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  • 301.
    Vikeved, Elisabet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    "Ligand fishing" in chemical space reveals new potential leishmanicidals2015Ingår i: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 81, nr 16, s. 1473-1473Artikel i tidskrift (Övrigt vetenskapligt)
  • 302.
    Vikeved, Elisabet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Alsmark, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Natl Vet Inst SVA, Dept Microbiol, Uppsala, Sweden..
    The Dynamics of Lateral Gene Transfer in Genus Leishmania - A Route for Adaptation and Species Diversification2016Ingår i: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 10, nr 1, artikel-id e0004326Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The genome of Leishmania major harbours a comparably high proportion of genes of prokaryote origin, acquired by lateral gene transfer (LGT). Some of these are present in closely related trypanosomatids, while some are detected in Leishmania only. We have evaluated the impact and destiny of LGT in genus Leishmania. Methodology/Principal Findings To study the dynamics and fate of LGTs we have performed phylogenetic, as well as nucleotide and amino acid composition analyses within orthologous groups of LGTs detected in Leishmania. A set of universal trypanosomatid LGTs was added as a reference group. Both groups of LGTs have, to some extent, ameliorated to resemble the recipient genomes. However, while virtually all of the universal trypanosomatid LGTs are distributed and conserved in the entire genus Leishmania, the LGTs uniquely present in genus Leishmania are more prone to gene loss and display faster rates of evolution. Furthermore, a PCR based approach has been employed to ascertain the presence of a set of twenty LGTs uniquely present in genus Leishmania, and three universal trypanosomatid LGTs, in ten additional strains of Leishmania. Evolutionary rates and predicted expression levels of these LGTs have also been estimated. Ten of the twenty LGTs are distributed and conserved in all species investigated, while the remainder have been subjected to modifications, or undergone pseudogenization, degradation or loss in one or more species. Conclusions/Significance LGTs unique to the genus Leishmania have been acquired after the divergence of Leishmania from the other trypanosomatids, and are evolving faster than their recipient genomes. This implies that LGT in genus Leishmania is a continuous and dynamic process contributing to species differentiation and speciation. This study also highlights the importance of carefully evaluating these dynamic genes, e.g. as LGTs have been suggested as potential drug targets.

  • 303.
    Vinnersten, Annika
    et al.
    Uppsala universitet, Enheten för musik och museer, Uppsala linneanska trädgårdar, Botaniska trädgården.
    Larsson, Sonny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Colchicine is still a chemical marker for the expanded Colchicaceae2010Ingår i: Biochemical Systematics and Ecology, ISSN 0305-1978, E-ISSN 1873-2925, Vol. 38, nr 6, s. 1193-1198Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Samples from 25 genera of the lily family, in its widest circumscription, were subjected to nanospray mass spectrometry analysis to investigate the presence of colchicine. This alkaloid has been proposed to have a restricted distribution within the former lilioid subfamily Wurmbeoideae. After the disintegration of the broadly circumscribed lily family this subfamily has been known as Colchicaceae. Phylogenetic analysis of lilioid monocotyledons has shown that the family Colchicaceae includes a number of genera previously not placed in Wurmbeoideae, eg. Burchardia, Disporum, Schelhammera, Tripladenia and Uvularia. By using the sensitive technique of nanospray mass spectrometry we here show that these genera do contain colchicine. In the case of Burchardia and Uvularia this is contrary to published reports. To test the assumption that colchicine is restricted to Colchicaceae we analysed samples from all genera in the family lacking information, or having conflicting reports, for colchicine content. We also sampled the closest relatives of the family according to phylogenetic results, and a number of genera with historical reports of colchicine presence. All samples from Colchicaceae contained colchicine, while none of the samples from genera in other families did. This implies that the biosynthesis of colchicine evolved within the common ancestor to Colchicaceae, and that this alkaloid may be regarded as a synapomorphic character for the family.

  • 304. Wagner Smitt, Ulla
    et al.
    Sandberg, Finn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Mysteriet om oldtidens beroemte laegeplante Silphium2006Ingår i: Naturens verden, ISSN 0028-0895, Vol. 89, nr 3, s. 28-37Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [da]

    Selv om lægeplanten Silphium var så betydningsfuld for antikkens grækere og romere at den i mere end 500 år blev afbildet på græske mønter er det hidtil ikke lykkedes at løse mysteriet om hvad det var for en plante. Nye undersøgelser viser at skærmplanten Thapsia garganica må anses for identisk med oldtidens Silphium.

  • 305. Wang, Conan K
    et al.
    Hu, Shu-Hong
    Martin, Jennifer L
    Sjögren, Tove
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Hajdu, Janos
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Bohlin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Claeson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Rosengren, K Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Tang, Jun
    Tan, Ning-Hua
    Craik, David J
    Combined X-ray and NMR Analysis of the Stability of the Cyclotide Cystine Knot Fold That Underpins Its Insecticidal Activity and Potential Use as a Drug Scaffold2009Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 284, nr 16, s. 10672-10683Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cyclotides are a family of plant defense proteins that are highly resistant to adverse chemical, thermal, and enzymatic treatment. Here, we present the first crystal structure of a cyclotide, varv F, from the European field pansy, Viola arvensis, determined at a resolution of 1.8 A. The solution state NMR structure was also determined and, combined with measurements of biophysical parameters for several cyclotides, provided an insight into the structural features that account for the remarkable stability of the cyclotide family. The x-ray data confirm the cystine knot topology and the circular backbone, and delineate a conserved network of hydrogen bonds that contribute to the stability of the cyclotide fold. The structural role of a highly conserved Glu residue that has been shown to regulate cyclotide function was also determined, verifying its involvement in a stabilizing hydrogen bond network. We also demonstrate that varv F binds to dodecylphosphocholine micelles, defining the binding orientation and showing that its structure remains unchanged upon binding, further demonstrating that the cyclotide fold is rigid. This study provides a biological insight into the mechanism by which cyclotides maintain their native activity in the unfavorable environment of predator insect guts. It also provides a structural basis for explaining how a cluster of residues important for bioactivity may be involved in self-association interactions in membranes. As well as being important for their bioactivity, the structural rigidity of cyclotides makes them very suitable as a stable template for peptide-based drug design.

  • 306. Wang, Conan K L
    et al.
    Colgrave, Michelle L
    Gustafson, Kirk R
    Ireland, David C
    Goransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Craik, David J
    Anti-HIV cyclotides from the Chinese medicinal herb Viola yedoensis2008Ingår i: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 71, nr 1, s. 47-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cyclotides are macrocyclic plant peptides characterized by a knotted arrangement of three disulfide bonds. They display a range of interesting bioactivities, including anti-HIV and insecticidal activities. More than 100 different cyclotides have been isolated from two phylogenetically distant plant families, the Rubiaceae and Violaceae. In this study we have characterized the cyclotides from Viola yedoensis, an important Chinese herb from the Violaceae family that has been reported to contain potential anti-HIV agents. From V. yedoensis five new and three known cyclotides were identified and shown to have anti-HIV activity. The most active of these is cycloviolacin Y5, which is one of the most potent of all cyclotides tested so far using in vitro XTT-based anti-HIV assays. Cycloviolacin Y5 is the most hydrophobic of the cyclotides from V. yedoensis. We show that there is a positive correlation between the hydrophobicity and the anti-HIV activity of the new cyclotides and that this trend tracks with their ability to disrupt membranes, as judged from hemolytic assays on human erythrocytes.

  • 307. Wang, Likui
    et al.
    Gao, Shijuan
    Jiang, Wei
    Luo, Cheng
    Xu, Maonian
    Bohlin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Rosendahl, Markus
    Huang, Wenlin
    Antioxidative Dietary Compounds Modulate Gene Expression Associated with Apoptosis, DNA Repair, Inhibition of Cell Proliferation and Migration2014Ingår i: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 15, nr 9, s. 16226-16245Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Many dietary compounds are known to have health benefits owing to their antioxidative and anti-inflammatory properties. To determine the molecular mechanism of these food-derived compounds, we analyzed their effect on various genes related to cell apoptosis, DNA damage and repair, oxidation and inflammation using in vitro cell culture assays. This review further tests the hypothesis proposed previously that downstream products of COX-2 (cyclooxygenase-2) called electrophilic oxo-derivatives induce antioxidant responsive elements (ARE), which leads to cell proliferation under antioxidative conditions. Our findings support this hypothesis and show that cell proliferation was inhibited when COX-2 was down-regulated by polyphenols and polysaccharides. Flattened macrophage morphology was also observed following the induction of cytokine production by polysaccharides extracted from viili, a traditional Nordic fermented dairy product. Coix lacryma-jobi (coix) polysaccharides were found to reduce mitochondrial membrane potential and induce caspase-3- and 9-mediated apoptosis. In contrast, polyphenols from blueberries were involved in the ultraviolet-activated p53/Gadd45/MDM2 DNA repair system by restoring the cell membrane potential. Inhibition of hypoxia-inducible factor-1 by saponin extracts of ginsenoside (Ginsen) and Gynostemma and inhibition of S100A4 by coix polysaccharides inhibited cancer cell migration and invasion. These observations suggest that antioxidants and changes in cell membrane potential are the major driving forces that transfer signals through the cell membrane into the cytosol and nucleus, triggering gene expression, changes in cell proliferation and the induction of apoptosis or DNA repair.

  • 308.
    Wedén, Christina
    et al.
    systematisk biologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Systematisk botanik.
    Backlund, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Systematisk botanik. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Danell, Eric
    Uppsala universitet, Enheten för musik och museer, Evolutionsmuseet. botansiska sektionen. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Systematisk botanik.
    Stjärnhovstryffel - Släktet Choiromyces i Sverige och Europa2007Ingår i: Systematikdagarna 2007: Lund 28-29 november, 2007Konferensbidrag (Övrigt vetenskapligt)
    Abstract [sv]

    Forskning om tryffeln på Gotland och odling av Tuber aestivum startades 1997. Ett grundläggande arbete var att genetiskt och morfologiskt visa att T. aestivum och det i Frankrike använda namnet T. uncinatum är synonyma, trots tidigare hävdade morfologiska och genetiska skillnader. Intresse finns idag att odla tryffel även på det svenska fastlandet. Tryffelodling innebär plantering av ympade trädplantor av ex. ek och hassel. På det svenska fastlandet växer Choiromyces venosus (stjärnhovstryffel), en intressant kandidat för utveckling av tryffelodling. Till skillnad från T. aestivum som växer på Gotland och Öland, har stjärnhovstryffeln ätits av lokalbefolkningen i mer än hundra år i Sverige, men mycket lite är känt om dess ekologi och biologi. Den är även en uppskattad delikatess i ex. Tyskland och Ungern, medan den i Frankrike och Italien anses giftig. I det pågående forskningsprojektet ämnar vi undersöka systematik, ekologi, vitamininnehåll, kemi och möjlighet till odling av stjärhovstryffeln. Släktet Choiromyces är dåligt utrett i Europa. Choiromyces venosus och C. meandriformis används som synonymer, ibland också C. gangliiformis. Nyinsamlat- och herbariematerial från Sverige och Europa kommer att studeras morfologiskt, genetiskt (DNA) och kemiskt för att utreda systematik och möjliga fylogenetiska kopplingar till dess påstådda giftighet i södra Europa.

  • 309.
    Wedén, Christina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Systematisk botanik.
    Danell, Eric
    Uppsala universitet, Enheten för musik och museer, Evolutionsmuseet. botaniska sektionen. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Systematisk botanik.
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Jägerstad, Margaretha
    Systematics, ecology, pharmacognosy, vitamin content and cultivation of Choiromyces in Sweden2007Ingår i: The fifth international workshop of edible mycorrhizal mushrooms, 2007Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    In spite of a world market for mushrooms estimated at 5 million tonnes, and in spite of fungi being six times richer in species than plants, and in spite of the demand for functional foods, research on edible and medicinal mushrooms has been neglected in Sweden. Our Tuber aestivum (syn. T. uncinatum) truffle project on the Swedish island of Gotland has been scientifically and economically a success. Since landowners familiar with Choiromyces truffles in Sweden have urged for research, we intend to illuminate the following questions: Are there one or several species in Europe? What are the preferred mycorrhizal hosts, soils and climate? Can mycelium be cultivated in large scale? Is it possible to synthesise mycorrhiza and to establish truffle orchards? Does the Swedish Choiromyces contain any toxic or anti-inflammatory substances? Could Choiromyces be an important source of vitamins?

    From 2006 we have confirmed three new localities for Choiromyces venosus in Sweden, using a trained truffle dog to find the mature fruit bodies. By using the dog, completely hypogeous, mature fruit bodies were found in contrast to the former observations that mature fruit bodies always protrude up through the soil surface. We have pure cultures of C. venosus growing on modified Fries media, confirmed by PCR.

    This project combines basic and applied research with the aim to create a new cash crop and new products of benefit to rural economy and Swedish industry. The project also addresses important questions about the taxonomy and biology of a mushroom genus. A successful project may generate new plantations on the Swedish main land of benefit to rural economy and biodiversity, new export products similar to the Gotland project mentioned above and more research devoted at edible and medicinal mushrooms.

  • 310.
    Wedén, Christina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Systematisk botanik.
    Danell, Eric
    Uppsala universitet, Enheten för musik och museer, Evolutionsmuseet.
    Camacho, Francisco J.
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    The population of the hypogeous fungus Tuber aestivum syn T. uncinatum on the island of Gotland2004Ingår i: Mycorrhiza, ISSN 0940-6360, E-ISSN 1432-1890, Vol. 14, nr 1, s. 19-23Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of our study was to examine the genetic variation within Tuber aestivum on the Baltic island of Gotland, Sweden. Variation in such a limited geographical area should help illuminate the dispersal abilities of T. aestivum. Knowledge of the genetic variation in this northern outpost could also be useful in the selection of inoculum for the establishment of truffle orchards. Genetic structure and homogeneity of the population were studied using principal component and parsimony analyses of randomly amplified polymorphic DNA data. Our inventories showed that T. aestivum is abundantly distributed in suitable habitats on Gotland. The genetic variation observed suggests sexual reproduction and slow dispersal on the island. It is possible that the present population was established from one introduction, which may be due to ability to survive in this habitat rather than to rare colonising events. The T. aestivum population on Gotland may be an ecotype adapted to the climate and soil conditions on the island.

  • 311.
    Wedén, Christina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Larsson, Sonny
    Jodrell Laboratory, Royal Botanic Garden, Kew, UK.
    Burman, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    The edible truffle Choiromyces venosus and its use in Sweden2009Ingår i: Acta Botanica Yunnanica, ISSN 0253-2700, Vol. 31, nr S16, s. 94-96Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The ascomycete truffle Choiromyces venosus is still largely unknown with respect to its biology, ecology and physiology. C. venosus has been collected and consumed as a delicacy in Sweden for at least 100 years. The species was first described by Fries in 1830 , and has been regarded synonymous with C. meandriformis, described by Vittadini 1831. In southern Europe there is a widespread belief that C. venosus is toxic to humans, but no record of C. venosus poisoning has ever been reported from northern Europe. Whether there is a taxonomic/phylogenetic explanation underlying the different traditions in different parts of Europe is currently under investigation. Our studies in this field include cytotoxicity data and are under completion. This is a highly important aspect in the attempts to establish a new cash crop. Preliminary results indicate that the amounts of C. venosus extract required to achieve cell death in the cytotoxicity assay is similar to that of other commonly consumed fungi including Agaricus bisporus and Tuber aestivum.

  • 312.
    Wedén, Christina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Pettersson, Lina
    Danell, Eric
    Uppsala universitet, Museer m.m., Evolutionsmuseet.
    Truffle cultivation in Sweden: Results from Quercus robur and Corylus avellana field trials on the island of Gotland2009Ingår i: Scandinavian Journal of Forest Research, ISSN 0282-7581, E-ISSN 1651-1891, Vol. 24, nr 1, s. 37-53Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The edible, ectomycorrhizal Burgundy truffle, Tuber aestivum Vitt., grows naturally on the islands of Gotland and Oland, Sweden. In 1999, 240 inoculated Quercus robur and Corylus avellana seedlings inoculated with French T. aestivum were planted in 10 experimental truffle orchards (truffieres) on Gotland to investigate the possibility of truffle cultivation in Sweden. Truffle orchard management, mycorrhizal development and seedling growth were studied. Fourteen additional truffle orchards containing more than 2000 Q. robur were established during 2000 and 2001. In 2004, T. aestivum mycorrhizae were detected in all truffle orchards. In 2005, the first T. aestivum truffle was found, 6 years after planting. This is the first cultivated truffle in Scandinavia and despite the northerly location they were produced within a timescale comparable with France. Tuber aestivum mycorrhizae survived in soils which differed from naturally producing locations by having a sand content > 95%, pH ≤6.4 and calcium content ≤0.1%. In a second series of experiments Swedish Q. robur, C. avellana and Carpinus betulus seedlings were inoculated with Swedish T. aestivum. Eleven months after inoculation T. aestivum mycorrhizae were found in 0-78% of the seedlings, depending on species, inoculation treatment and substrate. Because of the continuing decline of oaks in Sweden and associated fauna and flora, truffle cultivation may favour oak forest restoration programmes as well as making a direct contribution to rural economies.

  • 313. Weimann, C
    et al.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Pongprayoon-Claeson, Ubonwan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Claeson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Bohlin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Rimpler, H
    Heinrich, M
    Spasmolytic effects of baccharis conferta and some of its constituents2002Ingår i: Journal of Pharmacy and Pharmacology (JPP), ISSN 0022-3573, E-ISSN 2042-7158, Vol. 54, nr 1, s. 99-104Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Nahua of the Mexican state of Veracruz use Baccharis conferta in the treatment of a variety of gastrointestinal illnesses, especially diarrhoea associated with gastrointestinal cramps. The aerial parts of B. conferta were investigated phytochemically and pharmacologically using the guinea pig ileum assay as a model (histamine, KCI and electric stimulation). The crude ethanolic extract showed a dose-dependent antispasmodic effect that was particularly strong in flavonoid-rich fractions (e.g. IC50 value for fraction E.3.1 from the ethyl acetate fraction, in histamine-induced contraction, 10 microg mL(-1)). Several flavonoids (apigenin-4',7-dimethylether, naringenin-4',7-dimethylether, pectolinarigenin and cirsimaritin) were isolated, while others were identified in complex fractions by GC-MS. The flavonoids play an important role in the antispasmodic activity of this indigenous drug. Additionally, oleanolic acid and its methyl ester as well as erythrodiol were isolated. Oleanolic acid methyl ester shows weak antibacterial activity against M. luteusand E. coli (20 microg/spot in a TLC assay). The phytochemical as well as the pharmacological data provide some in-vitro evidence forthe use of B. conferta in thetreatment of gastrointestinal cramps.

  • 314.
    Xavier, Joana R.
    et al.
    Univ Bergen, Dept Biol, Ctr Geobiol, N-5006 Bergen, Norway..
    Cardenas, Paco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Cristobo, Javier
    Ctr Oceanog Gijon, Inst Espanol Oceanog, Gijon 33212, Asturias, Spain..
    Van Soest, Rob
    Nat Biodivers Ctr, NL-2300 RA Leiden, Netherlands..
    Rapp, Hans Tore
    Univ Bergen, Dept Biol, Ctr Geobiol, N-5006 Bergen, Norway..
    Systematics and biodiversity of deep-sea sponges of the Atlanto-Mediterranean region2015Ingår i: Journal of the Marine Biological Association of the United Kingdom, ISSN 0025-3154, E-ISSN 1469-7769, Vol. 95, nr 7, s. 1285-1286Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sponges are a key component of the deep-sea benthos, where they form structurally complex habitats and provide numerous ecosystem goods and services. However, there is still an enormous knowledge gap regarding the diversity, distribution and systematics of this group. This special volume presents the results of the 1st International Workshop on Taxonomy of Atlanto-Mediterranean Deep-Sea Sponges, whereby world experts worked together to start filling in this gap. Herein, new species are described, new sponge-dominated communities are reported, and diversity and distribution patterns are enlightened for this area.

  • 315.
    Yang, Lu
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. China Pharmaceut Univ, Dept Complex Prescript TCM, Jiangsu Prov Key Lab TCM Evaluat & Translat Res, 639 Longmian Rd, Nanjing 211198, Jiangsu, Peoples R China..
    Chai, Cheng-Zhi
    China Pharmaceut Univ, Dept Complex Prescript TCM, Jiangsu Prov Key Lab TCM Evaluat & Translat Res, 639 Longmian Rd, Nanjing 211198, Jiangsu, Peoples R China..
    Yan, Yan
    Shanxi Univ, Modern Res Ctr Tradit Chinese Med, 92,Wucheng Rd, Taiyuan 030006, Shanxi, Peoples R China..
    Duan, Ying-Dan
    China Pharmaceut Univ, Dept Complex Prescript TCM, Jiangsu Prov Key Lab TCM Evaluat & Translat Res, 639 Longmian Rd, Nanjing 211198, Jiangsu, Peoples R China..
    Henz, Astrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Zhang, Bo-Li
    Tianjin Univ Tradit Chinese Med, Inst Tradit Chinese Med, Tianjin 300193, Peoples R China..
    Backlund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Yu, Bo-Yang
    China Pharmaceut Univ, Dept Complex Prescript TCM, Jiangsu Prov Key Lab TCM Evaluat & Translat Res, 639 Longmian Rd, Nanjing 211198, Jiangsu, Peoples R China..
    Spasmolytic Mechanism of Aqueous Licorice Extract on Oxytocin-Induced Uterine Contraction through Inhibiting the Phosphorylation of Heat Shock Protein 272017Ingår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, nr 9, artikel-id 1392Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Licorice derived from the roots and rhizomes of Glycyrrhiza uralensis Fisch. (Fabaceae), is one of the most widely-used traditional herbal medicines in China. It has been reported to possess significant analgesic activity for treating spastic pain. The aim of this study is to investigate the spasmolytic molecular mechanism of licorice on oxytocin-induced uterine contractions and predict the relevant bioactive constituents in the aqueous extract. The aqueous extraction from licorice inhibited the amplitude and frequency of uterine contraction in a concentration-dependent manner. A morphological examination showed that myometrial smooth muscle cells of oxytocin-stimulated group were oval-shaped and arranged irregularly, while those with a single centrally located nucleus of control and licorice-treated groups were fusiform and arranged orderly. The percentage of phosphorylation of HSP27 at Ser-15 residue increased up to 50.33% at 60 min after oxytocin stimulation. Furthermore, this increase was significantly suppressed by licorice treatment at the concentration of 0.2 and 0.4 mg/mL. Colocalization between HSP27 and alpha-SMA was observed in the myometrial tissues, especially along the actin bundles in the oxytocin-stimulated group. On the contrary, the colocalization was no longer shown after treatment with licorice. Additionally, employing ChemGPS-NP provided support for a preliminary assignment of liquiritigenin and isoliquiritigenin as protein kinase C (PKC) inhibitors in addition to liquiritigenin, isoliquiritigenin, liquiritin and isoliquiritin as MAPK-activated protein kinase 2 (MK2) inhibitors. These assigned compounds were docked with corresponding crystal structures of respective proteins with negative and low binding energy, which indicated a high affinity and tight binding capacity for the active site of the kinases. These results suggest that licorice exerts its spasmolytic effect through inhibiting the phosphorylation of HSP27 to alter the interaction between HSP27 and actin. Furthermore, our results provide support for the prediction that potential bioactive constituents from aqueous licorice extract inhibit the relevant up-stream kinases that phosphorylate HSP27.

  • 316.
    Yeshak, Mariamawit Y
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Burman, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Asres, Kaleab
    Addis Ababa University.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Cyclotides from an Extreme Habitat: Characterization of Cyclic Peptides from Viola abyssinica of the Ethiopian Highlands2011Ingår i: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 74, nr 4, s. 727-731Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    As part of ongoing explorations of the structural diversity of cyclotides, the cyclotide content of a native violet of the East African highlands, Viola abyssinica (which grows at altitudes up to 3400 m), was studied. Six new cyclotides, vaby A-E (1-5) and varv E (6), were isolated and characterized by employing HPLC and MS techniques and quantitative amino acid analysis. Cyclotides 1-5 were found to have new sequences, and 1-3 have a further novel feature in their sequences, an alanine moiety in loop 2. Two of the cyclotides (1 and 4) also exhibited cytotoxic properties in a flourometric microculture cytotoxicity assay. The findings corroborate the hypothesis that investigating the cyclotide contents of violets growing in diverse environments is a promising approach for extending our knowledge of both the structural and biological diversity of cyclotides.

  • 317.
    Yeshak, Mariamawit Y
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Burman, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Asres, Kaleab
    Addis Ababa University, School of Pharmacy.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Plant cyclotides from an extreme habitat: Characterization of six cyclic peptides from a Violet growing at 3400 m.2010Ingår i: Journal of Peptide Research, ISSN 1397-002X, E-ISSN 1399-3011, Vol. 16, nr S2, s. 110-110Artikel i tidskrift (Refereegranskat)
  • 318.
    Yeshak, Mariamawit Y.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Burman, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Eriksson, Camilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Optimization of cyclotide extraction parameters2012Ingår i: Phytochemistry Letters, ISSN 1874-3900, E-ISSN 1876-7486, Vol. 5, nr 4, s. 776-781Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cyclotides are gene-encoded plant mini-proteins that contain a unique circular and cystine knotted amide backbone. Because of that ultra stable scaffold and the ability to harness a wide variety of sequences and biological activities within the scaffold, cyclotides find interesting potential applications for drug discovery and in agriculture. However, some fundamental knowledge is still missing to exploit these plant compounds, including finding the optimal process of their extraction from plant material. In the current work, the extraction parameters solvent type, time of extraction, number of re-macerations and the plant material to solvent ratio have been compared using the sweet violet (Viola odorata L.) as a model plant. That species is a well-characterized and rich source of cyclotides that contains prototypic cyclotides with different chemical and physical properties. We found that hydroalcoholic solutions of medium polarity give good yield of the cyclotide cocktail. In conclusion, single maceration with 50% MeOH for 6 h at a plant material to solvent ratio of 0.5:10 (g/mL) represents an optimum extraction method.

  • 319.
    Yeshak, Mariamawit Y
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Göransson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Burman, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Hellman, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Genotoxicity and Cellular Uptake of Cyclotides: Evidence for Multiple Mode of Action2012Ingår i: Mutation research. Genetic toxicology and environmental mutagenesis, ISSN 1383-5718, E-ISSN 1879-3592, Vol. 747, nr 2, s. 176-181Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cyclotides are a family of ultra stable, head-to-tail cyclic plant mini-proteins with each member comprising about 30 amino acid residues. Their stability is associated with the unique structural topology where the cyclic backbone and two disulfide bonds make up an embedded ring which is knotted by a third disulfide bond. The cyclotides find potential applications in drug industry as a drug scaffolds for unstable drugs and also as medicinal agents due to the wide range of inherent pharmacological activities they possess. However, there is a lack of fundamental toxicological studies on these classes of compounds. The current study determined a possible DNA damaging effect of three cyclotides, i.e., cycloviolacin O2, vaby D, and kalata B1 in human lymphoma cells using the alkaline version of the comet assay. The three cyclotides induced massive DNA fragmentation at lethal concentrations. At a sublethal concentration, cycloviolacin O2 and vaby D gave a bell shaped dose-response curve for their DNA-damaging effect. Kalata B1 caused no significant DNA damage at sub cytotoxic concentrations. Single cell microautoradiography was carried out on tritium labeled cycloviolacin O2 in order to understand the mechanism behind the dose-response curve. The results revealed that the peptide is taken up into the cell, at both cytotoxic and at low concentrations. Most biological effects of the cyclotides have been taken to follow from the disruption of cell membranes, but even if the intracellular mechanisms/targets still remain unknown, the current study has unequivocally demonstrated that these compounds also must have other dose-dependent modes of action. 

  • 320. Zahedifard, Maryam
    et al.
    Faraj, Fadhil Lafta
    Paydar, Mohammadjavad
    Looi, Chung Yeng
    Hasandarvish, Pouya
    Hajrezaie, Maryam
    Kamalidehghan, Behnam
    Majid, Nazia Abdul
    Khalifa, Shaden A. M.
    Ali, Hapipah Mohd
    Abdulla, Mahmood Ameen
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells2015Ingår i: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 21, nr 23, s. 3417-3426Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The anti-carcinogenic effect of the new quinazolinone compound, named MMD, was tested on MCF-7 human breast cancer cell line. The synthesis of quinazolinone-based compounds attracted strong attention over the past few decades as an alternative mean to produce analogues of natural products. Quinazolinone compounds sharing the main principal core structures are currently introduced in the clinical trials and pharmaceutical markets as anti-cancer agents. Thus, it is of high clinical interest to identify a new drug that could be used to control the growth and expansion of cancer cells. Quinazolinone is a metabolite derivative resulting from the conjugation of 2-aminobenzoyhydrazide and 5-methoxy-2-hydroxybenzaldehyde based on condensation reactions. In the present study, we analysed the influence of MMD on breast cancer adenoma cell morphology, cell cycle arrest, DNA fragmentation, cytochrome c release and caspases activity. MCF-7 is a type of cell line representing the breast cancer adenoma cells that can be expanded and differentiated in culture. Using different in vitro strategies and specific antibodies, we demonstrate a novel role for MMD in the inhibition of cell proliferation and initiation of the programmed cell death. MMD was found to increase cytochrome c release from the mitochondria to the cytosol and this effect was enhanced over time with effective IC50 value of 5.85 +/- 0.71 mu g/mL detected in a 72-hours treatment. Additionally, MMD induced cell cycle arrest at G0/G1 phase and caused DNA fragmentation with obvious activation of caspase-9 and caspases-3/7. Our results demonstrate a novel role of MMD as an anti-proliferative agent and imply the involvement of mitochondrial intrinsic pathway in the observed apoptosis.

  • 321. Zajmi, Asdren
    et al.
    Hashim, Najihah Mohd
    Noordin, Mohamed Ibrahim
    Khalifa, Shaden A. M.
    Ramli, Faiqah
    Ali, Hapipah Mohd
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
    Ultrastructural Study on the Antibacterial Activity of Artonin E versus Streptomycin against Staphylococcus aureus Strains2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 6, artikel-id e0128157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Staphylococci are facultative anaerobes, perfectly spherical un-encapsulated cocci, with a diameter not exceeding 1 micrometer in diameter. Staphylococcus aureus are generally harmless and remain confined to the skin unless they burrow deep into the body, causing life-threatening infections in bones, joints, bloodstream, heart valves and lungs. Among the 20 medically important staphylococci species, Staphylococcus aureus is one of the emerging human pathogens. Streptomycin had its highest potency against Staphylococcus infections despite the likelihood of getting a resistant type of staphylococcus strains. Methicillin-resistant S. aureus (MRSA) is the persister type of Staphylococcus aureus and was evolved after decades of antibiotic misuse. Inadequate penetration of the antibiotic is one of the principal factors related to success/failure of the therapy. The active drug needs to reach the bacteria at concentrations necessary to kill or suppress the pathogen's growth. In turn the effectiveness of the treatment relied on the physical properties of Staphylococcus aureus. Thus understanding the cell integrity, shape and roughness is crucial to the overall influence of the therapeutic agent on S. aureus of different origins. Hence our experiments were designed to clarify ultrastructural changes of S. aureus treated with streptomycin (synthetic compound) in comparison to artonin E (natural compound). In addition to the standard in vitro microbial techniques, we used transmission electron microscopy to study the disrupted cell architecture under antibacterial regimen and we correlate this with scanning electron microscopy (SEM) to compare results of both techniques.

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