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Henz Ryen, A. & Backlund, A. (2019). Charting Angiosperm Chemistry: Evolutionary Perspective on Specialized Metabolites Reflected in Chemical Property Space. Journal of Natural Products, 82(4), 798-812
Open this publication in new window or tab >>Charting Angiosperm Chemistry: Evolutionary Perspective on Specialized Metabolites Reflected in Chemical Property Space
2019 (English)In: Journal of Natural Products, ISSN 0163-3864, E-ISSN 1520-6025, Vol. 82, no 4, p. 798-812Article in journal (Refereed) Published
Abstract [en]

Plants possess an outstanding chemical diversity of specialized metabolites developed to adapt to environmental niches and increase fitness. The observed diversity is hypothesized to result from various evolutionary mechanisms, such as the continuous branching off and extension of existing biosynthetic pathways or enhanced levels of catalytic promiscuity in certain enzymes. In this study, ChemGPS-NP has been employed to chart the distribution and diversity of physicochemical properties for selected types of specialized metabolites from the angiosperms. Utilizing these charts, it is analyzed how different properties of various types of specialized metabolites change in different plant groups, and the chemical diversity from the volume they occupy in chemical property space is evaluated. In this context, possible underlying evolutionary mechanisms are discussed, which could explain the observed distribution and behavior in chemical property space. Based on these studies, it is demonstrated that evolutionary processes in plant specialized metabolism and the resultant metabolic diversification are reflected in chemical property space.

National Category
Bioinformatics and Systems Biology Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-383876 (URN)10.1021/acs.jnatprod.8b00767 (DOI)000466442100014 ()30912945 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 606895-MedPlant
Available from: 2019-06-12 Created: 2019-06-12 Last updated: 2020-01-04Bibliographically approved
Xiang, C., Dong, H., Landrein, S., Zhao, F., Yu, W., Soltis, D. E., . . . Peng, H. (2019). Revisiting the phylogeny of Dipsacales: New insights from phylogenomic analyses of complete plastomic sequences. Journal of Systematics and Evolution
Open this publication in new window or tab >>Revisiting the phylogeny of Dipsacales: New insights from phylogenomic analyses of complete plastomic sequences
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2019 (English)In: Journal of Systematics and Evolution, ISSN 1674-4918, E-ISSN 1759-6831Article in journal (Refereed) Published
Abstract [en]

Phylogenetic relationships in Dipsacales have long been a major challenge. Although considerable progress has been made during the past two decades, questions remain; the uncertain systematic positions of HeptacodiumTriplostegia, and Zabelia, in particular, impede our understanding of Dipsacales evolution. Here we use 75 complete plastomic sequences to reconstruct the phylogeny of Dipsacales, of which 28 were newly generated. Two primary clades were recovered that form the phylogenetic backbone of Dipsacales. Seven of the primary clades correspond to the recognized families Adoxaceae, Caprifoliaceae s. str., Diervillaceae, Dipsacaceae, Linnaeaceae, Morinaceae, and Valerianaceae, and one corresponds to Zabelia, which was found to be the closest relative of Morinaceae in all analyses. Additionally, our results, with greatly increased confidence in most branches, show that Heptacodium and Triplostegia are members of Caprifoliaceae s. str. and Dipsacaceae, respectively. The results of our study indicate that the complete plastomic sequences provide a fully‐resolved and well‐supported representation of the phylogenetic relationships within Dipsacales.

Keywords
Adoxaceae, Caprifoliaceae, Heptacodium, Morinaceae, Triplostegia, Zabelia
National Category
Natural Sciences Botany
Identifiers
urn:nbn:se:uu:diva-401802 (URN)10.1111/jse.12526 (DOI)
Available from: 2020-01-09 Created: 2020-01-09 Last updated: 2020-02-05Bibliographically approved
Xu, J.-H., Lai, K.-H., Su, Y.-D., Chang, Y.-C., Peng, B.-R., Backlund, A., . . . Sung, P.-J. (2018). Briaviolides K-N, New Briarane-Type Diterpenoids from Cultured Octocoral Briareum violaceum. Marine Drugs, 16(3), Article ID 75.
Open this publication in new window or tab >>Briaviolides K-N, New Briarane-Type Diterpenoids from Cultured Octocoral Briareum violaceum
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2018 (English)In: Marine Drugs, ISSN 1660-3397, E-ISSN 1660-3397, Vol. 16, no 3, article id 75Article in journal (Refereed) Published
Abstract [en]

Four new briarane diterpenoids, briaviolides K-N (1-4), have been obtained from the cultured-type octocoral Briareum violaceum. Using a spectroscopic approach, the structures of briaranes 1-4 were identified. This study employed an in vitro model of lipopolysaccharide (LPS)-induced inflammation in the murine macrophage RAW264.7 cell line, and found that among the four briaranes, briarane 2 possessed anti-inflammatory activity against inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions in cells. In addition, principal component analysis using the chemical global positioning system (ChemGPS) for natural products (ChemGPS-NP) was employed in order to analyze the structure-activity relationship (SAR), and the results indicated that the ring conformation of the compound has a leading role in suppressing the expressions of pro-inflammatory iNOS and COX-2 proteins in macrophages.

Place, publisher, year, edition, pages
MDPI, 2018
Keywords
Briareum violaceum, briarane, briaviolide, iNOS, COX-2, ChemGPS-NP
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-357766 (URN)10.3390/md16030075 (DOI)000428510200001 ()29495481 (PubMedID)
Available from: 2018-08-23 Created: 2018-08-23 Last updated: 2018-08-23Bibliographically approved
Korinek, M., Tsai, Y.-H., El-Shazly, M., Lai, K.-H., Backlund, A., Wu, S.-F., . . . Chang, F.-R. (2017). Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP. Frontiers in Pharmacology, 8, Article ID 356.
Open this publication in new window or tab >>Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP
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2017 (English)In: Frontiers in Pharmacology, ISSN 1663-9812, E-ISSN 1663-9812, Vol. 8, article id 356Article in journal (Refereed) Published
Abstract [en]

Increasing prevalence of allergic diseases with an inadequate variety of treatment drives forward search for new alternative drugs. Fatty acids, abundant in nature, are regarded as important bioactive compounds and powerful nutrients playing an important role in lipid homeostasis and inflammation. Phytochemical study on Typhonium blumei Nicolson and Sivadasan (Araceae), a folk anti-cancer and anti-inflammatory medicine, yielded four oxygenated fatty acids, 12R-hydroxyoctadec-9Z, 13E-dienoic acid methyl ester (1) and 10R-hydroxyoctadec-8E, 12Z-dienoic acid methyl ester (2), 9R-hydroxy-10E-octadecenoic acid methyl ester (3), and 12R *-hydroxy-10E-octadecenoic acid methyl ester (4). Isolated compounds were identified by spectroscopic methods along with GC-MS analysis. Isolated fatty acids together with a series of saturated, unsaturated and oxygenated fatty acids were evaluated for their anti-inflammatory and anti-allergic activities in vitro. Unsaturated (including docosahexaenoic and eicosapentaenoic acids) as well as hydroxylated unsaturated fatty acids exerted strong anti-inflammatory activity in superoxide anion generation (IC50 2.14-3.73 mu M) and elastase release (IC50 1.26-4.57 mu M) assays. On the other hand, in the anti-allergic assays, the unsaturated fatty acids were inactive, while hydroxylated fatty acids showed promising inhibitory activity in A23187-and antigen-induced degranulation assays (e.g., 9S-hydroxy-10E, 12Z-octadecadienoic acid, IC50 92.4 and 49.7 mu M, respectively). According to our results, the presence of a hydroxy group in the long chain did not influence the potent anti-inflammatory activity of free unsaturated acids. Nevertheless, hydroxylation of fatty acids (or their methyl esters) seems to be a key factor for the anti-allergic activity observed in the current study. Moreover, ChemGPS-NP was explored to predict the structure-activity relationship of fatty acids. The anti-allergic fatty acids formed different cluster distant from clinically used drugs. The bioactivity of T. blumei, which is historically utilized in folk medicine, might be related to the content of fatty acids and their metabolites.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2017
Keywords
Typhonium blumei, hydroxy fatty acids, polyunsaturated fatty acids (PUFA), anti-allergic, anti-inflammatory, cytotoxic, ChemGPS-NP
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-329661 (URN)10.3389/fphar.2017.00356 (DOI)000403539700001 ()28674495 (PubMedID)
Available from: 2017-09-20 Created: 2017-09-20 Last updated: 2018-01-13Bibliographically approved
Park, S., Yoo, K.-O., Marcussen, T., Backlund, A., Jacobsson, E., Rosengren, K. J., . . . Göransson, U. (2017). Cyclotide Evolution: Insights from the Analyses of Their Precursor Sequences, Structures and Distribution in Violets (Viola). Frontiers in Plant Science, 8, Article ID 2058.
Open this publication in new window or tab >>Cyclotide Evolution: Insights from the Analyses of Their Precursor Sequences, Structures and Distribution in Violets (Viola)
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2017 (English)In: Frontiers in Plant Science, ISSN 1664-462X, E-ISSN 1664-462X, Vol. 8, article id 2058Article in journal (Refereed) Published
Abstract [en]

Cyclotides are a family of plant proteins that are characterized by a cyclic backbone and a knotted disulfide topology. Their cyclic cystine knot (CCK) motif makes them exceptionally resistant to thermal, chemical, and enzymatic degradation. By disrupting cell membranes, the cyclotides function as host defense peptides by exhibiting insecticidal, anthelmintic, antifouling, and molluscicidal activities. In this work, we provide the first insight into the evolution of this family of plant proteins by studying the Violaceae, in particular species of the genus Viola. We discovered 157 novel precursor sequences by the transcriptomic analysis of six Viola species: V. albida var. takahashii, V. mandshurica, V. orientalis, V. verecunda, V. acuminata, and V. canadensis. By combining these precursor sequences with the phylogenetic classification of Viola, we infer the distribution of cyclotides across 63% of the species in the genus (i.e., ~380 species). Using full precursor sequences from transcriptomes, we show an evolutionary link to the structural diversity of the cyclotides, and further classify the cyclotides by sequence signatures from the non-cyclotide domain. Also, transcriptomes were compared to cyclotide expression on a peptide level determined using liquid chromatography-mass spectrometry. Furthermore, the novel cyclotides discovered were associated with the emergence of new biological functions.

Keywords
cyclotide evolution, viola phylogeny, sequence signature, cyclotide precursor, neofunctionality, novel cyclotide, precursor domain
National Category
Plant Biotechnology
Identifiers
urn:nbn:se:uu:diva-339782 (URN)10.3389/fpls.2017.02058 (DOI)000418117800001 ()29326730 (PubMedID)
Funder
Swedish Research Council, 2012-5063
Available from: 2018-02-09 Created: 2018-02-09 Last updated: 2018-02-09Bibliographically approved
Yang, L., Chai, C.-Z., Yan, Y., Duan, Y.-D., Henz, A., Zhang, B.-L., . . . Yu, B.-Y. (2017). Spasmolytic Mechanism of Aqueous Licorice Extract on Oxytocin-Induced Uterine Contraction through Inhibiting the Phosphorylation of Heat Shock Protein 27. Molecules, 22(9), Article ID 1392.
Open this publication in new window or tab >>Spasmolytic Mechanism of Aqueous Licorice Extract on Oxytocin-Induced Uterine Contraction through Inhibiting the Phosphorylation of Heat Shock Protein 27
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2017 (English)In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, no 9, article id 1392Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
MDPI AG, 2017
Keywords
licorice, uterine contraction, HSP27 phosphorylation, ChemGPS-NP prediction, molecular docking
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-336490 (URN)10.3390/molecules22091392 (DOI)000411499400010 ()
Available from: 2017-12-20 Created: 2017-12-20 Last updated: 2017-12-20Bibliographically approved
Backlund, A. & Bittrich, V. (2016). Adoxaceae. In: K. Kubitzki, J. Kadereit, and V. Bittrich (Ed.), The Families and Genera of Vascular Plants: (pp. 19-29). Springer
Open this publication in new window or tab >>Adoxaceae
2016 (English)In: The Families and Genera of Vascular Plants / [ed] K. Kubitzki, J. Kadereit, and V. Bittrich, Springer, 2016, p. 19-29Chapter in book (Refereed)
Place, publisher, year, edition, pages
Springer, 2016
National Category
Botany
Research subject
Pharmacognosy
Identifiers
urn:nbn:se:uu:diva-343259 (URN)10.1007/978-3-319-28534-4 (DOI)978-3-319-28532-0 (ISBN)
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-02-26
Lai, K. H., Lu, M. C., Chang, F. R., Su, J. H., El-Shazly, M., Du, Y. C., . . . Wu, Y. C. (2016). Antileukemic sesterterpenoids from a marine sponge, Luffariella sp.. Paper presented at 9th Joint Meeting of AFERP, ASP, GA, JSP, PSE and SIF, JUL 24-27, 2016, Copenhagen, DENMARK. Planta Medica, 82
Open this publication in new window or tab >>Antileukemic sesterterpenoids from a marine sponge, Luffariella sp.
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2016 (English)In: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 82Article in journal, Meeting abstract (Other academic) Published
Keywords
Luffarilla sp., sesterterpenoids, manoalide, Molt4, ROS-mediated apoptosis, DNA damage
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-346856 (URN)10.1055/s-0036-1596640 (DOI)000411789300464 ()
Conference
9th Joint Meeting of AFERP, ASP, GA, JSP, PSE and SIF, JUL 24-27, 2016, Copenhagen, DENMARK
Available from: 2018-03-26 Created: 2018-03-26 Last updated: 2018-03-26Bibliographically approved
Backlund, A. (2016). Bioactivity mapping of chemical property space - possible applications in natural products research. Paper presented at 9th Joint Meeting of AFERP, ASP, GA, JSP, PSE and SIF, JUL 24-27, 2016, Copenhagen, DENMARK. Planta Medica, 82
Open this publication in new window or tab >>Bioactivity mapping of chemical property space - possible applications in natural products research
2016 (English)In: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 82Article in journal, Meeting abstract (Other academic) Published
Keywords
ChemGPS-NP, biological activity, prediction
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-346850 (URN)10.1055/s-0036-1596151 (DOI)000411789300948 ()
Conference
9th Joint Meeting of AFERP, ASP, GA, JSP, PSE and SIF, JUL 24-27, 2016, Copenhagen, DENMARK
Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2018-03-27Bibliographically approved
Backlund, A. (2016). Columelliaceae. In: K. Kubitzki, J. Kadereit, and V. Bittrich (Ed.), The Families and Genera of Vascular Plants: (pp. 141-144). Springer
Open this publication in new window or tab >>Columelliaceae
2016 (English)In: The Families and Genera of Vascular Plants / [ed] K. Kubitzki, J. Kadereit, and V. Bittrich, Springer, 2016, p. 141-144Chapter in book (Refereed)
Place, publisher, year, edition, pages
Springer, 2016
National Category
Botany
Research subject
Pharmacognosy
Identifiers
urn:nbn:se:uu:diva-343261 (URN)10.1007/978-3-319-28534-4 (DOI)978-3-319-28532-0 (ISBN)
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-02-26
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2043-4183

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