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Leontopodic Acid (I) — A Novel Highly Substituted Glucaric Acid Derivative from Edelweiss (Leontopodium alpinum Cass.) and Its Antioxidative and DNA Protecting Properties.

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Abstract

Leontopodic acid—a novel full substituted hexaric acid derivative, was isolated from the aerial parts of Edelweiss (Leontopodium alpinum Cass.) as one of the major compounds. The complex structure of leontopodic acid-2-[(3S)-3-hydroxybutanoate]-3,4,5-tris-[(2E)-3-(3,4-dihydroxyphenyl)-2-propenoate]-D-glucaric acid—was elucidated by mass spectrometry, 1D-and 2D NMR spectroscopy and HPLC monitored transesterification. Leontopodic acid exhibited pronounced antioxidative effects in the Briggs-Rauscher (BR) model [(r.a.c.) m 3.4G0.5] and the trolox equivalent antioxidant capacity (TEAC) method (TEAC value of 1.53G0.11). The antioxidative properties of this compound were confirmed by the 3D method, an in vitro assay evaluating DNA protection against oxidative damage (IC 50 : 1.89 mM).

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... Following that criterion the structure of 2 can be refined to be 2,4,5-tricaffeoylglucaric acid. Chemical structure of leontopodic acid B (Schwaiger et al., 2006) was determined to be 3,4,5-tricaffeoylglucaric acid on the basis of the similarity of its chemical shifts with those of leontopodic acid (2-hydroxybutyryl-3,4,5-tricaffeoylglucaric acid) (Schwaiger et al., 2005). Yet, the exact place of substitution was not determined unambiguously in the cited references. ...
... However, further more complex compounds were mostly isolated and identified by NMR or identified by LC-MS method in Asteraceae family: Leontopodium alpinum Cass. (Schwaiger et al., 2006;Schwaiger et al., 2005), Gnaphalium genus (by LC-MS method) (Cicek et al., 2012), Eupatorium perfoliatum L. (Maas et al., 2009), Smallanthus sonchifolius Poepp. and Endl. ...
... The biological activity of caffeoyl-hexaric acid derivatives have not been deeply studied so far and were limited to leontopodic acid (2-hydroxybutyryl-3,4,5-tricaffeoylglucaric acid) and some altraric acids derivatives. In a Trolox Equivalent Antioxidant Capacity (TEAC) test leontopodic acid showed an antioxidant activity comparable to caffeic acid, and the capacity to protect the DNA from the oxidative damage much more significantly than chlorogenic acid (Schwaiger et al., 2005), while di-and tricaffeoyl derivatives were reported to have high DPPH radical scavenging activities (Takenaka et al., 2006). In the present study all tested compounds were weaker DPPH scavengers in comparison to the positive control quercetin (Table 5). ...
Article
Four new caffeoyl -glucaric and -altraric acid derivatives along with eleven known compounds were isolated from aerial parts of Galinsonga parviflora. Their structures were elucidated by high-resolution spectroscopic studies. The four new compounds were determined as being 2,3,4,5-tetracaffeoylglucaric acid (1), 2,4,5-tricaffeoylglucaric acid (2), 2,3,4- or 3,4,5-tricaffeoylaltraric acid (3) and 2,3(4,5)-dicaffeoylaltraric acid (4). A reliable criterion for the determination of the linkage position of caffeic acids moieties in glucaric acid derivatives has been proposed, on the basis of detailed analysis of the respective J-couplings, including substitution and solvent influence on the observed values. All hexaric acids derivatives appeared as inhibitors of reactive oxygen species production by stimulated neutrophils.
... This molecule exhibited a pronounced chemical antioxidant power. In the TEAC (trolox equivalent antioxidant capacity, pH 7.4) assay, the antioxidant activity was comparable with that of caffeic acid and in the Briggs-Rauscher model LA showed an anti-oxidative capacity twice as high as that of caffeic acid (Schwaiger et al., 2005). ...
... Leontopodic acid (purity 95%) was obtained by extraction and purification as described by Schwaiger et al. (2005): all data on LA are reported in Schwaiger et al. (2005). AFB1, DON, dihydrodichlorofluorescein diacetate (H 2 DCF-DA), MTT and Bradford reagent were purchased from Sigma-Aldrich S.r.l. ...
... Leontopodic acid (purity 95%) was obtained by extraction and purification as described by Schwaiger et al. (2005): all data on LA are reported in Schwaiger et al. (2005). AFB1, DON, dihydrodichlorofluorescein diacetate (H 2 DCF-DA), MTT and Bradford reagent were purchased from Sigma-Aldrich S.r.l. ...
Article
Several in vitro studies showed that free radical scavengers possess chemopreventive properties against mycotoxin-induced cell damage which are at least partially associated with the induction of phase II detoxifying enzymes and antioxidant enzymes like glutathione S-transferase (GST) and glutathione peroxidase (GPx). The aim of this project was to study the chemopreventive effects of leontopodic acid (LA), a potent natural occurring free radical scavenger isolated from the aerial parts of Leontopodium alpinum. Different mycotoxins were evaluated in two different cell lines on the basis of their specific toxicity: aflatoxin B1 (AFB1) on HepG2 cells and deoxynivalenol (DON) on U937 cells. Cell viability and reactive oxygen species concentration were determined, and the effects of pre-treatment with LA on these parameters were investigated together with the GST and GPx activity as well as the concentration of reduced glutathione. The results show that LA protects U937 cells from DON-induced cell damage but not HepG2 cells from AFB1. Moreover LA is able to enhance GPx activity in U937, but not GST activity in HepG2. We hypothesize that the increase in detoxifying enzymes is probably the main mechanism of antioxidant mediated chemoprevention.
... Previous investigations [6][7][8][9][10][11][12] of Leontopodium alpinum phytochemical composition highlighted a number of compound classes, such as phenylpropanoid, sesquiterpene, benzofuran and lignan derivatives. However, data regarding the composition of callus cultures is rather limited [13,14]. ...
... So far, only the most abundant compounds have been identified, namely derivatives of quinic acid (chlorogenic acid and di-caffeoylquinic acid) and derivatives of glucaric acid (leontopodic acids A and B). The two leontopodic acids are specific to edelweiss and structurally are derivatives of glucaric acid substituted with caffeoyl and 3-hydroxybutanyl moieties [6], showing strong antioxidant potential. ...
... Using in vitro models, polyphenols were previously described to possess anticarcinogenic properties, capable of inhibiting tumor growth, metastasis and inflammatory processes [31][32][33]. The major constituents of the edelweiss callus culture extract have been previously reported to possess strong antioxidant properties, protecting cells against DNA damage [6]. For example, chlorogenic acid, one of the major constituents of the extract, can affect GSK-3β, APC and β-catenin gene expression acting as an antitumor agent [34]. ...
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Leontopodium alpinum Cass. (edelweiss) is recognized as a frequent constituent of anti-aging skin care products, providing increased antioxidant and anti-inflammatory defense. Considering the growing demand and the protected status of edelweiss in many countries, alternative methods of production have been developed, one of them being callus culturing. This study reports the phytochemical composition of a methanolic extract of L. alpinum callus cultures, characterized by liquid chromatography coupled to ion-mobility high resolution mass spectrometry (UPLC/IM-HRMS). The methanolic extract exhibited strong free radical scavenging activity (122.19 ± 7.28 mg AAE/g dw), while the quantitative evaluation revealed that four major constituents (phenylpropanoid derivatives) represent 57.13% (m/m) of the extract. Consequently, a screening of antiproliferative effects was performed on ten cancer cell lines, representative of prostate, colon, lung and breast cancer, showing inhibition of colony formation in all cases. These results provide a comprehensive phytochemical characterization of L. alpinum callus cultures using advanced IM-HRMS, while the in vitro explorations confirmed the potent antioxidant properties of edelweiss which are worth exploring further in cancer prevention.
... This molecule exhibited a pronounced chemical antioxidant power. In the TEAC (trolox equivalent antioxidant capacity, pH 7.4) assay, the antioxidant activity was comparable with that of caffeic acid and in the Briggs-Rauscher model LA showed an anti-oxidative capacity twice as high as that of caffeic acid (Schwaiger et al., 2005). ...
... Leontopodic acid (purity 95%) was obtained by extraction and purification as described by Schwaiger et al. (2005): all data on LA are reported in Schwaiger et al. (2005). AFB1, DON, dihydrodichlorofluorescein diacetate (H 2 DCF-DA), MTT and Bradford reagent were purchased from Sigma-Aldrich S.r.l. ...
... Leontopodic acid (purity 95%) was obtained by extraction and purification as described by Schwaiger et al. (2005): all data on LA are reported in Schwaiger et al. (2005). AFB1, DON, dihydrodichlorofluorescein diacetate (H 2 DCF-DA), MTT and Bradford reagent were purchased from Sigma-Aldrich S.r.l. ...
Article
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Mycotoxins are secondary metabolites of various moulds that contaminate several alimentary substrates. One of the most dangerous of these is ochratoxin A (OTA). Reactive oxygen species (ROS) play an important role in the toxicity mechanism of OTA, so the use of natural or synthetic free radical scavengers could be a potential chemopreventive strategy. Carnosic acid (CA) is the major polyphenolic compound present in rosemary plants. This work aimed to determine whether CA could counteract OTA-induced cell damage. Free radical scavenging properties of CA were chemically determined at pH 7.4. Cytotoxicity of CA and OTA on LLC-PK1 cells, and the protective effects of CA, were assessed using the Alamar Blue test. The effects in vitro of CA pre-treatment on the production of ROS, the DNA oxidation and the induction of apoptosis induced by OTA were studied. It was found that CA has free radical scavenging properties at both the considered pH values. Moreover, a pre-treatment of 24 h with 10, 20 and 30 mu M CA is able to reduce OTA-induced cytotoxicity; a pre-treatment of 24 h with 20 and 30 mu M CA achieved ROS reduction and with 30 mu M CA decreased the OTA-induced increase of 8-OH-2'-deoxyguanosine and of DNA fragmentation in LLC-PK1. These findings suggest a starting point to develop alimentary strategies against OTA-induced cell damage. Moreover, our results provide further evidence that oxidative stress plays an important role in the OTA cytotoxicity mechanism.
... Historical literature records Edelweiss being applied either orally-i.e. the herb was boiled in wine and mixed with milk; or topically, where the material was boiled in water and the extract so acquired was applied as a compress (especially in the treatment of breast cancer) (Tabernaemontanus 1993;Dobner et al. 2003b). Today, extracts of the aerial parts of Edelweiss are used for their antioxidant properties in cosmetic preparations such as sunscreen products (Schwaiger et al. 2005. ...
... The species is nowadays regarded as rare, however it is listed as Least Concern (LC) in the IUCN Red List of Threatened Species (Khela 2013). The collection of wild individuals of Edelweiss is currently forbidden by law in many countries (Blascakova et al. 2011;Keller and Vittoz 2015), hence the main bulk of its production comes from successful cultivation in Switzerland (Schwaiger et al. 2005. Besides which, Edelweiss has demonstrated promising results when propagated via cell tissue culture techniques, facilitating even more the commercial availability of this plant for industrial uses (e.g. ...
... Leontopodic acid is the only constituent of Edelweiss ever submitted to antioxidant assays (Cicek et al. 2012). Schwaiger et al. (2005) have determined its antioxidant efficacy with the use of various in vitro methods-i.e. the Briggs-Rauscher oscillating reaction (BR) method, a trolox equivalent antioxidant capacity (TEAC) assay and a damaged DNA detection (3D) assay. Leontopodic acids demonstrated significant free radical scavenging ability; the compound was shown to possess approximately 4-times higher activity than resorcinol in a BR assay and a 2-times higher efficacy than trolox in a TEAC assay. ...
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Leontopodium nivale ssp. alpinum (syn. Leontopodium alpinum) is a perennial herb commonly known as Edelweiss, which has a long tradition in Alpine countries and adjacent regions as a medicinal plant. This review discusses current knowledge on the traditional uses, chemistry, biological activities and toxicology of this species. Several different classes of compounds such as terpenoids (analogues of sesquiterpenes, bisabolenes), phenylpropanoids (phenolic acids, flavonoids, coumarins, lignans), fatty acids and polyacetylenes were previously isolated from various parts of Edelweiss. Different types of extracts and compounds derived from this plant have been found to possess a broad spectrum of pharmacological activities on the cardiovascular and nervous systems. Furthermore, the plant have known anti-inflammatory, antimicrobial, antioxidant and chemo-protective effects. The observed pharmacological activities as well as toxicological profile of preparations and isolated compounds of Edelweiss support the view that these might be used in the development of agents with therapeutic benefit in various human diseases. Some suggestions for further research on chemical characterization and pharmacological properties are also given in this review.
... The great majority of health properties of this plant have been attributed to the presence and the spectrum of polyphenolic secondary metabolites. Edelweiss contains a wide variety of polyphenols belonging to classes of phenylpropanoids (phenolic acids, glycosides, flavonoids, coumarines, and lignans), terpenes (sesquiterpenes and diterpene acids), and alkaloids (benzofuran and pyrane derivatives) [11]. The ethnopharmacological use of Edelweiss is supported by the isolation of a number of phenylpropanoids possessing antiinflammatory and antibacterial properties from the plant root, its aerial parts, or from hairy root cultures [2]. ...
... contain four phenylpropanoid moieties connected to a backbone of glucaric acid. Later publications described LA1 and LA2 as having the greatest impact on beneficial biological effects of Edelweiss herb extracts [6, 11]. The extracts also display antioxidant, DNA-protecting, and analgesic effects, proven in different in vivo models [5]. ...
... Higher plants respond to a variety of oxidative stimuli, including enhanced UV irradiation by increasing the biosynthesis of UVA and UVB-absorbing compounds with pronounced antioxidant properties [15]. LA has been shown to possess remarkable antioxidant properties [5, 11]. An increase in the intracellular levels of NO in UV-exposed keratinocytes occurs by two ways: by the activation of constitutive NO synthases (cNOS) in the early postirradiation period and by the induction of inducible NO synthase (iNOS) at more than 6 h after irra- diation [27]. ...
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Edelweiss (Leontopodium alpinum Cass.) is traditionally employed in folk medicine as an anti-inflammatory remedy. In nature, the plant is sparsely available and protected; therefore production of callus cultures was established. A concentrated ethanolic extract of culture homogenate, with leontopodic acid representing 55 ± 2% of the total phenolic fraction (ECC55), was characterized for anti-inflammatory properties in primary human keratinocytes (PHKs) and endotheliocytes (HUVECs). Inflammatory responses were induced by UVA+UVB, lipopolysaccharide (LPS), oxidized low-density lipoprotein (oxLDL), and a mixture of proinflammatory cytokines. Trichostatin A, a sirtuin inhibitor, was used to induce keratinocyte inflammatory senescence. ECC55 (10-50 μg/mL) protected PHK from solar UV-driven damage, by enhancing early intracellular levels of nitric oxide, although not affecting UV-induced expression of inflammatory genes. Comparison of the dose-dependent inhibition of chemokine (IL-8, IP-10, MCP-1) and growth factor (GM-CSF) release from PHK activated by TNFα + IFNγ showed that leontopodic acid was mainly responsible for the inhibitory effects of ECC55. Sirtuin-inhibited cell cycle, proliferation, and apoptosis markers were restored by ECC55. The extract inhibited LPS-induced IL-6 and VCAM1 genes in HUVEC, as well as oxLDL-induced selective VCAM1 overexpression. Conclusion. Edelweiss cell cultures could be a valuable source of anti-inflammatory substances potentially applicable for chronic inflammatory skin diseases and bacterial and atherogenic inflammation.
... Foto: Rokus Cornelis für die oberirdischen Teile, die auch ursprünglich in der alpenländischen Volksmedizin verwendet wurden, ca. 20 Inhaltsstoffe identifiziert und strukturell aufgeklärt [2], [7], [8], [11], [24], [25], [31]: Neben zahlreichen Flavonoiden, die sich fast ausschließlich von den Flavonen Apigenin und Luteolin ableiten und in mono-oder diglykosidischer Form vorliegen (z. B. Luteolin-4´-O-glucopyranosid, Luteolin-7-O-glucopyranosid), und Dicaffeoylchinasäure-Derivaten und Chlorogensäure finden sich in den oberirdischen Teilen von L. alpinum die Leontopodiumsäure ("leontopodic acid") und die Leontopodiumsäure B (▶Abb. ...
... Im Briggs-Rauscher-Test, einem In-vitro-Testsystem zur Untersuchung, ob Testsubstanzen Hydroperoxyl-Radikale abfangen können, konnten moderate relative Aktivitäten für Extrakte aus den unter-und oberirdischen Teilen von L. alpinum ermittelt werden [26]. In weiterführenden Untersuchungen konnten in diesem Testsystem starke antioxidative Wirkungen für die Leontopodiumsäure nachgewiesen werden [24]. In weiteren Testassays, u. a. den TEAC-Assay, in dem die Entfärbung des ABTS-Radikals in Gegenwart von Testsubstanzen untersucht wird, wurde für Leontopodiumsäure eine antioxidative Aktivität gezeigt [24]. ...
... In weiterführenden Untersuchungen konnten in diesem Testsystem starke antioxidative Wirkungen für die Leontopodiumsäure nachgewiesen werden [24]. In weiteren Testassays, u. a. den TEAC-Assay, in dem die Entfärbung des ABTS-Radikals in Gegenwart von Testsubstanzen untersucht wird, wurde für Leontopodiumsäure eine antioxidative Aktivität gezeigt [24]. Der sog. ...
Article
The aerial parts of Leontopodium alpinum Cass. and preparations thereof were used in the folk medicine of the alp region for the treatment of abdominal disorders, angina, bronchitis, diarrhea and dysentery. Today Lion´s Foot is only used in homeopathic and cosmetic preparations and rarely in food stuff. The phytochemical analysis of the whole plant lead to the isolation of a broad spectrum of natural compounds including leontopodic acids, caffeoyl quinic acids, flavonoids, lignans, coumarins and an essential oil with numerous terpenes. Modern pharmacological assays confirm anti-inflammatory, analgetic and antimicrobial acitivies of L. alpinum as well as an inhibition of gastrointestinal motility thus confirming the traditional application of the aerial parts of L. alpinum in folk medicine. --- Keywords Leontopodium alpinum, Asteraceae, Herba Leontopodii, Lion´s foot, folk medicine of the alps -------------------------------------------------------- In der Alpenregion wurde das Kraut von Leontopodium alpinum Cass. bzw. daraus hergestellte Zubereitungen arzneilich eingesetzt bei Bauchschmerzen, Angina, Bronchitis, Diarrhoe und Dysenterie; heute werden Edelweiss bzw. daraus gewonnene Extrakte nur noch in homöopathischen Mitteln, in kosmetischen Zubereitungen und vereinzelt in Lebensmitteln angewendet. Die phytochemische Untersuchung der gesamten Pflanze ergab ein breites Spektrum an Naturstoffen, wobei die Leontopodiumsäuren, Caffeoylchinasäuren, Flavonoide, Lignane, Cumarine sowie ein ätherisches Öl mit zahlreichen Terpenkomponenten charakteristisch sind. Moderne pharmakologische Untersuchungen bestätigen für Extrakte aus Edelweiss und daraus isolierte Einzelstoffe antiinflammatorische, analgetische und antimikrobiellen Wirkungen sowie eine Hemmung der Peristaltik des Gastroinstestinaltrakts und damit letztendlich die volksmedizinischen Anwendungsgebiete der Krautdroge von L. alpinum.
... Analytes 1-12 were isolated and characterised by UV, IR and NMR. The data of 2-8, 11 and 12 were found to be identical to those provided in the literature (Kellam et al., 1993;Nawwar et al., 1994;Slimestad et al., 1995;Pieroni et al., 1996;Lewis et al., 1998;Pauli et al., 1998;Yinrong and Yeap, 2000;Schwaiger et al., 2005) and are summarised in Table 2. Compound 9 is a new natural product; its analytical data is summarised in the following paragraph. Analyte 10 was found to be insufficiently characterised in the literature (Pieroni et al. 1996), thus the data are reported here in detail. ...
... The assigned 1 H-and 13 C-NMR data of 9 are presented above. The optical rotations of 9 proved the configuration of the hexaric acid backbone as Dglucaric acid (Schwaiger et al., 2005). The trivial name of leontopodic acid B is suggested for this new secondary plant metabolite. ...
... Leontopodic acid (12) and leontopodic acid B (9) were present in all investigated samples. Taking into account that this secondary metabolite class of glucaric acid derivatives has rarely been found outside the genus Leontopodium so far (Schwaiger et al., 2005), the chemotaxonomical relevance of these analytes cannot be ruled out at this stage of investigations. ...
Article
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The analytical assessment of edelweiss (Leontopodium alpinum) herb extracts, used in traditional alpine medicine, has resulted in the development of a HPLC-PAD-MS method that allows baseline separation of almost all constituents. Peak assignment of 14 analytes was achieved by comparison of retention times, UV and mass spectra with those of reference compounds either commercially available (luteolin, apigenin and chlorogenic acid) or isolated from edelweiss plants by column chromatography. Ten of the isolated analytes were identified as the known natural products: quercetin-3-O-beta-D-glucoside, luteolin-7-O-beta-D-glucoside, luteolin-3'-O-beta-D-glucoside, luteolin-4'-O-beta-D-glucoside, apigenin-7-O-beta-D-glucoside, 6-hydroxy-luteolin-7-O-beta-D-glucoside, luteolin-7,4'-di-O-beta-D-glucoside, chrysoeriol-7-O-beta-D-glucoside, leontopodic acid and 3,5-dicaffeolyquinic acid. One analyte, 3,4,5-tri-(E)-caffeoly-D-glucaric acid proved to be a new natural product and was named leontopodic acid B. Structure elucidation was carried out by means of MS and NMR spectroscopy in all cases. The aerial plant parts of L. alpinum (capitula, inflorescence leaves, stems, stem leaves and leaves of the basal rosette) showed variable amounts of the above-mentioned constituents, although qualitative differences were not observable.
... The compound represented by peak 12 was an unknown derivative of dicaffeoylquinic acid judging from the presence of fragmentation ions at m/z 353, 335 and 179. Peak 15 was tentatively identified as a signal of hydroxybutyryl-tricaffeoyl hexaric acid (leontopodic acid) by looking at the fragmentation pattern of the compound described by Schwaiger et al. [14]. The compound corresponding to the peak 17 [13,14]. ...
... Peak 15 was tentatively identified as a signal of hydroxybutyryl-tricaffeoyl hexaric acid (leontopodic acid) by looking at the fragmentation pattern of the compound described by Schwaiger et al. [14]. The compound corresponding to the peak 17 [13,14]. ...
... Four sesquiterpene lactones: reynosin (12), santamarine (13) [25], 2,3-dihydroaromaticin (14) [26] and 2-deoxy-4-epi-pulchellin (16) [27] (see Figure 3) together with one apocarotenoide-loliolide (15) [28] were isolated from a chloroform extract of X. speciosissima aerial parts. The compounds were identified based on their experimental 1 H-NMR spectroscopic data and their chromatographic parameters. ...
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Xerolekia speciosissima (L.) Anderb., a rare plant from the north of Italy, is a member of the Inuleae-Inulinae subtribe of the Asteraceae. Despite its close taxonomic relationship with many species possessing medicinal properties, chemical composition of the plant has remained unknown until now. A hydroalcoholic extract from the aerial parts of X. speciosissima was analyzed by HPLC-DAD-MSn revealing the presence of caffeic acid derivatives and flavonoids. In all, 19 compounds, including commonly found chlorogenic acids and less frequently occurring butyryl and methylbutyryl conjugates of dicaffeoylquinic and tricaffeoylhexaric acids, plus two flavonoids, were tentatively identified. Chromatographic separation of a hydroalcoholic extract from the capitula of the plant led to the isolation of (+)-dehydrodiconiferyl alcohol 4-O-β-glucopyranoside, quercimeritrin, astragalin, isoquercitrin, 6-hydroxykaempferol-7-O-β-glucoside, quercetagitrin, methyl caffeate, caffeic acid, protocatechuic acid, chlorogenic acid and 1,5-dicaffeoylquinic acid. Composition of a nonpolar extract from the aerial parts of the plant was analyzed by chromatographic methods supported with 1H NMR spectroscopy. The analysis revealed the presence of loliolide, reynosin, samtamarine, 2,3-dihydroaromaticin, 2-deoxy-4-epi-pulchellin and thymol derivatives as terpenoid constituents of the plant. One of the latter compounds - 7,10-diisobutyryloxy-8,9-epoxythymyl isobutyrate, at concentrations 0.5, 1.0 and 2.5 μM, significantly reduced IL-8, IL-1β and CCL2 excretion by LPS stimulated human neutrophils.
... The compounds have been previously described as constituents of other plants of the Asteraceae family [10][11][12][13], including the systematically related species Inula helenium [14]. Compounds corresponding to peaks 10 [17]. Finally, the compounds corresponding to peaks 16 and 17, with molecular ion masses and fragmentation ion masses being 14 mass units higher than those of 15, could be tentatively identified as 2-methylbutyryl/isovaleryl-tri-O-caffeoylhexaric acids. ...
... Taking into consideration that esterification of both terpenoid and phenolic metabolites with isobutyric acid and/or 2-methylbutyric/isovaleric acid is quite common within Inuleae [7,35,36], we postulated that the compounds eluted at 22.9 min and 23.8 min were 2-methylbutyryl/isovaleryl-DCQAs. Finally, on the basis of spectral data of leontopodic acid, given by Schwaiger et al. [17], we tentatively identified the three remaining compounds as isobutyryl-tricaffeoylhexaric acid (m/z at 765 [M − H] − ) and 2-methylbutyryl/isovaleryl-tricaffeoylhexaric acids (m/z at 779 [M − H] − ). The estimated contents of 5-CQA (1.23% dry weight) and 3,5-DCQA (1.46% dry weight), together with the relation of peak areas of the two compounds to the areas of remaining hydroxycinnamate signals visible on the chromatogram, allow us to conclude that aerial parts of C. divaricatum could be a rich dietary source of these compounds [37]. ...
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Carpesium divaricatum Sieb. & Zucc. has a long history of use as both a medicinal and a food plant. However, except for terpenoids, its chemical constituents have remained poorly investigated. The composition of hydroalcoholic extract from aerial parts of C. divaricatum was analyzed by HPLC-DAD-MSn, revealing the presence of numerous caffeic acid derivatives that were formerly unknown constituents of the plant. In all, 17 compounds, including commonly found chlorogenic acids and rarely occurring butyryl and methylbutyryl tricaffeoylhexaric acids, were tentatively identified. Fractionation of lipophilic extract from cultivated shoots led to the isolation of 12-oxo-phytodienoic acid (12-OPDA), which is a newly identified constituent of the plant. The compound, at concentrations of 0.5, 1.0, and 2.5 μM, significantly reduced IL-8, IL-1β, TNFα, and CCL2 excretion by lipopolysaccharide (LPS)-stimulated human neutrophils. Reactive oxygen species (ROS) production induced by f-MLP was also significantly diminished in the neutrophils pretreated by 12-OPDA. The newly identified constituents of the plant seem to be partly responsible for its pharmacological activity and elevate the value of C. divaricatum as a potential functional food.
... Recently, two unique caffeoyl-D-glucaric acid derivatives, leontopodic acid and leontopodic acid B, were identified in Leontopodium alpinum Cass. [4,7]. Subsequent studies demonstrated a chemoprotective bio-activity of leontopodic acid against toxins aflatoxin B1 and deoxynivalenol [8]. ...
... Table 1. Occurrence of caffeic acid derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) in members of the genera Gnaphalium and Leontopodium from the Alps based on HPLC/MS/DAD data: (+) traces, + present. ...
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A chemosystematic survey was carried out to specify whether leontopodic acid and leontopodic acid B, two unique caffeoyl-D-glucaric acid derivatives, recently identified in the emblematic alpine edelweiss (Leontopodium alpinum Cass.) are also found in members of the genus Gnaphalium from the Alps. Gnaphalium is closely related to Leontopodium and both genera are assigned to the Gnaphaliinae subtribe (Asteraceae, Gnaphalieae). In all investigated Gnaphalium species, G. hoppeanum W.D.J.Koch, G. norvergicum Gunnerus, G. supinum L., G. sylvaticum L., and G. uliginosum L., both leontopodic acid and leontopodic acid B were detected. Moreover, a number of related compounds were detected by HPLC/MS and their assumed structures are discussed. The chemosystematic data reported here are of interest to explore new sources for the biologically active compounds leontopodic acid and leontopodic acid B and they also hint to the occurrence of novel caffeoyl-D-glucaric acid derivatives in Gnaphalium not detected in Leontopodium, yet.
... Depsides of coumaric and ferulic acid with glucaric and galactaric acid were found both in Secale cereale, Poaceae [34] and Citrus species, Rutaceae [35,36]. Two reports describe the occurrence of hydroxycinnamoylhexaric acid derivatives in the Asteraceae family: in yacon root (Smallanthus sonchifolius) 2,4-or 3,5-dicaffeoyl-, 2,5-dicaffeoyl-and 2,3,5-or 2,4,5-tricaffeoylaltraric acid have been found [27], and 2-[(3S)-3-hydroxybutanoat]-3,4,5tricaffeoylglucaric acid and 3,4,5-tricaffeoylglucaric acid (Leontopodic acid and Leontopodic acid B) have been isolated in edelweiss (Leontopodium alpinum) [37,38]. Concerning the two Leontopodic acids it is not clear why the authors excluded the 2,3,4-tricaffeoylglucaric acid derivatives as possible conformational isomers. ...
... The hexaric acid derivatives of edelweiss and yacon have been shown to exhibit antioxidative and radical scavenging activities [37,40] and the caffeoylglucaric acid from tomato possesses inhibiting activity against the tomato fruit worm [32]. Beside these data, nothing is known about possible pharmacological properties of this group of substances. ...
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From the ethyl acetate soluble fraction of a methanol/water extract of the herb Eupatorium perfoliatum L. (Asteraceae) six caffeic acid derivatives have been isolated and identified by 1D- and 2D-NMR spectroscopic data. Besides the common quinic acid derivatives 5-caffeoylquinic acid (chlorogenic acid), 3-caffeoylquinic acid (neochlorogenic acid) and 3,5-dicaffeoylquinic acid, three up to now unknown depsides of caffeic acid with glucaric acid have been isolated: 2,5-dicaffeoylglucaric acid, 3,4-dicaffeoylglucaric acid, and 2,4- or 3,5-dicaffeoylglucaric acid.
... In folk medicine, extracts of Edelweiss are used for the therapy of several diseases such as bronchitis or cancer. Wild Edelweiss is protected by the law but the plant is now cultivated in large numbers and extracts of the aerial parts are used for their anti-oxidative properties (1,2). In order to improve clinical research and provide high quality standards, the production of three new antioxidants from Edelweiss plant is required, namely: leontopodic acid A, leontopodic acid B and 3,5-dicaffeoylquinic acid. ...
... In order to improve clinical research and provide high quality standards, the production of three new antioxidants from Edelweiss plant is required, namely: leontopodic acid A, leontopodic acid B and 3,5-dicaffeoylquinic acid. HPLC analysis exhibits the complexity of this plant extract (1,2). Unfortunately, the compounds of interest have very close chemical structures which prevents their isolation by HPLC at preparative scale due to insufficient resolution. ...
Poster
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Complementary use of CPC and LC techniques to isolate specific markers of Edelweiss (Leontopodium sp.): Leontopodic acids and 3,5-Dicaffeoyl quinic acid.
... References from the year 1582 mentioned the use of Edelweiss for the treatment of diarrhoea and dysentery (Tabernaemontanus, 1582). Several other applications for extracts and plant parts of Edelweiss have been described throughout the years, and recent phytochemical research has resulted in the detection of unknown and uncommon secondary metabolites, some with strong biological activities (Stuppner et al., 2002;Dobner et al., 2003aDobner et al., , b, 2004Schwaiger et al., 2004Schwaiger et al., , 2005Speroni et al., 2006;Hornick et al., 2008;Reisinger et al., 2009). These promising results have increased the interest in other species of this genus for pharmaceutical research, and thus the need for a more predictive system of classification within the genus. ...
Article
The genus Leontopodium comprises 30–41 species. The centre of diversity is the Sino-Himalayan region in south-western China, where about 15 species occur. The two species native to Europe, L. alpinum (known as the common ‘Edelweiss’) and L. nivale, are part of the cultural heritage of the people living there. Despite its importance, very little is known about the systematics of the genus. Because recent molecular studies have shown that species within this genus are closely related and difficult to distinguish with rDNA and cpDNA data, we used AFLPs to obtain a more detailed understanding of the phylogeny of the genus. Our main aims were as follows: (1) to clarify species relationships within the genus; and (2) to reveal information about the biogeography of the genus. We used AFLPs with six primer combinations to investigate 216 individuals in 38 populations of 16 different species. With AFLPs, we were able to recognize 10 different groups, all of which had strong bootstrap support. These results were also congruent with the morphology-based taxonomy of the genus. Most private and rare fragments were found in the Yunnan region (south-western China) relative to Europe and Mongolia/central China, suggesting a long-lasting in situ history of populations in the centre of diversity of the genus. Our results illustrate the utility of AFLPs to resolve phylogenetic relationships between these closely related species. © 2011 The Linnean Society of London, Botanical Journal of the Linnean Society, 2011, 165, 364–377.
... Edelweiss is a protected plant in many countries. While it is cultivated in large quantities in Switzerland [14], the isolation of relevant amounts from Edelweiss roots remains a laborious task due to the low content [10,15] and the thin and fibrous nature of the roots of cultivated plants [16]. As the chemical synthesis has not yet been described the biotechnological production might be an alternative approach to the procurement of relevant amounts of these lignans. ...
Article
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A hairy root line of Edelweiss (Leontopodium nivale ssp. alpinum (Cass.) Greuter) was obtained upon transformation with Agrobacterium rhizogenes strain ATCC15834. Elicitation of this line with silver nitrate, sucrose, methyl jasmonate and yeast extract at various concentrations in most cases resulted in a stimulation of lignan biosynthesis. Through elicitation with 6% sucrose the roots accumulated the pharmacologically active lignans leoligin and 5-methoxy-leoligin at levels of 0.0678% and 0.0372%, respectively, without significant growth inhibition. These lignan levels were comparable to those found in intact roots of cultivated Edelweiss. The biotechnological production of leoligin could be an attractive option for the continuous, field culture-independent production of the valuable secondary metabolites leoligin and 5-methoxy-leoligin.
... Moreover, in the tested extracts the presence of caffeoylglucaric acids (Fig. 5) (caffeoyl glucarate, dicaffeoyl glucarate and tricaffeoyl glucarate), as dominating compounds was detected. Caffeic acid glucarates were identified based on the negative ion MS 2 fragmentation: compounds showed a cleavage of one to three caffeoyl [MÀHÀ162] À moieties resulting in m/z 209 fragment, indicating the presence of glucaric acid (Maas et al., 2009;Ruiz et al., 2013;Schwaiger et al., 2005). Interestingly, what is more abundant in these compounds are aqueous extracts, while the ethanolic extracts contain mainly tricaffeoyl glucarates. ...
Article
Galinsoga ciliata Raf. Blake like G. parviflora Cav., comes from the Andes region. The chemical composition, activity and use are similar for both species. Galinsoga species are used in folk medicine as anti-inflammatory agents and accelerators for wound healing. Extracts from are applied topically onto the skin, to treat dermatological diseases, eczemas, lichens and hard-healing-wounds, and also to treat snakebites. Orally they used to cure flu and colds. In the studies using HPTLC method, different stationary phases, including unmodified silica gel, silica gels modified with CN, NH2, DIOL and RP18 groups were tried. The best separation of the tested compounds was achieved on silica gel plates, when as mobile phases mixtures- ethyl acetate-acetic acid-formic acid-water (100:11:11:26, v/v/v/v), ethyl acetate-methanol-formic acid-water (50:3:4:6, v/v/v/v) and ethyl acetate-methyl ethyl ketone-formic acid-water (30:9:3:3, v/v/v/v) - were used. Using reference substances, in the examined extracts the presence of flavonoids: patulitrin, quercimeritrin, quercitagetrin, and phenolic acids – caffeic and chlorogenic acids was found. HPLC analyses of extracts were carried out on a reversed-phase Zorbax SB column (150 x 2.1 mm, 1.9 µm). The mobile phase (A) was water/acetonitrile/formic acid (95:5:0.1, v/v/v) and the mobile phase (B) was acetonitrile/formic acid (100:0.1, v/v). A linear gradient system was used: 0-30 min., 1-30 % B. Application of HPLC-DAD-MS method confirmed the results obtained by HPTLC method. Moreover, in the tested extracts the presence of caffeoylglucaric acids as dominating compounds was detected.
... In order to compare the effect of the topology in the electrochemical behaviour of 7-9, the anodic oxidation of monomeric benzylic ester of FA, compound 10, is also discussed here. On the other hand, inspired by Leontopodic acid (a natural triester derived from CA with interesting antioxidant and protective DNA properties) [30], we prepared the new tripodal ester 11, whose conformational preferences were previously analysed in silico by our group [31]. Its electrochemical behaviour is also presented here through cyclic voltammetry results. ...
Article
The electrochemical behaviour of new ferulic acid derivatives, three dimeric and one tripodal esters as well as the monomeric benzylic ester, is described. All of them follow an ECE (electrochemical–chemical–electrochemical) oxidation mechanism. Electrografting processes were observed too, except in the case of the monomeric ester. Interestingly, topology seems to play an important role in their capacity of being adsorbed by the electrode, which suggest that a greater reactivity of the bi- and tri- radicals, probably generated during the first steps of electrochemical oxidation of this type of compounds or an increase of the van der Waals interactions between huge molecules and the electrode surface, could be the main responsible. In addition, electrodonating power, as that defined within the density functional theory, was estimated for the benzylic ester, one dimeric ester, the tripodal ester, and the ferulic acid. This quantity was compared with the corresponding experimental values of the oxidation potential. Results show that monomers are more effective for the process of donating electrons; however, a higher number of ferulic units increases the ability of the bis and tris structures to increase their electrodonating power.
... The new compound 1 and 21 known compounds were isolated after extraction and chromatographic separation over polyamide, SiO 2 , RP-SiO 2 , Sephadex LH-20, and preparative HPLC during a study of the constituent composition of PC from the aerial part of G. uliginosum collected in the Republic of Sakha (Yakutia). UV, MS, PMR, and 13 C NMR spectral data identified the known constituents as nepetin-7-O-glucoside (2); jaceosidin-7-O-glucoside (3); gnaphaloside A (4); gnaphaloside B (5); quercimeritrin (6); quercetagetrin (7); patulitrin (8); quercetagetin-7-O-(6s-O-caffeoyl)glucoside (9); tinctoside (10); spinacetin-7-O-glucoside (11); caffeic acid (12); 3-O-(13), 4-O- (14), 1,3-di-O- (15), 1,5-di-O- (16), 3,4-di-O-(17), 3,5-di-O- (18), 4,5-di-O- (19), 1,3,5-tri-O- (20), 3,4,5-tri-O-(21) caffeoylquinic acids; and leontopodic acid (22). Compounds 2-6, 12-20, and 22 were found previously in G. uliginosum [2][3][4][5]; 7-11 and 21 were detected for the first time. ...
Article
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The new flavonoid gnaphaloside C, which was identified based on UV, MS, and NMR spectral data as spinacetin-7-O-(6″-O-caffeoyl)-β-D-glucopyranoside, and 24 known compounds including for the first time from this species quercetagetrin, quercetagetin-7-O-(6″-O-caffeoyl)glucoside, patulitrin, tinctoside, and spinacetin-7-O-glucoside were isolated from the aerial part of Gnaphalium uliginosum. HPLC determined that G. uliginosum contained mainly caffeoylquinic acids (10.54–48.48 mg/g). The flavonoid content was 1.20–16.55 mg/g.
... The presence of this rare type of compounds was not reported in Inula sp. before, although the presence of di-tri-and tetracaffeoylglucaric acid derivatives was demonstrated in other genera of Asteroideae subfamily such as Leontopodium, Gnaphalium and Eupatorium (Schwaiger et al. 2005;Maas et al. 2009;Cicek et al. 2012 Quantification of caffeic acid derivatives in I. helenium callus culture was done by HPLC/PDA (results are shown in Table 1). Total content of hydroxycinnamic acid derivatives in the analyzed plant material, calculated as a sum of detected compounds, was about 1.4 % (on a DW basis). ...
Article
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Hydroalcoholic extract from Inula helenium callus tissue showed remarkable reducing capacity. An HPLC/DAD analysis revealed the presence of numerous hydroxycinnamic acid derivatives, including chlorogenic acid (5-O-CQA, 0.1 % dry weight) and 3,5-dicaffeoylquinic acid (3,5-DCQA, 0.3 % dry weight), which were among major constituents of the examined extract. Application of a hyphenated chromatographic method—UHPLC/DAD/MSn—allowed identification of sixteen compounds, derivatives of caffeic acid. Apart from the compounds commonly found in Inula sp., the plant material contained eight conjugates of caffeic acid with aldaric acid. The aldarates constituted over 50 % of the hydroxycinnamate fraction in the examined tissue. This is the first report on the occurrence of the caffeoylaldaric acids in Inula sp. and in a plant tissue culture.
... Edelweiss, Leontopodium alpinum, is an alpine plant that grows at high altitudes under harsh environmental conditions. It contains high amounts of flavonoids and leontopodic acid, and has been shown to have anti-bacterial, anti-oxidative and DNA-protective potential as well as antiinflammatory efficacy (51)(52)(53). Moreover, it was shown to have anti-aging effects in skin in a recent clinical study (54). ...
Article
Objectives: Hair loss and reduction of hair volume are hallmarks of hair disorders, such as telogen effluvium, or male or female pattern hair loss, and hair aging, which can cause severe distress in both men and women. Common anti-hair loss drugs carry some side-effects, therefore, novel, safer approaches targeting milder phenotypes are highly advocated. In this context, we investigated an extract of the alpine plant Edelweiss, Leontopodium alpinum var. Helvetia, for its ability to modulate hair follicle (HF) growth ex vivo and inhibit hair loss while increasing hair regeneration in vivo. Methods: Human amputated HFs were micro-dissected from three donors, two females and one male, and cultured ex vivo for 6 days. After treatment with 0.001% Edelweiss extract (EWDE), we investigated hair shaft production, and anagen/catagen conversion, and measured known parameters associated with hair growth, i.e., hair matrix keratinocyte proliferation and apoptosis, dermal papilla inductivity, and growth factors, by quantitative (immuno-) histomorphometry. To assess the anti-hair loss potential of the alpine plant compound, we performed a randomized, placebo-controlled human study enrolling Caucasian women and men, aged 18 to 65 years, with normal hair loss. After five months' daily use of an extract containing leave-on serum, we analysed hair density and anagen to catagen/telogen ratio by Trichogram analysis. Results: Our results revealed a significant prolongation in the anagen phase in HFs treated with 0.001% Edelweiss, as indicated by an increase in HFs remaining in anagen and a significant decrease in hair cycle score. In line with this effect, EWDE significantly stimulated hair matrix (HM) keratinocyte proliferation, and dermal papilla inductivity, as shown by a significant up-regulation of versican expression and alkaline phosphatase activity, and a tendential increase in FGF7 immunoreactivity in the dermal papilla of all HFs or only anagen VI HFs. Corroborating the ex vivo results, we observed a significant increase in growing hair shaft numbers (hair density) after treatment with Edelweiss extract formulation, and a tendential up-regulation in the anagen to catagen-telogen ratio. Conclusions: We show here, through several lines of evidence, that the selected extract of the alpine plant Leontopodium alpinum var Helvetia (Edelweiss) inhibits premature catagen induction, possibly by stimulating dermal papilla inductivity. It is therefore worth exploiting this extract clinically as an anti-hair loss agent, both for preventing aging-associated hair shedding and as an adjuvant therapy for hair loss disorders.
... To better interpret the BR results we report here the relative antioxidant (r.a.c.) value of a methanol extract from Wulfenia carinthiaca Jacq., that is (0.15 ð 0.01) μg/ml resorcinol (Re) equivalents: it must be taken into account that the W. carinthiaca extract contains the very powerful antioxidants phenylpropanoid glycosides (Cervellati et al., 2004b). Chlorogenic acid is a well-known antioxidant with DNA-protecting properties (Schweiger et al., 2005); its r.a.c. value is indeed high. ...
Article
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Deoxypodophyllotoxin content of the aerial parts of Anthriscus sylvestris Hoffm. growing at different altitudes was evaluated in comparison to the roots. The lignan accumulation in ground parts was at least double compared to aerial ones. In addition antioxidant-guided fractionation of the crude methanol extract of aerial parts was performed with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test. Active fractions contained mainly luteolin-7-O-glucoside and chlorogenic acid. Antioxidant properties of both crude extract and isolated compounds were also investigated with the Briggs-Rauscher (BR) oscillating reaction. A satisfactory agreement between the results obtained with the two methods was observed.
... In the second part of the 20 th century, some studies investigated the biology, ecology and chorology of L. alpinum (Sokolowska-Kulczycka, 1959;Maugini, 1962;Tira, Galeffi & Dimodica, 1970;Erhardt, 1993;Hook, 1994). At the beginning of the 21 st century, several unknown secondary metabolites were found in several species (Stuppner et al., 2002;Dobner et al., 2003aDobner et al., , b, 2004Schwaiger et al., 2004Schwaiger et al., , 2005Speroni et al., 2006;Hornick et al., 2008;Reisinger et al., 2009). Because some of these compounds now show biological activity (Safer et al., 2011), interest in other species and the whole genus has increased. ...
Article
We analysed pappus characters in 31 of the c. 34 accepted Leontopodium spp. (edelweiss). Micromorphological pappus character states were useful for discriminating between individual species and intrageneric groups. The pappus differs in number, length, breadth, surface structure, colour and the tips of the bristles. Several features characterize single species, for example a unique fan-like tip that is only found in L. franchetii. Leontopodium section Nobilia is supported by unusual pappus characters. Experimental evidence shows that the pappus of Leontopodium, previously thought to be caducous, is well suited for wind dispersal of the fruit. One clear trend is that species growing in sparsely vegetated, high-altitude regions often have more numerous and longer pappus bristles, particularly on the female flowers.
... The antioxidant activity of LACCE (1%) was comparable to that of NAC or much higher than vitamin C. LACCE contains a higher amount of chlorogenic acid, 3,5-Dicaffeoylquinic acid, leontopodic acid B, and leontopodic acid A than normal edelweiss callus cultures, as shown in a previous study [4]. In particular, a previous study identifying two leontopodic acids from edelweiss demonstrated the functional role of LACCE as an antioxidant agent [23]. ...
Article
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Edelweiss (Leontopodium Alpinum) in the family Asteraceae is a wildflower that grows in rocky limestone places. Here, we investigated the efficacy of edelweiss callus culture extract (Leontopodium Alpinum callus culture extract; LACCE) using multiple assays from in vitro to in vivo as well as transcriptome profiling. Several in vitro assay results showed the strong antioxidant activity of LACCE in response to UVB treatment. Moreover, LACCE suppressed inflammation and wrinkling; however, moisturizing activity was increased by LACCE. The clinical test in vivo demonstrated that constant application of LACCE on the face and skin tissues improved anti-periorbital wrinkles, skin elasticity, dermal density, and skin thickness compared with the placebo. The RNA-Sequencing results showed at least 16.56% of human genes were expressed in keratinocyte cells. LACCE up-regulated genes encoding several KRT proteins; DDIT4, BNIP3, and IGFBP3 were involved in the positive regulation of the developmental process, programmed cell death, keratinization, and cornification forming skin barriers, which provide many advantages in the human skin. By contrast, down-regulated genes were stress-responsive genes, including metal, oxidation, wounding, hypoxia, and virus infection, suggesting LACCE did not cause any harmful stress on the skin. Our comprehensive study demonstrated LACCE is a promising agent for anti-aging cosmetics.
... acid (Strack and Gross, 1990). Di-, tri-and tetracaffeoylglucaric acid derivatives have also been found in different species of asteraceous plants (Maas et al., 2009;Schwaiger et al., 2005;Stojakowska et al., 2016). In contrast, the acyl groups in the glucaric acid conjugates in I. tinctoria leaves were variable and situated biosynthetically upstream and downstream of caffeic acid. ...
... LA is a fully substituted hexaric acid derivative obtained from Leontopodium alpinum Cass., commonly known as edelweiss [86]. This molecule exerts a strong antioxidant capacity, and in particular was shown to protect U937 cells from DON-induced oxidative damage and increase GPx activity in these cells [87]. ...
Article
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Trichothecenes are a group of mycotoxins mainly produced by fungi of genus Fusarium. Due to high toxicity and widespread dissemination, T-2 toxin and deoxynivalenol (DON) are considered to be the most important compounds of this class. Trichothecenes generate free radicals, including reactive oxygen species (ROS), which induce lipid peroxidation, decrease levels of antioxidant enzymes, and ultimately lead to apoptosis. Consequently, oxidative stress is an active area of research on the toxic mechanisms of trichothecenes, and identification of antioxidant agents that could be used against trichothecenes is crucial for human health. Numerous natural compounds have been analyzed and have shown to function very effectively as antioxidants against trichothecenes. In this review, we summarize the molecular mechanisms underlying oxidative stress induced by these compounds, and discuss current knowledge regarding such antioxidant agents as vitamins, quercetin, selenium, glucomannan, nucleotides, antimicrobial peptides, bacteria, polyunsaturated fatty acids, oligosaccharides, and plant extracts. These products inhibit trichotheceneinduced oxidative stress by (1) inhibiting ROS generation and induced DNA damage and lipid peroxidation; (2) increasing antioxidant enzyme activity; (3) blocking the MAPK and NF-κB signaling pathways; (4) inhibiting caspase activity and apoptosis; (5) protecting mitochondria; and (6) regulating anti-inflammatory actions. Finally, we summarize some decontamination methods, including bacterial and yeast biotransformation and degradation, as well as mycotoxin-binding agents. This review provides a comprehensive overview of antioxidant agents against trichothecenes and casts new light on the attenuation of oxidative stress.
... LA is a fully substituted hexaric acid derivative obtained from Leontopodium alpinum Cass., commonly known as edelweiss [86]. This molecule exerts a strong antioxidant capacity, and in particular was shown to protect U937 cells from DON-induced oxidative damage and increase GPx activity in these cells [87]. ...
... However, popular references in Val d'Herens (Switzerland) and Tirol (Austria) say, that it can help reduce diarrhoea, tuberculosis, stomach ache. In fact, leotopdic acid, a secondary metabolite with antimicrobial and antioxidative properties has been identified (Schwaiger et al., 2005). Small and medium sized enterprises (SMEs) are highly interested in this plant without specific genetic improvement for health and other purposes so far and which in Switzerland is not available due to the protection by law, mentioned above. ...
Conference Paper
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Sustainability is a concept and a vision for how mankind deals with the resources of planet earth. Although this concept has a basis that is not time-bound, technological opportunities and pressing challenges for achieving a sustainable development change with time. At present, continued IT-development and miniaturisation (micro, nano) offer new opportunities for technological developments. Food concerns (e.g., pesticide residues in food), globalisation, human health problems in industrialised (and increasingly also other) societies and climate change are actual challenges which directly affect the development of horticulture . This paper presents examples of projects that address environmental, economic or social aspects of horticulture for contributing to a sustainable development. For instance, the European project ISAFRUIT works on innovative IT-controlled spraying technology aiming at a reduction of 80% in pesticide use. Another case presented shows the overriding importance of energy prices in greenhouse vegetable production and how it might remain nevertheless competitive. The domestication of Edelweiss (Leontopodium alpinum Cass.) for medicinal and cosmetic purposes contributes to sustainability by developing an economical alternative for the horticultural sector in marginal Alpine areas. Since 2005, Chalara black root rot has endangered Swiss carrot production, while with a focused total chain approach, and complementary networking, a R&D-based solution for the problem could be developed within a short time. Finally, the study on environmental footprints and sustainability of horticulture in the United Kingdom shows how it can be valued with regard to sustainability as compared to other sectors of agriculture. Finally, the paper provides some conceptual guidance how, with a simple concept, sustainability can be improved while applying various methods for monitoring and quantifying it.
... Recent studies show that the root extract exhibits analgesic effects in the rat paw edema test (Speroni et al., 2006). Leontopodic acid, one of the active compounds of the plant, is a potent antioxidant (Schwaiger et al., 2005). ...
Article
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The rhizosphere of plants is enriched in nutrients facilitating growth of microorganisms, some of which are recruited as endophytes. Endophytes, especially Actinobacteria, are known to produce a plethora of bioactive compounds. We hypothesized that Leontopodium nivale subsp. alpinum (Edelweiss), a rare alpine medicinal plant, may serve as yet untapped source for uncommon Actinobacteria associated with this plant. Rhizosphere soil of native Alpine plants was used, after physical and chemical pre-treatments, for isolating Actinobacteria. Isolates were selected based on morphology and identified by 16S rRNA gene-based barcoding. Resulting 77 Actinobacteria isolates represented the genera Actinokineospora, Kitasatospora, Asanoa, Microbacterium, Micromonospora, Micrococcus, Mycobacterium, Nocardia, and Streptomyces. In parallel, Edelweiss plants from the same location were surface-sterilized, separated into leaves, roots, rhizomes, and inflorescence and pooled within tissues before genomic DNA extraction. Metagenomic 16S rRNA gene amplicons confirmed large numbers of actinobacterial operational taxonomic units (OTUs) descending in diversity from roots to rhizomes, leaves and inflorescences. These metagenomic data, when queried with isolate sequences, revealed an overlap between the two datasets, suggesting recruitment of soil bacteria by the plant. Moreover, this study uncovered a profound diversity of uncultured Actinobacteria from Rubrobacteridae, Thermoleophilales, Acidimicrobiales and unclassified Actinobacteria specifically in belowground tissues, which may be exploited by a targeted isolation approach in the future.
... L. alpinum Cass.), Asteraceae). [17,18] 3,4-Di-O-caffeoylquinic acid methyl ester (9), 3,4-Di-O-caffeoyl-epi-quinic acid methyl ester (10), and 3,5-Di-O-caffeoyl-epi-quinic acid methyl ester (11) were isolated from the ethanol extract of the roots of Calea urticifolia (Mill.) DC. (Asteraceae) (unpublished data, manuscript under preparation). ...
... References from the year 1582 mentioned the use of Edelweiss for the treatment of diarrhoea and dysentery (Tabernaemontanus 1582). Several other applications for extracts and plant parts of Edelweiss have been described throughout the years, and recent phytochemical research has resulted in the detection of unknown and uncommon secondary metabolites, some with strong anti-tumour and anti-inflammatory biological activities, and they promote choles- terol efflux etc. (Comey & al. 1997;Hook & Sheridan 2001;Stuppner & al. 2002;Dobner & al. 2003a, 2003b, 2004, Dweck 2004Schwaiger & al. 2004Schwaiger & al. , 2005Speroni & al. 2006;Hornick & al. 2008;Reisinger & al. 2009;Tauchen & Kokoska 2016;Wang & al. 2016). ...
Article
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Autecology and ex situ growth of Leontopodium nivale subsp. nivale (Asteraceae) from North Pirin marbles (SW Bulgaria) Abstract Kozuharova, E., Panayotov, M. & Spadaro, V.: Autecology and ex situ growth of Leontopodium nivale subsp. nivale (Asteraceae) from North Pirin marbles (SW Bulgaria).-Fl. Medit. 28: 187-206. 2018.-ISSN: 1120-4052 printed, 2240-4538 online. Leontopodium nivale subsp. nivale is a local and disjunct endemic of the central Apennines in Italy and the Pirin Mountains in Bulgaria. The aim of this study is to investigate in situ micro-habitat specifics and ex situ ontogenesis regarding the possible future cultivation and to evaluate hazards for wild populations in conditions of human impact and climate change. Leontopodium nivale subsp. nivale is stenobiont which is difficult to grow ex situ and therefore particularly vulnerable. Its wild habitats and populations in Pirin Mts. should be efficiently protected. The results of our study indicate that the stenobiontic plants such as Leontopodium nivale subsp. nivale are particularly subject to hazard.
Chapter
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A recent report on an intense CO 2 and CO evolution in the Briggs-Rauscher (BR) reaction revealed that iodination of malonic acid (MA) is not the only important organic reaction in the classical BR oscillator. To disclose the source of the gas evolution, iodomalonic (IMA) and diiodomalonic (I2MA) acids were prepared by iodinating MA with nascent iodine in a semibatch reactor. The nascent iodine was generated by an iodide inflow into the reactor, which contained a mixture of MA and acidic iodate. Some CO2 and a minor CO production was observed during these iodinations. It was found that in an aqueous acidic medium the produced I2MA is not stable but decomposes slowly to diiodoacetic acid and CO2. The first-order rate constant of the I 2MA decarboxylation at 20 degrees C was found to be k1 = 9 x 10(-5) s(-1), which is rather close to the rate constant of the analogous decarboxylation of dibromomalonic acid under similar conditions (7 x 10(-5)s(-1)). From the rate of the CO2 evolution, the I2MA concentration can be calculated in a MA-IMA-I2MA mixture as only I2MA decarboxylates spontaneously but MA and IMA are stable. Following CO2 evolution rates, it was proven that I2MA can react with MA in the reversible reaction I2MA + MA <--> 2 IMA. The equilibrium constant of this reaction was calculated as K = 380 together with the rate constants of the forward k 2 = 6.2 x 10 (-2) M (-1)s(-1) and backward k-2 = 1.6 x 10(-4) M(-1)s(-1) reactions. The probable mechanism of the reaction is I(+1) transfer from I2MA to MA. The presence of I(+1) in a I2MA solution is demonstrated by its reduction with ascorbic acid. To estimate the fraction of CO2 coming from the decarboxylation of I2MA in an oscillatory BR reaction, the oscillations were inhibited by resorcinol. Unexpectedly, all CO2 and CO evolution was interrupted for more than one hour after injecting a small amount of resorcinol (10(-5) M initial concentration in the reactor). Finally, some implications of the newly found I(+1) transfer reactions and the surprisingly effective inhibition by resorcinol regarding the mechanism of the oscillatory BR reaction are discussed. The latter is explained by the ability of resorcinol to scavenge free radicals including iodine atoms without producing iodide ions.
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It was found that the inhibitory effect of resorcinol is less pronounced if it is added in a later stage of the Briggs-Rauscher reaction, which indicates that an accumulating intermediate--most probably iodomalonic acid--can suppress the inhibition. In fact, when iodomalonic acid was added to the reaction mixture, the inhibitory period was shortened considerably even at micromolar levels of the iodomalonic acid concentration. Moreover, iodomalonic acid can accelerate the rate of the reaction when applied in the same low concentrations, suggesting that it can be an autocatalytic intermediate of the Briggs-Rauscher reaction.
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A new method for monitoring the relative activity of antioxidants is presented, and its advantages and limits are discussed. The method is based on the previously reported inhibitory effects of free-radical scavengers on the oscillations of the Briggs-Rauscher reaction. The effect consists of an immediate cessation of oscillations, an inhibition time that linearly depends on the concentration of the antioxidant added, and subsequent regeneration of oscillations. Here the effects of ten antioxidants (pyrocatechol (=benzene-1,2-diol), ferulic acid (=3-(4-hydroxy-3-methoxyphenyl)prop-2-enoic acid), caffeic acid (=3-(3,4-dihydroxyphenyl)prop-2-enoic acid), 2,6-, 3,4-, 2,4-, 3,5-, and 2,5-dihydroxybenzoic acids, homovanillic acid (=4-hydroxy-3-methoxybenzeneacetic acid), and resorcinol (=benzene-1,3-diol)) were studied in detail. Relative antioxidant activities of these substances with respect to resorcinol were determined in different ways on the basis of inhibition times. The limits of the calculated values of relative activity based on the Briggs-Rauscher reaction are the same as those obtained with other analytical procedures and are discussed here. The new method is inexpensive: reagents and apparatus are commonly used in all chemical laboratories. The thermochemical behavior of the Briggs-Rauscher reaction and the dependence of inhibition time on the temperature were also carefully investigated and taken into account. A semiquantitative mechanistic interpretation of the inhibitory effects based on a suitable kinetic model is given.
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A method to determine the relative antioxidant capacity of radical scavengers based on the inhibition of the oscillations of the BriggsRauscher (BR) oscillating reaction was previously reported. A semiquantitative mechanistic interpretation of the inhibitory effects required two steps to obtain simulated inhibition times in very good agreement with the experimental ones. The first step is inhibitory, involving H-atom transfer from antioxidant to the HOO. radical; the second step is a first-order degradation of the antioxidant to unspecified products. Since the degradation may be due to oxidation and/or iodination of the antioxidant, we studied the kinetics of the subsystems IO(H+)+antioxidant and I2(H+)+antioxidant. We used 2,5- and 2,6-dihydroxybenzoic acids, caffeic acid (=3-(3,4-dihydroxyphenyl)prop-2-enoic acid), ferulic acid (=3-(4-hydroxy-3-methoxyphenyl)prop-2-enoic acid), pyrocatechol (=benzene-1,2-diol), and hydroquinone (=benzene-1,4-diol) as antioxidants. Spectra in the wavelength range 500–250 nm were repeated at given time intervals to follow the peaks of the iodine and oxidation products, which were mainly quinones. For the iodination of the above diphenols (=benzenediol derivatives) the substitution and/or addition reactions with I2 or HOI were found to be relatively slow compared to oxidation by IO. Approximate rate constants for oxidation were obtained on the basis of a reasonable kinetic model by using a suitable numerical integration program. Although these complexities can arise also in the completely inhibited BR oscillator, we believe that the inhibitory effects are due to the HOO. scavenging action by diphenols or by quinones since HOO. radicals are also potential reducing agents. We propose two steps that could maintain a small reservoir of diphenol, while both quinone and diphenol deplete HOO. radicals. In short, the complexities do not affect the method for monitoring the relative activity of antioxidants based on the BR oscillating reaction. The effects of temperature on the inverse of the oscillatory time in the BR-uninhibited system, on the inverse of inhibition times, and on the time length of the resumed oscillations for four antioxidants were also investigated. Apparent average activation energies were obtained.
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This article provides a study of a new method recently reported and its applicability for the measurements of antioxidant activity of several German white wines. The results obtained are compared with those of a commonly used method, total antioxidant status (TAS) measurements. This new method is based on the inhibitory effects by antioxidants scavengers of free radicals on the Briggs-Rauscher (BR) oscillating reaction. The effect consists of an immediate cessation of the oscillatory regime, an inhibition time that depends linearly on the quantity of the antioxidant added, and subsequent regeneration of oscillations. Sixteen German white wines were tested with the new method, recording potentiometrically the inhibition times produced on an active BR mixture. The different results concerning the ranking order of the antioxidant activity of the examined wines is ascribed to the different pH values at which the two testing methods work. The method based on the BR reaction works in fact at pH&#442, which is similar to that of the fluids in the human stomach while the TAS method works at a pH value near that of the blood (pH=7.4). The mechanism of the antioxidant action of phenols contained in the wines at pHƺ is qualitatively illustrated. The benefits of the novel method are described.
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The antioxidant capacity of aqueous extracts of 20 vegetables and 16 fruits have been determined using the Briggs-Rauscher (BR) reaction method. Like other methods, the BR reaction method is also based on the generation of free radicals in the reaction mixture. Antioxidant scavengers of free radicals added to an active oscillatory BR regime cause an immediate cessation of the oscillatory regime, an inhibition time that linearly depends on the amount of the antioxidant added, and subsequent regeneration of oscillations. The BR reaction method works at pH≈2, which is similar to that of the fluids in the human stomach. It is known that a vegetarian diet can reduce the risk of stomach cancer and it is therefore interesting to determine the activity of antioxidants at low pH values. Different plants were tested with the BR reaction method, recording potentiometrically the inhibition times produced by their extracts on an active BR mixture. The results concerning the order of the antioxidant activity of the examined plants are illustrated and discussed. A comparison with the ranking order obtained with other methods is also given.
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In this study, six common tests for measuring antioxidant activity were evaluated by comparing four antioxidants and applying them to beverages (tea and juices): Trolox equivalent antioxidant capacity assay (TEAC I-III assay), Total radical-trapping antioxidant parameter assay (TRAP assay), 2,2-diphenyl-l-picrylhydrazyl assay (DPPH assay), N,N-dimethyl-p-phenylendiamine assay (DMPD assay), Photochemiluminescence assay (PCL assay) and Ferric reducing ability of plasma assay (FRAP assay). The antioxidants included gallic acid representing the group of polyphenols, uric acid as the main antioxidant in human plasma, ascorbic acid as a vitamin widely spread in fruits and Trolox as water soluble vitamin E analogue. The six methods presented can be divided into two groups depending on the oxidising reagent. Five methods use organic radical producers (TEAC I-III, TRAP, DPPH, DMPD, PCL) and one method works with metal ions for oxidation (FRAP). Another difference between these tests is the reaction procedure. Three assays use the delay in oxidation and determine the lag phase as parameter for the antioxidant activity (TEAC I, TRAP, PCL). They determine the delay of radical generation as well as the ability to scavenge the radical. In contrast, the assays TEAC II and III, DPPH, DMPD and FRAP analyse the ability to reduce the radical cation (TEAC II and III, DPPH, DMPD) or the ferric ion (FRAP). The three tests acting by radical reduction use preformed radicals and determine the decrease in absorbance while the FRAP assay measures the formed ferrous ions by increased absorbance. Gallic acid was the strongest antioxidant in all tests with exception of the DMPD assay. In contrast, uric acid and ascorbic acid showed low activity in some assays. Most of the assays determine the antioxidant activity in the micromolar range needing minutes to hours. Only one assay (PCL) is able to analyse the antioxidant activity in the nanomolar range. Black currant juice showed highest antioxidant activity in all tests compared to tea, apple juice and tomato juice. Despite these differences, results of these in vitro assays give an idea of the protective efficacy of secondary plant products. It is strongly recommended to use at least two methods due to the differences between the test systems investigated.
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Cynara scolymus leaves extracts have long been used in folk medicine for their choleretic and hepatoprotective activities, that are often related to the cynarin content. These therapeutic properties are also attributed to mono- and di-caffeoylquinic acids and since commercial C. scolymus preparations can differ for their activities, we studied four extracts to evaluate, if present, a relationship between the hepatobiliary properties of the different preparations and their content in phenolics. The antioxidant activity of the commercial preparations examined was also considered in an in vitro system. The results showed that the extract with the highest content in phenolic derivatives (GAE) exerted the major effect on bile flow and liver protection. Also the results of the antioxidant capacity (BR) of the different preparations are in good agreement with the results obtained in vivo. On the contrary, administering rats with doses of chlorogenic acid, equivalent to those present in this extract, we did not observe any choleretic or protective action. An histopathological analysis of liver sections confirmed the biochemical results. Perhaps caffeoyl derivatives have a role in the therapeutic properties of C. scolymus extracts, as reported in literature for "in vitro" studies, but when administered alone, they are not so effective in exerting this action.
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Relative antioxidant activities of a methanolic extract of three phenylpropanoid glycosides and three iridoid glycosides from Wulfenia carinthiaca were evaluated using the Briggs-Rauscher (BR) reaction method. This method is based on the inhibitory effects by antioxidants on oscillations of the BR reaction. The total extract showed a certain antioxidant activity with respect to resorcinol chosen as standard. The three phenylpropanoid glycosides showed a very high relative antioxidant activity while iridoid glycosides had practically no activity. These experimental results were confirmed by empirical calculations based on the BDE (Bond Dissociation Enthalpy) theory. The total phenolic content was also measured for the phenylpropanoid glycosides using the Folin-Ciocalteu reagent. The obtained values as gallic acid equivalents were in perfect agreement with the relative antioxidant activities. From a pharmacological point of view the results obtained demonstrate that the methanolic extract of W. carinthiaca have antinociceptive and antiedematogenic effects in the different models adopted. The plant extract produced a significant inhibition, dose related, of the rat paw edema induced by carrageenin. The anti-inflammatory activity is probably due to the phenylpropanoid compounds present in the plant. The histological sections of paw tissue in animals treated with Wulfenia carinthiaca extract confirmed the anti-inflammatory effects. The results of the antinociceptive assay indicated a significant reduction on the number of abdominal writhes of mice, induced by acetic acid.
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A method for the screening of antioxidant activity is reported as a decolorization assay applicable to both lipophilic and hydrophilic antioxidants, including flavonoids, hydroxycinnamates, carotenoids, and plasma antioxidants. The pre-formed radical monocation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+) is generated by oxidation of ABTS with potassium persulfate and is reduced in the presence of such hydrogen-donating antioxidants. The influences of both the concentration of antioxidant and duration of reaction on the inhibition of the radical cation absorption are taken into account when determining the antioxidant activity. This assay clearly improves the original TEAC assay (the ferryl myoglobin/ABTS assay) for the determination of antioxidant activity in a number of ways. First, the chemistry involves the direct generation of the ABTS radical monocation with no involvement of an intermediary radical. Second, it is a decolorization assay; thus the radical cation is pre-formed prior to addition of antioxidant test systems, rather than the generation of the radical taking place continually in the presence of the antioxidant. Hence the results obtained with the improved system may not always be directly comparable with those obtained using the original TEAC assay. Third, it is applicable to both aqueous and lipophilic systems.
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New hydroxycinnamic acid esters have been isolated from primary leaves of rye and identified as positional isomers of (E)-0-feruloylgluconic acids on the basis of TLC, HPLC, FAB mass spectrometry, 1H NMR and 13C NMR spectroscopy. The 2-(E)-0-feruloylgluconic acid was the major isomer. A second ferulic acid ester, a very minor constituent in rye, was identified as 2(E)-0-feruloyl-4-methoxyaldaric acid, which is probably a glucaric acid derivative.
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Three new compounds, including a benzofuran, 1-{(2R*,3S*)-3-(β-D-glucopyranosyloxy)-2,3-dihydro-2-[1-(hydroxymethyl)vinyl]-1-benzofuran-5-yl}ethanone (1), a lignan, [(2S,3R,4R)-4-(3,4-dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)tetrahydrofuran-3-yl]methyl (2E)-2-methylbut-2-enoate (2), and a silphiperfolene-type sesquiterpene, [(1S,2Z,3aS,5aS,6R,8aR)-1,3a,4,5,5a,6,7,8-octahydro-1,3a,6-trimethylcyclopenta[c]pentalen-2-yl]methyl acetate (3), together with the known coumarins obliquin (4) and its 5-methoxy derivative 5 were isolated from the roots of Leontopodium alpinum. Another known coumarin derivative, 5-hydroxyobliquin (6), was isolated from the roots of L. leontopodioides. The structures of these compounds were established by spectroscopic studies.
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The TEAC (Trolox equivalent antioxidant capacity) assay is based on scavenging of 2,2′-azinobis-(3- ethylbenzothiazoline-6-sulfonate) radical anions (ABTS−). In this report we describe a modification based on pre-generation of the ABTS radical anions with a thermolabile azo compound, 2,2′-azobis- (2-amidinopropane)HCl (ABAP). This modification makes the assay less susceptible to artefacts, e.g. influence on the radical generation process. For most antioxidants tested, a biphasic reaction pattern was seen, i.e. a fast and slow scavenging rate. We evaluated application of the assay with both lipophilic and hydrophilic compounds with antioxidant capacity. Several organic solvents, compatible with water, were tested with α-tocopherol, quercetin and β-carotene. It was found that the TEACs differed in various solvents. Under standardized conditions additivity of TEACs obtained from individual antioxidants could be demonstrated. This might enable application of the assay for the identification of “unknown” antioxidants.
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1. A new method has been developed for measuring the total antioxidant capacity of body fluids and drug solutions, based on the absorbance of the ABTS*+ radical cation. 2. An automated method for use on a centrifugal analyser, as well as a manual method, is described. 3. The procedure has been applied to physiological antioxidant compounds and radical-scavenging drugs, and an antioxidant ranking was established based on their reactivity relative to a 1.0 mmol/l Trolox standard. 4. The Trolox equivalent antioxidant capacity of plasma from an adult reference population has been measured, and the method optimized and validated. 5. The method has been applied to investigate the total plasma antioxidant capacity of neonates and how this may be compromised in prematurity.
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A method for the screening of antioxidant activity is reported as a decolorization assay applicable to both lipophilic and hydrophilic antioxidants, including flavonoids, hydroxycinnamates, carotenoids, and plasma antioxidants. The pre-formed radical monocation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+) is generated by oxidation of ABTS with potassium persulfate and is reduced in the presence of such hydrogen-donating antioxidants. The influences of both the concentration of antioxidant and duration of reaction on the inhibition of the radical cation absorption are taken into account when determining the antioxidant activity. This assay clearly improves the original TEAC assay (the ferryl myoglobin/ABTS assay) for the determination of antioxidant activity in a number of ways. First, the chemistry involves the direct generation of the ABTS radical monocation with no involvement of an intermediary radical. Second, it is a decolorization assay; thus the radical cation is pre-formed prior to addition of antioxidant test systems, rather than the generation of the radical taking place continually in the presence of the antioxidant. Hence the results obtained with the improved system may not always be directly comparable with those obtained using the original TEAC assay. Third, it is applicable to both aqueous and lipophilic systems.
Article
A procedure based on density functional theory is used for the calculation of the gas-phase bond dissociation enthalpy (BDE) and ionization potential for molecules belonging to the class of phenolic antioxidants. We show that use of locally dense basis sets (LDBS) vs full basis sets gives very similar results for monosubstituted phenols, and that the LDBS procedure gives good agreement with the change in experimental BDE values for highly substituted phenols in benzene solvent. Procedures for estimating the O--H BDE based on group additivity rules are given and tested. Several interesting classes of phenolic antioxidants are studied with these methods, including commercial antioxidants used as food additives, compounds related to Vitamin E, flavonoids in tea, aminophenols, stilbenes related to resveratrol, and sterically hindered phenols. On the basis of these results we are able to interpret relative rates for the reaction of antioxidants with free radicals, including a comparison of both H-atom-transfer and single-electron-transfer mechanisms, and conclude that in most cases H-atom transfer will be dominant.
Article
The radical cation 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate), (ABTS*+) was utilized in an on-line HPLC method for the detection of radical scavengers in complex matrixes. The HPLC-separated analytes react postcolumn with the preformed ABTS*+, and the induced bleaching is detected as a negative peak by an absorbance detector at 734 nm. An optimized instrumental and experimental setup is presented. The method is suitable for both isocratic and gradient HPLC runs using mobile phases containing 100% organic solvent or its solution in water, weak acids, or buffers (pH 3-7.4). The method is sensitive, selective, relatively simple, applicable to compounds of different chemical natures; uses common instruments and inexpensive reagents; and has a time-saving, nonlaborious experimental protocol. It can also be used for quantitative analysis. The method was applied to several pure natural antioxidants and plant extracts. The minimum detectable concentration varied from 0.02 to 0.13 microg/mL, depending on the compound tested. The method can be applied to perform kinetic studies, which is illustrated by determination of Trolox equivalent antioxidant capacities (TEAC) of several known antioxidants in flow injection mode.
Article
The oxidation of D-(+)-glucose to D-glucaric acid using the TEMPO-like nitroxide oxidation catalyst, 4-acetamido-2,2,6,6-tetramethyl-1-piperidinyloxy (4-acetamido-TEMPO) was carried out using several oxidizing agents and co-catalyst. The pH and temperature of the reactions were closely monitored to decrease degradations during the oxidation, and several isolation methods were explored.
Article
A modified version of the comet assay was employed to investigate the effect in vitro of dietary antioxidants in the subcellular environment. Human lymphocytes were isolated, embedded in agarose gel, lysed in high ionic strength solution with Triton X-100, and then incubated for 30 min with antioxidants at different concentrations. Gels were washed, and the comet assay performed on cells stressed by 5 min incubation with 45 microM hydrogen peroxide and on unstressed cells in parallel. Results showed that alpha-tocopherol was protective against oxidant stress, whereas caffeic acid did not protect, and at high concentration (100 microM) caused increased DNA damage. Results for quercetin suggested a direct damaging effect, but this did not reach statistical significance. However, at low concentration (3.1 microM), quercetin appeared protective. Thus some dietary antioxidants that have been shown previously to have a protective effect in the 'standard', whole-cell, comet assay cause DNA damage in this lysed-cell version. The cell membrane may have an important role in limiting cellular access of these 'double-edged' antioxidants. Furthermore, the absolute concentration and the presence of complementary or synergistic intracellular antioxidants may delineate the type of action of a putative antioxidant. We suggest that, used in conjunction with the standard comet assay, this lysed-cell version is useful for assessing the effect of the cell membrane and intracellular systems on susceptibility of DNA to oxidative damage, and will help determine the mechanism of protection or damage by phytochemicals.
Article
A new method based on the inhibitory effects of antioxidants on the oscillations of the hydrogen peroxide, acidic iodate, malonic acid, and Mn(II)-catalyzed system (known as the Briggs-Rauscher reaction), was used for the evaluation of antioxidative capacity. With this method, which works near the pH of the fluids in the stomach (pH approximately 2), a group of natural compounds present in fruits and vegetables or in medicinal plants assumed to have antioxidant capacity, was tested successfully. The aim of the present study is to evaluate the antioxidative properties of some active principles contained in vegetables and aromatic plants, namely, cynarin (from Cynara scolymus), rosmarinic acid (from Rosmarinus officinalis), echinacoside (from Echinacea species), puerarin (from Pueraria lobata), and oleuropein (from Olea europea). Also studied with the Briggs-Rauscher reaction method was the antioxidant activity of cyanidin 3-O-beta-glucopyranoside (from Citrus aurantium) in order to compare the results with those obtained by other methods. The conclusions on the dependency of the antioxidative activity on the pH of the testing system are given.
Article
Five caffeic acid derivatives were found in the roots of yacon, Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson, Asteraceae, as the major water-soluble phenolic compounds. The structures of these compounds were determined by analysis of spectroscopic data. Two of these were chlorogenic acid (3-caffeoylquinic acid) and 3,5-dicaffeoylquinic acid, common phenolic compounds in plants of the family Asteraceae. Three were esters of caffeic acid with the hydroxy groups of aldaric acid, derived from hexose. The structure of the aldaric moiety was determined by hydrolysis and comparison of NMR spectra with those of standard aldaric acids. The compounds were novel caffeic acid esters of altraric acid: 2,4- or 3,5-dicaffeoylaltraric acid, 2,5-dicaffeoylaltraric acid, and 2,3,5- or 2,4,5-tricaffeoylaltraric acid.
Article
Extracts and individual constituents of Leontopodium alpinum Cass. (Asteraceae) were tested for their antimicrobial activity in two different assays. Extracts were screened in agar diffusion assays, whereas the minimum inhibitory concentrations (MIC) of single compounds were determined by the microbroth dilution method according to NCCLS criteria. Significant antimicrobial activities were found against various strains of Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes strains. These results support the ethnomedicinal use of Leontopodium alpinum for the treatment of respiratory and abdominal disorders.
Article
The Trolox Equivalent Antioxidant Capacity (TEAC) assay is based on the scavenging of the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical (ABTS(*)) converting it into a colorless product. The degree of decolorization induced by a compound is related to that induced by trolox, giving the TEAC value. The assay is frequently used for constructing structure activity relationships (SARs). HPLC analysis of the reaction mixture, obtained after scavenging of ABTS(*) by the flavonoid chrysin, shows that a product is formed that also reacts with ABTS(*). The product has a higher antioxidant capacity and reacts faster with ABTS(*) than the parent compound, chrysin. In contrast to the reaction product of chrysin, the reaction product of trolox, which is formed during scavenging of ABTS(*), i.e. trolox quinone, does not react with ABTS(*). The experiments show that the TEAC is the antioxidant capacity of the parent compound plus the potential antioxidant capacity of the reaction product(s). This means that the TEAC assay does not necessarily reflect the antioxidant effect of only one structure. This hampers the applicability of the assay for the construction of SARs and for ranking antioxidants.
Article
An increasing body of evidence from animal models, human specimens and cell lines points to reactive oxygen species as likely involved in the pathways, which convey both extracellular and intracellular signals to the nucleus, under a variety of pathophysiological conditions. Indeed, reactive oxygen species (ROS), in a concentration compatible with that detectable in human pathophysiology, appear able to modulate a number of kinases and phosphatases, redox sensitive transcription factors and genes. This type of cell signalling consistently implies the additional involvement of other bioactive molecules that stem from ROS reaction with cell membrane lipids. The present review aims to comprehensively report on the most recent knowledge about the potential role of ROS and oxidised lipids in signal transduction processes in the major events of cell and tissue pathophysiology. Among the lipid oxidation products of ROS-dependent reactivity, which appear as candidates for a signalling role, there are molecules generated by oxidation of cholesterol, polyunsaturated fatty acids and phospholipids, as well as lysophosphatidic acid and lysophospholipids, platelet activating factor-like lipids, isoprostanes, sphingolipids and ceramide.
Article
Phytochemical investigations of the roots of Leontopodium alpinum Cass. resulted in the isolation and structure elucidation of six novel compounds and two known compounds. Novel constituents could be identified as the polyacetylenes 1-acetoxy-3-angeloyloxy-(4 E,6 E)-tetradeca-4,6-diene-8,10,12-triyne and its (6 Z)-isomer, the kaurenic acid derivative methyl ent-7alpha,9alpha-dihydroxy-15beta-[(2 Z)-2-methyl-but-2-enoyloxy]kaur-16-en-19-oate, the bisabolane derivative (1 R*,3 S*,4 R*,6 S*)-9-(acetoxy)-4-hydroxy-1-[(2Z)-2-methylbut-2-enoyloxy]bisabol-10(11)-ene and the lignans [(2 S,3 R,4 R)-4-(3,4-dimethoxybenzyl)-2-(3,4,5-trimethoxyphenyl)-tetrahydrofuran-3-yl]-methyl-(2 Z)-2-methylbut-2-enoate and its 3,4,5-trimethoxybenzyl derivative. Known compounds, reported here for the first time for the genus Leontopodium, were identified as ent-kaur-16-en-19-oic acid and T-cadinol. The obtained compounds were tested together with 15 previously described compounds of L. alpinum in an ex vivo leukotriene biosynthesis inhibition assay. The highest activities were determined for the bisabolane derivates (IC50: 7.7 to 11.4 microM), one lignan (IC50: 10.7 microM) and the ent-kaurenoate (IC50: 10.4 microM).
  • R Cervellati
  • E Speroni
  • P Govoni
  • M C Guerra
  • S Costa
  • U W Arnold
  • H Stuppner
Cervellati, R.; Speroni, E.; Govoni, P.; Guerra, M. C.; Costa, S.; Arnold, U. W.; Stuppner, H. Wulfenia carinthiaca Jacq., antioxidant and pharmacological activities. Z. Naturforsch. 2004, 59c, 255-262.
Sesquiterpenes from Leontopodium alpinum
  • A I Grey
  • I L Hook
  • P James
  • H Sheridan
Grey, A. I.; Hook, I. L.; James, P.; Sheridan, H. Sesquiterpenes from Leontopodium alpinum. Phytochemistry 1999, 50, 1057-1060. Corrigendum: Phytochemistry 2000, 54, 551.
A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates
  • N J Miller
  • C A Rice-Evans
  • M J Davies
  • V Gopinhathan
  • A Milner
Miller, N. J.; Rice-Evans, C. A.; Davies, M. J.; Gopinhathan, V.; Milner, A. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin. Sci. 1993, 84, 407-412.
Oxidative stress and cell signaling
  • Poli