results showed that HG enhanced migration, albumin filtration and MCP-1 expression in podocytes. At the molecular level, HG promoted the phosphorylation of NF-κB/p65, IKKβ, IκBα, mitogen-activated protein kinase (MAPK) and the nuclear translocation of p65. LJ reversed the effects of HG in a dose-dependent manner. Furthermore, our data provided the first demonstration that the receptor activator for NF-κB ligand (RANKL) and its cognate receptor RANK were overexpressed in HG-induced podocytes and were downregulated by LJ. RANK siRNA also attenuated HG-induced podocyte injury and markedly inhibited the activation of NF-κB and MAPK signaling pathways. LJ attenuates HG-induced podocyte injury by suppressing RANKL/RANK-mediated NF-κB and MAPK signaling pathways. Copyright © 2016 Elsevier Inc. All rights reserved.
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Espinoza, Luis; Madrid, Alejandro; Pizarro, Leonardo
2018-01-01
Currently, the most effective treatment for recurrent urinary tract infections in women is antibiotics. However, the limitation for this treatment is the duration and dosage of antibiotics and the resistance that bacteria develop after a long period of administration. With the aim of identifying mainly novel natural agents with antibacterial activity, the present study was undertaken to investigate the biological and phytochemical properties of extracts from the leaves Taraxacum officinale. The structural identification of compounds present in hexane (Hex) and ethyl acetate (AcOEt) extracts was performed by mass spectrometry (GC-MS) spectroscopic techniques and nuclear magnetic resonance (NMR) with the major compounds corresponding to different sesquiterpene lactones (α-santonin, glabellin, arborescin, and estafiatin), monoterpene (9,10-dimethyltricycle [4.2.1.1 (2,5)]decane-9,10-diol), phytosterol (Stigmasta-5,22-dien-3β-ol acetate), terpenes (lupeol acetate, pregn-5-en-20-one-3β-acetyloxy-17-hydroxy, 2-hydroxy-4-methoxy benzaldehyde), and coumarin (benzofuranone 5,6,7,7-a-tetraaldehyde-4,4,7a-trimethyl). The results obtained show that the Hex extract was highly active against Staphylococcus aureus showing a MIC of 200 μg/mL and moderately active against Escherichia coli and Klebsiella pneumoniae with MIC values of 400 μg/mL and 800 μg/mL for the other Gram-negative strains tested with Proteus mirabilis as uropathogens in vitro. Therefore, the effective dandelion extracts could be used in the development of future products with industrial application. PMID:29507587
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Díaz, Katy; Espinoza, Luis; Madrid, Alejandro; Pizarro, Leonardo; Chamy, Rolando
2018-01-01
Currently, the most effective treatment for recurrent urinary tract infections in women is antibiotics. However, the limitation for this treatment is the duration and dosage of antibiotics and the resistance that bacteria develop after a long period of administration. With the aim of identifying mainly novel natural agents with antibacterial activity, the present study was undertaken to investigate the biological and phytochemical properties of extracts from the leaves Taraxacum officinale. The structural identification of compounds present in hexane (Hex) and ethyl acetate (AcOEt) extracts was performed by mass spectrometry (GC-MS) spectroscopic techniques and nuclear magnetic resonance (NMR) with the major compounds corresponding to different sesquiterpene lactones ( α -santonin, glabellin, arborescin, and estafiatin), monoterpene (9,10-dimethyltricycle [4.2.1.1 (2,5)]decane-9,10-diol), phytosterol (Stigmasta-5,22-dien-3 β -ol acetate), terpenes (lupeol acetate, pregn-5-en-20-one-3 β -acetyloxy-17-hydroxy, 2-hydroxy-4-methoxy benzaldehyde), and coumarin (benzofuranone 5,6,7,7-a-tetraaldehyde-4,4,7a-trimethyl). The results obtained show that the Hex extract was highly active against Staphylococcus aureus showing a MIC of 200 μ g/mL and moderately active against Escherichia coli and Klebsiella pneumoniae with MIC values of 400 μ g/mL and 800 μ g/mL for the other Gram-negative strains tested with Proteus mirabilis as uropathogens in vitro . Therefore, the effective dandelion extracts could be used in the development of future products with industrial application.
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A Herbivore Tag-and-Trace System Reveals Contact- and Density-Dependent Repellence of a Root Toxin.
Bont, Zoe; Arce, Carla; Huber, Meret; Huang, Wei; Mestrot, Adrien; Sturrock, Craig J; Erb, Matthias
2017-03-01
Foraging behavior of root feeding organisms strongly affects plant-environment-interactions and ecosystem processes. However, the impact of plant chemistry on root herbivore movement in the soil is poorly understood. Here, we apply a simple technique to trace the movement of soil-dwelling insects in their habitats without disturbing or restricting their interactions with host plants. We tagged the root feeding larvae of Melolontha melolontha with a copper ring and repeatedly located their position in relation to their preferred host plant, Taraxacum officinale, using a commercial metal detector. This method was validated and used to study the influence of the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G) on the foraging of M. melolontha. TA-G is stored in the latex of T. officinale and protects the roots from herbivory. Using behavioral arenas with TA-G deficient and control plants, we tested the impact of physical root access and plant distance on the effect of TA-G on M. melolontha. The larvae preferred TA-G deficient plants to control plants, but only when physical root contact was possible and the plants were separated by 5 cm. Melolontha melolontha showed no preference for TA-G deficient plants when the plants were grown 15 cm apart, which may indicate a trade-off between the cost of movement and the benefit of consuming less toxic food. We demonstrate that M. melolontha integrates host plant quality and distance into its foraging patterns and suggest that plant chemistry affects root herbivore behavior in a plant-density dependent manner.
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Cynaropicrin attenuates UVB-induced oxidative stress via the AhR-Nrf2-Nqo1 pathway.
Takei, Kenjiro; Hashimoto-Hachiya, Akiko; Takahara, Masakazu; Tsuji, Gaku; Nakahara, Takeshi; Furue, Masutaka
2015-04-16
Due to its antioxidant and anti-inflammatory activities, artichoke (Cynara scolymus) has been used as folk medicine to treat various diseases. Cynaropicrin (Cyn), a sesquiterpene lactone, is the major bioactive phytochemical in the artichoke; however, its pharmacological mechanism remains unknown. Because some phytochemicals exert their antioxidant activity by activating aryl hydrocarbon receptor (AhR), leading to subsequent induction of the antioxidant pathway including nuclear factor E2-related factor 2 (Nrf2) and quinone oxidoreductase 1 (Nqo1), we investigated whether Cyn also activates the AhR-Nrf2-Nqo1 pathway. Cyn indeed induced the activation (nuclear translocation) of AhR, leading to nuclear translocation of Nrf2 and dose-dependent upregulation of Nrf2 and Nqo1 mRNAs in human keratinocytes. The Cyn-induced AhR-Nrf2-Nqo1 activation was AhR- and Nrf2-dependent, as demonstrated by the observation that it was absent in keratinocytes transfected by siRNA against either AhR or Nrf2. In accordance with these findings, Cyn actively inhibited generation of reactive oxygen species from keratinocytes irradiated with ultraviolet B (UVB) in a Nrf2-dependent manner. Cyn also inhibited the production of proinflammatory cytokines such as interleukin 6 and tumor necrosis factor-α from UVB-treated keratinocytes. Our findings demonstrate that Cyn is a potent activator of the AhR-Nrf2-Nqo1 pathway, and could therefore be applied to prevention of UVB-induced photo aging. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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Li, Yuanjun; Gou, Junbo; Chen, Fangfang; Li, Changfu; Zhang, Yansheng
2016-01-01
Xanthium strumarium L. is a traditional Chinese herb belonging to the Asteraceae family. The major bioactive components of this plant are sesquiterpene lactones (STLs), which include the xanthanolides. To date, the biogenesis of xanthanolides, especially their downstream pathway, remains largely unknown. In X. strumarium, xanthanolides primarily accumulate in its glandular trichomes. To identify putative gene candidates involved in the biosynthesis of xanthanolides, three X. strumarium transcriptomes, which were derived from the young leaves of two different cultivars and the purified glandular trichomes from one of the cultivars, were constructed in this study. In total, 157 million clean reads were generated and assembled into 91,861 unigenes, of which 59,858 unigenes were successfully annotated. All the genes coding for known enzymes in the upstream pathway to the biosynthesis of xanthanolides were present in the X. strumarium transcriptomes. From a comparative analysis of the X. strumarium transcriptomes, this study identified a number of gene candidates that are putatively involved in the downstream pathway to the synthesis of xanthanolides, such as four unigenes encoding CYP71 P450s, 50 unigenes for dehydrogenases, and 27 genes for acetyltransferases. The possible functions of these four CYP71 candidates are extensively discussed. In addition, 116 transcription factors that are highly expressed in X. strumarium glandular trichomes were also identified. Their possible regulatory roles in the biosynthesis of STLs are discussed. The global transcriptomic data for X. strumarium should provide a valuable resource for further research into the biosynthesis of xanthanolides. PMID:27625674
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Vermicomposting transforms allelopathic parthenium into a benign organic fertilizer.
Hussain, Naseer; Abbasi, Tasneem; Abbasi, S A
2016-09-15
Vermicompost, which had been derived solely by the action of the epigeic earthworm Eisenia fetida on parthenium (Parthenium hysterophorus), was tested for its impact on the germination and early growth of green gram (Vigna radiata), ladies finger (Abelmoschus esculentus) and cucumber (Cucumis sativus). Seedlings were germinated and grown in soil amended with 0 (control), 0.75, 1.5, 2, 4, 8, 20 and 40% (by weight) parthenium vermicompost. Even though parthenium is known to possess strong negative allelopathy, as also plant/animal toxicity in other forms, its vermicompost (VC) manifested none of these attributes. Rather the VC enhanced germination success, introduced plant-friendly physical features in the container media, increased biomass carbon, and was seen to promote early growth as reflected in several morphological and biochemical characteristics in plants which had received parthenium VC in comparison to those which had not. All these effects were statistically significant. Fourier Transform Infrared (FTIR) Spectrometry revealed that the phenols and the sesquiterpene lactones that are responsible for the negative allelopathic impact of parthenium were largely destroyed in the course of vermicomposting. FTIR spectra also indicated that lignin content of parthenium was reduced during its vermicomposting. The findings open up the possibility that several other invasives known for their negative allelopathy and toxicity may also produce vermicompost which may be plant-friendly and soil-friendly. It also makes it appear possible that the huge quantities of phytomass that is generated annually by parthenium can be gainfully utilized in producing organic fertilizer via vermicomposting, thereby providing a means of exercising some control over parthenium's rampant growth and invasion. Copyright © 2016. Published by Elsevier Ltd.
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Peña-Espinoza, Miguel; Thamsborg, Stig M; Desrues, Olivier; Hansen, Tina V A; Enemark, Heidi L
2016-09-01
Two experiments studied the effects of dietary chicory against gastrointestinal nematodes in cattle. In Experiment (Exp.) 1, stabled calves were fed chicory silage (CHI1; n = 9) or ryegrass/clover hay (CTL1; n = 6) with balanced protein/energy intakes between groups. After 16 days, all calves received 10 000 Ostertagia ostertagi and 66 000 Cooperia oncophora third-stage larvae (L3) [day (D) 0 post-infection (p.i.)]. In Exp. 2, calves were assigned to pure chicory (CHI2; n=10) or ryegrass/clover (CTL2; n = 10) pastures. After 7 days, animals received 20 000 O. ostertagi L3/calf (D0 p.i.) and were moved regularly preventing pasture-borne infections. Due to poor regrowth of the chicory pasture, CHI2 was supplemented with chicory silage. At D40 p.i. (Exp. 1) and D35 p.i. (Exp. 2) calves were slaughtered for worm recovery. In Exp.1, fecal egg counts (FEC) were similar between groups. However, O. ostertagi counts were significantly reduced in CHI1 by 60% (geometric mean; P < 0·01), whereas C. oncophora burdens were unaffected (P = 0·12). In Exp. 2, FEC were markedly lowered in CHI2 from D22 p.i onwards (P < 0·01). Ostertagia ostertagi adult burdens were significantly reduced in CHI2 by 66% (P < 0·001). Sesquiterpene lactones were identified only in chicory (fresh/silage). Chicory shows promise as an anti-Ostertagia feed for cattle and further studies should investigate its on-farm use.
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Fu, Jianjiang; Ke, Xiaoqin; Tan, Songlin; Liu, Ting; Wang, Shan; Ma, Junchao; Lu, Hong
2016-01-01
Codonolactone (CLT), a natural product, is the major bioactive component of Atractylodes lancea, and also found in a range of other medical herbs, such as Codonopsis pilosula, Chloranthus henryi Hemsl and Atractylodes macrocephala Koidz. This sesquiterpene lactone has been demonstrated to exhibit a range of activities, including anti-allergic activity, anti-inflammatory, anticancer, gastroprotective and neuroprotective activity. Previously, we found that CLT showed significant anti-metastatic properties in vitro and in vivo. In order to determine whether EMT-involved mechanisms contribute to the anti-metastatic effects of CLT, we checked the anti-EMT properties of CLT and its potential mechanisms. Here it was demonstrated that CLT inhibited TGF-β1-induced epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, downregulation of TGF-β signaling was associated with the anti-EMT properties of CLT. Data from western blotting showed that, in breast cancer cells, TGF-β1 stimulated the activation of Runx2, and CLT blocked the activation of Runx2. Finally, to verify whether CLT-induced EMT inhibition leads to suppression of metastatic potential, the effects of CLT on cell invasion and migration were determined. It was found that TGF-β1-induced migration and invasion was significantly blocked by CLT in both MDA-MB-231 and MDA-MB-468 cells. Collectively, our findings demonstrated that CLT inhibited programming of EMT in vitro and in vivo, resulting in inhibition of motility of metastatic breast cancer cells. The inhibitory effect of CLT was due to its ability to inhibit TGF-β signaling and Runx2 phosphorylation.
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Anti-inflammatory intestinal activity of Arctium lappa L. (Asteraceae) in TNBS colitis model.
de Almeida, Ana Beatriz Albino; Sánchez-Hidalgo, Marina; Martín, Antonio Ramón; Luiz-Ferreira, Anderson; Trigo, José Roberto; Vilegas, Wagner; dos Santos, Lourdes Campaner; Souza-Brito, Alba Regina Monteiro; de la Lastra, Catalina Alarcón
2013-03-07
In Brazilian traditional medicine, Arctium lappa (Asteraceae), has been reported to relieve gastrointestinal symptoms. In the present study, we investigated the effects of the lactone sesquiterpene onopordopicrin enriched fraction (ONP fraction) from Arctium lappa in an experimental colitis model induced by 2,4,6 trinitrobenzene sulfonic acid and performed experiments to elucidate the underlying action mechanisms involved in that effect. ONP fraction (25 and 50 mg/kg/day) was orally administered 48, 24 and 1 h prior to the induction of colitis and 24 h after. The inflammatory response was assessed by gross appearance, myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) levels and a histological study of the lesions. We determined cyclooxygenase (COX)-1 and -2 protein expressions by western blotting and immunohistochemistry assays. TNBS group was characterized by increased colonic wall thickness, edema, diffuse inflammatory cell infiltration, increased MPO activity and TNF-α levels. On the contrary, ONP fraction (25 and 50 mg/kg) treatment significantly reduced the macroscopic inflammation scores (p<0.05 and p<0.01, respectively) and morphological alterations associated with an increase in the mucus secretion. Similarly, the degree of neutrophil infiltration and the cytokine levels were significantly ameliorated. Moreover, COX-2 expression was up regulated in TNBS-treated rats. In contrast, ONP fraction (50 mg/kg) administration reduced COX-2 overexpression. We have shown that the ONP fraction obtained from Arctium lappa exert marked protective effects in acute experimental colitis, confirming and justifying, at least in part, the popular use of this plant to treat gastrointestinal diseases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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Lohans, Christopher T.; van Groesen, Emma; Kumar, Kiran; Tooke, Catherine L.; Spencer, James; Paton, Robert S.; Brem, Jürgen
2018-01-01
Abstract β‐Lactamases threaten the clinical use of carbapenems, which are considered antibiotics of last resort. The classical mechanism of serine carbapenemase catalysis proceeds through hydrolysis of an acyl‐enzyme intermediate. We show that class D β‐lactamases also degrade clinically used 1β‐methyl‐substituted carbapenems through the unprecedented formation of a carbapenem‐derived β‐lactone. β‐Lactone formation results from nucleophilic attack of the carbapenem hydroxyethyl side chain on the ester carbonyl of the acyl‐enzyme intermediate. The carbapenem‐derived lactone products inhibit both serine β‐lactamases (particularly class D) and metallo‐β‐lactamases. These results define a new mechanism for the class D carbapenemases, in which a hydrolytic water molecule is not required. PMID:29236332
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Steingass, Christof B; Langen, Johannes; Carle, Reinhold; Schmarr, Hans-Georg
2015-02-01
Headspace solid phase microextraction and chirospecific gas chromatography-mass spectrometry in selected ion monitoring mode (HS-SPME-GC-SIM-MS) allowed quantitative determination of δ-lactones (δ-C8, δ-C10) and γ-lactones (γ-C6, γ-C8, γ-C10). A stable isotope dilution assay (SIDA) with d7-γ-decalactone as internal standard was used for quantitative analysis of pineapple lactones that was performed at three progressing post-harvest stages of fully ripe air-freighted and green-ripe sea-freighted fruits, covering the relevant shelf-life of the fruits. Fresh pineapples harvested at full maturity were characterised by γ-C6 of high enantiomeric purity remaining stable during the whole post-harvest period. In contrast, the enantiomeric purity of γ-C6 significantly decreased during post-harvest storage of sea-freighted pineapples. The biogenetical background and the potential of chirospecific analysis of lactones for authentication and quality evaluation of fresh pineapple fruits are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Four new bisabolane-type sesquiterpenes from Ligularia lankongensis.
Hirota, Hiroshi; Horiguchi, Yurie; Kawaii, Satoru; Kuroda, Chiaki; Hanai, Ryo; Gong, Xun
2012-04-01
The chemical constituents of the roots of two Ligularia lankongensis samples collected in Yunnan and Sichuan Provinces, China, were investigated, together with the DNA sequence of the atpB-rbcL and ITS regions. Four new highly oxygenated bisabolane-type sesquiterpenes (1 - 4) were obtained. Intraspecific diversity in the DNA sequence was found to be limited.
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... most common types are atopic dermatitis (often called eczema) and contact dermatitis. Atopic Dermatitis (Eczema) Eczema is a chronic ... contact with your skin, they may cause a rash called contact dermatitis. There are two kinds of contact dermatitis: ...
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Ketopantoyl lactone reductase is a conjugated polyketone reductase.
Hata, H; Shimizu, S; Hattori, S; Yamada, H
1989-03-01
Ketopantoyl lactone reductase (EC 1.1.1.168) of Saccharomyces cerevisiae was found to catalyze the reduction of a variety of natural and unnatural conjugated polyketone compounds and quinones, such as isatin, ninhydrin, camphorquinone and beta-naphthoquinone in the presence of NADPH. 5-Bromoisatin is the best substrate for the enzyme (Km = 3.1 mM; Vmax = 650 mumol/min/mg). The enzyme is inhibited by quercetin, and several polyketones. These results suggest that ketopantoyl lactone reductase is a carbonyl reductase which specifically catalyzes the reduction of conjugated polyketones.
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Kaneko, Ryosuke; Sato, Atsuko; Hamada, Shun; Yagi, Takeshi; Ohsawa, Ichiro; Ohtsuki, Mamitaro; Kobayashi, Eiji; Hirabayashi, Masumi; Murakami, Takashi
2016-08-01
Childhood-onset dermatitis is one of the most common skin disorders in children. Although various mouse models that mirror aspects of dermatitis have become available, there is still a need for an animal model that develops dermatitis in childhood and is more suitable for performing tissue transplantation experiments. There is emerging evidence that peripheral blood T lymphocytes from patients with dermatitis have significantly increased telomerase activity. Here, we developed telomerase reverse transcriptase (TERT)-expressing transgenic (Tg) rats that spontaneously developed eczematous skin inflammation in childhood. Newborn TERT-Tg rats developed visible dermatitis in 56 % of cases, and the skin lesions microscopically showed spongiosis and acanthosis with infiltration of lymphocytes, eosinophils and mast cells. TERT-Tg rats with dermatitis exhibited increased CD4 (2.5-fold) and CD8 (fivefold) T cell numbers compared with dermatitis-free TERT-Tg rats. Stronger TERT activity was observed in the peripheral lymphocytes of dermatitis-positive TERT-Tg rats than those of dermatitis-free TERT-Tg rats. RT-PCR analysis revealed that IL-4 was markedly elevated in the spleen of dermatitis-positive TERT-Tg rats, and that interferon-gamma was increased in the dermatitis lesions. Moreover, skin grafting of TERT-Tg rats with dermatitis onto T cell-deficient nude rats demonstrated that the inflamed skin lesions could not be maintained. Taken together, the results suggest that TERT activation in T lymphocytes is one of the potential predisposing factors for dermatitis. Moreover, our results demonstrated that the TERT-Tg rats mirror aspects of human childhood-onset dermatitis and that these animals represent a potential animal model system for studying childhood-onset dermatitis.
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Atopic dermatitis phenotypes and the need for personalized medicine
Cabanillas, Beatriz; Brehler, Ann-Christin; Novak, Natalija
2017-01-01
Purpose of review To describe recent developments in therapies which target the molecular mechanisms in atopic dermatitis. Recent findings Current advances in the understanding of the molecular basis of atopic dermatitis are leading to the stratification of different atopic dermatitis phenotypes. New therapies offer the option to target-specific molecules involved in the pathophysiology of atopic dermatitis. Current new therapies under investigation aim to modulate specific inflammatory pathways associated with distinctive atopic dermatitis phenotypes, which would potentially translate into the development of personalized, targeted-specific treatments of atopic dermatitis. Summary Despite the unmet need for well tolerated, effective, and personalized treatment of atopic dermatitis, the current standard treatments of atopic dermatitis do not focus on the individual pathogenesis of the disease. The development of targeted, phenotype-specific therapies has the potential to open a new promising era of individualized treatment of atopic dermatitis. PMID:28582322
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Hamann, Dathan; Ridpath, Alyson; Fernandez Faith, Esteban
2018-06-26
Consort dermatitis refers to an allergic contact dermatitis caused by transfer from an intimate contact to a sensitized patient. Although close contact with other humans most commonly provokes consort dermatitis, pets have been the source in a minority of cases. We present a unique case of transfer dermatitis from a patient's cat litter to her forearms. Pediatric dermatologists should be aware of the possibility of consort or "transfer" allergic contact dermatitis from pets. © 2018 Wiley Periodicals, Inc.
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Macrocyclic lactones: A versatile source for omega radiohalogenated fatty acid analogs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dougan, A.H.; Lyster, D.M.; Robertson, K.A.
For each omega halogenated fatty acid there exists a potential omega hydroxy fatty acid and the corresponding macrocyclic lactone. The authors have utilized such lactones as starting materials for omega /sup 123/I fatty acid analogs intended for myocardial imaging. Macrocyclic musk lactones are industrially available; 120 analogs are described in the literature. The preparation requires saponification, tosylation, and radio-iodide substitution. Iodo-fatty acids are readily separated from tosylate fatty acids on TLC. While providing a secure source of 16-iodo-hexadecanoic acid and 17-iodo-heptadecanoic acid, the scheme allows ready access to a large number of untried fatty acid analogs. Examples presented are 16-iodo-hexadecanoicmore » acid, 16-iodo-7-hexadecanoic acid, 16-iodo-12-oxa-hexadecanoic acid, 15-iodo-pentadecanoic acid, and 15-iodo-12-keto-pentadecanoic acid. Metabolic studies are in progress in mice and dogs to assess the utility of these analogs for myocardial imaging.« less
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Frank, Oliver; Blumberg, Simone; Krümpel, Gudrun; Hofmann, Thomas
2008-10-22
Recent investigations on the bitterness of coffee as well as 5- O-caffeoyl quinic acid roasting mixtures indicated the existence of another, yet unknown, bitter lactone besides the previously identified bitter compounds 5- O-caffeoyl- muco-gamma-quinide, 3- O-caffeoyl-gamma-quinide, 4- O-caffeoyl- muco-gamma-quinide, 5- O-caffeoyl- epi-delta-quinide, and 4- O-caffeoyl-gamma-quinide. In the present study, this orphan bitter lactone was isolated from the reaction products generated by dry heating of 5- O-caffeoylquinic acid model, and its structure was determined as the previously unreported 3- O-caffeoyl- epi-gamma-quinide by means of liquid chromatography-mass spectrometry (LC-MS) and one-/two-dimensional NMR experiments. The occurrence of this bitter lactone, exhibiting a low bitter recognition threshold of 58 micromol/L, in coffee beverages could be confirmed by LC-MS/MS (negative electrospray ionization) operating in the multiple reaction monitoring mode.
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2012-01-01
Background Sesquiterpenes are a class of natural products with a diverse range of attractive industrial proprieties. Due to economic difficulties of sesquiterpene production via extraction from plants or chemical synthesis there is interest in developing alternative and cost efficient bioprocesses. The hydrocarbon α-santalene is a precursor of sesquiterpenes with relevant commercial applications. Here, we construct an efficient Saccharomyces cerevisiae cell factory for α-santalene production. Results A multistep metabolic engineering strategy targeted to increase precursor and cofactor supply was employed to manipulate the yeast metabolic network in order to redirect carbon toward the desired product. To do so, genetic modifications were introduced acting to optimize the farnesyl diphosphate branch point, modulate the mevalonate pathway, modify the ammonium assimilation pathway and enhance the activity of a transcriptional activator. The approach employed resulted in an overall α-santalene yield of a 0.0052 Cmmol (Cmmol glucose)-1 corresponding to a 4-fold improvement over the reference strain. This strategy, combined with a specifically developed continuous fermentation process, led to a final α-santalene productivity of 0.036 Cmmol (g biomass)-1 h-1. Conclusions The results reported in this work illustrate how the combination of a metabolic engineering strategy with fermentation technology optimization can be used to obtain significant amounts of the high-value sesquiterpene α-santalene. This represents a starting point toward the construction of a yeast “sesquiterpene factory” and for the development of an economically viable bio-based process that has the potential to replace the current production methods. PMID:22938570
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Alipour, Ziba; Taheri, Poroshat; Samadi, Nasrin
2015-04-01
Ferula cupularis (Boiss.) Spalik et S. R. Downie (Apiaceae) is a common plant in Iran that grows in the foothills of Dena Mountain. In traditional folk medicine, this plant has different applications, but there are no studies proving their uses. This study is the first attempt to investigate the chemical composition and antibacterial effect of the essential oils of F. cupularis. The essential oils from flower, leaf, and stem of F. cupularis were analyzed by using GC and GC-MS. Antibacterial activity of essential oils was determined by microdilution method against Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The essential oil from flower of F. cupularis contained 15 monoterpene, 13 oxygenated monoterpene, and 2 sesquiterpene hydrocarbons. The leaf essential oil contained 12 monoterpene, 13 oxygenated monoterpene, 2 sesquiterpene, 6 oxygenated sesquiterpene hydrocarbons, and 3 non-terpenoid components. Stem essential oil contained one monoterpene, 23 oxygenated monoterpene, 2 sesquiterpene, and 6 oxygenated sesquiterpene hydrocarbons. The MIC value of stem essential oil was 2.85 mg/mL against both Gram-positive bacteria and Gram-negative bacteria except P. aeruginosa which was inhibited at 22.75 mg/mL. The MIC values of leaf and flower essential oils were higher than 5.69 and 22.75 mg/mL, respectively. This study highlighted the strong antibacterial effect of Ferula cupularis's essential oil which might be due to its high content of oxygenated monoterpene hydrocarbons. Our results suggested that this plant may be a good candidate for further biological and pharmacological investigations.
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Aschenbrenner, Anna-Katharina; Kwon, Moonhyuk; Conrad, Jürgen; Ro, Dae-Kyun; Spring, Otmar
2016-04-01
Sunflower is known to produce a variety of bisabolene-type sesquiterpenes and accumulates these substances in trichomes of leaves, stems and flowering parts. A bioinformatics approach was used to identify the enzyme responsible for the initial step in the biosynthesis of these compounds from its precursor farnesyl pyrophosphate. Based on sequence similarity with a known bisabolene synthases from Arabidopsis thaliana AtTPS12, candidate genes of Helianthus were searched in EST-database and used to design specific primers. PCR experiments identified two candidates in the RNA pool of linear glandular trichomes of sunflower. Their sequences contained the typical motifs of sesquiterpene synthases and their expression in yeast functionally characterized them as bisabolene synthases. Spectroscopic analysis identified the stereochemistry of the product of both enzymes as (Z)-γ-bisabolene. The origin of the two sunflower bisabolene synthase genes from the transcripts of linear trichomes indicates that they may be involved in the synthesis of sesquiterpenes produced in these trichomes. Comparison of the amino acid sequences of the sunflower bisabolene synthases showed high similarity with sesquiterpene synthases from other Asteracean species and indicated putative evolutionary origin from a β-farnesene synthase. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Núñez, Marvin J; Jiménez, Ignacio A; Mendoza, Cristina R; Chavez-Sifontes, Marvin; Martinez, Morena L; Ichiishi, Eiichiro; Tokuda, Ryo; Tokuda, Harukuni; Bazzocchi, Isabel L
2016-03-23
Inhibition of tumour promotion in multistage chemical carcinogenesis is considered a promising strategy for cancer chemoprevention. In an ongoing investigation of bioactive secondary metabolites from Celastraceae species, five new dihydro-β-agarofuran sesquiterpenes (1-5), named Chiapens A-E, and seventeen known ones, were isolated from Maytenus chiapensis. Their structures were elucidated by extensive NMR spectroscopic and mass spectrometric techniques, and their absolute configurations were determined by circular dichroism studies, chemical correlations and biogenic means. The isolated compounds, along with twenty known sesquiterpenes, previously isolated from Zinowiewia costaricensis, have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorpol-13-acetate (TPA). Thirty three compounds from this series showed stronger effects than that of β-carotene, the reference inhibitor. The structure-activity relationship (SAR) analysis revealed that the type of substituent, in particular at the C-1 position of the sesquiterpene scaffold, was able to modulate the anti-tumour promoting activity. Compounds 3, 6, and 33 showed significant effects in an in vivo two-stage mouse-skin carcinogenesis model. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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Piskorski, Rafal; Hanus, Robert; Vasícková, Sona; Cvacka, Josef; Sobotník, Jan; Svatos, Ales; Valterová, Irena
2007-09-01
Frontal gland contents of soldiers of three Prorhinotermes species, Prorhinotermes canalifrons, Prorhinotermes inopinatus, and Prorhinotermes simplex, consisted of two groups of compounds: nitroalkenes and sesquiterpene hydrocarbons. Analysis by gas chromatography-mass spectrometry revealed (E)-1-nitropentadec-1-ene as the major component of the glands with mean values of 152, 207, and 293 microg/individual for P. canalifrons, P. inopinatus, and P. simplex, respectively. Four other 1-nitroalkenes (C13, C14, C16, and C17), and two nitrodienes (C15 and C17) were also detected in the three species. The C17:1 nitroalkene was identified as (E)-1-nitroheptadec-1-ene. The sesquiterpene composition of the gland was species-specific: P. simplex contained (3Z,6E)-alpha-farnesene (mean of 39 microg/individual), while P. canalifrons and P. inopinatus contained the same compound (means of 0.5 and 1.5 microg/individual, respectively) as well as the (3E,6E) isomer (means of 1.8 and 0.7 microg/individual, respectively). Two other sesquiterpenes, trans-beta-bergamotene and (Z)-gamma-bisabolene, were also found in low quantities in the frontal gland of P. canalifrons.
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2017-12-18
Moderate-to-Severe Atopic Dermatitis; Dermatitis, Dermatitis Atopic; Eczema, Skin Diseases, Skin; Diseases Genetic, Genetic; Diseases Inborn, Skin; Disease, Eczematous Skin; Hypersensitivity, Immediate; Hypersensitivity, Immune System Diseases; Dermatitis, Atopic
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Pattern of occupational allergic dermatitis in the Dermatology Clinic, Hospital Kuala Lumpur.
Rohna, R; Ganesapillai, T; Salbiah, D; Zaiton, I
1999-03-01
A two years retrospective analysis of patients diagnosed as contact allergic dermatitis with positive patch test attending the Dermatology clinic was performed. Of the 346 patients with a positive patch test, 14% had occupational dermatitis. This condition affected mainly young and inexperienced workers. An inverse relationship was seen between age and prevalence of occupational allergic dermatitis. Allergic hand dermatitis was the commonest presentation in occupational allergic dermatitis. This was followed by dermatitis of the exposed skin (face, neck, hands and forearms). The common sensitising agents identified were rubber chemicals and nickel. The two main groups at risk were factory workers and medical personnel. The common allergens found in factory workers were epoxy resin, pewter, nickel and rubber chemicals. Exposure dermatitis occurred in patients working in the pewter industry. Two thirds of medical personnel with hand dermatitis were allergic to rubber gloves. One year follow up after patch testing showed that 19% of patients still suffered from chronic dermatitis. Dermatitis improved in 34% of patients. Forty-seven percent were cured and stopped attending the clinic after patch testing and adequate counselling.
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Arima, Kazuhiko; Gupta, Shaloo; Gadkari, Abhijit; Hiragun, Takaaki; Kono, Takeshi; Katayama, Ichiro; Demiya, Sven; Eckert, Laurent
2018-04-01
Atopic dermatitis is a chronic inflammatory skin disease. The objective of this study was to characterize the burden of atopic dermatitis in Japanese adult patients relative to the general population. Japanese adults (≥18 years) with a self-reported diagnosis of atopic dermatitis and adult controls without atopic dermatitis/eczema/dermatitis were identified from the 2013 Japan National Health and Wellness Survey. Atopic dermatitis patients were propensity-score matched with non-atopic dermatitis controls (1:2 ratio) on demographic variables. Patient-reported outcome data on comorbidities, mood and sleep disorders, health-related quality of life, work productivity and activity impairment, and health-care resource utilization were analyzed in atopic dermatitis patients and matched controls. A total of 638 Japanese adult patients with atopic dermatitis were identified, of whom 290 (45.5%) rated their disease as "moderate/severe" and 348 (54.5%) as "mild". The analysis cohort comprised 634 atopic dermatitis patients and 1268 matched controls. Atopic dermatitis patients reported a significantly higher prevalence of arthritis, asthma, nasal allergies/hay fever, anxiety, depression and sleep disorders compared with controls (all P < 0.001). Atopic dermatitis patients also reported a significantly poorer health-related quality of life, higher overall work and activity impairment, and higher health-care resource utilization (all P < 0.001). Self-rated disease severity was not associated with disease burden, except for a significantly higher overall work and activity impairment. In conclusion, Japanese adult patients with atopic dermatitis reported a substantial disease burden relative to adults without atopic dermatitis, suggesting an unmet need for effective strategies targeting disease management. © 2018 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.
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Smith, Suzanne M; Nedorost, Susan T
2010-01-01
The term "dermatitis" can be defined narrowly or broadly, clinically or histologically. A common and costly condition, dermatitis is underresourced compared to other chronic skin conditions. The lack of a collectively understood definition of dermatitis and its subcategories could be the primary barrier. To investigate how dermatologists define the term "dermatitis" and determine if a consensus on the definition of this term and other related terms exists. A seven-question survey of dermatologists nationwide was conducted. Of respondents (n = 122), half consider dermatitis to be any inflammation of the skin. Nearly half (47.5%) use the term interchangeably with "eczema." Virtually all (> 96%) endorse the subcategory "atopic" under the terms "dermatitis" and "eczema," but the subcategories "contact," "drug hypersensitivity," and "occupational" are more highly endorsed under the term "dermatitis" than under the term "eczema." Over half (55.7%) personally consider "dermatitis" to have a broad meaning, and even more (62.3%) believe that dermatologists as a whole define the term broadly. There is a lack of consensus among experts in defining dermatitis, eczema, and their related subcategories.
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Lakshmi, Chembolli; Srinivas, C. R.; Pillai, Suma B.; Shanthakumari, S.
2011-01-01
Parthenium dermatitis is a widespread and distressing dermatoses in rural and urban India caused by the air borne allergen of the Compositae weed Parthenium hysterophorus. Parthenium dermatitis has been thought to be mediated solely by type IV hypersensitivity, but recently a combined immediate (type I) and delayed (type IV) hypersensitivity mechanism has been postulated in the initiation and perpetuation of parthenium dermatitis, especially in sensitized subjects with an atopic diathesis. Initially, the exposed sites of the body are involved. Later in the course of the disease, unexposed sites may get involved. Various clinical presentations have been described in parthenium dermatitis. Typically, it presents as an air borne contact dermatitis (ABCD) involving the eyelids and nasolabial folds Other presentations include a photodermatitis (essentially a pseudo photodermatitis), atopic dermatitis, seborrheic dermatitis, exfoliative dermatitis, hand dermatitis. Photosensitive lichenoid dermatitis and prurigo nodularis are rarer presentations. Uncommon presentations have been described in parthenium dermatitis. They include prurigo nodularis-like lesions and photosensitive lichenoid eruption. Three cases are presented, two of whom presented as polymorphic-like lesions and one as prurigo nodularis. All three patch tested positive to parthenium on Day 2. Prick testing was positive in two of the three patients. Parthenium dermatitis mimicking polymorphic light eruption has not been reported. Histopathology revealed vasculitis in the lesional skin in two of the patients. Although leukocytoclastic vasculitis has been reported earlier from the prick-tested site, this is the first report demonstrating the presence of vasculitis in lesional skin of parthenium dermatitis. PMID:23130236
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Diet and Dermatitis: Food Triggers
Schlichte, Megan
2014-01-01
Given increasing awareness of the link between diet and health, many patients are concerned that dietary factors may trigger dermatitis. Research has found that dietary factors can indeed exacerbate atopic dermatitis or cause dermatitis due to systemic contact dermatitis. In atopic dermatitis, dietary factors are more likely to cause an exacerbation among infants or children with moderate-to-severe atopic dermatitis relative to other populations. Foods may trigger rapid, immunoglobulin E-mediated hypersensitivity reactions or may lead to late eczematous reactions. While immediate reactions occur within minutes to hours of food exposure, late eczematous reactions may occur anywhere from hours to two days later. Screening methods, such as food allergen-specific serum immunoglobulin E tests or skin prick tests, can identify sensitization to specific foods, but a diagnosis of food allergy requires specific signs and symptoms that occur reproducibly upon food exposure. Many patients who are sensitized will not develop clinical findings upon food exposure; therefore, these tests may result in false-positive tests for food allergy. This is why the gold standard for diagnosis remains the double-blind, placebo-controlled food challenge. In another condition, systemic contact dermatitis, ingestion of a specific food can actually cause dermatitis. Systemic contact dermatitis is a distinct T-cell mediated immunological reaction in which dietary exposure to specific allergens results in dermatitis. Balsam of Peru and nickel are well-known causes of systemic contact dermatitis, and reports have implicated multiple other allergens. This review seeks to increase awareness of important food allergens, elucidate their relationship with atopic dermatitis and systemic contact dermatitis, and review available diagnostic and treatment strategies. PMID:24688624
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Mandal, Samir K; Paira, Moumita; Roy, Subhas C
2008-05-16
Baylis-Hillman adduct underwent smooth radical-induced condensation with activated bromo compounds and epoxides using titanocene(III) chloride (Cp2TiCl) as the radical generator. The reactions of activated bromo compounds with 3-acetoxy-2-methylene alkanoates provided (E)-alkenes exclusively, whereas similar reactions with 3-acetoxy-2-methylenealkanenitriles led to (Z)-alkenes as the major product. The reactions of epoxides with Baylis-Hillman adduct furnished alpha-methylene/arylidene-delta-lactones in good yield via addition followed by in situ lactonization.
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Qin, Hui-Min; Yamamura, Akihiro; Miyakawa, Takuya; Kataoka, Michihiko; Nagai, Takahiro; Kitamura, Nahoko; Urano, Nobuyuki; Maruoka, Shintaro; Ohtsuka, Jun; Nagata, Koji; Shimizu, Sakayu; Tanokura, Masaru
2014-01-01
Conjugated polyketone reductase C2 (CPR-C2) from Candida parapsilosis IFO 0708, identified as a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent ketopantoyl lactone reductase, belongs to the aldo-keto reductase superfamily. This enzyme reduces ketopantoyl lactone to D-pantoyl lactone in a strictly stereospecific manner. To elucidate the structural basis of the substrate specificity, we determined the crystal structures of the apo CPR-C2 and CPR-C2/NADPH complex at 1.70 and 1.80 Å resolutions, respectively. CPR-C2 adopted a triose-phosphate isomerase barrel fold at the core of the structure. Binding with the cofactor NADPH induced conformational changes in which Thr27 and Lys28 moved 15 and 5.0 Å, respectively, in the close vicinity of the adenosine 2'-phosphate group of NADPH to form hydrogen bonds. Based on the comparison of the CPR-C2/NADPH structure with 3-α-hydroxysteroid dehydrogenase and mutation analyses, we constructed substrate binding models with ketopantoyl lactone, which provided insight into the substrate specificity by the cofactor-induced structure. The results will be useful for the rational design of CPR-C2 mutants targeted for use in the industrial manufacture of ketopantoyl lactone.
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The presence and role of bacterial quorum sensing in activated sludge
Chong, Grace; Kimyon, Onder; Rice, Scott A.; Kjelleberg, Staffan; Manefield, Mike
2012-01-01
Summary Activated sludge used for wastewater treatment globally is composed of a high‐density microbial community of great biotechnological significance. In this study the presence and purpose of quorum sensing via N‐acylated‐l‐homoserine lactones (AHLs) in activated sludge was explored. The presence of N‐heptanoyl‐l‐homoserine lactone in organic extracts of sludge was demonstrated along with activation of a LuxR‐based AHL monitor strain deployed in sludge, indicating AHL‐mediated gene expression is active in sludge flocculates but not in the bulk aqueous phase. Bacterial isolates from activated sludge were screened for AHL production and expression of phenotypes commonly but not exclusively regulated by AHL‐mediated gene transcription. N‐acylated‐l‐homoserine lactone and exoenzyme production were frequently observed among the isolates. N‐acylated‐l‐homoserine lactone addition to sludge upregulated chitinase activity and an AHL‐ and chitinase‐producing isolate closely related to Aeromonas hydrophila was shown to respond to AHL addition with upregulation of chitinase activity. N‐acylated‐l‐homoserine lactones produced by this strain were identified and genes ahyI/R and chiA, encoding AHL production and response and chitinase activity respectively, were sequenced. These experiments provide insight into the relationship between AHL‐mediated gene expression and exoenzyme activity in activated sludge and may ultimately create opportunities to improve sludge performance. PMID:22583685
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Edmonds, M D; Vatta, A F; Marchiondo, A A; Vanimisetti, H B; Edmonds, J D
2018-03-15
In 2013, a 118-day study was initiated to investigate the efficacy of concurrent treatment at pasture turnout with an injectable macrocyclic lactone with activity up to 28 days and an oral benzimidazole, referred to as "conventional" anthelmintics, when compared to treatment with conventional macrocyclic lactone alone or an injectable macrocyclic lactone with extended activity of 100 days or longer. A group of 210 steers were obtained from a ranch in California and transported to Idaho, USA. A total of 176 steers with the highest fecal egg counts were blocked by pre-treatment body weights and pasture location. A total of 44 pasture paddocks were assigned with 4 steers per paddock with 12 paddocks per therapeutic treatment group and 8 paddocks per controls. The four treatments were injectable doramectin (Dectomax ® , Zoetis Inc., 0.2 mg kg -1 BW, SC), injectable doramectin concurrently with oral albendazole (Valbazen ® , Zoetis Inc., 10 mg kg -1 BW, PO), extended release injectable eprinomectin (LongRange™, Merial Limited, 1 mg kg -1 BW, SC) or saline. Cattle were individually weighed and sampled for fecal egg count on Days 0, 31/32, 61, 88, and 117/118 with an additional fecal sample on Day 14. At conclusion, one steer per paddock was euthanized for nematode recovery. The results from the first 32 days found evidence of macrocyclic lactone resistance against injectable doramectin and extended release eprinomectin. During this period the concurrent therapy provided nearly 100% efficacy based on fecal egg count reduction and a 19.98% improvement in total weight gain compared to controls (P = 0.039). At the conclusion of the 118-day study and past the approved efficacy for the conventional anthelmintics, the concurrent therapy with conventional anthelmintics provided a 22.98% improvement in total weight gain compared to controls (P = 0.004). The 118-day improvement in weight gain for the extended release eprinomectin group (29.06% compared to control) was not statistically different from the concurrent therapy with conventional anthelmintics. The results indicate that concurrent treatment with a conventional macrocyclic lactone and benzimidazole may provide production benefits early in the grazing period that continue throughout the entire period for cattle harboring macrocyclic lactone resistant nematodes. By using two different anthelmintic classes together, macrocyclic lactone resistant parasites were effectively controlled early in the period. Furthermore, the use of an effective conventional anthelmintic treatment regimen without an extended period of drug release may help to promote refugia and decrease the further selection for anthelmintic resistant parasites. Copyright © 2018 Elsevier B.V. All rights reserved.
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Patch Test Negative Generalized Dermatitis.
Spiker, Alison; Mowad, Christen
2016-01-01
Allergic contact dermatitis is a common condition in dermatology. Patch testing is the criterion standard for diagnosis. However, dermatitis is not always caused by an allergen, and patch testing does not identify a culprit in every patient. Generalized dermatitis, defined as eczematous dermatitis affecting greater than 3 body sites, is often encountered in dermatology practice, especially patch test referral centers. Management for patients with generalized dermatitis who are patch test negative is challenging. The purpose of this article is to outline an approach to this challenging scenario and summarize the paucity of existing literature on patch test negative generalized dermatitis.
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Chen, Jih-Jung; Kuo, Wen-Lung; Chen, Ih-Sheng; Peng, Chien-Fang; Sung, Ping-Jyun; Cheng, Ming-Jen; Lim, Yun-Ping
2014-08-01
A new dihydroagarofuran-based sesquiterpene, microjaponin (1), was isolated from the stem of Microtropis japonica. Its structure was determined by in-depth spectroscopic and mass-spectrometric analyses. Microjaponin (1) exhibited potent in vitro antituberculosis activity, with an MIC value of 12.5 μg/ml against Mycobacterium tuberculosis H37 Rv. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.
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A series of sesquiterpenes were individually oxidized under a range of conditions, including irradiation in the presence of NOx, reactions with O3 or reactions with NO3 radicals. Experiments were conducted in either static mode to observe temporal...
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... ulcers; Ulcers - venous; Venous ulcer; Venous insufficiency - stasis dermatitis; Vein - stasis dermatitis ... veins. Some people with venous insufficiency develop stasis dermatitis. Blood pools in the veins of the lower ...
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Hirata, Yoshihiko; Ryu, Mizuyuki; Igarashi, Keisuke; Nagatsuka, Asami; Furuta, Taro; Kanaya, Shigenori; Sugiura, Masaki
2009-01-01
Sophorolipids (SLs) naturally produced from Candida bombicola are a mixture of lactonic (SL-lactone) and acidic (SL-acid) sophorosides of 17-L-hydroxydecanoic acid with an SL-lactone:SL-acid ratio of 72:28. SLs are biodegradable low-foaming surfactants with high detergency and hardness-tolerance properties. To analyze the effect of the SL-lactone:SL-acid ratio on these properties, SL-LXs containing X% SL-lactone, in which X varied from 0 to 100, were prepared and their interfacial activities and cytotoxicities examined. The minimum surface tension values for all SLs examined were comparable. The critical micelle concentration (CMC) was 680 mg/L for SL-L0 and 62-110 mg/L for the other SLs. Interestingly, natural SL (SL-L72) had the lowest surface tension and CMC among all of the SLs examined. The foaming ability and stability of the SLs were dependent on the SL-L content. SL-L0 and L17 had higher foaming values than the other SLs examined in 0-ppm hardness water. These values greatly reduced and became constant when the SL-L content increased over 55%. The detergencies of all of the SLs examined were comparable, except for those of SL-L0 and SL-L100, which were slightly lower than those of the other SLs. These results suggest that natural synergism between SLs creates a better balance for many interfacial activities. The cytotoxicity of SL-L72 was higher than that of SL-L0, but was comparable to that of surfactin, which is commercially available for cosmetic use. The low cytotoxicities and high interfacial properties of SLs increase their usefulness as biocompatible surface active agents for many applications.
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Xu, Yuquan; Espinosa-Artiles, Patricia; Schubert, Vivien; Xu, Ya-ming; Zhang, Wei; Lin, Min; Gunatilaka, A. A. Leslie; Süssmuth, Roderich
2013-01-01
10,11-Dehydrocurvularin is a prevalent fungal phytotoxin with heat shock response and immune-modulatory activities. It features a dihydroxyphenylacetic acid lactone polyketide framework with structural similarities to resorcylic acid lactones like radicicol or zearalenone. A genomic locus was identified from the dehydrocurvularin producer strain Aspergillus terreus AH-02-30-F7 to reveal genes encoding a pair of iterative polyketide synthases (A. terreus CURS1 [AtCURS1] and AtCURS2) that are predicted to collaborate in the biosynthesis of 10,11-dehydrocurvularin. Additional genes in this locus encode putative proteins that may be involved in the export of the compound from the cell and in the transcriptional regulation of the cluster. 10,11-Dehydrocurvularin biosynthesis was reconstituted in Saccharomyces cerevisiae by heterologous expression of the polyketide synthases. Bioinformatic analysis of the highly reducing polyketide synthase AtCURS1 and the nonreducing polyketide synthase AtCURS2 highlights crucial biosynthetic programming differences compared to similar synthases involved in resorcylic acid lactone biosynthesis. These differences lead to the synthesis of a predicted tetraketide starter unit that forms part of the 12-membered lactone ring of dehydrocurvularin, as opposed to the penta- or hexaketide starters in the 14-membered rings of resorcylic acid lactones. Tetraketide N-acetylcysteamine thioester analogues of the starter unit were shown to support the biosynthesis of dehydrocurvularin and its analogues, with yeast expressing AtCURS2 alone. Differential programming of the product template domain of the nonreducing polyketide synthase AtCURS2 results in an aldol condensation with a different regiospecificity than that of resorcylic acid lactones, yielding the dihydroxyphenylacetic acid scaffold characterized by an S-type cyclization pattern atypical for fungal polyketides. PMID:23335766
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Ding, Xue-Qiang; Chen, Dan; Wang, An-Xun; Li, Su; Chen, Yu; Wang, Ji
2007-01-01
Therapeutic use of hydroxycamptothecin (HCPT), a promising antitumor agent, is limited by its poor solubility and rapid destruction. Amphiphilic block copolymer micelle carriers possess significant potential for improving drug solubility and stability. Poly[ethylene glycol]-poly[gamma-benzyl-L-glutamate] (PEG-PBLG) micelles were prepared and loaded with the active lactone form of HCPT using an uncomplicated dialysis method. HPLC and scanning electron microscopy studies revealed an encapsulation efficiency of 56.8% and a core-shell figure with a mean diameter of 200 nm. Encapsulated HCPT lactone was compared with the less active, open ring-carboxylated HCPT-Na+ soluble form generated in vivo from the free active lactone for activity against oral squamous cell carcinoma. Cytotoxicity in vitro was measured in cultured Tca8113 cells by the MTT assay and microscopy techniques. The golden hamster cheek pouch squamous cell carcinoma model was employed for in vivo studies; encapsulated lactone and open ring-carboxylated forms of HCPT were administered intraperitoneally, followed by determinations of tumor growth rate and inhibition ratio. PEG-PBLG micelles were not cytotoxic in vitro. At 48 h of treatment, open ring-carboxylated HCPT proved significantly more cytotoxic in vitro than encapsulated HCPT lactone. At 96 h, however, the open ring-carboxylated and encapsulated drugs displayed comparable in vitro cytotoxicities. In the in vivo squamous cell carcinoma model, encapsulated HCPT lactone produced greater and more prolonged tumor suppression compared to the open ring-carboxylated form. The antitumor effects of HCPT/PEG-PBLG micelles against oral squamous cell carcinoma in vivo are concluded to be superior to those exerted by open ring-carboxylated HCPT.
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Occupational dermatitis in hairdressers - influence of individual and environmental factors.
Carøe, Tanja K; Ebbehøj, Niels E; Agner, Tove
2017-03-01
Hairdressers are at risk of developing occupational contact dermatitis because of their intense contact with wet work in combination with chemicals. To perform an analysis of a cohort study of hairdressers with occupational contact dermatitis recognized in the period 2006-2011, focusing on individual and environmental factors associated with the disease. The study was a descriptive, register-based survey including all hairdressers with recognized occupational contact dermatitis in Denmark in the period January 2006 to September 2011. Data were obtained from the Danish National Board of Industrial Injuries. The study comprised 381 patients (373 women and 8 men). The median age was 25 years, 64.8% were apprentices, and 35.2% were fully trained hairdressers. The prevalence of atopic dermatitis was 36.0%, and was significantly higher among apprentices than among fully trained hairdressers (44.9% and 19.4%, respectively) (p < 0.001). Of the patients, 48.3% had their dermatitis recognized as occupational irritant contact dermatitis, 46.7% had their dermatitis recognized as as occupational allergic contact dermatitis or combined allergic and irritant contact dermatitis, and 5.0% were recognized as having occupational contact urticaria. The low median age, the high percentages of atopic dermatitis in apprentices and the fact that more apprentices than fully trained hairdressers had recognized occupational contact dermatitis underlines the importance of early prevention. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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... dermatitis URL of this page: //medlineplus.gov/ency/article/001455.htm Perioral dermatitis To use the sharing features on this page, please enable JavaScript. Perioral dermatitis is a skin disorder resembling acne ...
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Köllner, Tobias G.; Schnee, Christiane; Gershenzon, Jonathan; Degenhardt, Jörg
2004-01-01
The mature leaves and husks of Zea mays release a complex blend of terpene volatiles after anthesis consisting predominantly of bisabolane-, sesquithujane-, and bergamotane-type sesquiterpenes. The varieties B73 and Delprim release the same volatile constituents but in significantly different proportions. To study the molecular genetic and biochemical mechanisms controlling terpene diversity and distribution in these varieties, we isolated the closely related terpene synthase genes terpene synthase4 (tps4) and tps5 from both varieties. The encoded enzymes, TPS4 and TPS5, each formed the same complex mixture of sesquiterpenes from the precursor farnesyl diphosphate but with different proportions of products. These mixtures correspond to the sesquiterpene blends observed in the varieties B73 and Delprim, respectively. The differences in the stereoselectivity of TPS4 and TPS5 are determined by four amino acid substitutions with the most important being a Gly instead of an Ala residue at position 409 at the catalytic site of the enzyme. Although both varieties contain tps4 and tps5 alleles, their differences in terpene composition result from the fact that B73 has only a single functional allele of tps4 and no functional alleles of tps5, whereas Delprim has only a functional allele of tps5 and no functional alleles of tps4. Lack of functionality was shown to be attributable to frame-shift mutations or amino acid substitutions that greatly reduce the activity of their encoded proteins. Therefore, the diversity of sesquiterpenes in these two maize cultivars is strongly influenced by single nucleotide changes in the alleles of two terpene synthase genes. PMID:15075399
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Schnee, Christiane; Köllner, Tobias G.; Gershenzon, Jonathan; Degenhardt, Jörg
2002-01-01
Maize (Zea mays) emits a mixture of volatile compounds upon attack by the Egyptian cotton leafworm (Spodoptera littoralis). These substances, primarily mono- and sesquiterpenes, are used by parasitic wasps to locate the lepidopteran larvae, which are their natural hosts. This interaction among plant, lepidopteran larvae, and hymenopteran parasitoids benefits the plant and has been termed indirect defense. The committed step in the biosynthesis of the different skeletal types of mono- and sesquiterpenes is catalyzed by terpene synthases, a class of enzymes that forms a large variety of mono- and sesquiterpene products from prenyl diphosphate precursors. We isolated a terpene synthase gene, terpene synthase 1 (tps1), from maize that exhibits only a low degree of sequence identity to previously identified terpene synthases. Upon expression in a bacterial system, the encoded enzyme produced the acyclic sesquiterpenes, (E)-β-farnesene, (E,E)-farnesol, and (3R)-(E)-nerolidol, the last an intermediate in the formation of (3E)-4,8-dimethyl-1,3,7-nonatriene. Both (E)-β-farnesene and (3E)-4,8-dimethyl-1,3,7-nonatriene are prominent compounds of the maize volatile blend that is emitted after herbivore damage. The biochemical characteristics of the encoded enzyme are similar to those of terpene synthases from both gymnosperms and dicotyledonous angiosperms, suggesting that catalysis involves a similar electrophilic reaction mechanism. The transcript level of tps1 in the maize cv B73 was elevated after herbivory, mechanical damage, and treatment with elicitors. In contrast, the increase in the transcript level of the tps1 gene or gene homolog in the maize cv Delprim after herbivory was less pronounced, suggesting that the regulation of terpene synthase expression may vary among maize varieties. PMID:12481088
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Köllner, Tobias G; Schnee, Christiane; Gershenzon, Jonathan; Degenhardt, Jörg
2004-05-01
The mature leaves and husks of Zea mays release a complex blend of terpene volatiles after anthesis consisting predominantly of bisabolane-, sesquithujane-, and bergamotane-type sesquiterpenes. The varieties B73 and Delprim release the same volatile constituents but in significantly different proportions. To study the molecular genetic and biochemical mechanisms controlling terpene diversity and distribution in these varieties, we isolated the closely related terpene synthase genes terpene synthase4 (tps4) and tps5 from both varieties. The encoded enzymes, TPS4 and TPS5, each formed the same complex mixture of sesquiterpenes from the precursor farnesyl diphosphate but with different proportions of products. These mixtures correspond to the sesquiterpene blends observed in the varieties B73 and Delprim, respectively. The differences in the stereoselectivity of TPS4 and TPS5 are determined by four amino acid substitutions with the most important being a Gly instead of an Ala residue at position 409 at the catalytic site of the enzyme. Although both varieties contain tps4 and tps5 alleles, their differences in terpene composition result from the fact that B73 has only a single functional allele of tps4 and no functional alleles of tps5, whereas Delprim has only a functional allele of tps5 and no functional alleles of tps4. Lack of functionality was shown to be attributable to frame-shift mutations or amino acid substitutions that greatly reduce the activity of their encoded proteins. Therefore, the diversity of sesquiterpenes in these two maize cultivars is strongly influenced by single nucleotide changes in the alleles of two terpene synthase genes.
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Lane, Alexander; Boecklemann, Astrid; Woronuk, Grant N; Sarker, Lukman; Mahmoud, Soheil S
2010-03-01
We are developing Lavandula angustifolia (lavender) as a model system for investigating molecular regulation of essential oil (a mixture of mono- and sesquiterpenes) production in plants. As an initial step toward building the necessary 'genomics toolbox' for this species, we constructed two cDNA libraries from lavender leaves and flowers, and obtained sequence information for 14,213 high-quality expressed sequence tags (ESTs). Based on homology to sequences present in GenBank, our EST collection contains orthologs for genes involved in the 1-deoxy-D: -xylulose-5-phosphate (DXP) and the mevalonic acid (MVA) pathways of terpenoid biosynthesis, and for known terpene synthases and prenyl transferases. To gain insight into the regulation of terpene metabolism in lavender flowers, we evaluated the transcriptional activity of the genes encoding for 1-deoxy-D: -xylulose-5-phosphate synthase (DXS) and HMG-CoA reductase (HMGR), which represent regulatory steps of the DXP and MVA pathways, respectively, in glandular trichomes (oil glands) by real-time PCR. While HMGR transcripts were barely detectable, DXS was heavily expressed in this tissue, indicating that essential oil constituents are predominantly produced through the DXP pathway in lavender glandular trichomes. As anticipated, the linalool synthase (LinS)-the gene responsible for the production of linalool, a major constituent of lavender essential oil-was also strongly expressed in glands. Surprisingly, the most abundant transcript in floral glandular trichomes corresponded to a sesquiterpene synthase (cadinene synthase, CadS), although sesquiterpenes are minor constituents of lavender essential oils. This result, coupled to the weak activity of the MVA pathway (the main route for sesquiterpene production) in trichomes, indicates that precursor supply may represent a bottleneck in the biosynthesis of sesquiterpenes in lavender flowers.
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Use of aromatherapy products and increased risk of hand dermatitis in massage therapists.
Crawford, Glen H; Katz, Kenneth A; Ellis, Elliot; James, William D
2004-08-01
To determine the 12-month prevalence of hand dermatitis among massage therapists, to investigate a potential association between hand dermatitis and the use of aromatherapy products, and to study potential associations with other known risk factors for hand dermatitis. Mailed survey. Philadelphia, Pa. Members of a national massage therapy organization who live in the greater Philadelphia region. Self-reported and symptom-based prevalences of hand dermatitis. The number of respondents was 350 (57%). The 12-month prevalence of hand dermatitis in subjects was 15% by self-reported criteria and 23% by a symptom-based method. In multivariate analysis, statistically significant independent risk factors for self-reported hand dermatitis included use of aromatherapy products in massage oils, lotions, or creams (odds ratio, 3.27; 95% confidence interval, 1.53-7.02; P =.002) and history of atopic dermatitis (odds ratio, 8.06; 95% confidence interval, 3.39-19.17; P<.001). The prevalence of hand dermatitis in massage therapists is high. Significant independent risk factors include use of aromatherapy products in massage oils, creams, or lotions and history of atopic dermatitis.
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Ma, Jiang-Hao; Wang, Ying; Liu, Yue; Gao, Su-Yu; Ding, Li-Qin; Zhao, Feng; Chen, Li-Xia; Qiu, Feng
2015-05-01
Three new guaiane-type sesquiterpenes named phaeocaulisins K-M (1-3), and one germacrane-type sesquiterpenoid with new ring system of 1,5- and 1,8-ether groups named phagermadiol (4), were isolated from rhizomes of Curcuma phaeocaulis. Their structures were established based on extensive spectroscopic analysis. Compound 1, the first example of norsesquiterpene with tropone backbone, and compound 3 with a novel 1,2-dioxolane sesquiterpene alcohol were isolated from the genus Curcuma. All of the isolated compounds were tested for inhibitory activity against lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compound 3 inhibited NO production with IC50 value of 6.05 ± 0.43 μM. The plausible biosynthetic pathway for compounds 3 and 4 in C. phaeocaulis was also discussed.
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USDA-ARS?s Scientific Manuscript database
Variecolactol (1), a new sesterterpene lactone related to variecolin (2), has been isolated from the organic extracts of Aspergillus auricomus. Structure determination of this compound was achieved primarily through HMQC, HMBC, and NOESY experiments. The known compounds dihydropenicillic acid (3) ...
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Yunos, Nina Yusrina Muhamad; Tan, Wen-Si; Koh, Chong-Lek; Sam, Choon-Kook; Mohamad, Nur Izzati; Tan, Pui-Wan; Adrian, Tan-Guan-Sheng; Yin, Wai-Fong; Chan, Kok-Gan
2014-01-01
Quorum sensing (QS) is a bacterial cell-to-cell communication system controlling QS-mediated genes which is synchronized with the population density. The regulation of specific gene activity is dependent on the signaling molecules produced, namely N-acyl homoserine lactones (AHLs). We report here the identification and characterization of AHLs produced by bacterial strain ND07 isolated from a Malaysian fresh water sample. Molecular identification showed that strain ND07 is clustered closely to Pseudomonas cremoricolorata. Spent culture supernatant extract of P. cremoricolorata strain ND07 activated the AHL biosensor Chromobacterium violaceum CV026. Using high resolution triple quadrupole liquid chromatography-mass spectrometry, it was confirmed that P. cremoricolorata strain ND07 produced N-octanoyl-l-homoserine lactone (C8-HSL) and N-decanoyl-l-homoserine lactone (C10-HSL). To the best of our knowledge, this is the first documentation on the production of C10-HSL in P. cremoricolorata strain ND07. PMID:24984061
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Synthesis of 3 alpha, 5 alpha-tetrahydroaldosterone.
Harnik, M; Kashman, Y; Morris, D J
1984-06-01
3 alpha, 5 alpha-Tetrahydroaldosterone (12a), a metabolite of aldosterone, has been synthesized from the lactone 2a or, preferably 11 beta, 21-dihydroxy-5-pregnene-3,20-dione-18-oic acid 3,20-di-(ethylene glycol)-ketal (18----11) lactone 21-acetate (6b), via 11 beta, 21-dihydroxy-5 alpha-pregnane-3,20-dione-18-oic acid 3,20-di-(ethylene glycol) ketal (18----11) lactone 21-acetate (4b). Selective hydrolysis of the latter at C-3 furnished the monoketal 5 which, on reduction with potassium tri-sec-butylborohydride, yielded predominantly 3 alpha, 11 beta, 21-trihydroxy-5 alpha-pregnan-20-one-18-oic acid 20-(ethylene glycol)-ketal (18----11) lactone (8a) and its acetate 8b. Further reduction with diisobutylaluminum hydride afforded 3 alpha, 5 alpha-tetrahydroaldosterone-20-ketal (10a), which was directly hydrolyzed to 12a with dilute acid in tetrahydrofuran-dioxan. Periodate oxidation led to the gamma-etiolactone 14a, which was then further converted into 5 alpha-dihydroaldosterone-gamma-etiolactone (14c).
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Pérez-Olivero, S. J.; Pérez-Pont, M. L.; Conde, J. E.; Pérez-Trujillo, J. P.
2014-01-01
Application of headspace solid-phase microextraction (HS-SPME) coupled with high-resolution gas chromatographic (HRGC) analysis was studied for determining lactones in wines. Six different SPME fibers were tested, and the influence of different factors such as temperature and time of desorption, ionic strength, time of extraction, content of sugar, ethanol, tannins and anthocyanins, and pH and influence of SO2 were studied. The proposed HS-SPME-GC method is an appropriate technique for the quantitative analysis of γ-butyrolactone, γ-hexalactone, trans-whiskey lactone, γ-octalactone, cis-whiskey lactone, γ-nonalactone, γ-decalactone, δ-decalactone, and γ-undecalactone in wines. Method reproducibility and repeatability ranged between 0.6 and 5.2% for all compounds. Detection limit for γ-butyrolactone was 0.17 mg/L and a few μg/L for the rest of the compounds. The optimized method has been applied to several wine samples. PMID:24782943
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Ghani, Norshazliza Ab; Sulaiman, Joanita; Ismail, Zahidah; Chan, Xin-Yue; Yin, Wai-Fong; Chan, Kok-Gan
2014-04-09
Two microbial isolates from a Malaysian shoreline were found to be capable of degrading N-acylhomoserine lactones. Both Matrix Assisted Laser Desorption Ionization-Time of Flight-Mass Spectrometry and 18S rDNA phylogenetic analyses confirmed that these isolates are Rhodotorula mucilaginosa. Quorum quenching activities were detected by a series of bioassays and rapid resolution liquid chromatography analysis. The isolates were able to degrade various quorum sensing molecules namely N-hexanoyl-L-homoserine lactone (C6-HSL), N-(3-oxo-hexanoyl)-L-homoserine lactone (3-oxo-C6-HSL) and N-(3-hydroxyhexanoyl)-L-homoserine lactone (3-hydroxy-C6-HSL). Using a relactonisation assay to verify the quorum quenching mechanism, it is confirmed that Rh. mucilaginosa degrades the quorum sensing molecules via lactonase activity. To the best of our knowledge, this is the first documentation of the fact that Rh. mucilaginosa has activity against a broad range of AHLs namely C6-HSL, 3-oxo-C6-HSL and 3-hydroxy-C6-HSL.
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Pomini, Armando M; Paccola-Meirelles, Luzia D; Marsaioli, Anita J
2007-02-21
The "maize white spot" foliar disease is a problem of increasing importance to Brazilian maize crops. A bacterium isolated from water-soaked lesions from infected maize leaves was pathogenic in biological assays in vivo. It was identified as a Gram-negative, nonsporulating, facultative anaerobic bacterium, belonging to the genus Pantoea. Chemical study of the extracts from bacterial cultivation media allowed the identification of (S)-(-)-N-butanoyl-homoserine lactone and trace amounts of N-hexanoyl-homoserine lactone, widely recognized quorum-sensing signaling substances employed in cell-to-cell communication systems. The absolute configuration of natural (S)-(-)-N-butanoyl-homoserine lactone was determined by gas chromatography-flame ionization detection with a chiral stationary phase and by comparison of circular dichroism spectroscopic data with enantiopure synthetic substances. Biological evaluations with reporter Agrobacterium tumefaciens NTL4(pZLR4) were carried out with synthetic and natural products and also with extracts from maize leaves contaminated with the isolated bacterium, as well as from healthy leaves.
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Duan, Dehui; Sigano, Dina M.; Kelley, James A.; Lai, Christopher C.; Lewin, Nancy E.; Kedei, Noemi; Peach, Megan L.; Lee, Jeewoo; Abeyweera, Thushara P.; Rotenberg, Susan A.; Kim, Hee; Kim, Young Ho; Kazzouli, Saïd El; Chung, Jae-Uk; Young, Howard A.; Young, Matthew R.; Baker, Alyson; Colburn, Nancy H.; Haimovitz-Friedman, Adriana; Truman, Jean-Philip; Parrish, Damon A.; Deschamps, Jeffrey R.; Perry, Nicholas A.; Surawski, Robert J.; Blumberg, Peter M.; Marquez, Victor E.
2008-01-01
Diacylglycerol-lactone (DAG-lactone) libraries generated by a solid-phase approach using IRORI technology produced a variety of unique biological activities. Subtle differences in chemical diversity in two areas of the molecule, the combination of which generates what we have termed “chemical zip codes”, are able to transform a relatively small chemical space into a larger universe of biological activities, as membrane-containing organelles within the cell appear to be able to decode these “chemical zip codes”. It is postulated that after binding to protein kinase C (PKC) isozymes or other non-kinase target proteins that contain diacylglycerol responsive, membrane interacting domains (C1 domains), the resulting complexes are directed to diverse intracellular sites where different sets of substrates are accessed. Multiple cellular bioassays show that DAG-lactones, which bind in vitro to PKCα to varying degrees, expand their biological repertoire into a larger domain, eliciting distinct cellular responses. PMID:18698758
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Ghani, Norshazliza Ab; Sulaiman, Joanita; Ismail, Zahidah; Chan, Xin-Yue; Yin, Wai-Fong; Chan, Kok-Gan
2014-01-01
Two microbial isolates from a Malaysian shoreline were found to be capable of degrading N-acylhomoserine lactones. Both Matrix Assisted Laser Desorption Ionization-Time of Flight-Mass Spectrometry and 18S rDNA phylogenetic analyses confirmed that these isolates are Rhodotorula mucilaginosa. Quorum quenching activities were detected by a series of bioassays and rapid resolution liquid chromatography analysis. The isolates were able to degrade various quorum sensing molecules namely N-hexanoyl-L-homoserine lactone (C6-HSL), N-(3-oxo-hexanoyl)-L-homoserine lactone (3-oxo-C6-HSL) and N-(3-hydroxyhexanoyl)-L-homoserine lactone (3-hydroxy-C6-HSL). Using a relactonisation assay to verify the quorum quenching mechanism, it is confirmed that Rh. mucilaginosa degrades the quorum sensing molecules via lactonase activity. To the best of our knowledge, this is the first documentation of the fact that Rh. mucilaginosa has activity against a broad range of AHLs namely C6-HSL, 3-oxo-C6-HSL and 3-hydroxy-C6-HSL. PMID:24721765
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Yamauchi, Satoshi; Wukirsari, Tuti; Ochi, Yoshiaki; Nishiwaki, Hisashi; Nishi, Kosuke; Sugahara, Takuya; Akiyama, Koichi; Kishida, Taro
2017-09-01
The new lignano-9,9'-lactones (α,β-dibenzyl-γ-butyrolactone lignans), which showed the higher cytotoxicity than arctigenin, were synthesized. The well-known cytotoxic arctigenin showed activity against HL-60 cells (EC 50 =12μM), however, it was inactive against HeLa cells (EC 50 >100μM). The synthesized (3,4-dichloro, 2'-butoxy)-derivative 55 and (3,4-dichloro, 4'-butyl)-derivative 66 bearing the lignano-9,9'-lactone structures showed the EC 50 values of 10μM and 9.4μM against HL-60 cells, respectively. Against HeLa cells, the EC 50 value of the derivative 66 was 27μM. By comparing the activities with the corresponding 9,9'-epoxy structure (tetrahydrofuran compounds), the importance of the lactone structure of 55 and 66 for the higher activities was shown. The substituents on the aromatic ring of the lignano-9,9'-lactones affected the cytotoxicity level, observing more than 10-fold difference. Copyright © 2017. Published by Elsevier Ltd.
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Marukami, T; Kishi, A; Yoshikawa, M
2001-08-01
Following the characterization of hypoglycemic, gastric emptying inhibitory, and gastroprotective principles and the structure elucidation of calendasaponins A, B, C, and D, two new ionone glucosides (officinosides A and B), and two sesquiterpene oligoglycosides (officinosides C and D), were isolated from the flowers of Egyptian Calendula officinalis. The structures of the officinosides were elucidated on the basis of chemical and physicochemical evidence.
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UFVA, A Combined Linear and Nonlinear Factor Analysis Program Package for Chemical Data Evaluation.
1980-11-01
that one cluster consists of the monoterpenes and Isoprene; the second is of the sesquiterpenes. Compound 8 (Caryophyllene) should therefore belong to...two clusters very clearly (Fig. 6). Figure 6 The very similar fragmentation pattern of Isoprene and the monoterpenes is reflected by their close...13 of another set of 13 terpene components. These are Isoprene, four monoterpenes (Myrcene, Menthol, Camphene, Umbellulone), four sesquiterpenes
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Penicillipyrones A and B, meroterpenoids from a marine-derived Penicillium sp. fungus.
Liao, Lijuan; Lee, Jung-Ho; You, Minjung; Choi, Tae Joon; Park, Wanki; Lee, Sang Kook; Oh, Dong-Chan; Oh, Ki-Bong; Shin, Jongheon
2014-02-28
Penicillipyrones A (1) and B (2), two novel meroterpenoids, were isolated from the marine-derived fungus Penicillium sp. On the basis of the results of combined spectroscopic analyses, these compounds were structurally elucidated to be sesquiterpene γ-pyrones from a new skeletal class derived from a unique linkage pattern between the drimane sesquiterpene and pyrone moieties. Compound 2 elicited significant induction of quinone reductase.
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... long time. True False False: This is called contact dermatitis, which is often due to nickel. Question 9 ... dermatitis. True False True: This is called Irritant contact dermatitis which is more common than allergic contact dermatitis. ...
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Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus
Agger, Sean; Lopez-Gallego, Fernando; Schmidt-Dannert, Claudia
2009-01-01
SUMMARY Fungi are a rich source of bioactive secondary metabolites and mushroom-forming fungi (Agaricomycetes) are especially known for the synthesis of numerous bioactive and often cytotoxic sesquiterpenoid secondary metabolites. Compared to the large number of sesquiterpene synthases identified in plants, less than a handful of unique sesquiterpene synthases have been described from fungi. Here we describe the functional characterization of six sesquiterpene synthases (Cop1 to Cop6) and two terpene oxidizing cytochrome P450 monooxygenases (Cox1 and Cox2) from Coprinus cinereus. The genes were cloned and, except for cop5, functionally expressed in Escherichia coli and/or Saccharomyces cerevisiae. Cop1 and Cop2 each synthesize germacrene A as the major product. Cop3 was identified as a α-muurolene synthase, an enzyme that has not been described previously, while Cop4 synthesizes δ-cadinene as its major product. Cop6 was originally annotated as a trichodiene synthase homolog, but instead was found to catalyze highly specific the synthesis of α-cuprenene. Co-expression of cop6 and the two monooxygenase genes next to it yields oxygenated α-cuprenene derivatives, including cuparophenol, suggesting that these genes encode the enzymes for the biosynthesis of antimicrobial quinone sesquiterpenoids (known as lagopodins) that were previously isolated from C. cinereus and other Coprinus species. PMID:19400802
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Caryophyllane sesquiterpenes inhibit DNA-damage by tobacco smoke in bacterial and mammalian cells.
Di Giacomo, Silvia; Abete, Lorena; Cocchiola, Rossana; Mazzanti, Gabriela; Eufemi, Margherita; Di Sotto, Antonella
2018-01-01
In the present study, the ability of the natural sesquiterpene β-caryophyllene (CRY) and its metabolite β-caryophyllene oxide (CRYO) to inhibit the genotoxicity of a condensate of cigarette smoke (CSC) was evaluated both in bacterial and mammalian cells. Also, the inhibition of the CSC-mediated STAT3 phosphorylation and intracellular oxidative stress was evaluated as potential chemopreventive mechanism. Under our experimental conditions, both the sesquiterpenes exhibited antimutagenic properties, being CRY the most potent compound. The antimutagenicity was highlighted in all experimental protocols, being particularly strong in the co- and post-treatments. The test substances also reduced the micronuclei frequency induced by CSC, with a major effectiveness of CRY. CRY was also able to reduce the CSC-mediated increase of the Y705- pSTAT3 levels, in spite of a lacking effect of CRYO. Furthermore, the sesquiterpenes CRY and CRYO displayed a moderate antioxidant activity, with a 25 % and 40 % inhibition of the ROS-levels increased by CSC, respectively. On the basis of these results, CRY seems to be a multi-target chemopreventive agent, although the genoprotective and antioxidant effects of CRYO suggest that both compounds deserve to be deeply investigated for a possible application in the prevention and treatment of different smoke-related ailments. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Li, Jian-Song; Zhang, Hui; Zhang, Shao-Yong; Wang, Hai-Yan; Zhang, Ji; Chen, An-Liang; Wang, Ji-Dong; Xiang, Wen-Sheng
2017-04-01
Two new macrocyclic lactones, 4,25-diethyl-4,25-demethyl-milbemycin β 3 (1) and 27-formaldehyde-milbemycin β 14 (2), were isolated from a genetically engineered strain Streptomyces bingchenggensis BCJ60. Their structures were determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as ESI-MS and comparison with data from the literature. The acaricidal and nematocidal capacities of compounds 1 and 2 were evaluated against Tetranychus cinnabarinus and Bursaphelenchus xylophilus, respectively. The results showed that the two new macrocyclic lactones 1 and 2 possessed potent acaricidal and nematocidal activities.
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Stoma dermatitis: prevalent but often overlooked.
Agarwal, Shilpa; Ehrlich, Alison
2010-01-01
Peristomal dermatoses commonly afflict the area around stoma openings in ostomy patients. These complications, however, are often unreported by patients and remain untreated for years, thus affecting maintenance and recovery from the surgery. These dermatoses can have chemical, mechanical, irritant, bacterial, immunologic, or disease-related etiologies. Examples of common forms of dermatitis that occur peristomally include fecal or urine irritant contact dermatitis, chronic papillomatous dermatitis, mechanical dermatitis, and allergic contact dermatitis. This article summarizes various skin irritations that can occur after an ostomy and also reviews previously published reports of peristomal allergic contact dermatitis. In addition, the clinical importance of identifying these dermatoses (most important, their effects on the patient's quality of life), risk factors for the skin irritations, the importance of patch testing, treatment of stoma dermatitis, and the importance of patient education and patient-doctor communication are also discussed.
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Cohen, Philip R
2014-01-01
Follicular contact dermatitis clinically presents as individual papules that include a central hair follicle. Pathologic features involve the follicle and the surrounding dermis: spongiosis and vesicle formation of the follicular epithelium associated with perifollicular and perivascular lymphocytic inflammation. Using the PubMed database, an extensive literature search was performed on follicular contact dermatitis and neomycin. Relevant papers were reviewed and the clinical and pathologic features, the associated chemicals (including a more detailed description of neomycin), the hypothesized pathogenesis, and the management of follicular contact dermatitis were described. Several agents-either as allergens or irritants-have been reported to elicit follicular contact dermatitis. Several hypotheses have been suggested for the selective involvement of the follicles in follicular contact dermatitis: patient allergenicity, characteristics of the agent, vehicle containing the agent, application of the agent, and external factors. The differential diagnosis of follicular contact dermatitis includes not only recurrent infundibulofolliculitis, but also drug eruption, mite infestation, viral infection, and dermatoses that affect hair follicles. The primary therapeutic intervention for follicular contact dermatitis is withdrawal of the causative agent; treatment with a topical corticosteroid preparation may also promote resolution of the dermatitis. In conclusion, follicular contact dermatitis may be secondary to allergens or irritants; topical antibiotics, including neomycin, may cause this condition. Several factors may account for the selective involvement of the hair follicle in this condition. Treatment of the dermatitis requires withdrawal of the associated topical agent; in addition, topical corticosteroids may be helpful to promote resolution of lesions. PMID:25516854
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Tang, Khanh G; Kent, Greggory T; Erden, Ihsan; Wu, Weiming
2017-10-04
cis -β-Bromostyrene derivatives were synthesized stereospecifically from cinnamic acids through β-lactone intermediates. The synthetic sequence did not require the purification of the β-lactone intermediates although they were found to be stable and readily purified in most cases.
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Schnermann, Martin J; Beaudry, Christopher M; Genung, Nathan E; Canham, Stephen M; Untiedt, Nicholas L; Karanikolas, Breanne D W; Sütterlin, Christine; Overman, Larry E
2011-11-02
The synthesis and direct comparison of the chemical reactivity of the two highly oxidized bicyclic lactone fragments found in rearranged spongian diterpenes (8-substituted 6-acetoxy-2,7-dioxabicyclo[3.2.1]octan-3-one and 6-substituted 7-acetoxy-2,8-dioxabicyclo[3.3.0]octan-3-one) are reported. Details of the first synthesis of the 6-acetoxy-2,7-dioxabicyclo[3.2.1]octan-3-one ring system, including an examination of several possibilities for the key bridging cyclization reaction, are described. In addition, the first synthesis of 7-acetoxy-2,8-dioxabicyclo[3.3.0]octanones containing quaternary carbon substituents at C6 is disclosed. Aspects of the chemical reactivity and Golgi-modifying properties of these bicyclic lactone analogs of rearranged spongian diterpenes are also reported. Under both acidic and basic conditions, 8-substituted 2,7-dioxabicyclo[3.2.1]octanones are converted to 6-substituted-2,8-dioxabicyclo[3.3.0]octanones. Moreover, these dioxabicyclic lactones react with primary amines and lysine side chains of lysozyme to form substituted pyrroles, a conjugation that could be responsible for the unique biological properties of these compounds. These studies demonstrate that acetoxylation adjacent to the lactone carbonyl group, in either the bridged or fused series, is required to produce fragmented Golgi membranes in the pericentriolar region that is characteristic of macfarlandin E.
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Hazards of domestic pets. Ringworm and other skin conditions.
Keep, J M
1977-12-01
Domestic pets may be responsible for a number of skin eruptions in man. Whilst ringworm due to Microsporum canis is one of the most common of these conditions in this country, trichophyton infection, flea bite dermatitis, cheyletiella dermatitis, canine scabies and traumatic dermatitis are by no means rare. Less frequently encountered conditions include creeping eruption, favus, fowl-mite dermatitis and allergic dermatitis.
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Acute radiation dermatitis in breast cancer patients: challenges and solutions
Kole, Adam J; Kole, Lauren; Moran, Meena S
2017-01-01
Nearly all women who receive radiotherapy (RT) for breast cancer experience some degree of radiation dermatitis. However, evidence describing the appropriate management of radiation dermatitis is often lacking or contradictory. Here, we summarize the available literature regarding radiation dermatitis causes, the presentation and timing of symptoms, methods for dermatitis assessment and prevention, and review evidence-based management strategies. PMID:28503074
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Frank, Fernanda M.; Laurella, Laura C.; Muschietti, Liliana V.; Catalán, Cesar A.; Martino, Virginia S.; Malchiodi, Emilio L.
2013-01-01
Among the natural compounds, terpenoids play an important role in the drug discovery process for tropical diseases. The aim of the present work was to isolate antiprotozoal compounds from Ambrosia elatior and A. scabra. The sesquiterpene lactone (STL) cumanin was isolated from A. elatior whereas two other STLs, psilostachyin and cordilin, and one sterol glycoside, daucosterol, were isolated from A. scabra. Cumanin and cordilin were active against Trypanosoma cruzi epimastigotes showing 50% inhibition concentrations (IC50) values of 12 µM and 26 µM, respectively. Moreover, these compounds are active against bloodstrean trypomastigotes, regardless of the T. cruzi strain tested. Psilostachyin and cumanin were also active against amastigote forms with IC50 values of 21 µM and 8 µM, respectively. By contrast, daucosterol showed moderate activity on epimastigotes and trypomastigotes and was inactive against amastigote forms. We also found that cumanin and psilostachyin exhibited an additive effect in their trypanocidal activity when these two drugs were tested together. Cumanin has leishmanicidal activity with growth inhibition values greater than 80% at a concentration of 5 µg/ml (19 µM), against both L. braziliensis and L. amazonensis promastigotes. In an in vivo model of T. cruzi infection, cumanin was more active than benznidazole, producing an 8-fold reduction in parasitemia levels during the acute phase of the infection compared with the control group, and more importantly, a reduction in mortality with 66% of the animals surviving, in comparison with 100% mortality in the control group. Cumanin also showed nontoxic effects at the doses assayed in vivo, as determined using markers of hepatic damage. PMID:24130916
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Jurkiewicz, Anna; Ryszka, Przemyslaw; Anielska, Teresa; Waligórski, Piotr; Białońska, Dobroslawa; Góralska, Katarzyna; Tsimilli-Michael, Merope; Turnau, Katarzyna
2010-06-01
Arnica montana is a rare plant that needs special protection because of its intensive harvesting for medicinal purposes. The present work was aimed at finding optimal culture conditions for Arnica plants in order to enable their successful reintroduction into their natural stands. Plants were cultivated under controlled greenhouse conditions on substrata with different nitrogen (N) concentration. As Arnica is always colonized by arbuscular mycorrhizal fungi (AMF) in nature, a fact that has been overlooked in other similar projects, we, here, applied and tested different inocula. We found that they differed in their effectiveness, both in establishing symbiosis, assessed by the colonization parameters, and in improving the performance of Arnica, evaluated by the photosynthetic parameters derived from the fluorescence transients (JIP-test), with the inocula containing G. intraradices or composed of several Glomus strains being the most effective. The comparison was possible only on substrata with medium N, since high N did not permit the formation of mycorrhiza, while at low N, few nonmycorrhizal plants survived until the measurements and mycorrhizal plants, which were well growing, exhibited a high heterogeneity. Analysis of secondary metabolites showed clearly that mycorrhization was associated with increased concentrations of phenolic acids in roots. For some of the inocula used, a tendency for increase of the level of phenolic acids in shoots and of sesquiterpene lactones, both in roots and in shoots, was also observed. We also studied the interactions between A. montana and Dactylis glomerata, known to compete with Arnica under field conditions. When specimens from both species were cultured together, there was no effect on D. glomerata, but Arnica could retain a photosynthetic performance that permitted survivability only in the presence of AMF; without AMF, the photosynthetic performance was lower, and the plants were eventually totally outcompeted.
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The Physiological Effects of Dandelion (Taraxacum Officinale) in Type 2 Diabetes.
Wirngo, Fonyuy E; Lambert, Max N; Jeppesen, Per B
2016-01-01
The tremendous rise in the economic burden of type 2 diabetes (T2D) has prompted a search for alternative and less expensive medicines. Dandelion offers a compelling profile of bioactive components with potential anti-diabetic properties. The Taraxacum genus from the Asteraceae family is found in the temperate zone of the Northern hemisphere. It is available in several areas around the world. In many countries, it is used as food and in some countries as therapeutics for the control and treatment of T2D. The anti-diabetic properties of dandelion are attributed to bioactive chemical components; these include chicoric acid, taraxasterol (TS), chlorogenic acid, and sesquiterpene lactones. Studies have outlined the useful pharmacological profile of dandelion for the treatment of an array of diseases, although little attention has been paid to the effects of its bioactive components on T2D to date. This review recapitulates previous work on dandelion and its potential for the treatment and prevention of T2D, highlighting its anti-diabetic properties, the structures of its chemical components, and their potential mechanisms of action in T2D. Although initial research appears promising, data on the cellular impact of dandelion are limited, necessitating further work on clonal β-cell lines (INS-1E), α-cell lines, and human skeletal cell lines for better identification of the active components that could be of use in the control and treatment of T2D. In fact, extensive in-vitro, in-vivo, and clinical research is required to investigate further the pharmacological, physiological, and biochemical mechanisms underlying the effects of dandelion-derived compounds on T2D.
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A Latex Metabolite Benefits Plant Fitness under Root Herbivore Attack.
Huber, Meret; Epping, Janina; Schulze Gronover, Christian; Fricke, Julia; Aziz, Zohra; Brillatz, Théo; Swyers, Michael; Köllner, Tobias G; Vogel, Heiko; Hammerbacher, Almuth; Triebwasser-Freese, Daniella; Robert, Christelle A M; Verhoeven, Koen; Preite, Veronica; Gershenzon, Jonathan; Erb, Matthias
2016-01-01
Plants produce large amounts of secondary metabolites in their shoots and roots and store them in specialized secretory structures. Although secondary metabolites and their secretory structures are commonly assumed to have a defensive function, evidence that they benefit plant fitness under herbivore attack is scarce, especially below ground. Here, we tested whether latex secondary metabolites produced by the common dandelion (Taraxacum officinale agg.) decrease the performance of its major native insect root herbivore, the larvae of the common cockchafer (Melolontha melolontha), and benefit plant vegetative and reproductive fitness under M. melolontha attack. Across 17 T. officinale genotypes screened by gas and liquid chromatography, latex concentrations of the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G) were negatively associated with M. melolontha larval growth. Adding purified TA-G to artificial diet at ecologically relevant concentrations reduced larval feeding. Silencing the germacrene A synthase ToGAS1, an enzyme that was identified to catalyze the first committed step of TA-G biosynthesis, resulted in a 90% reduction of TA-G levels and a pronounced increase in M. melolontha feeding. Transgenic, TA-G-deficient lines were preferred by M. melolontha and suffered three times more root biomass reduction than control lines. In a common garden experiment involving over 2,000 T. officinale individuals belonging to 17 different genotypes, high TA-G concentrations were associated with the maintenance of high vegetative and reproductive fitness under M. melolontha attack. Taken together, our study demonstrates that a latex secondary metabolite benefits plants under herbivore attack, a result that provides a mechanistic framework for root herbivore driven natural selection and evolution of plant defenses below ground.
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The Physiological Effects of Dandelion (Taraxacum Officinale) in Type 2 Diabetes
Wirngo, Fonyuy E.; Lambert, Max N.; Jeppesen, Per B.
2016-01-01
The tremendous rise in the economic burden of type 2 diabetes (T2D) has prompted a search for alternative and less expensive medicines. Dandelion offers a compelling profile of bioactive components with potential anti-diabetic properties. The Taraxacum genus from the Asteraceae family is found in the temperate zone of the Northern hemisphere. It is available in several areas around the world. In many countries, it is used as food and in some countries as therapeutics for the control and treatment of T2D. The anti-diabetic properties of dandelion are attributed to bioactive chemical components; these include chicoric acid, taraxasterol (TS), chlorogenic acid, and sesquiterpene lactones. Studies have outlined the useful pharmacological profile of dandelion for the treatment of an array of diseases, although little attention has been paid to the effects of its bioactive components on T2D to date. This review recapitulates previous work on dandelion and its potential for the treatment and prevention of T2D, highlighting its anti-diabetic properties, the structures of its chemical components, and their potential mechanisms of action in T2D. Although initial research appears promising, data on the cellular impact of dandelion are limited, necessitating further work on clonal β-cell lines (INS-1E), α-cell lines, and human skeletal cell lines for better identification of the active components that could be of use in the control and treatment of T2D. In fact, extensive in-vitro, in-vivo, and clinical research is required to investigate further the pharmacological, physiological, and biochemical mechanisms underlying the effects of dandelion-derived compounds on T2D. PMID:28012278
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Lee, Jongkyu; Tae, Nara; Lee, Jung Joon; Kim, Taeho; Lee, Jeong-Hyung
2010-06-25
Inula britannica is a traditional medicinal plant used to treat bronchitis, digestive disorders, and inflammation in Eastern Asia. Here, we identified eupatolide, a sesquiterpene lactone from I. britannica, as an inhibitor of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Eupatolide inhibited the production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) as well as iNOS and COX-2 protein expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Eupatolide dose-dependently decreased the mRNA levels and the promoter activities of COX-2 and iNOS in LPS-stimulated RAW264.7 cells. Moreover, eupatolide significantly suppressed the LPS-induced expression of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) reporter genes. Pretreatment of eupatolide inhibited LPS-induced phosphorylation and degradation of I kappaB alpha, and phosphorylation of RelA/p65 on Ser-536 as well as the activation of mitogen-activated protein kinases (MAPKs) and Akt in LPS-stimulated RAW264.7 cells. Eupatolide induced proteasomal degradation of tumor necrosis factor receptor-associated factor-6 (TRAF6), and subsequently inhibited LPS-induced TRAF6 polyubiquitination. These results suggest that eupatolide blocks LPS-induced COX-2 and iNOS expression at the transcriptional level through inhibiting the signaling pathways such as NF-kappaB and MAPKs via proteasomal degradation of TRAF6. Taken together, eupatolide may be a novel anti-inflammatory agent that induces proteasomal degradation of TRAF6, and a valuable compound for modulating inflammatory conditions. (c) 2010 Elsevier B.V. All rights reserved.
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Desrosiers, Matthew R; Weathers, Pamela J
2016-08-22
Artemisia annua L. produces the antimalarial sesquiterpene lactone, artemisinin (AN), and was traditionally used by the Chinese to treat fever, which was often caused by malaria. To measure effects of plant-based and dietary components on release of artemisinin and flavonoids from A. annua dried leaves (DLA) after simulated digestion. Simulated digestion was performed on DLA in four types of capsules, or in conjunction with protein, and protein-based foods: dry milk, casein, bovine serum albumin, peanuts, peanut butter, Plumpy'nut(®), and A. annua essential oils. Artemisinin and total flavonoids were measured in the liquid phase of the intestinal stage of digestion. After simulated digestion, peanuts and Plumpy'nut(®) lowered AN and flavonoids, respectively, recovered from the liquid digestate fraction. None of the compositions of the tested capsules altered AN or flavonoid release. Surprisingly, bovine serum albumin (BSA) increased both AN and flavonoids recovered from liquid simulated digestate fractions while casein had no effect. AN delivered as DLA was about 4 times more soluble in digestates than AN delivered as pure drug. Addition of a volume of essential oil equivalent to that found in a high essential oil producing A. annua cultivar also significantly increased AN solubility in simulated digestates. These results indicate encapsulating DLA may provide a way to mask the taste of A. annua without altering bioavailability. Similarly, many peanut-based products can be used to mask the flavor with appropriate dosing. Finally, the essential oil fraction of A. annua contributes to the increased AN solubility in DLA after simulated digestion. Our results suggest that use of DLA in the treatment of malaria and other artemisinin-susceptible diseases should be further tested in animals and humans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Radulović, Niko S; Denić, Marija S; Stojanović-Radić, Zorica Z
2014-01-01
Recently, a potent anti-staphylococcal activity of Inula helenium L. (Asteraceae) root essential oil was reported. Also, bioassay guided fractionation of the oil pointed to eudesmane sesquiterpene lactones and a series of unidentified constituents as the main carriers of the observed activity. To identify nine new constituents (long-chain 3-methyl-2-alkanones) from a fraction of this root essential oil with a low minimum inhibitory concentration value (0.8 µg/mL) by employing a synthetic methodology that leads to the formation of a small combinatorial library of these compounds. The identity of these constituents was inferred from mass spectral fragmentation patterns and GC retention data. A library of 3-methyl-2-alkanones (C11 -C19 homologous series) was synthesised in three steps starting from methyl acetoacetate and the corresponding alkyl halides. The synthetic library was also screened for in vitro anti-microbial activity. Gas chromatographic analyses of I. helenium essential oil samples with spiked compounds from the synthesised library corroborated the tentative identifications of the long-chain 3-methyl-2-alkanones. The availability of these anti-microbial compounds from this library made it possible to construct GC/FID calibration curves and determine their content in the plant material: 0.08 - 24.2 mg/100 g of dry roots. The small combinatorial library approach enabled the first unequivocal identification of long-chain 3-methyl-2-alkanones as plant secondary metabolites, and, also, allowed determination of not only a single compound and biological properties, but those of a group of structurally related compounds. Copyright © 2013 John Wiley & Sons, Ltd.
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Response of Sunflower (Helianthus annuus L.) Leaf Surface Defenses to Exogenous Methyl Jasmonate
Rowe, Heather C.; Ro, Dae-kyun; Rieseberg, Loren H.
2012-01-01
Helianthus annuus, the common sunflower, produces a complex array of secondary compounds that are secreted into glandular trichomes, specialized structures found on leaf surfaces and anther appendages of flowers. The primary components of these trichome secretions are sesquiterpene lactones (STL), a diverse class of compounds produced abundantly by the plant family Compositae and believed to contribute to plant defense against herbivory. We treated wild and cultivated H. annuus accessions with exogenous methyl jasmonate, a plant hormone that mediates plant defense against insect herbivores and certain classes of fungal pathogens. The wild sunflower produced a higher density of glandular trichomes on its leaves than the cultivar. Comparison of the profiles of glandular trichome extracts obtained by liquid chromatography–mass spectroscopy (LC-MS) showed that wild and cultivated H. annuus were qualitatively similar in surface chemistry, although differing in the relative size and proportion of various compounds detected. Despite observing consistent transcriptional responses to methyl jasmonate treatment, we detected no significant effect on glandular trichome density or LC-MS profile in cultivated or wild sunflower, with wild sunflower exhibiting a declining trend in overall STL production and foliar glandular trichome density of jasmonate-treated plants. These results suggest that glandular trichomes and associated compounds may act as constitutive defenses or require greater levels of stimulus for induction than the observed transcriptional responses to exogenous jasmonate. Reduced defense investment in domesticated lines is consistent with predicted tradeoffs caused by selection for increased yield; future research will focus on the development of genetic resources to explicitly test the ecological roles of glandular trichomes and associated effects on plant growth and fitness. PMID:22623991
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Response of sunflower (Helianthus annuus L.) leaf surface defenses to exogenous methyl jasmonate.
Rowe, Heather C; Ro, Dae-kyun; Rieseberg, Loren H
2012-01-01
Helianthus annuus, the common sunflower, produces a complex array of secondary compounds that are secreted into glandular trichomes, specialized structures found on leaf surfaces and anther appendages of flowers. The primary components of these trichome secretions are sesquiterpene lactones (STL), a diverse class of compounds produced abundantly by the plant family Compositae and believed to contribute to plant defense against herbivory. We treated wild and cultivated H. annuus accessions with exogenous methyl jasmonate, a plant hormone that mediates plant defense against insect herbivores and certain classes of fungal pathogens. The wild sunflower produced a higher density of glandular trichomes on its leaves than the cultivar. Comparison of the profiles of glandular trichome extracts obtained by liquid chromatography-mass spectroscopy (LC-MS) showed that wild and cultivated H. annuus were qualitatively similar in surface chemistry, although differing in the relative size and proportion of various compounds detected. Despite observing consistent transcriptional responses to methyl jasmonate treatment, we detected no significant effect on glandular trichome density or LC-MS profile in cultivated or wild sunflower, with wild sunflower exhibiting a declining trend in overall STL production and foliar glandular trichome density of jasmonate-treated plants. These results suggest that glandular trichomes and associated compounds may act as constitutive defenses or require greater levels of stimulus for induction than the observed transcriptional responses to exogenous jasmonate. Reduced defense investment in domesticated lines is consistent with predicted tradeoffs caused by selection for increased yield; future research will focus on the development of genetic resources to explicitly test the ecological roles of glandular trichomes and associated effects on plant growth and fitness.
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Aftab, Tariq; Khan, M Masroor A; Idrees, Mohd; Naeem, M; Moinuddin; Hashmi, Nadeem
2011-07-01
Boron is an essential plant micronutrient, but it is phytotoxic if present in excessive amounts in soil for certain plants such as Artemisia annua L. that contains artemisinin (an important antimalarial drug) in its areal parts. Artemisinin is a sesquiterpene lactone with an endoperoxide bridge. It is quite expensive compound because the only commercial source available is A. annua and the compound present in the plant is in very low concentration. Since A. annua is a major source of the antimalarial drug and B stress is a deadly threat to its cultivation, the present research was conducted to determine whether the exogenous application of methyl jasmonate (MeJA) could combat the ill effects of excessive B present in the soil. According to the results obtained, the B toxicity induced oxidative stress and reduced the stem height as well as fresh and dry masses of the plant remarkably. The excessive amounts of soil B also lowered the net photosynthetic rate, stomatal conductance, internal CO(2) concentration and total chlorophyll content in the leaves. In contrast, the foliar application of MeJA enhanced the growth and photosynthetic efficiency both in the stressed and non-stressed plants. The excessive B levels also increased the activities of antioxidant enzymes, such as catalase, peroxidase and superoxide dismutase. Endogenous H(2)O(2) and O(2)(-) levels were also high in the stressed plants. However, the MeJA application to the stressed plants reduced the amount of lipid peroxidation and stimulated the synthesis of antioxidant enzymes, enhancing the content and yield of artemisinin as well. Thus, it was concluded that MeJA might be utilized in mitigating the B toxicity and improving the content and yield of artemisinin in A. annua plant.
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Mohan, Shikha; Gupta, Damodar
2017-05-01
The root of Inula racemosa is known for its antifungal, hypolipdemic and antimicrobial properties in traditional Indian Ayurvedic and Chinese system of medicine. The biological efficacy of Inula species is mainly due to the presence sesquiterpene lactone (Isoalantolactone and Alantolactone), which are reported to be inducers of Nrf2 antioxidant pathway. The investigation of properties and efficacy of root extracts of I. racemosa and their comparison was done with a view to find most efficacious extract for use at cellular level (both normal and transformed). In the present study different extracts of root of I. racemosa (aqueous, ethanolic, and 50% aqueous-ethanolic) were prepared and compared for their antioxidant potential, reducing capacity, polyphenol content and flavonoid content. Our investigations suggested that the aqueous extract possess highest antioxidant capacity and reducing potential. The polyphenol content was found to be highest in aqueous extract in comparison with other two extracts. However, all the three extracts showed less flavonoid content. Further, the preliminary phytochemical screening of all the extracts revealed the presence of terpenoids, phytosterols and glycosides. The TLC profile of ethanolic and 50% aqueous-ethanolic extracts showed the presence of alantolactone while aqueous extracts did not exhibit its strong presence. This warrants the need of more stringent techniques for characterization of aqueous extract in future. The in vitro cell based toxicity assays revealed that the aqueous extract was less toxic to kidneys cells while ethanolic extract was toxic to cells even at low concentrations. Hence, the current investigations showed better efficacy of the aqueous extract with respect to other extracts and found to be promising for its future application at in vitro levels. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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Pouyfung, Phisit; Sarapusit, Songklod; Rongnoparut, Pornpimol
2017-12-01
Vernonia cinerea has been widely used in traditional medicines for various diseases and shown to aid in smoking abstinence and has anticancer properties. V. cinerea bioactive compounds, including flavonoids and hirsutinolide-type sesquiterpene lactones, have shown an inhibition effect on the nicotine-metabolizing cytochrome P450 2A6 (CYP2A6) enzyme and hirsutinolides reported suppressing cancer growth. In this study, V. cinerea ethanol extract and its bioactive compounds, including four flavonoids and four hirsutinolides, were investigated for an inhibitory effect on human liver microsomal CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 using cocktail inhibition assays combined with LC-MS/MS analysis. Among tested flavonoids, chrysoeriol was more potent in inhibition on CYP2A6 and CYP1A2 than other liver CYPs, with better binding efficiency toward CYP2A6 than CYP1A2 (K i values in competitive mode of 1.93 ± 0.05 versus 3.39 ± 0.21 μM, respectively). Hirsutinolides were prominent inhibitors of CYP2A6 and CYP2D6, with IC 50 values of 12-23 and 15-41 μM, respectively. These hirsutinolides demonstrated time-dependent inhibition, an indication of mechanism-based inactivation, toward CYP2A6. Quantitative prediction of microsomal metabolism of these flavonoids and hirsutinolides, including half-lives and hepatic clearance rate, was examined. These findings may have implications for further in vivo studies of V. cinerea. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
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Prasopthum, Aruna; Pouyfung, Phisit; Sarapusit, Songklod; Srisook, Ekaruth; Rongnoparut, Pornpimol
2015-04-01
The human cytochrome P450 2A6 (CYP2A6) and monoamine oxidases (MAO-A and MAO-B), catalyzing nicotine and dopamine metabolisms, respectively, are two therapeutic targets of nicotine dependence. Vernonia cinerea, a medicinal plant commonly used for treatment of diseases such as asthma and bronchitis, has been shown reducing tobacco dependence effect among tobacco users. In the present study, we found eight active compounds isolated from V. cinerea that comprise inhibitory activity toward CYP2A6 and MAO-A and MAO-B enzymes using activity-guided assays, with coumarin as substrate of CYP2A6 and kynuramine of MAOs. These compounds were three flavones (apigenin, chrysoeriol, luteolin), one flavonol (quercetin), and four hirsutinolide-type sesquiterpene lactones (8α-(2-methylacryloyloxy)-hirsutinolide-13-O-acetate, 8α-(4-hydroxymethacryloyloxy)-hirsutinolide-13-O-acetate, 8α-tigloyloxyhirsutinolide-13-O-acetate, and 8α-(4-hydroxytigloyloxy)-hirsutinolide-13-O-acetate). Modes and kinetics of inhibition against the three enzymes were determined. Flavonoids possessed strong inhibitory effect on CYP2A6 in reversible mode, while inhibition by hirsutinolides was mechanism-based (NADPH-, concentration-, and time-dependence) and irreversible. Inhibition by hirsutinolides could not be reversed by dialysis and by addition of trapping agents or potassium ferricyanide. Flavonoids inhibited MAOs with variable degrees and were more prominent in inhibition toward MAO-A than hirsutinolides, while two of hirsutinolides inhibited MAO-B approximately comparable to two flavonoids. These results could have implications in combination of drug therapy for smoking cessation. Copyright © 2014 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.
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Nogueira, Mauro S; Da Costa, Fernando B; Brun, Reto; Kaiser, Marcel; Schmidt, Thomas J
2016-09-15
Aldama discolor (syn.Viguiera discolor) is an endemic Asteraceae from the Brazilian "Cerrado", which has not previously been investigated for its chemical constituents and biological activity. Diterpenes are common secondary metabolites found in Aldama species, some of which have been reported to present potential antiprotozoal and antimicrobial activities. In this study, the known ent-3-α-hydroxy-kaur-16-en-18-ol (1), as well as three new diterpenes, namely, ent-7-oxo-pimara-8,15-diene-18-ol (2), ent-2S,4S-2-19-epoxy-pimara-8(3),15-diene-7β-ol (3) and ent-7-oxo-pimara-8,15-diene-3β-ol (4), were isolated from the dichloromethane extract of A. discolor leaves and identified by means of MS and NMR. The compounds were assayed in vitro against Trypanosoma brucei rhodesiense, T. cruzi and Leishmania donovani, Plasmodium falciparum and also tested for cytotoxicity against mammalian cells (L6 cell line). The ent-kaurane 1 showed significant in vitro activity against both P. falciparum (IC 50 = 3.5 μ M) and L. donovani (IC 50 = 2.5 μ M) and ent-pimarane 2 against P. falciparum (IC 50 = 3.8 μ M). Both compounds returned high selectivity indices (SI >10) in comparison with L6 cells, which makes them interesting candidates for in vivo tests. In addition to the diterpenes, the sesquiterpene lactone budlein A (5), which has been reported to possess a strong anti-T. b. rhodesiense activity, was identified as major compound in the A. discolor extract and explains its high activity against this parasite (100% growth inhibition at 2 μ g/mL).
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Participation of PLA2 and PLC in DhL-induced activation of Rhinella arenarum oocytes.
Zapata-Martínez, J; Medina, M F; Gramajo-Bühler, M C; Sánchez-Toranzo, G
2016-08-01
Rhinella arenarum oocytes can be artificially activated, a process known as parthenogenesis, by a sesquiterpenic lactone of the guaianolide group, dehydroleucodine (DhL). Transient increases in the concentration of cytosolic Ca2+ are essential to trigger egg activation events. In this sense, the 1-4-5 inositol triphosphate receptors (IP3R) seem to be involved in the Ca2+ transient release induced by DhL in this species. We analyzed the involvement of phosphoinositide metabolism, especially the participation of phospholipase A2 (PLA2) and phospholipase C (PLC) in DhL-induced activation. Different doses of quinacrine, aristolochic acid (ATA) (PLA2 inhibitors) or neomycin, an antibiotic that binds to PIP2, thus preventing its hydrolysis, were used in mature Rhinella arenarum oocytes. In order to assay the participation of PI-PLC and PC- PLC we used U73122, a competitive inhibitor of PI-PLC dependent events and D609, an inhibitor of PC-PLC. We found that PLA2 inhibits quinacrine more effectively than ATA. This difference could be explained by the fact that quinacrine is not a specific inhibitor for PLA2 while ATA is specific for this enzyme. With respect to the participation of PLC, a higher decrease in oocyte activation was detected when cells were exposed to neomycin. Inhibition of PC-PLC with D609 and IP-PLC with U73122 indicated that the last PLC has a significant participation in the effect of DhL-induced activation. Results would indicate that DhL induces activation of in vitro matured oocytes of Rhinella arenarum by activation of IP-PLC, which in turn may induce IP3 formation which produces Ca2+ release.
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Effect of dehydroleucodine on meiosis reinitiation in Bufo arenarum denuded oocytes.
Sánchez Toranzo, G; Giordano, O S; López, L A; Bühler, M I
2007-05-01
In amphibian oocytes meiosis, the transition from G2 to M phase is regulated by the maturation promoting factor (MPF), a complex of the cyclin-dependent kinase p34/cdc2 and cyclin B. In immature oocytes there is an inactive complex (pre-MPF), in which cdc2 is phosphorylated on both Thr-161 and Thr-14/Tyr-15 residues. The dephosphorylation of Thr-14/Tyr-15 is necessary for the start of MPF activation and it is induced by the activation of cdc25 phosphatase. Late, to complete the activation, a small amount of active MPF induces an auto-amplification loop of MPF stimulation (MPF amplification). Dehydroleucodine (DhL) is a sesquiterpenic lactone that inhibits mammalian cell proliferation in G2. We asked whether DhL interferes with MPF activation. For this question, the effect of DhL (up to 30 microM) on the resumption of meiosis was evaluated, and visualized by germinal vesicle break down (GVBD), of Bufo arenarum oocytes induced in vitro by either: (i) removing follicle cells; (ii) progesterone stimulation; (iii) VG-content injection; or (iv) injection of mature cytoplasm. The results show that DhL induced GVBD inhibition, in a dose-dependent manner, in spontaneous and progesterone-induced oocyte maturation. Nevertheless, DhL at the doses assayed had no effect on GVBD induced by mature cytoplasm injection, but exerted an inhibitory effect on GVBD induced by GV content. On the basis of these results, we interpreted that DhL does not inhibit MPF amplification and that the target of DhL is any event in the early stages of the cdc25 activation cascade.
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Passoni, Flávia Donaire; Oliveira, Rejane Barbosa; Chagas-Paula, Daniela Aparecida; Gobbo-Neto, Leonardo; Da Costa, Fernando Batista
2013-05-20
Tithonia diversifolia (Hemsl.) A. Gray has been commonly used in folk medicine to treat abscesses, microbiological infections, snake bites, malaria and diabetes. Both anti-inflammatory and anti-malarial properties have been identified using appropriate assays, but the effective doses have demonstrated toxic effects for the experimental animals. Most of the pharmacological activities have been attributed to sesquiterpene lactones (STLs) and some chlorogenic acid derivatives (CAs) in the leaves of this species. This work aimed to evaluate the repeated-dose toxicity of an aqueous extract (AE) from Tithonia diversifolia leaves and to compare the results with an extract rich in STLs (LRE) and a polar extract (PE) without STLs but rich in CAs. The purpose of this work was to provide insights into the identity of the compounds responsible for the toxic effects of Tithonia diversifolia. The major classes of compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling using previously isolated or standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days. The AE is composed of both STLs and CAs, the LRE is rich in STLs, and the PE is rich in CAs. The AE caused alterations in haematological parameters but few alterations in biochemical parameters and was relatively safe at doses lower than 100mg/kg. However, the PE and LRE demonstrated several adverse effects by damaging the liver and kidneys, respectively. STLs and CAs can be toxic in prolonged use at higher doses in extracts prepared from Tithonia diversifolia by affecting the kidneys and liver. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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A Latex Metabolite Benefits Plant Fitness under Root Herbivore Attack
Huber, Meret; Epping, Janina; Schulze Gronover, Christian; Fricke, Julia; Aziz, Zohra; Brillatz, Théo; Swyers, Michael; Köllner, Tobias G.; Vogel, Heiko; Hammerbacher, Almuth; Triebwasser-Freese, Daniella; Robert, Christelle A. M.; Verhoeven, Koen; Preite, Veronica; Gershenzon, Jonathan; Erb, Matthias
2016-01-01
Plants produce large amounts of secondary metabolites in their shoots and roots and store them in specialized secretory structures. Although secondary metabolites and their secretory structures are commonly assumed to have a defensive function, evidence that they benefit plant fitness under herbivore attack is scarce, especially below ground. Here, we tested whether latex secondary metabolites produced by the common dandelion (Taraxacum officinale agg.) decrease the performance of its major native insect root herbivore, the larvae of the common cockchafer (Melolontha melolontha), and benefit plant vegetative and reproductive fitness under M. melolontha attack. Across 17 T. officinale genotypes screened by gas and liquid chromatography, latex concentrations of the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G) were negatively associated with M. melolontha larval growth. Adding purified TA-G to artificial diet at ecologically relevant concentrations reduced larval feeding. Silencing the germacrene A synthase ToGAS1, an enzyme that was identified to catalyze the first committed step of TA-G biosynthesis, resulted in a 90% reduction of TA-G levels and a pronounced increase in M. melolontha feeding. Transgenic, TA-G-deficient lines were preferred by M. melolontha and suffered three times more root biomass reduction than control lines. In a common garden experiment involving over 2,000 T. officinale individuals belonging to 17 different genotypes, high TA-G concentrations were associated with the maintenance of high vegetative and reproductive fitness under M. melolontha attack. Taken together, our study demonstrates that a latex secondary metabolite benefits plants under herbivore attack, a result that provides a mechanistic framework for root herbivore driven natural selection and evolution of plant defenses below ground. PMID:26731567
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Steely, Andrea M; Willoughby, Jamin A; Sundar, Shyam N; Aivaliotis, Vasiliki I; Firestone, Gary L
2017-10-01
Androgen receptor (AR) expression and activity is highly linked to the development and progression of prostate cancer and is a target of therapeutic strategies for this disease. We investigated whether the antimalarial drug artemisinin, which is a sesquiterpene lactone isolated from the sweet wormwood plant Artemisia annua, could alter AR expression and responsiveness in cultured human prostate cancer cell lines. Artemisinin treatment induced the 26S proteasome-mediated degradation of the receptor protein, without altering AR transcript levels, in androgen-responsive LNCaP prostate cancer cells or PC-3 prostate cancer cells expressing exogenous wild-type AR. Furthermore, artemisinin stimulated AR ubiquitination and AR receptor interactions with the E3 ubiquitin ligase MDM2 in LNCaP cells. The artemisinin-induced loss of AR protein prevented androgen-responsive cell proliferation and ablated total AR transcriptional activity. The serine/threonine protein kinase AKT-1 was shown to be highly associated with artemisinin-induced proteasome-mediated degradation of AR protein. Artemisinin treatment activated AKT-1 enzymatic activity, enhanced receptor association with AKT-1, and induced AR serine phosphorylation. Treatment of LNCaP cells with the PI3-kinase inhibitor LY294002, which inhibits the PI3-kinase-dependent activation of AKT-1, prevented the artemisinin-induced AR degradation. Furthermore, in transfected receptor-negative PC-3 cells, artemisinin failed to stimulate the degradation of an altered receptor protein (S215A/S792A) with mutations in its two consensus AKT-1 serine phosphorylation sites. Taken together, our results indicate that artemisinin induces the degradation of AR protein and disrupts androgen responsiveness of human prostate cancer cells, suggesting that this natural compound represents a new potential therapeutic molecule that selectively targets AR levels.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Jang, Byeong-Churl, E-mail: jangbc123@gw.kmu.ac.kr
Differentiation of preadipocyte, also called adipogenesis, leads to the phenotype of mature adipocyte. However, excessive adipogenesis is closely linked to the development of obesity. Artesunate, one of artemisinin-type sesquiterpene lactones from Artemisia annua L., is known for anti-malarial and anti-cancerous activities. In this study, we investigated the effect of artesunate on adipogenesis in 3T3-L1 preadipocytes. Artesunate strongly inhibited lipid accumulation and triglyceride (TG) synthesis during the differentiation of 3T3-L1 preadipocytes into adipocytes at 5 μM concentration. Artesunate at 5 μM also reduced not only the expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A butmore » also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) during adipocyte differentiation. Moreover, artesunate at 5 μM reduced leptin, but not adiponectin, mRNA expression during adipocyte differentiation. Taken together, these findings demonstrate that artesunate inhibits adipogenesis in 3T3-L1 preadipoytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. -- Highlights: •Artesunate, an artemisinin derivative, inhibits adipogenesis. •Artesunate inhibits C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3 in 3T3-L1 adipocytes. •Artesunate reduces leptin, but not adiponectin, expression in 3T3-L1 adipocytes. •Artesunate thus may have therapeutic potential against obesity.« less
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Fonseca, Jorge M; Rushing, James W; Rajapakse, Nihal C; Thomas, Ronald L; Riley, Melissa B
2005-05-01
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.
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González, María Laura; Joray, Mariana Belén; Laiolo, Jerónimo; Crespo, María Inés; Palacios, Sara María; Ruiz, Gustavo Miguel
2018-01-01
Plants are a significant reservoir of cytotoxic agents, including compounds with the ability to interfere with multidrug-resistant (MDR) cells. With the aim of finding promising candidates for chemotherapy, 91 native and naturalized plants collected from the central region of Argentina were screened for their cytotoxic effect toward sensitive and MDR P-glycoprotein (P-gp) overexpressing human leukemia cells by means of MTT assays. The ethanol extracts obtained from Aldama tucumanensis, Ambrosia elatior, Baccharis artemisioides, Baccharis coridifolia, Dimerostemma aspilioides, Gaillardia megapotamica, and Vernonanthura nudiflora presented outstanding antiproliferative activity at 50 μg/mL, with inhibitory values from 93 to 100%, when tested on the acute lymphoblastic leukemia (ALL) cell line CCRF-CEM and the resistant derivative CEM-ADR5000, while 70–90% inhibition was observed against the chronic myelogenous leukemia (CML) cell K562 and its corresponding resistant subline, Lucena 1. Subsequent investigation showed these extracts to possess marked cytotoxicity with IC50 values ranging from 0.37 to 29.44 μg/mL, with most of them being below 7 μg/mL and with ALL cells, including the drug-resistant phenotype, being the most affected. G. megapotamica extract found to be one of the most effective and bioguided fractionation yielded helenalin (1). The sesquiterpene lactone displayed IC50 values of 0.63, 0.19, 0.74, and 0.16 μg/mL against K562, CCRF-CEM, Lucena 1, and CEM/ADR5000, respectively. These results support the potential of these extracts as a source of compounds for treating sensitive and multidrug-resistant leukemia cells and support compound 1 as a lead for developing effective anticancer agents. PMID:29861776
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Repin-induced neurotoxicity in rodents.
Robles, M; Choi, B H; Han, B; Santa Cruz, K; Kim, R C
1998-07-01
Russian knapweed is a perennial weed found in many parts of the world, including southern California. Chronic ingestion of this plant by horses has been reported to cause equine nigropallidal encephalomalacia (ENE), which is associated with a movement disorder simulating Parkinson's disease (PD). Repin, a principal ingredient purified from Russian knapweed, is a sesquiterpene lactone containing an alpha-methylenebutyrolactone moiety and epoxides and is a highly reactive electrophile that can readily undergo conjugation with various biological nucleophiles, such as proteins, DNA, and glutathione (GSH). We show in this study that repin is highly toxic to C57BL/6J mice and Sprague-Dawley rats and acutely induces uncoordinated locomotion associated with postural tremors, hypothermia, and inability to respond to sonic and tactile stimuli. We also show that repin intoxication reduces striatal and hippocampal GSH and increases total striatal dopamine (DA) levels in mice. Striatal microdialysis in rats, however, has demonstrated a significant reduction of extracellular DA levels. These findings, coupled with the absence of any demonstrable change in striatal DOPAC levels, suggest that repin acts by inhibiting DA release, a hypothesis that is further supported by our demonstration that, in cultured PC12 cells, repin inhibits the release of DA without affecting its uptake. We believe, therefore, that inhibition of DA release represents one of the earliest pathogenetic events in ENE, leading eventually to striatal extracellular DA denervation, oxidative stress, and degeneration of nigrostriatal pathways. Since the neurotoxic effects of repin appear to be mediated via oxidative stress, and since repin is a natural product isolated from a plant in our environment that can cause a movement disorder associated with degeneration of nigrostriatal pathways, clarification of the mechanism of repin neurotoxicity may provide new insights into our understanding of the pathogenesis of PD. Copyright 1998 Academic Press.
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Kim, Jae Kwang; Lee, Ji Eun; Jung, Eun Hye; Jung, Ji Yun; Jung, Dae Hwa; Ku, Sae Kwang; Cho, Il Je; Kim, Sang Chan
2018-01-01
Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata (Bunge) Bunge. We investigated the anti-inflammatory effects of HsA and sought to determine its mechanisms of action in macrophages. HsA pretreatment inhibited nitric oxide production, and reduced the expression of iNOS and COX-2 in Toll-like receptor ligand-stimulated RAW 264.7 cells. Additionally, HsA decreased the secretion of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated Kupffer cells as well as in RAW 264.7 cells. HsA inhibited phosphorylation of IKKα/β and degradation of IκBα, resulting in decreased nuclear translocation of nuclear factor-κB (NF-κB) and its transcriptional activity. Moreover, HsA phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2), increased expression levels of antioxidant genes, and attenuated LPS-stimulated H 2 O 2 production. Phosphorylation of p38 and c-Jun N-terminal kinase was required for HsA-mediated Nrf2 phosphorylation. In a D-galactosamine/LPS-induced liver injury model, HsA ameliorated D-galactosamine/LPS-induced hepatocyte degeneration and inflammatory cells infiltration. Moreover, immunohistochemical analyses using nitrotyrosine, 4-hydroxynonenal, and cleaved poly (ADP-ribose) polymerase antibodies revealed that HsA protected the liver from oxidative stress. Furthermore, HsA reduced the numbers of proinflammatory cytokine-positive cells in hepatic tissues. Thus, these results suggest HsA may be a promising natural product to manage inflammation-mediated tissue injuries through inhibition of NF-κB and activation of Nrf2. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Smad4 re-expression increases the sensitivity to parthenolide in colorectal cancer.
Li, Xuemei; Yang, Huike; Ke, Jia; Liu, Baoquan; Lv, Xiaohong; Li, Xinlei; Zhang, Yafang
2017-10-01
Parthenolide (PT), a sesquiterpene lactone extracted from the plant feverfew, has been demonstrated to have anti-inflammatory and anticancer properties. Although PT has been revealed to markedly inhibit colorectal cancer cell proliferation, the inhibitory effects decrease with administration time. These findings revealed that colorectal cancer cells develop resistance to PT. However, the underlying mechanism is unclear. In the present study we observed significantly low expression of Smad4 in 3 PT-resistant cell lines (HCT‑116/PT, HT-29/PT and Caco-2/PT), which were obtained using in vitro concentration gradient-increased induction, but not in their parental cells. In the present study we used the lentiviral‑mediated transfection method to upregulate Smad4 in resistant colorectal cancer cell lines. Flow cytometry assay was used to assess cell apoptosis. Cell migration was detected using a QCM™ 24-well Fluorimetric Cell Migration Assay kit. Our study showed that Smad4 overexpression notably decreased the half maximal inhibitory concentration (IC50) values for PT in the 3 PT-resistant cell lines, and improved the inhibitory effects of PT on cell migration and enhanced apoptosis in vitro as well as suppressed xenografted tumors in a PT-resistant colorectal cancer mouse model. Further study by western blotting into the underlying mechanism demonstrated that Smad4 overexpression suppressed the expression of MDR1 in the resistant cells, and resulted in the accumulation of PT, which in turn promoted the expession of caspase-3 and Bax and inhibited the expression of Bcl-2 and the phosphorylation of NF-κB p65. In short, Smad4 re-expression may be crucial for enhancing the sensitivity and reversing the resistance to PT in PT-resistant colorectal cancer cells.
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Bagnarello, Gina; Hilje, Luko; Bagnarello, Vanessa; Cartín, Victor; Calvo, Marco
2009-12-01
Bemisia tabaci (Gennadius) is a polyphagous, cosmopolitan and worldwide relevant pest, mainly acting as a virus vector on many crops. A sound preventive approach to deal with it would be the application of repellent or deterrent substances hopefully present in tropical plants, which in turn may contribute to take advantage of the remarkable rich Mesoamerican biodiversity. Therefore, extracts of two wild plants belonging to family Asteraceae, titonia (Tithonia diversifolia) and "tora" (Montanoa hibiscifolia), were tested for phagodeterrence to B. tabaci adults. The crude leaf extract of each one, as well as four fractions thereof (hexane, dichlorometane, ethyl acetate, and methanol) were tested under greenhouse conditions; in addition, the extracts were submitted to a phytochemical screening to determine possible metabolites causing phagodeterrence. Both restricted-choice and unrestricted-choice experiments were conducted. In the former ones, each fraction was tested at four doses (0.1, 0.5, 1.0 and 1.5% v/v), which were compared with four control treatments: distilled water, endosulfan, an agricultural oil (Aceite Agricola 81 SC), and the emulsifier Citowett. Tomato plants were sprayed and placed inside sleeve cages, where 50 B. tabaci adults were released. The criterion to appraise phagodeterrence was the number of landed adults on plants at 48h. For the unrestricted-choice experiments, only the two highest doses (1.0 and 1.5%) of the crude extracts of each species were tested, and compared to distilled water and the agricultural oil. The titonia and "tora" crude extracts caused phagodeterrence, and for both plant species the methanol fraction stood out. Results suggest that metabolites causing phagodeterrence are several sesquiterpenic lactones, polyphenolic compounds (flavonoids and tannins) and saponins.
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Costantino, Valeria V; Lobos-Gonzalez, Lorena; Ibañez, Jorge; Fernandez, Dario; Cuello-Carrión, F Darío; Valenzuela, Manuel A; Barbieri, Manuel A; Semino, Silvana N; Jahn, Graciela A; Quest, Andrew F G; Lopez, Luis A
2016-03-01
Malignant melanoma represents the fastest growing public health risk of all cancer types worldwide. Several strategies and anti-cancer drugs have been used in an effort to improve treatments, but the development of resistance to anti-neoplastic drugs remains the major cause of chemotherapy failure in melanomas. Previously, we showed that the sesquiterpene lactone, dehydroleucodine (DhL), promotes the accumulation of DNA damage markers, such as H2AX and 53BP1, in human tumor cells. Also DhL was shown to trigger either cell senescence or apoptosis in a concentration-dependent manner in HeLa and MCF7 cells. Here, we evaluated the effects of DhL on B16F0 mouse melanoma cells in vitro and in a pre-clinical melanoma model. DhL inhibited the proliferation of B16F0 cells by inducing senescence or apoptosis in a concentration-dependent manner. Also, DhL reduced the expression of the cell cycle proteins cyclin D1 and B1 and the inhibitor of apoptosis protein, survivin. In melanomas generated by subcutaneous injection of B16F0 cells into C57/BL6 mice, the treatment with 20 mg DhL /Kg/day in preventive, simultaneous and therapeutic protocols reduced tumor volumes by 70%, 60% and 50%, respectively. DhL treatments reduced the number of proliferating, while increasing the number of senescent and apoptotic tumor cells. To estimate the long-term effects of DhL, a mathematical model was applied to fit experimental data. Extrapolation beyond experimental time points revealed that DhL administration following preventive and therapeutic protocols is predicted to be more effective than simultaneous treatments with DhL in restricting tumor growth. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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Cynaropicrin targets the trypanothione redox system in Trypanosoma brucei.
Zimmermann, Stefanie; Oufir, Mouhssin; Leroux, Alejandro; Krauth-Siegel, R Luise; Becker, Katja; Kaiser, Marcel; Brun, Reto; Hamburger, Matthias; Adams, Michael
2013-11-15
In mice cynaropicrin (CYN) potently inhibits the proliferation of Trypanosoma brucei-the causative agent of Human African Trypanosomiasis-by a so far unknown mechanism. We hypothesized that CYNs α,β-unsaturated methylene moieties act as Michael acceptors for glutathione (GSH) and trypanothione (T(SH)2), the main low molecular mass thiols essential for unique redox metabolism of these parasites. The analysis of this putative mechanism and the effects of CYN on enzymes of the T(SH)2 redox metabolism including trypanothione reductase, trypanothione synthetase, glutathione-S-transferase, and ornithine decarboxylase are shown. A two step extraction protocol with subsequent UPLC-MS/MS analysis was established to quantify intra-cellular CYN, T(SH)2, GSH, as well as GS-CYN and T(S-CYN)2 adducts in intact T. b. rhodesiense cells. Within minutes of exposure to CYN, the cellular GSH and T(SH)2 pools were entirely depleted, and the parasites entered an apoptotic stage and died. CYN also showed inhibition of the ornithine decarboxylase similar to the positive control eflornithine. Significant interactions with the other enzymes involved in the T(SH)2 redox metabolism were not observed. Alongside many other biological activities sesquiterpene lactones including CYN have shown antitrypanosomal effects, which have been postulated to be linked to formation of Michael adducts with cellular nucleophiles. Here the interaction of CYN with biological thiols in a cellular system in general, and with trypanosomal T(SH)2 redox metabolism in particular, thus offering a molecular explanation for the antitrypanosomal activity is demonstrated. At the same time, the study provides a novel extraction and analysis protocol for components of the trypanosomal thiol metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Angel, Lee Pei Lee; Yusof, Mohd Termizi; Ismail, Intan Safinar; Ping, Bonnie Tay Yen; Mohamed Azni, Intan Nur Ainni; Kamarudin, Norman Hj; Sundram, Shamala
2016-11-01
Ganoderma boninense is the causal agent of a devastating disease affecting oil palm in Southeast Asian countries. Basal stem rot (BSR) disease slowly rots the base of palms, which radically reduces productive lifespan of this lucrative crop. Previous reports have indicated the successful use of Trichoderma as biological control agent (BCA) against G. boninense and isolate T. virens 7b was selected based on its initial screening. This study attempts to decipher the mechanisms responsible for the inhibition of G. boninense by identifying and characterizing the chemical compounds as well as the physical mechanisms by T. virens 7b. Hexane extract of the isolate gave 62.60% ± 6.41 inhibition against G. boninense and observation under scanning electron microscope (SEM) detected severe mycelial deformation of the pathogen at the region of inhibition. Similar mycelia deformation of G. boninense was observed with a fungicide treatment, Benlate ® indicating comparable fungicidal effect by T. virens 7b. Fraction 4 and 5 of hexane active fractions through preparative thin layer chromatography (P-TLC) was identified giving the best inhibition of the pathogen. These fractions comprised of ketones, alcohols, aldehydes, lactones, sesquiterpenes, monoterpenes, sulphides, and free fatty acids profiled through gas chromatography mass spectrometry detector (GC/MSD). A novel antifungal compound discovery of phenylethyl alcohol (PEA) by T. virens 7b is reported through this study. T. virens 7b also proved to be an active siderophore producer through chrome azurol S (CAS) agar assay. The study demonstrated the possible mechanisms involved and responsible in the successful inhibition of G. boninense.
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Zheng, Hong; Chen, Yuling; Zhang, Jingze; Wang, Lei; Jin, Zhaoxiang; Huang, Hanhan; Man, Shuli; Gao, Wenyuan
2016-04-25
The aim of the present study was to evaluate the anti-ulcerogenic activity of costunolide (Co) and dehydrocostuslactone (De) on ethanol-induced gastric ulcer in mice and to elucidate the potential mechanisms of the action involved. Mice were pretreated orally with Co (5 or 20 mg/kg), De (5 or 20 mg/kg) and omeprazole (OME, 20 mg/kg) for 7 consecutive days, followed by ulcer induction using absolute ethanol (0.2 mL/20 g body weight). Treatment with Co had a remarkable gastroprotection compared to the ethanol-ulcerated mice that significantly reduced the ulcerative lesion index (ULI) and histopathological damage. Daily intragastric administration of Co exerted a powerful anti-inflammatory activity as evidenced by the suppression of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, as well as increased interleukin (IL)-10. Also, pretreatment with Co effectively inhibited ethanol-induced malondialdehyde (MDA) overproduction, increased the depleted superoxide dismutase (SOD) and promoted gastric mucosa epithelial cell proliferation by up-regulating proliferating cell nuclear antigen (PCNA) expression. Similarly, De had a protective effect on ethanol-induced ulcer, which was dependent on the inhibition of inflammatory cytokines and MDA generation, but independent of IL-10, SOD and PCNA improvement. Conclusively, the results have clearly demonstrated the anti-ulcerogenic potential of Co and De on ethanol-induced gastric ulcer; nevertheless, the gastroprotective activity of Co was superior to De due to more multi-pathway regulation than De. These findings suggested that Co or De could be a new useful natural gastroprotective tool against gastric ulcer, which provided a scientific basis for the gastroprotection of sesquiterpene lactones. Copyright © 2016. Published by Elsevier Ireland Ltd.
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van Haaften, Caroline; Boot, Arnoud; Corver, Willem E; van Eendenburg, Jaap D H; Trimbos, Baptist J M Z; van Wezel, Tom
2015-04-25
Ovarian cancer remains still the leading cause of death of gynecological malignancy, in spite of first-line chemotherapy with cisplatin and paclitaxel. Although initial response is favorably, relapses are common and prognosis for women with advanced disease stays poor. Therefore efficacious approaches are needed. Previously, an anti-cancer agent, EPD exhibited potent cytotoxic effects towards ovarian cancer and not towards normal cells. Cell viability and cell cycle analysis studies were performed with EPD, in combination with cisplatin and/or paclitaxel, using the ovarian carcinoma cell lines: SK-OV-3, OVCAR-3, JC, JC-pl and normal fibroblasts. Cell viability was measured using Presto Blue and cell cycle analysis using a flow cytometer. Apoptosis was measured in JC and JC-pl , using the caspase 3 assay kit. In JC-pl, SK-OV-3 and JC, synergistic interactions between either EPD and cisplatin or EPD and paclitaxel were observed. For the first time the effects of EPD on the cell cycle of ovarian cancer cells and normal cells was studied. EPD and combinations of EPD with cisplatin and/ or paclitaxel showed cell cycle arrest in the G2/M phase. The combination of EPD and cisplatin showed a significant synergistic effect in cell line JC-pl, while EPD with paclitaxel showed synergistic interaction in JC. Additionally, synergistic drug combinations showed increased apoptosis. Our results showed a synergistic effect of EPD and cisplatin in an ovarian drug resistant cell line as well as a synergistic effect of EPD and paclitaxel in two other ovarian cell lines. These results might enhance clinical efficacy, compared to the existing regimen of paclitaxel and cisplatin.
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Chemosensitivity of BRCA1-Mutated Ovarian Cancer Cells and Established Cytotoxic Agents.
van Haaften, Caroline; van Eendenburg, Jaap; Boot, Arnoud; Corver, Willem E; Haans, Lucien; van Wezel, Tom; Trimbos, J Baptist
2017-10-01
Serous adenocarcinomas that arise in patients with inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 are initially well treatable with platinum/paclitaxel. For recurrent disease in patients with BRCA1 or BRCA2 mutations, olaparib treatment is available. To study additional therapeutic regimens, a better understanding of the cellular and molecular mechanisms of the tumors in in vitro models is important. From a high-grade serous ovarian tumor of a BRCA1 mutation carrier, we established 3 distinct cell line subclones, OVCA-TR3.1, -2, and -3. Immunohistochemical characterization, flow cytometric analyses, chemosensitivity, and somatic mutation profiling were performed. The cell lines expressed AE1/AE3, Pax8, WT-1, OC125, estrogen receptor (ER), and p53, comparable to the primary tumor. Synergism could be shown in the combination treatment eremophila-1-(10)-11(13)-dien-12,8β-olide (EPD), with cisplatin, whereas combination with olaparib did not show synergism. Eremophila-1-(10)-11(13)-dien-12,8β-olide, a sesquiterpene lactone, is a novel chemotherapeutic agent. The inherited BRCA1 c.2989_2990dupAA mutation was confirmed in the cell lines. Loss of heterozygosity of BRCA1 was detected in each cell line, as well as a homozygous TP53 c.722C>A mutation. Flow cytometry showed that all cell lines had a distinct DNA index. Three new isogenic ovarian cancer cell lines were developed from a patient with a germ line BRCA1 mutation. Chemosensitivity profiling of the cell lines showed high tolerance for olaparib. Treatment with EPD proved synergistic with cisplatin. The effects of EPD will be further investigated for future clinical efficacy.
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Cressey, Brienne D; Belum, Viswanath R; Scheinman, Pamela; Silvestri, Dianne; McEntee, Nancy; Livingston, Vashti; Lacouture, Mario E; Zippin, Jonathan H
2017-01-01
Peristomal dermatitis is a common complication for the >700 000 patients in the United States with an ostomy. The role of stoma skin care products in peristomal dermatitis is poorly understood. To evaluate stoma skin care products as a cause of peristomal dermatitis. A retrospective chart review of patients with peristomal dermatitis at four academic hospitals from January 2010 to March 2014 was performed. Patient demographics, clinical information and use test and patch test results were documented. Eighteen patients identified as having peristomal dermatitis were tested. Twelve of these had peristomal contact dermatitis. We identified numerous stoma skin care products as triggers of irritant and/or allergic contact dermatitis. The most common stoma skin care product used and/or involved in dermatitis was Cavilon™ No Sting Barrier Film. Our data support a paradigm shift whereby healthcare workers treating patients with peristomal dermatitis, which is currently considered to be a reaction mainly to bodily fluids, must consider those products used to protect the skin as potential triggers for this disease. Therefore, patients with peristomal dermatitis should be tested with their stoma skin care agents to determine the need for removal or change of these products. Additionally, full ingredient labelling by manufacturers would help identify new allergens and irritants. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Triacetic acid lactone production in industrial Saccharomyces yeast strains
USDA-ARS?s Scientific Manuscript database
Triacetic acid lactone (TAL) is a potential platform chemical that can be produced in yeast. To evaluate the potential for industrial yeast strains to produce TAL, the g2ps1 gene encoding 2-pyrone synthase was transformed into thirteen industrial yeast strains of varied genetic background. TAL produ...
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Triacetic acid lactone production from Saccharomyces cerevisiae
USDA-ARS?s Scientific Manuscript database
Triacetic acid lactone (TAL) is a potential platform chemical produced from acetyl-CoA and malonyl-CoA by the Gerbera hybrida 2-pyrone synthase (2PS) gene. Studies are ongoing to optimize production, purification, and chemical modification of TAL, which can be used to create the commercial chemicals...
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SELECTIVE HYDROGENATION OF ANHYDRIDES TO LACTONES UNDER SUPERCRITICAL CARBON DIOXIDE MEDIUM
Selective Hydrogenation of Anhydrides to Lactones Under Supercritical Carbon Dioxide Medium
Endalkachew Sahle-Demessie Unnikrishnan R Pillai
U.S. EPA , 26 W. Martin Luther King Dr. Cincinnati, OH 45268 Phone: 513-569-7739
Fax: 513-569-7677
Abstract:
Hydrogenat... -
Complete prevention of radiation-induced dermatitis using topical adrenergic vasoconstrictors.
Fahl, William E
2016-12-01
Radiation dermatitis is a commonly occurring, painful, side effect of cancer radiotherapy that causes some patients to withdraw from the radiotherapy course. Our goal was to test and optimize topical application of an adrenergic vasoconstrictor to rat skin in a preclinical test to prevent radiation-induced dermatitis. A radiation dermatitis assay was developed in which 17.2 Gy to a 1.5 × 3.0 cm rectangle on the clipped dorsal back of rats yielded Grade 3 radiation dermatitis over the irradiated area 13 days later. Single, topical applications of each of three adrenergic vasoconstrictors, epinephrine, norepinephrine, or phenylephrine, in various vehicle formulations, doses, and application schedules, were tested to determine their efficacy in preventing radiation dermatitis. Each of the three adrenergic agonists conferred 100 % prevention of radiation dermatitis in linear, dose-dependent manners and their EC 50 potencies in preventing radiation dermatitis correlated well with their individual K d association constants for binding to mammalian α-adrenergic receptors. Topical vasoconstrictor application as little as 3-12 min before irradiation gave 80-100 % prevention, respectively, of radiation dermatitis. There was a strong correlation between the extent (0-100 %) of skin blanch present in skin immediately before irradiation and prevention of radiation dermatitis scored 13 days after irradiation. The data presented here demonstrate that topical application of adrenergic vasoconstrictors to rat skin before a large, 17.2 Gy, radiation insult confers 100 % protection against radiation dermatitis and support ongoing clinical trials and commercial development of a vasoconstrictor-based product to prevent radiotherapy-induced dermatitis.
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A dihydro-β-agarofuran sesquiterpene from Maytenus boaria.
Paz, Cristian; von Dossow, Daniela; Tiznado, Victor; Suarez, Sebastián; Cukiernik, Fabio D; Baggio, Ricardo
2017-06-01
The natural compound (1S,4S,5S,6R,7R,8R,9R,10S)-6-acetoxy-4,9,10-trihydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepin-5-yl furan-3-carboxylate, C 22 H 30 O 9 , (I), is a β-agarofuran sesquiterpene isolated from the seeds of Maytenus boaria as part of a study of the secondary metabolites from Chilean flora. The compound presents a central structure formed by a decalin system esterified with acetate at site 1 and furan-3-carboxylate at site 9. The chirality of the skeleton can be described as 1S,4S,5S,6R,7R,8R,9R,10S, which is consistent with that suggested by NMR studies. Unlike previously reported structures of sesquiterpenes containing a pure dihydro-β-agarofuran skeleton, (I) exhibits a three-dimensional hydrogen-bonded network.
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Miao, Ruidong; Wei, Juan; Zhang, Qi; Sajja, Venkateswara; Yang, Jinbo; Wang, Qin
2008-12-01
Bisabolane-type sesquiterpenes are a class of biologically active compounds that has antitumour,antifungal, antibacterial,antioxidant and antivenom properties.We investigated the effect of two new highly oxygenated bisabolane-type sesquiterpenes (HOBS)isolated from Cremanthodium discoideum (C.discoideum) on tumour cells. Our results showed that HOBS induced morphological differentiation and reduced microvilli formation on the cell surface in SMMC-7721 cells.Flow cytometry analysis demonstrated that HOBS could induce cell-cycle arrest in the G1 phase. Moreover,HOBS was able to increase tyrosine-alpha ketoglutarate transaminase activity,decrease alpha- foetoprotein level and gamma-glutamyl transferase activity. In addition,we found that HOBS inhibited the anchorage- independent growth of SMMC-7721 cells in a dose-dependent manner.Taken together,all the above observations indicate that HOBS might be able to normalize malignant SMMC-7721 cells by inhibiting cell proliferation and inducing redifferentiation.
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Kwon, Moonhyuk; Cochrane, Stephen A; Vederas, John C; Ro, Dae-Kyun
2014-12-20
Drimenol, a sesquiterpene alcohol, and its derivatives display diverse bio-activities in nature. However, a drimenol synthase gene has yet to be identified. We identified a new sesquiterpene synthase cDNA (VoTPS3) in valerian plant (Valeriana officinalis). Purification and NMR analyses of the VoTPS3-produced terpene, and characterization of the VoTPS3 enzyme confirmed that VoTPS3 synthesizes (-)-drimenol. In feeding assays, possible reaction intermediates, farnesol and drimenyl diphosphate, could not be converted to drimenol, suggesting that the intermediate remains tightly bound to VoTPS3 during catalysis. A mechanistic consideration of (-)-drimenol synthesis suggests that drimenol synthase is likely to use a protonation-initiated cyclization, which is rare for sesquiterpene synthases. VoTPS3 can be used to produce (-)-drimenol, from which useful drimane-type terpenes can be synthesized. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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London-born black Caribbean children are at increased risk of atopic dermatitis.
Williams, H C; Pembroke, A C; Forsdyke, H; Boodoo, G; Hay, R J; Burney, P G
1995-02-01
Previous reports suggest that atopic dermatitis is more common in black Caribbean children born in the United Kingdom than in white children. It is unclear whether these differences are caused by selection bias or variations in the use of the word "eczema" in the groups studied. Our objective was to explore ethnic group differences in the prevalence of atopic dermatitis in London schoolchildren. A cross-sectional prevalence survey of 693 junior school children in three schools was performed. Atopic dermatitis was defined in three ways: (1) by a dermatologist, (2) by visible flexural dermatitis as recorded by an independent observer, and (3) by a history of flexural dermatitis according to the child's parents. The prevalence of atopic dermatitis according to examination by a dermatologist was 16.3% in black Caribbean children and 8.7% in white children. This increased risk was present for different methods of defining of a atopic dermatitis and persisted after adjustment for potential confounders. London-born black Caribbean children appear to be at an increased risk of having atopic dermatitis.
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Ehrlich, Emily; Bunn, Terry; Kanotra, Sarojini; Fussman, Chris; Rosenman, Kenneth D.
2016-01-01
Background The US employer-based surveillance system for work-related health conditions underestimates the prevalence of work-related dermatitis. Objective The authors sought to utilize information from workers to improve the accuracy of prevalence estimates for work-related dermatitis. Methods Three state health departments included questions in the 2011 Behavioral Risk Factor Surveillance System survey designed to ascertain the prevalence of dermatitis in the working population, as well as healthcare experiences, personal perceptions of work-relatedness, and job changes associated with dermatitis. Results The percentage of working respondents who reported receiving a clinician’s opinion that their dermatitis was work-related was between 3.8% and 10.2%. When patients’ perceptions were considered, the work-related dermatitis prevalence estimate increased to between 12.9% and 17.6%. Conclusions Including patients’ perceptions of work-relatedness produced a larger prevalence estimate for work-related dermatitis than the previously published estimate of 5.6%, which included only those cases of dermatitis attributed to work by healthcare professionals. PMID:24619601
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Milia after allergic contact dermatitis from poison ivy: two cases.
Berk, David R; Hurt, Mark A; Reese, Lester T; Wagner, Laura; Bayliss, Susan J
2010-01-01
Milia have rarely been reported as a complication of severe allergic contact dermatitis. To our knowledge, milia have not previously been associated with poison ivy dermatitis. We present two cases of milia after allergic contact dermatitis to poison ivy.
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Battlefield Acquired Immunogenicity to Metals Affects Orthopedic Implant Outcome
2013-10-01
WJ. Nickel, cobalt and chromium in consumer products: a role in allergic contact dermatitis ? Contact Dermatitis 1993;28:15-25. (13) Cramers M...of 14 (14) Fisher AA. Allergic dermatitis presumably due to metallic foreign bodies containing nickel or cobalt. Current Contact News 1977;19...metals, and a case of allergic contact dermatitis from stainless steel. Contact Dermatitis 1994;31:299-303. (29) Haudrechy P, Foussereau J, Mantout B
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A Rare Case of Oestrogen Dermatitis.
Bourgeault, Emilie; Bujold, Janie; Doucet, Marie-Eve
Oestrogen dermatitis is a rare disorder characterised by cyclical eruptions in association with a woman's menstrual cycle. A 43-year-old woman with an 8-year history of cyclical inguinal dermatitis, with a negative patch test, was tested with intradermal progesterone and oestrogen. Intradermal testing was positive for oestrogen only. In a female patient with cyclical dermatitis, it is important to consider oestrogen or progesterone dermatitis in the differential diagnosis.
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Seborrheic dermatitis: an update.
Bukvić Mokos, Zrinka; Kralj, Martina; Basta-Juzbašić, Aleksandra; Lakoš Jukić, Ines
2012-01-01
Seborrheic dermatitis is a chronic relapsing inflammatory skin disorder clinically characterized by scaling and poorly defined erythematous patches. The prevalence of adult seborrheic dermatitis is estimated at 5%. Although the exact cause of seborrheic dermatitis has yet to be understood, Malassezia yeasts, hormones (androgens), sebum levels and immune response are known to play important roles in its development. Additional factors including drugs, winter temperatures and stress may exacerbate seborrheic dermatitis. A variety of treatment modalities are available, including antifungal agents, topical low-potency steroids and calcineurin inhibitors (immunomodulators). This review summarizes current knowledge on the etiopathogenesis and therapy of adult seborrheic dermatitis.
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Hand dermatitis--differential diagnoses, diagnostics, and treatment options.
Mahler, Vera
2016-01-01
The pathogenesis of hand dermatitis is multifactorial, and includes factors such as genetic predisposition and exposure. A high incidence rate is associated with female gender, contact allergy, atopic dermatitis, and wet work. The most important risk factors for the persistence of hand dermatitis include its extent, contact allergic or atopic etiology, childhood dermatitis, and early onset (before the age of 20). The cost of illness of hand dermatitis corresponds to this seen in moderate to severe psoriasis. The diagnostic workup of hand dermatitis and its differential diagnoses requires a detailed assessment of occupational and recreational exposure. In case of possible work-related triggers, early notification of the accident insurer should be sought (via the dermatologist's report). Exposure to a contact allergen is a contributing factor in one-half of all cases of hand dermatitis. It is therefore imperative that all patients with hand dermatitis persisting for more than three months undergo patch testing. Successful and sustainable treatment of hand dermatitis starts with the proper identification and elimination of individual triggers, including the substitution of identified contact allergens and irritants, as well as optimizing preventive measures. Graded therapy taking the clinical severity into account is essential. Validated instruments may be used to monitor therapeutic efficacy. © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.
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Risk factors and common contact allergens in facial allergic contact dermatitis patients.
Kasemsarn, Pranee; Iamphonrat, Thanawan; Boonchai, Waranya
2016-04-01
Facial dermatitis is commonly encountered in dermatologic practice. It is sometimes difficult to manage because its causative factors may be multiple and difficult to diagnose. This study was designed to identify the characteristics, patch test results, and final diagnoses of facial dermatitis patients who were referred to a contact dermatitis clinic and to identify factors associated with facial allergic contact dermatitis (ACD). We retrospectively reviewed case records of facial dermatitis patients who underwent patch testing at the clinic during the period from July 2006 to June 2011. Of the 891 patients patch-tested, 244 (27.4%) had facial dermatitis. Female patients were 9.1 times more predominant than male patients. The mean ± standard deviation age of patients was 37.3 ± 14.8 years. A total of 199 (81.6%) patients demonstrated at least one positive reaction to a patch test, 66.7% of which were clinically relevant. Allergic contact dermatitis was diagnosed in 45.5% of patients. Independent factors predisposing towards facial dermatitis were female sex, having a previous history of cosmetic allergy, a positive patch test reaction to hairdressing product-related allergens, and a positive allergic reaction to preservative allergens. The prevalence of facial dermatitis was 27.4%. Almost half of all patients with facial dermatitis demonstrated ACD. Factors associated with facial ACD were female gender, a history of cosmetic allergy, and positive patch test reactions to hairdressing product-related allergens and preservatives. © 2015 The International Society of Dermatology.
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NASA Astrophysics Data System (ADS)
Kim, Manjae; Kim, Sewoong; Hwang, Minjoo; Kim, Jihun; Je, Minkyu; Jang, Jae Eun; Lee, Dong Hun; Hwang, Jae Youn
2017-02-01
To date, the incident rates of various skin diseases have increased due to hereditary and environmental factors including stress, irregular diet, pollution, etc. Among these skin diseases, seborrheic dermatitis and psoriasis are a chronic/relapsing dermatitis involving infection and temporary alopecia. However, they typically exhibit similar symptoms, thus resulting in difficulty in discrimination between them. To prevent their associated complications and appropriate treatments for them, it is crucial to discriminate between seborrheic dermatitis and psoriasis with high specificity and sensitivity and further continuously/quantitatively to monitor the skin lesions during their treatment at other locations besides a hospital. Thus, we here demonstrate a mobile multispectral imaging system connected to a smartphone for selfdiagnosis of seborrheic dermatitis and further discrimination between seborrheic dermatitis and psoriasis on the scalp, which is the more challenging case. Using the system developed, multispectral imaging and analysis of seborrheic dermatitis and psoriasis on the scalp was carried out. It was here found that the spectral signatures of seborrheic dermatitis and psoriasis were discernable and thus seborrheic dermatitis on the scalp could be distinguished from psoriasis by using the system. In particular, the smartphone-based multispectral imaging and analysis moreover offered better discrimination between seborrheic dermatitis and psoriasis than the RGB imaging and analysis. These results suggested that the multispectral imaging system based on a smartphone has the potential for self-diagnosis of seborrheic dermatitis with high portability and specificity.
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USDA-ARS?s Scientific Manuscript database
In this study, we synthesized sophorolipids (SLs) from glucose and either palmitic, stearic or oleic acid via fermentation using the osmophilic yeast Starmerella bombicola, purified and separated the SLs into lactonic and free-acid forms and assessed their antimicrobial efficacy against 5 strains of...
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Sun, Yongquan; Yu, Binxun; Wang, Xiaolei; Tang, Shibing; She, Xuegong; Pan, Xinfu
2010-06-18
The highly stereoselective syntheses of four diastereomers of natural 3,9,12-trihydroxycalamenene are described. The syntheses highlight the utility of an unusual framework of benzobicyclo[3.3.1] lactones, which were accomplished via an intramolecular Friedel-Crafts-type Michael addition of alpha,beta-unsaturated lactones.
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Toth, I K; Newton, J A; Hyman, L J; Lees, A K; Daykin, M; Ortori, C; Williams, P; Fray, R G
2004-08-01
Many gram-negative bacteria employ N-acylhomoserine lactones (AHL) to regulate diverse physiological processes in concert with cell population density (quorum sensing [QS]). In the plant pathogen Erwinia carotovora, the AHL synthesized via the carI/expI genes are responsible for regulating the production of secreted plant cell wall-degrading exoenzymes and the antibiotic carbapen-3-em carboxylic acid. We have previously shown that targeting the product of an AHL synthase gene (yenI) from Yersinia enterocolitica to the chloroplasts of transgenic tobacco plants caused the synthesis in planta of the cognate AHL signaling molecules N-(3-oxohexanoyl)-L-homoserine lactone (3-oxo-C6-HSL) and N-hexanoylhomoserine lactone (C6-HSL), which in turn, were able to complement a carI-QS mutant. In the present study, we demonstrate that transgenic potato plants containing the yenI gene are also able to express AHL and that the presence and level of these AHL in the plant increases susceptibility to infection by E. carotovora. Susceptibility is further affected by both the bacterial level and the plant tissue under investigation.
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Xia, Xi; Li, Xiaowei; Ding, Shuangyang; Zhang, Suxia; Jiang, Haiyang; Li, Jiancheng; Shen, Jianzhong
2009-03-20
This work reports a rapid, reliable and sensitive multi-residue method for the simultaneous determination of six resorcylic acid lactones in bovine milk by ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The resorcylic acid lactones were extracted, purified, and concentrated from milk samples in one step using a solid-phase extraction (SPE) cartridge that contained a polymeric mixed-mode anion-exchange sorbent. The analysis was performed on a Waters Acquity BEH C(18) column utilizing a gradient elution profile. Each LC run was completed in 3.5 min. The analytes were detected by multiple reaction monitoring (MRM) using electrospray ionization (ESI) negative mode. Mean recoveries from fortified samples ranged from 92.6% to 112.5%, with relative standard deviations lower than 11.4%. Using 5 mL bovine milk, the limits of detection and quantification for resorcylic acid lactones were in the ranges of 0.01-0.05 and 0.05-0.2 microg/L, respectively. The application of this newly developed method was demonstrated by analyzing bovine milk samples from markets.
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[Determination of terpene lactones in Ginkgo biloba leaves in different ages by UPLC-TQ-MS].
Yao, Xin; Zhou, Gui-Sheng; Tang, Yu-Ping; Qian, Ye-Fei; Shang, Er-Xin; Su, Shu-Lan; Qian, Da-Wei; Duan, Jin-Ao
2013-02-01
To establish an ultra-high performance liquid chromatography coupled with triple quadrupole mass (UPLC-TQ-MS) for determination of four terpene lactones. Chromatographic separation was carried out on a ACQUITY UPLC BEH C18 column (2.1 mm x 100 mm, 1.7 microm) with isocratic elution of 70% methanol at a flow rate of 0.4 mL x min(-1), the column temperature was set at 30 degrees C; Waters Xevo TQ worked in multiple reaction monitoring mode. All calibration curves were linear (r > 0.990 3) over the tested ranges. The average recoveries ranged from 98.83% to 103.9% with RSD value below 3.0%. The contents of total terpene lactones in Ginkgo biloba leaves were significantly different in different ages. The contents in the leaves of young ginkgo tree were higher than that in old tree. The method was simple and fast with high precision, sensitivity and repeatability, which can be used for qualitative and quantitative analysis of terpene lactones in G. biloba leaves.
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Quorum Sensing Activity of Serratia fonticola Strain RB-25 Isolated from an Ex-landfill Site
Ee, Robson; Lim, Yan-Lue; Tee, Kok-Keng; Yin, Wai-Fong; Chan, Kok-Gan
2014-01-01
Quorum sensing is a unique bacterial communication system which permits bacteria to synchronize their behaviour in accordance with the population density. The operation of this communication network involves the use of diffusible autoinducer molecules, termed N-acylhomoserine lactones (AHLs). Serratia spp. are well known for their use of quorum sensing to regulate the expression of various genes. In this study, we aimed to characterized the AHL production of a bacterium designated as strain RB-25 isolated from a former domestic waste landfill site. It was identified as Serratia fonticola using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry analysis and this was confirmed by 16S ribosomal DNA sequencing. High resolution triple quadrupole liquid chromatography-mass spectrometry analysis of S. fonticola strain RB-25 spent culture supernatant indicated the existence of three AHLs namely: N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL) and N-(3-oxohexanoyl) homoserine-lactone (3-oxo-C6 HSL). This is the first report of the production of these AHLs in S. fonticola. PMID:24625739
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Allergic contact dermatitis from color film developers: clinical and histologic features.
Brancaccio, R R; Cockerell, C J; Belsito, D; Ostreicher, R
1993-05-01
We evaluated two patients with allergic contact dermatitis that resulted from exposure to color film developers. A lichenoid eruption developed in one patient, whereas an eruption more characteristic of an acute spongiotic dermatitis developed in the second patient. Histologic findings in the first case were those of a "lichenoid dermatitis" but with features distinct from classic lichen planus. The biopsy specimens from the second patient showed a subacute spongiotic process with a bandlike infiltrate suggestive of an evolving lichenoid process. Contact allergy to color developers may result in eruptions similar to lichen planus. This process appears to evolve from an acute spongiotic dermatitis in its early phase to a lichenoid dermatitis in fully developed and more chronic forms. Although the histologic features are those of a "lichenoid" dermatitis, some features, such as the presence of spongiosis, eosinophils, and a less intense inflammatory infiltrate, may enable distinction between lichenoid allergic contact dermatitis and true lichen planus. In addition, clinicopathologic correlation with patch test results should permit accurate diagnosis in most cases.
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O'Neill, Jenna L; Chan, Yiong Huak; Rapp, Stephen R; Yosipovitch, Gil
2011-09-01
Differences in itch characteristics between different inflammatory dermatoses are not well described. The aim of this study was to assess differences in itch characteristics between patients with psoriasis and atopic dermatitis using a previously validated web-based questionnaire that was made available through the National Psoriasis Foundation and National Eczema Association for Science and Education websites. Participants rated frequency and intensity of itch, associated symptoms, itch descriptors, and effect of scratching. A total of 524 subjects with atopic dermatitis and 195 subjects with psoriasis completed the survey. Atopic dermatitis responders experienced more frequent and more intense itch. Associated sweating and heat sensation were also more common in atopic dermatitis. Scratching was considered pleasurable in both atopic dermatitis and psoriasis; pleasurability correlated weakly with itch intensity in atopic dermatitis. Psoriasis respondents reported higher embarrassment associated with itch. Itch sensation is experienced differently among patients with atopic dermatitis and psoriasis. Future therapeutic interventions may be developed to target these differences.
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Timmerman, Johan G; Heederik, Dick; Spee, Ton; van Rooy, Frits G; Krop, Esmeralda J M; Rustemeyer, Thomas; Smit, Lidwien A M
2017-10-01
A high contact dermatitis symptoms prevalence has been observed in Dutch construction workers. Contact dermatitis was diagnosed by an expert panel using questionnaire data and photographs of 751 subjects' hands. A subset was evaluated by two occupational physicians. Their diagnoses were compared to those of the expert panel. In addition, two self-reported questionnaire-based assessment methods were compared to the expert panel evaluation. Associations between contact dermatitis and determinants were assessed using log-binomial regression analysis. Contact dermatitis prevalence was high: 61.4% (expert panel's diagnosis) and 32.9% (self-reported). Agreement between occupational physicians and the expert panel was low but increased after training. Washing hands with solvents and performing job-related tasks at home were related to contact dermatitis. Contact dermatitis prevalence among construction workers is high. Recognition of contact dermatitis by occupational physicians is poor but can be improved by training. Awareness of skin disorders should be raised. © 2017 Wiley Periodicals, Inc.
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Elistratova, I V; Morozov, S G; Zakharova, I A; Tarasova, M V
2015-01-01
Aim of this work was to record the luminol-dependent spontaneous and induced chemiluminescence at the different stages of atopic dermatitis. Peripheral blood cells were obtained from adult patient with atopic dermatitis followed by the registration of luminol-dependent chemiluminescence on luminograph. Opsonized zymosan as well as yeasts Candida tropicalis have been used to induce the chemiluminescence. Spontaneous and induced chemiluminescence were slightly elevated at the mild atopic dermatitis but were decreased at the severe stage of disease. Statistically significant difference has been found between group with mild and severe atopic dermatitis, Skin contamination by yeasts Candida tropicalis causes the increased level of blood cells chemiluminescence at the first week of atopic relapse when the disease was mild. Severe stage of atopic dermatitis was coupled with statistically significant inhibition of both, spontaneous and induced chemiluminescence. Luminol-dependent chemiluminescence of peripheral blood cells from adult atopic dermatitis patients may be stimulated at the mild stage and suppressed at severe stage of atopic dermatitis.
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Cohen, L M; Cohen, J L
1998-09-01
Erythema multiforme (EM) is a hypersensitivity reaction that occurs mainly after exposure to certain medications or in the setting of infection, most commonly that due to herpes simplex virus. Rare cases of EM have been reported after allergic contact dermatitis due to various substances. There has been one case in the literature of EM following Rhus contact dermatitis. We report three patients who developed EM after allergic contact dermatitis due to poison ivy. In all three patients, targetoid lesions developed primarily on the palms and soles, either after a brief course of prednisone or during its taper. Two of the patients have had more than one episode of EM after poison ivy dermatitis. Although EM has been described after allergic contact dermatitis due to a variety of antigens (nickel being the most common), there is only one report in the literature of EM following Rhus contact dermatitis. Given the prevalence of allergic contact dermatitis due to poison ivy, this may be an under-reported complication.
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Grimalt, F; Romaguera, C; Vilaplana, J; Mascaro, J
1988-01-01
There are three types of hand dermatitis in housewives. The most usual are cured when housework is stopped. Another type is that of housewife contact dermatitis which appears on pre-existing endogenous lesions such as dyshidrosis or nummular eczema. The third form is housewife hand contact dermatitis which appears, or coexists with, localized endogenous lesions of the hands. The last two forms are not cured when housework is stopped. In some cases the three forms may coexist or appear one after another. It is not usual for a person suffering from typical flexural atopic dermatitis to present with one of the described three forms of hand dermatitis. Nevertheless, without having some relationship to atopic diathesis no woman could suffer from any of these three forms of dermatitis. In spite of the lack of analytical data, everyday clinical facts (one example being these different forms of housewife hand dermatitis) suggest the need to accept a subgroup of cutaneous atopic diathesis.
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Huang, Xinqi; Gao, Yan; Ma, Zhiping; Lin, Guanghui; Cai, Zhonghua; Zhou, Jin
2017-01-01
Marine algae provide a unique niche termed the phycosphere for microorganism inhabitation. The phycosphere environment is an important niche for mutualistic and competitive interactions between algae and bacteria. Quorum sensing (QS) serves as a gene regulatory system in the microbial biosphere that allows bacteria to sense the population density with signaling molecules, such as acyl-homoserine lactone (AHL), and adapt their physiological activities to their surroundings. Understanding the QS system is important to elucidate the interactions between algal-associated microbial communities in the phycosphere condition. In this study, we isolated an epidermal bacterium (ST2) from the marine dinoflagellate Scrippsiella trochoidea and evaluated its AHL production profile. Strain ST2 was classified as a member of the genus Citrobacter closely related to Citrobacter freundii by 16S rRNA gene sequence analysis. Thin-layer chromatography revealed that C. freundii ST2 secreted three active AHL compounds into the culture supernatant. Specific compounds, such as N-butyryl-L-homoserine lactone (C4-AHL), N-octanoyl-DL-homoserine lactone (C8-AHL), and N-decanoyl-DL-homoserine lactone (C10-AHL), were identified by high-resolution tandem mass spectrometry. Carbon metabolic profiling with Biolog EcoPlate™ indicated that C. freundii ST2 was widely used as a carbon source and preferred carbohydrates, amino acids, and carboxylic acids as carbon substrates. Our results demonstrated that C. freundii ST2 is a multi-AHL producer that participates in the phycosphere carbon cycle.
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A grapevine cytochrome P450 generates the precursor of wine lactone, a key odorant in wine.
Ilc, Tina; Halter, David; Miesch, Laurence; Lauvoisard, Florian; Kriegshauser, Lucie; Ilg, Andrea; Baltenweck, Raymonde; Hugueney, Philippe; Werck-Reichhart, Danièle; Duchêne, Eric; Navrot, Nicolas
2017-01-01
Monoterpenes are important constituents of the aromas of food and beverages, including wine. Among monoterpenes in wines, wine lactone has the most potent odor. It was proposed to form via acid-catalyzed cyclization of (E)-8-carboxylinalool during wine maturation. It only reaches very low concentrations in wine but its extremely low odor detection threshold makes it an important aroma compound. Using LC-MS/MS, we show here that the (E)-8-carboxylinalool content in wines correlates with their wine lactone content and estimate the kinetic constant for the very slow formation of wine lactone from (E)-8-carboxylinalool. We show that (E)-8-carboxylinalool is accumulated as a glycoside in grape (Vitis vinifera) berries and that one of the cytochrome P450 enzymes most highly expressed in maturing berries, CYP76F14, efficiently oxidizes linalool to (E)-8-carboxylinalool. Our analysis of (E)-8-carboxylinalool in Riesling × Gewurztraminer grapevine progeny established that the CYP76F14 gene co-locates with a quantitative trait locus for (E)-8-carboxylinalool content in grape berries. Our data support the role of CYP76F14 as the major (E)-8-carboxylinalool synthase in grape berries and the role of (E)-8-carboxylinalool as a precursor to wine lactone in wine, providing new insights into wine and grape aroma metabolism, and new methods for food and aroma research and production. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.
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Two lactones in the androconial scent of the lycaenid butterfly Celastrina argiolus ladonides
NASA Astrophysics Data System (ADS)
Ômura, Hisashi; Yakumaru, Kazuhisa; Honda, Keiichi; Itoh, Takao
2013-04-01
Male adult butterflies of many species have characteristic odors originating from the disseminating organs known as androconia. Despite the fact that androconia exist in several species, there have been few investigations on adult scents from the lycaenid species. Celastrina argiolus ladonides (Lycaenidae) is a common species in Eurasia. We have reported that male adults of this species emit a faint odor, and the major components causing this odor have been newly found in the Insecta. By using field-caught individuals, we determined the chemical nature and location of this odor in the butterfly. Gas chromatography-mass spectrometry (GC-MS) analyses revealed that two lactone compounds, lavender lactone and δ-decalactone, are present in the extracts of males but absent in those of the females. On an average, approximately 50 ng of each compound was found per male. Chiral GC analyses performed using enantiomerically pure standards revealed that the natural lavender lactone was a mixture of two enantiomers with an R/ S ratio of 32:68, whereas the natural δ-decalactone contained only the R-enantiomer. When the analyses were conducted using different parts—forewings, hindwings, and body—of three males, the lactones were more abundantly found on the forewings and hindwings than on the body. Microscopic observation of the wings demonstrated that battledore scales known as androconia are scattered on the upper surface of both the wings of C. argiolus ladonides males. These results indicate that the specialized scales on the wings of males serve as scent-disseminating organs.
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Yakabi, Keiko; Mathieux, Thibault; Milne, Kirstie; López‐Vidal, Eva M.; Buchard, Antoine
2017-01-01
Abstract The Baeyer–Villiger oxidation is a key transformation for sustainable chemical synthesis, especially when H2O2 and solid materials are employed as oxidant and catalyst, respectively. 4‐substituted cycloketones, which are readily available from renewables, present excellent platforms for Baeyer–Villiger upgrading. Such substrates exhibit substantially higher levels of activity and produce lactones at higher levels of lactone selectivity at all values of substrate conversion, relative to non‐substituted cyclohexanone. For 4‐isopropyl cyclohexanone, which is readily available from β‐pinene, continuous upgrading was evaluated in a plug‐flow reactor. Excellent selectivity (85 % at 65 % conversion), stability, and productivity were observed over 56 h, with over 1000 turnovers (mol product per mol Sn) being achieved with no loss of activity. A maximum space–time yield that was almost twice that for non‐substituted cyclohexanone was also obtained for this substrate [1173 vs. 607 g(product) kg(catalyst)−1 cm−3 h−1]. The lactone produced is also shown to be of suitable quality for ring opening polymerization. In addition to demonstrating the viability of the Sn‐β/H2O2 system to produce renewable lactone monomers suitable for polymer applications, the substituted alkyl cyclohexanones studied also help to elucidate steric, electronic, and thermodynamic elements of this transformation in greater detail than previously achieved. PMID:28804968
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Kaneda, N; Lee, I S; Gupta, M P; Soejarto, D D; Kinghorn, A D
1992-08-01
From the leaves and flowers of Lippia dulcis collected in Panama, a new sweet sesquiterpene identified as (+)-4 beta-hydroxyhernandulcin [2] was isolated, accompanied by (+)-hernandulcin [1], (-)-epihernandulcin [3] (a novel natural product), and 6-methyl-5-hepten-2-one [4]. Acteoside (verbascoside) [5], a known bitter phenylpropanoid glycoside, was isolated from the flowers of L. dulcis. The structure of (+)-4 beta-hydroxyhernandulcin was established by interpretation of its spectral data.
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Quantification of Terpenes by 1DGC-MS and 2DGC-TOF-MS
NASA Astrophysics Data System (ADS)
Flores, R. M.; Perlinger, J. A.; Doskey, P. V.
2009-12-01
Biogenic emissions are the primary source of volatile organic compounds in the global troposphere. Deciduous and coniferous forests are the principal emitters of a complex mixture of isoprene (C5H8), monoterpenes (C10H16), and sesquiterpenes (C15H24). Sesquiterpenes are readily oxidized in the atmosphere producing secondary organic aerosols (SOA) with 100% yields. The SOA are hydrophilic and scatter light, and thus, increase albedo and lead to a cooling effect. In addition, both monoterpene and sesquiterpene generated SOA are effective cloud condensation nuclei leading to an increase in the particle number concentration and to the formation of clouds that also increase albedo. To quantify the complex mixture of terpenes and their oxidation products requires development of on-line extraction and comprehensive two-dimensional gas chromatographic techniques. One objective of this work was to compare one-dimensional gas chromatography-mass spectrometry (1DGC-MS) and two-dimensional gas chromatography time-of-flight mass spectrometry (2DGC-TOFMS) for quantifying eight monoterpenes (alpha- and beta-pinene, limonene, 3-carene, linalool, terpinolene, myrcene and ocimene) and eight sesquiterpenes (beta-caryophyllene, humulene, alpha-cedrene, cis-nerolidol, trans-nerolidol, cedrol, camphene and farnesene) in air samples collected in Northern Michigan. Future research involves coupling thermal desorption and supercritical fluid extraction devices to a GC×2GC for routine quantification of the complex mixture of terpenes and their oxidation products in rural and urban air.
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Essential-Oil Variability in Natural Populations of Pinus mugo Turra from the Julian Alps.
Bojović, Srdjan; Jurc, Maja; Ristić, Mihailo; Popović, Zorica; Matić, Rada; Vidaković, Vera; Stefanović, Milena; Jurc, Dušan
2016-02-01
The composition and variability of the terpenes and their derivatives isolated from the needles of a representative pool of 114 adult trees originating from four natural populations of dwarf mountain pine (Pinus mugo Turra) from the Julian Alps were investigated by GC-FID and GC/MS analyses. In total, 54 of the 57 detected essential-oil components were identified. Among the different compound classes present in the essential oils, the chief constituents belonged to the monoterpenes, comprising an average content of 79.67% of the total oil composition (74.80% of monoterpene hydrocarbons and 4.87% of oxygenated monoterpenes). Sesquiterpenes were present in smaller amounts (average content of 19.02%), out of which 16.39% were sesquiterpene hydrocarbons and 2.62% oxygenated sesquiterpenes. The most abundant components in the needle essential oils were the monoterpenes δ-car-3-ene, β-phellandrene, α-pinene, β-myrcene, and β-pinene and the sesquiterpene β-caryophyllene. From the total data set of 57 detected compounds, 40 were selected for principal-component analysis (PCA), discriminant analysis (DA), and cluster analysis (CA). The overlap tendency of the four populations suggested by PCA, was as well observed by DA. CA also demonstrated similarity among the populations, which was the highest between Populations I and II. Copyright © 2016 Verlag Helvetica Chimica Acta AG, Zürich.
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Identification and Functional Characterization of Sesquiterpene Synthases from Xanthium strumarium.
Li, Yuanjun; Chen, Fangfang; Li, Zhenqiu; Li, Changfu; Zhang, Yansheng
2016-03-01
Xanthium strumarium synthesizes various pharmacologically active sesquiterpenes. The molecular characterization of sesquiterpene biosynthesis in X. strumarium has not been reported so far. In this study, the cDNAs coding for three sesquiterpene synthases (designated as XsTPS1, XsTPS2 and XsTPS3) were isolated using the X. strumarium transcriptome that we recently constructed. XsTPS1, XsTPS2 and XsTPS3 were revealed to have primary activities forming germacrene D, guaia-4,6-diene and germacrene A, respectively, by either ectopic expression in yeast cells or purified recombinant protein-based in vitro assays. Quantitative real-time PCRs and metabolite analysis for the different plant parts showed that the transcript abundance of XsTPS1-XsTPS3 is consistent with the accumulation pattern of their enzymatic products, supporting their biochemical functions in vivo. In particular, we discovered that none of the XsTPS2 product, guaia-4,6-diene, can be detected in one of the X. strumarium cultivars used in this study (it was named the Hubei-cultivar), in which a natural deletion of two A bases in the XsTPS2 cDNA disrupts its activity, which further confirmed the proposed biochemical role of XsTPS2 in X. strumarium in vivo. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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Essential oil composition from two species of Piperaceae family grown in Colombia.
Pino Benitez, Nayive; Meléndez León, Erika M; Stashenko, Elena E
2009-10-01
Essential oil compositions of aerial parts from two species in the Piper (Piperaceae family) genera: Piper lanceaefolium Kunth and Piper hispidum Sw., frequently called deflated (for the anti-inflammatory activity) or cord. Piperaceae leaves were collected in different regions of the Chocó department in northwestern Colombia and identified by botanists from Colombian National Herbarium, where a voucher of each specimen were deposited (No- COL 519993 and No- COL 519969, respectively). The essential oils were obtained by microwave-assisted hydrodistillation (MWHD) and analyzed by gas chromatography-mass spectrometry (GC-MS). The P. lanceaefolium essential oil was sesquiterpenoid type (71.7%). This composition was represented by sesquiterpenes hydrocarbons (58.5%) and by their oxygenated derivates (13.2%); the main compounds were, trans-beta-caryophyllene (11.6%) and germacrene D (10.7%) followed by alpha-selinene (7.8%), beta-pinene (5.4%), beta-selinene (4.8%), and alpha-cubebene (4.3%). The Piper hispidum essential oil also was sesquiterpene type (74.4%) and oxygenated sesquiterpenes (46.4%) followed by sesquiterpenes hydrocarbons (28.0%). The main compounds were trans-nerolidol (23.6%) and caryophyllene oxide (5.4%) followed by beta-elemene (5.1%), trans-beta-caryophyllene (5.1%), curzerene (4.9%), and germacrene B (4.5%). Trans-beta-caryophyllene presents the higher percentage of the common compounds in the two species' essential oil (11.6% and 5.1% in P. lanceaefolium and P. hispidum, respectively).
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Martins, Carla de M.; do Nascimento, Evandro A.; de Morais, Sérgio A. L.; de Oliveira, Alberto; Chang, Roberto; Cunha, Luís C. S.; Martins, Mário M.; Martins, Carlos Henrique G.; Moraes, Thaís da S.; Rodrigues, Paulla V.; da Silva, Cláudio V.; de Aquino, Francisco J. T.
2015-01-01
Many essential oils (EOs) of different plant species possess interesting antimicrobial effects on buccal microorganisms and cytotoxic properties. EOs of Kielmeyera coriacea Mart. & Zucc. were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). The EO from leaves is rich in sesquiterpenes hydrocarbons and oxygenated sesquiterpenes. The three major compounds identified were germacrene-D (24.2%), (E)-caryophyllene (15.5%), and bicyclogermacrene (11.6%). The inner bark EO is composed mainly of sesquiterpenes hydrocarbons and the major components are alpha-copaene (14.9%) and alpha-(E)-bergamotene (13.0%). The outer bark EO is composed mainly of oxygenated sesquiterpenes and long-chain alkanes, and the major components are alpha-eudesmol (4.2%) and nonacosane (5.8%). The wood EO is mainly composed of long-chain alkanes and fatty acids, and the major components are nonacosane (9.7%) and palmitic acid (16.2%). The inner bark EO showed the strongest antimicrobial activity against the anaerobic bacteria Prevotella nigrescens (minimum inhibitory concentration-MIC of 50 µg mL−1). The outer bark and wood EOs showed MICs of 100 µg mL−1 for all aerobic microorganisms tested. The EOs presented low toxicity to Vero cells. These results suggest that K. coriacea, a Brazilian plant, provide initial evidence of a new and alternative source of substances with medicinal interest. PMID:25960759
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Contact Dermatitis in Pediatrics.
Pelletier, Janice L; Perez, Caroline; Jacob, Sharon E
2016-08-01
Contact dermatitis is an umbrella term that describes the skin's reaction to contacted noxious or allergenic substances. The two main categories of contact dermatitis are irritant type and allergic type. This review discusses the signs, symptoms, causes, and complications of contact dermatitis. It addresses the testing, treatment, and prevention of contact dermatitis. Proper management of contact dermatitis includes avoidance measures for susceptible children. Implementation of a nickel directive (regulating the use of nickel in jewelry and other products that come into contact with the skin) could further reduce exposure to the most common allergens in the pediatric population. [Pediatr Ann. 2016;45(8):e287-e292.]. Copyright 2016, SLACK Incorporated.
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[News on occupational contact dermatitis].
Crépy, Marie-Noëlle; Bensefa-Colas, Lynda
2014-03-01
Contact dermatitis--irritant contact dermatitis, allergic contact dermatitis and protein contact dermatitis--are the most common occupational skin diseases, most often localized to the hands. Contact urticaria is rarer The main occupational irritants are wet work, detergents and disinfectants, cutting oils, and solvents. The main occupational allergens are rubber additives, metals (chromium, nickel, cobalt), plastics (epoxy resins, acrylic), biocides and plants. Diagnosis is based on clinical examination, medical history and allergy testing. For a number of irritating or sensitizing agents, irritant or allergic dermatitis can be notified as occupational diseases. The two main prevention measures are reducing skin contact with irritants and complete avoidance of skin contact with offending allergens.
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Toth, Anna M.; Bliss, Donna Z.; Savik, Kay; Wyman, Jean F.
2011-01-01
Perineal dermatitis is one of the main complications of incontinence and increases the cost of health care. The Minimum Data Set (MDS) contains data about factors associated with perineal dermatitis identified in a published conceptual model of perineal dermatitis. The purpose of this study was to determine the validity of MDS data related to perineal dermatitis risk factors by comparing them with data in nursing home chart records. Findings indicate that MDS items defining factors associated with perineal dermatitis were valid and supported use of the MDS in further investigation of a significant, costly, and understudied health problem of nursing home residents. PMID:18512629
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Patch test reactions to metal salts in patients with different types of dermatitis.
Turčić, Petra; Marinović Kulišić, Sandra; Lipozenčić, Jasna
2013-01-01
Metal allergies can be a clinical problem, especially in atopic individuals. This study is unique and contributes with new knowledge in everyday life skin care of irritant and atopic dermatitis patients. The aim of the study was to determine the frequency of positive patch test reactions to metal contact allergens (potassium dichromate, cobalt chloride, nickel sulfate, white mercury precipitate) in patients diagnosed with allergic contact dermatitis, irritant contact dermatitis, and atopic dermatitis. Between 2007 and 2011, patch testing was performed in 2185 patients according to the International Contact Dermatitis Research Group technique. Study results showed statistically significant differences in patch test responses to 2 allergens, nickel sulfate (χ(2)=24.22; p<0.001) and cobalt chloride (χ(2)=22.72; p<0.001). Nickel sulfate was the most common allergen in allergic contact dermatitis and atopic dermatitis, while for irritant contact dermatitis the most common allergen was cobalt chloride. Among the 4 tested metal allergens, the most common and relevant was nickel sulfate (χ(2)=17.25; p<0.004), found in almost all study subjects. In conclusion, the increased awareness of allergens and their potential sources may help limit the use of these chemicals in consumer product manufacturing.
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[A clinical analysis of 50 cases of medicament-like dermatitis due to trichloroethylene].
Xia, Li-hua; Huang, Han-lin; Kuang, Shou-ren; Liu, Hui-fang; Kong, Ling-zhen
2004-06-01
To investigate the clinical manifestations, complications and treatment of medicament-like dermatitis due to trichloroethylene (TCE), so as to provide basis for studying its etiology and mechanism. Fifty patients with dermatitis due to TCE from 1997 to 2000 were analysed retrospectively. The occurrence of the dermatitis was not parallel to TCE exposure levels, without significant dose-effect relationship. This disease could be caused by both inhalation and skin exposure. The latency period of TCE dermatitis ranged from 5 to 66 days, and the average was 31.5 d (Medium). The major clinical manifestations included skin lesions, fever, superficial lymph node swelling and liver dysfunction. Infection was the major complication. Glucocorticoid was effective for treatment of this disease. The clinical manifestations due to TCE exposure were similar to dermatitis medicamentosa. The major clinical types of TCE dermatitis included exfoliative dermatitis and erythema multiforme. The dermatitis is considered to be mediated by delayed-type (IV) hypersensitivity. The key factors to treat this disease successfully included the use of glucocorticoid in time with sufficient dose and full course, professional skin care, active treatment to protect the liver and to avoid infection.
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Crystal Structures of a Quorum-Quenching Antibody
Debler, Erik W.; Kaufmann, Gunnar F.; Kirchdoerfer, Robert N.; Mee, Jenny M.; Janda, Kim D.; Wilson, Ian A.
2007-01-01
Summary A large number of Gram-negative bacteria employ N-acyl homoserine lactones (AHLs) as signaling molecules in quorum sensing, which is a population density-dependent mechanism to coordinate gene expression. Antibody RS2-1G9 was elicited against a lactam mimetic of the N-acyl homoserine lactone and represents the only reported monoclonal antibody that recognizes the naturally-occuring N-acyl homoserine lactone with high affinity. Due to its high cross-reactivity, RS2-1G9 showed remarkable inhibition of quorum sensing signaling in Pseudomonas aeruginosa, a common opportunistic pathogen in humans. The crystal structure of Fab RS2-1G9 in complex with a lactam analog revealed complete encapsulation of the polar lactam moiety in the antibody combining site. This mode of recognition provides an elegant immunological solution for tight binding to an aliphatic, lipid-like ligand with a small head group lacking typical haptenic features, such as aromaticity or charge, which are often incorporated into hapten design to generate high-affinity antibodies. The ability of RS2-1G9 to discriminate between closely-related AHLs is conferred by six hydrogen bonds to the ligand. Conversely, cross-reactivity of RS2-1G9 towards the lactone is likely to originate from conservation of these hydrogen bonds as well as an additional hydrogen bond to the oxygen of the lactone ring. A short and narrow tunnel exiting at the protein surface harbors a portion of the acyl chain and would not allow for entry of the head group. The crystal structure of the antibody without its cognate lactam or lactone ligands revealed a considerably altered antibody combining site with a closed binding pocket, suggestive of an induced fit mechanism for ligand binding. Curiously, a completely buried ethylene glycol molecule mimics the lactam ring and, thus, serves as a surrogate ligand. The detailed structural delineation of this quorum-quenching antibody will now aid in further development of an antibody-based therapy against bacterial pathogens by interference with quorum sensing. PMID:17400249
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Veliz-Vallejos, Debora F; van Noorden, Giel E; Yuan, Mengqi; Mathesius, Ulrike
2014-01-01
N-acyl homoserine lactones (AHLs) act as quorum sensing signals that regulate cell-density dependent behaviors in many gram-negative bacteria, in particular those important for plant-microbe interactions. AHLs can also be recognized by plants, and this may influence their interactions with bacteria. Here we tested whether the exposure to AHLs affects the nodule-forming symbiosis between legume hosts and rhizobia. We treated roots of the model legume, Medicago truncatula, with a range of AHLs either from its specific symbiont, Sinorhizobium meliloti, or from the potential pathogens, Pseudomonas aeruginosa and Agrobacterium vitis. We found increased numbers of nodules formed on root systems treated with the S. meliloti-specific AHL, 3-oxo-C14-homoserine lactone, at a concentration of 1 μM, while the other AHLs did not result in significant changes to nodule numbers. We did not find any evidence for altered nodule invasion by the rhizobia. Quantification of flavonoids that could act as nod gene inducers in S. meliloti did not show any correlation with increased nodule numbers. The effects of AHLs were specific for an increase in nodule numbers, but not lateral root numbers or root length. Increased nodule numbers following 3-oxo-C14-homoserine lactone treatment were under control of autoregulation of nodulation and were still observed in the autoregulation mutant, sunn4 (super numeric nodules4). However, increases in nodule numbers by 3-oxo-C14-homoserine lactone were not found in the ethylene-insensitive sickle mutant. A comparison between M. truncatula with M. sativa (alfalfa) and Trifolium repens (white clover) showed that the observed effects of AHLs on nodule numbers were specific to M. truncatula, despite M. sativa nodulating with the same symbiont. We conclude that plant perception of the S. meliloti-specific 3-oxo-C14-homoserine lactone influences nodule numbers in M. truncatula via an ethylene-dependent, but autoregulation-independent mechanism.
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Schwensen, Jakob F; Menné, Torkil; Johansen, Jeanne D
2014-12-01
The diagnosis of combined allergic and irritant contact dermatitis is an accepted subdiagnosis for hand dermatitis, and it is often considered in a patient with contact dermatitis, a positive and relevant patch test result, and wet work exposure. We therefore hypothesize that it is arbitrary for wet work exposure to be taken into consideration in a patient with newly diagnosed relevant contact allergy. Furthermore, an overestimation of the diagnosis will probably occur if the criteria for wet work exposure are applied correctly, as many occupations have an element of wet work. To find the statistically expected number of combined allergic and irritant contact dermatitis cases in 1000 patients, and to evaluate the diagnostic criteria for the diagnosis. One thousand consecutive patients with occupational contact dermatitis from a hospital unit in Denmark were assessed. The expected number of cases with the diagnosis of combined allergic and irritant contact dermatitis was 0.33%, as compared with the observed number of 6.4%. Females occupied in wet occupations were often diagnosed with combined allergic and irritant contact dermatitis (p < 0.005). The diagnosis of combined allergic and irritant contact dermatitis should be used critically to avoid misclassification, and possible criteria for the diagnosis are proposed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Schwensen, Jakob F; Menné, Torkil; Veien, Niels K; Funding, Anne T; Avnstorp, Christian; Østerballe, Morten; Andersen, Klaus E; Paulsen, Evy; Mørtz, Charlotte G; Sommerlund, Mette; Danielsen, Anne; Andersen, Bo L; Thormann, Jens; Kristensen, Ove; Kristensen, Berit; Vissing, Susanne; Nielsen, Niels H; Thyssen, Jacob P; Johansen, Jeanne D
2014-12-01
Blue-collar workers have a high risk of occupational contact dermatitis, but epidemiological studies are scarce. To investigate allergic contact dermatitis in blue-collar workers with dermatitis registered by the Danish Contact Dermatitis Group. A retrospective analysis of patch test data from 1471 blue-collar workers and 1471 matched controls tested between 2003 and 2012 was performed. A logistic regression was used to test for associations. The blue-collar workers often had occupational hand dermatitis (p < 0.001). Atopic dermatitis was less commonly observed among blue-collar workers (19.6%) than among controls (23.9%) (p = 0.005). Allergens with a statistically significant association with the occupational group of blue-collar workers were epoxy resins, methyldibromo glutaronitrile, 2-bromo-2-nitro-1,3-propanediol, potassium dichromate, and methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI). The following occupations were additionally identified as risk factors for contact sensitization to MCI/MI and MI, epoxy resins, and potassium dichromate, respectively: painting, construction work, and tile setting/terrazzo work. Contact allergy is a major problem among blue-collar workers. The data indicate a healthy worker effect among blue-collar workers diagnosed with dermatitis, as blue-collar workers were diagnosed significantly less often with atopic dermatitis than were controls. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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T cell lymphomatoid contact dermatitis: a challenging case and review of the literature.
Knackstedt, Thomas J; Zug, Kathryn A
2015-02-01
Lymphomatoid contact dermatitis is a pseudolymphoma with clinical and histological features of allergic contact dermatitis and cutaneous T cell lymphoma. Incorrect diagnosis may lead to unnecessary testing, unnecessary treatment, or patient harm. The objective of this study is to present a case to demonstrate the diagnostic challenge and overlap between allergic contact dermatitis and cutaneous T cell lymphoma in a patient with lymphomatoid contact dermatitis caused by methylchoroisothiazolinone/methylisothiazolinone and paraben mix, and to review the existing literature in order to summarize the demographics, clinical features, allergens and treatments reported for lymphomatoid contact dermatitis. A search of major scientific databases was conducted for English-language articles reporting cases of lymphomatoid contact dermatitis or additional synonymous search headings. Nineteen articles with a total of 23 patients were analysed. Lymphomatoid contact dermatitis was more common in men, with an average age of 58.5 years. Fourteen unique allergens were identified and confirmed by patch testing. However, no single test or study was diagnostic of lymphomatoid contact dermatitis. Allergen avoidance was the most useful management tool, but selected patients required topical or systemic immunosuppression. In conclusion, without specific diagnostic features, evaluation for lymphomatoid contact dermatitis should include a thorough history and examination, patch testing, and biopsy with immunohistochemistry and clonality studies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Simonsen, A B; Johansen, J D; Deleuran, M; Mortz, C G; Skov, L; Sommerlund, M
2018-03-01
Whether children with atopic dermatitis have an altered risk of contact allergy than children without atopic dermatitis is frequently debated and studies have been conflicting. Theoretically, the impaired skin barrier in atopic dermatitis (AD) facilitates the penetration of potential allergens and several authors have highlighted the risk of underestimating and overlooking contact allergy in children with atopic dermatitis. To determine the prevalence of contact allergy in Danish children with atopic dermatitis and explore the problem of unacknowledged allergies maintaining or aggravating the skin symptoms. In a cross-sectional study, 100 children and adolescents aged 5-17 years with a diagnosis of atopic dermatitis were patch tested with a paediatric series of 31 allergens. Thirty per cent of the children had at least one positive patch test reaction, and 17% had at least one contact allergy that was relevant to the current skin symptoms. The risk of contact allergy was significantly correlated to the severity of atopic dermatitis. Metals and components of topical skincare products were the most frequent sensitizers. Patch testing is relevant as a screening tool in the management of children with atopic dermatitis as they may have unacknowledged contact allergies contributing to or maintaining their skin symptoms. Children with atopic dermatitis seem to be at greater risk of sensitization to certain allergens including metals and components of skincare products. © 2017 European Academy of Dermatology and Venereology.
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Economic Impact of Atopic Dermatitis in Korean Patients
Kim, Chulmin; Park, Kui Young; Ahn, Seohee; Kim, Dong Ha; Li, Kapsok; Kim, Do Won; Kim, Moon-Beom; Jo, Sun-Jin; Yim, Hyeon Woo
2015-01-01
Background Atopic dermatitis is a global public health concern owing to its increasing prevalence and socioeconomic burden. However, few studies have assessed the economic impact of atopic dermatitis in Korea. Objective We conducted a cost analysis of atopic dermatitis and evaluated its economic impacts on individual annual disease burden, quality of life, and changes in medical expenses with respect to changes in health related-quality of life. Methods The cost analysis of atopic dermatitis was performed by reviewing the home accounting records of 32 patients. The economic impact of the disease was evaluated by analyzing questionnaires. To handle uncertainties, we compared the results with the data released by the Health Insurance Review & Assessment Board on medical costs claimed by healthcare facilities. Results The direct cost of atopic dermatitis per patient during the 3-month study period was 541,280 Korean won (KRW), and expenditures on other atopic dermatitis-related products were 120,313 KRW. The extrapolated annual direct cost (including expenditures on other atopic dermatitis-related products) per patient was 2,646,372 KRW. The estimated annual indirect cost was 1,507,068 KRW. Thus, the annual cost of illness of atopic dermatitis (i.e., direct+indirect costs) was estimated to be 4,153,440 KRW. Conclusion The annual total social cost of atopic dermatitis on a national level is estimated to be 5.8 trillion KRW. PMID:26082587
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Huilaja, L; Kubin, M E; Riekki, R
2016-01-01
Allergic contact dermatitis caused by wood dust remains uncommon and most cases are occupational. Contact allergy to finished wooden products is even more rare and only few cases of contact dermatitis to wooden furnishings and furniture are described. During 2012-2014 surprisingly many patients with dermatitis associated to sauna baths were referred to our clinic. We report three novel cases with allergic contact dermatitis to western red cedar due to exposure during sauna baths. Three cases of non-occupational contact dermatitis to western red cedar were confirmed by patch testing. Allergic contact dermatitis to interior decoration or furniture is a rarity, but can be induced by novel exposures, like western red cedar in sauna interior decoration. © 2015 European Academy of Dermatology and Venereology.
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Current knowledge on biomarkers for contact sensitization and allergic contact dermatitis.
Koppes, Sjors A; Engebretsen, Kristiane A; Agner, Tove; Angelova-Fischer, Irena; Berents, Teresa; Brandner, Johanna; Brans, Richard; Clausen, Maja-Lisa; Hummler, Edith; Jakasa, Ivone; Jurakić-Tončic, Ružica; John, Swen M; Khnykin, Denis; Molin, Sonja; Holm, Jan O; Suomela, Sari; Thierse, Hermann-Josef; Kezic, Sanja; Martin, Stefan F; Thyssen, Jacob P
2017-07-01
Contact sensitization is common and affects up to 20% of the general population. The clinical manifestation of contact sensitization is allergic contact dermatitis. This is a clinical expression that is sometimes difficult to distinguish from other types of dermatitis, for example irritant and atopic dermatitis. Several studies have examined the pathogenesis and severity of allergic contact dermatitis by measuring the absence or presence of various biomarkers. In this review, we provide a non-systematic overview of biomarkers that have been studied in allergic contact dermatitis. These include genetic variations and mutations, inflammatory mediators, alarmins, proteases, immunoproteomics, lipids, natural moisturizing factors, tight junctions, and antimicrobial peptides. We conclude that, despite the enormous amount of data, convincing specific biomarkers for allergic contact dermatitis are yet to be described. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Management of Patients with Atopic Dermatitis: The Role of Emollient Therapy
Catherine Mack Correa, M.; Nebus, Judith
2012-01-01
Atopic dermatitis is a common inflammatory skin disorder that afflicts a growing number of young children. Genetic, immune, and environmental factors interact in a complex fashion to contribute to disease expression. The compromised stratum corneum found in atopic dermatitis leads to skin barrier dysfunction, which results in aggravation of symptoms by aeroallergens, microbes, and other insults. Infants—whose immune system and epidermal barrier are still developing—display a higher frequency of atopic dermatitis. Management of patients with atopic dermatitis includes maintaining optimal skin care, avoiding allergic triggers, and routinely using emollients to maintain a hydrated stratum corneum and to improve barrier function. Flares of atopic dermatitis are often managed with courses of topical corticosteroids or calcineurin inhibitors. This paper discusses the role of emollients in the management of atopic dermatitis, with particular emphasis on infants and young children. PMID:23008699
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[Contact dermatitis: an approach used by a medical officer].
Vologzhanin, D A; Bozhchenko, A A; Bala, A M
2012-01-01
The article deals with contact dermatitis issues, that are of interest not only for dermatologists and specialists in professional pathology, but as well as for general practitioners. Issues of contact dermatitis classification, pathogenic peculiarities of the disease main forms and their basic causes are discussed. Clinical manifestations of irritative and allergic contact dermatitis are described in detail, aspects of differential diagnostics analysed. A detailed consideration is given to allergic diagnostics of contact dermatitis using application test-systems with the most common contact allergens. Main principles of contact dermatitis treatment are outlined in the article. The necessity of a complex approach to this disease therapy that requires not only external therapy, but the compliance with an appropriate treatment regimen, diet as well as application of a particular system therapy is shown. Recommendations for contact dermatitis prophylaxis are given.
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Boleira, Manuela; Lupi, Omar; Pires, Gisele Vianna; Dias, Gabriela; Seba, Amanda Jaccobson; Guimarães, Daniel Boleira Sieiro
2014-01-01
BACKGROUND atopic dermatitis is directly related to psychological stress, reduced quality of life and psychosomatic symptoms. The Psychosomatic Scale for Atopic Dermatitis is the only questionnaire developed specifically for assessment of psychosomatization in atopic dermatitis. OBJECTIVES the objective of this study was to cross-culturally adapt and validate a Brazilian-Portuguese version of the Psychosomatic Scale for Atopic Dermatitis. METHODS adaptation consisted of independent translation and backtranslation by three bilingual translators, followed by a pre-test. The Psychosomatic Scale for Atopic Dermatitis and the Dermatology Life Quality Index were self-administered to 47 patients with atopic dermatitis. Disease severity was evaluated using the Eczema Area and Severity Index. Factor analysis was used to identify the dimensions of the Brazilian Portuguese version of the Psychosomatic Scale for Atopic Dermatitis. Internal consistency and convergence validity were also analyzed. Reproducibility was assessed using the Kappa coefficient. RESULTS factor analysis revealed a two-dimensional structure: stress/laziness/insecurity (I) and maladjustment/social relationships (II), explaining 54.4% of total variance. All dimensions revealed excellent internal consistency. External construct validity was confirmed by positive correlations between the Psychosomatic Scale for Atopic Dermatitis and the Dermatology Life Quality Index. Test-retest reliability was excellent, with k>0.7 for all questions. CONCLUSIONS the Brazilian Portuguese version of the Psychosomatic Scale for Atopic Dermatitis demonstrated acceptable psychometric properties and can be used for the evaluation of psychosomatic symptoms in patients with atopic dermatitis and as a tool in clinical and epidemiological research. PMID:25184916