Planta Med 2019; 85(03): 195-202
DOI: 10.1055/a-0690-9236
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Lanostane Triterpenes from Gloeophyllum odoratum and Their Anti-Influenza Effects

Ulrike Grienke
1   Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Austria
,
Julia Zwirchmayr
1   Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Austria
,
Ursula Peintner
2   Institute of Microbiology, University of Innsbruck, Austria
,
Ernst Urban
3   Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Austria
,
Martin Zehl
4   Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Austria
,
Michaela Schmidtke
5   Institute of Medical Microbiology, Section Experimental Virology, Jena University Hospital, Germany
,
Judith M. Rollinger
1   Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Austria
› Author Affiliations
Further Information

Publication History

received 05 July 2018
revised 08 August 2018

accepted 14 August 2018

Publication Date:
21 August 2018 (online)

Abstract

In an in vitro screening for anti-influenza agents from European polypores, the fruit body extract of Gloeophyllum odoratum dose-dependently inhibited the cytopathic effect of the H3N2 influenza virus A/Hong Kong/68 (HK/68) in Madin Darby canine kidney cells with a 50% inhibitory concentration (IC50) of 15 µg/mL, a noncytotoxic concentration. After a chromatographic work-up, eight lanostane triterpenes (18) were isolated and their structures were elucidated based on high-resolution electrospray ionization mass spectrometry analyses, and one- and two-dimensional nuclear magnetic resonance experiments. Constituents 1 (gloeophyllin K) and 2 (gloeophyllin L) are reported here for the first time, and compounds 5, 7, and 8 have not been described for the investigated fungal material so far. The highest activity was determined for trametenolic acid B (3) against HK/68 and the 2009 pandemic H1N1 strain A/Jena/8178/09 with IC50 values of 14 and 11 µM, respectively. In a plaque reduction assay, this compound was able to bind to cell-free viruses and to neutralize their infectivity.

Supporting Information

 
  • References

  • 1 Binder M, Justo A, Riley R, Salamov A, Lopez-Giraldez F, Sjokvist E, Copeland A, Foster B, Sun H, Larsson E, Larsson KH, Townsend J, Grigoriev IV, Hibbett DS. Phylogenetic and phylogenomic overview of the Polyporales. Mycologia 2013; 105: 1350-1373
  • 2 Garcia-Sandoval R, Wang Z, Binder M, Hibbett DS. Molecular phylogenetics of the Gloeophyllales and relative ages of clades of Agaricomycotina producing a brown rot. Mycologia 2011; 103: 510-524
  • 3 Grienke U, Zöll M, Peintner U, Rollinger JM. European medicinal polypores – a modern view on traditional uses. J Ethnopharmacol 2014; 154: 564-583
  • 4 Kahlos K. The characterization of some lipid metabolites of Gloeophyllum odoratum grown in vitro . Mycol Res 1996; 100: 23-26
  • 5 Rösecke J, Pietsch M, König WA. Volatile constituents of wood-rotting basidiomycetes. Phytochemistry 2000; 54: 747-750
  • 6 Rösecke J, König WA. Odorous compounds from the fungus Gloeophyllum odoratum . Flavour Fragrance J 2000; 15: 315-319
  • 7 Rösecke J, König WA. Constituents of various wood-rotting basidiomycetes. Phytochemistry 2000; 54: 603-610
  • 8 Cateni F, Lucchini V, Zacchigna M, Procida G, Doljak B, Anderluh M. New triterpenes from the fungus Gloeophyllum odoratum . Chem Nat Compd 2015; 51: 74-80
  • 9 Cateni F, Lucchini V, Anderluh M, Martinuzzi P, Zacchigna M, Piltaver A, Doljak B. Triterpenes from Gloeophyllum odoratum as potential leads towards potent thrombin inhibitors. Lett Drug Des Discov 2010; 7: 521-527
  • 10 Kahlos K, Kiviranta JLJ, Hiltunen RVK. Volatile constituents of wild and in vitro cultivated Gloeophyllum odoratum . Phytochemistry 1994; 36: 917-922
  • 11 Rasser F, Anke T, Sterner O. Secondary metabolites from a Gloeophyllum species. Phytochemistry 2000; 54: 511-516
  • 12 Halsall TG, Hodges R, Sayer GC. The chemistry of the triterpenes and related compounds. Part XXXVI. Some constituents of Trametes odorata (Wulf.) Fr. J Chem Soc 1959; 2036-2040
  • 13 Doskocil I, Havlik J, Verlotta R, Tauchen J, Vesela L, Macakova K, Opletal L, Kokoska L, Rada V. In vitro immunomodulatory activity, cytotoxicity and chemistry of some central European polypores. Pharm Biol 2016; 54: 2369-2376
  • 14 Zhu Q, Bang TH, Ohnuki K, Sawai T, Sawai K, Shimizu K. Inhibition of neuraminidase by Ganoderma triterpenoids and implications for neuraminidase inhibitor design. Sci Rep 2015; 5: 13194
  • 15 Mothana RA, Awadh Ali NA, Jansen R, Wegner U, Mentel R, Lindequist U. Antiviral lanostanoid triterpenes from the fungus Ganoderma pfeifferi . Fitoterapia 2003; 74: 177-180
  • 16 Grienke U, Kaserer T, Pfluger F, Mair CE, Langer T, Schuster D, Rollinger JM. Accessing biological actions of Ganoderma secondary metabolites by in silico profiling. Phytochemistry 2015; 114: 114-124
  • 17 Grienke U, Mair CE, Kirchmair J, Schmidtke M, Rollinger JM. Discovery of bioactive natural products for the treatment of acute respiratory infections – an integrated approach. Planta Med 2018; 84: 684-695
  • 18 Han JJ, Bao L, Tao QQ, Yao YJ, Liu XZ, Yin WB, Liu HW. Gloeophyllins A–J, cytotoxic ergosteroids with various skeletons from a Chinese Tibet fungus Gloeophyllum abietinum . Org Lett 2015; 17: 2538-2541
  • 19 Rösecke J, König WA. Steroids from the fungus Fomitopsis pinicola . Phytochemistry 1999; 52: 1621-1627
  • 20 Kobori M, Yoshida M, Ohnishi-Kameyama M, Takei T, Shinmoto H. 5alpha,8alpha-Epidioxy-22E-ergosta-6,9(11),22-trien-3beta-ol from an edible mushroom suppresses growth of HL60 leukemia and HT29 colon adenocarcinoma cells. Biol Pharm Bull 2006; 29: 755-759
  • 21 Kikuchi T, Uchiyama E, Ukiya M, Tabata K, Kimura Y, Suzuki T, Akihisa T. Cytotoxic and apoptosis-inducing activities of triterpene acids from Poria cocos . J Nat Prod 2011; 74: 137-144
  • 22 Su HJ, Fann YF, Chung MI, Won SJ, Lin CN. New lanostanoids of Ganoderma tsugae . J Nat Prod 2000; 63: 514-516
  • 23 Gilbertson B, Ng WC, Crawford S, McKimm-Breschkin JL, Brown LE. Mouse saliva inhibits transit of influenza virus to the lower respiratory tract by efficiently blocking influenza virus neuraminidase activity. J Virol 2017; 91: e00145-17
  • 24 Zeng LY, Yang J, Liu S. Investigational hemagglutinin-targeted influenza virus inhibitors. Expert Opin Investig Drugs 2017; 26: 63-73
  • 25 Hoffmann A, Richter M, von Grafenstein S, Walther E, Xu Z, Schumann L, Grienke U, Mair CE, Kramer C, Rollinger JM, Liedl KR, Schmidtke M, Kirchmair J. Discovery and characterization of diazenylaryl sulfonic acids as inhibitors of viral and bacterial neuraminidases. Frontiers Microbiol 2017; 8: 205
  • 26 Mair CE, Grienke U, Wilhelm A, Urban E, Zehl M, Schmidtke M, Rollinger JM. Anti-influenza triterpene saponins from the bark of Burkea africana . J Nat Prod 2018; 81: 515-523
  • 27 Scheuba J, Wronski VK, Rollinger JM, Grienke U. Fast and green – CO2 based extraction, isolation, and quantification of phenolic styrax constituents. Planta Med 2017; 83: 1068-1075
  • 28 Dresch P, MN DA, Rosam K, Grienke U, Rollinger JM, Peintner U. Fungal strain matters: colony growth and bioactivity of the European medicinal polypores Fomes fomentarius, Fomitopsis pinicola and Piptoporus betulinus . AMB Express 2015; 5: 4
  • 29 Walther E, Xu Z, Richter M, Kirchmair J, Grienke U, Rollinger JM, Krumbholz A, Saluz HP, Pfister W, Sauerbrei A, Schmidtke M. Dual acting neuraminidase inhibitors open new opportunities to disrupt the lethal synergism between Streptococcus pneumoniae and influenza virus. Front Microbiol 2016; 7: 357
  • 30 Bauer K, Richter M, Wutzler P, Schmidtke M. Different neuraminidase inhibitor susceptibilities of human H1N1, H1N2, and H3N2 influenza A viruses isolated in Germany from 2001 to 2005/2006. Antiviral Res 2009; 82: 34-41
  • 31 Reed LJ, Muench H. A simple method of estimating fifty per cent endpoints. Am J Epidemiol 1938; 27: 493-497
  • 32 Schmidtke M, Schnittler U, Jahn B, Dahse H, Stelzner A. A rapid assay for evaluation of antiviral activity against coxsackie virus B3, influenza virus A, and herpes simplex virus type 1. J Virol Methods 2001; 95: 133-143
  • 33 Pauwels R, Balzarini J, Baba M, Snoeck R, Schols D, Herdewijn P, Desmyter J, De Clercq E. Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. J Virol Methods 1988; 20: 309-321
  • 34 Makarov VA, Braun H, Richter M, Riabova OB, Kirchmair J, Kazakova ES, Seidel N, Wutzler P, Schmidtke M. Pyrazolopyrimidines: potent inhibitors targeting the capsid of rhino- and enteroviruses. ChemMedChem 2015; 10: 1629-1634