Advertisement

Lichen Secondary Metabolites as Possible Antiviral Agents

  • Damian C. Odimegwu
  • Kenneth Ngwoke
  • Chika Ejikeugwu
  • Charles O. EsimoneEmail author
Chapter

Abstract

The revised edition of this chapter has been carefully and entirely rewritten. As a general rule, all sections have been revised and updated with current knowledge, more recent references included, and some sections expanded. Of particular note is the incorporation of significant additional materials in both sections dealing with some biological activities of lichen-derived secondary metabolites with particular emphasis on antitumor and anti-cellular agents and antiviral activities of lichen secondary metabolites. Every other section has been thoroughly revised and enriched with more current references.

Section 7.1 deals with broad and specific definitions of lichens and antiviral agents. Here, we will focus briefly on viruses and antiviral agents: their nature, source, general characteristics, and effects. Attempt is made to briefly classify antiviral agents based on their mode of action and virus targets. Lichen as a broad group of useful source of phytochemical agents is briefly described with emphasis on their unique niche in natural product research.

Section 7.2 deals with issues related to secondary metabolites (phytochemicals) from lichen. Lichen compounds because they possess some biological effects will form also the focus of this section. Some classes of lichen compounds are presented as well as their molecular structures. How they influence biological host and agents would be described briefly in the latter part of this section with presentation of some that display antiviral activities. The exact sources of these compounds are fully elucidated. Attempt is also made to mention lichen-derived compounds yet-to-be-fully-validated antiviral property.

Section 7.3 will focus on conclusion beginning with a summary of narrated up-to-date available data of antiviral lichen compounds currently undergoing preliminary and extensive research and development. How these agents have been applied or would be applied to biomedical and pharmaceutical utility would be addressed. The pharmaceutical industry involvement in further product development would be mentioned to display existing link between basic research setting and industry development endpoint. Finally, statement is made speculating on the future of lichen research and the positive expected outcomes of improved research interest in this unique group of medicinal plants.

References

  1. Akram M, Tahir IM, Shah SMA, Mahmood Z, Altaf A, Ahmad K, Munir N, Daniyal M, Nasir S, Mehboob H (2018) Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: a systematic review. Phytother Res 32(5):811–822CrossRefGoogle Scholar
  2. Andersen DO, Weber ND, Wood SG, Hughes BG, Murray BK, North JA (1991) In vitro virucidal activity of selected anthraquinones and anthraquinone derivatives. Antivir Res 16:185–196CrossRefGoogle Scholar
  3. Atanasov AG, Waltenberger B, Pferschy Wenzig EM, Linder T, Wawrosch C, Uhrin P, Temml V, Wang L, Schwaiger S, Heiss EH (2015) Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv 33:1582–1614CrossRefGoogle Scholar
  4. Basile A, Rigano D, Loppi S et al (2015) Antiproliferative, antibacterial and antifungal activity of the lichen Xanthoria parietina and its secondary metabolite parietin. Int J Mol Sci 16:7861–7875CrossRefGoogle Scholar
  5. Bezivin C, Tomasi S, Rouaud I, Delcros J, Boustie J (2004) Cytotoxic activity of compounds from the lichen: Cladonia convoluta. Planta Med 70:874–877CrossRefGoogle Scholar
  6. Brightman FH, Seaward MRD (1977) Lichens of man-made substrates. In: Seaward MRD (ed) Lichen ecology. Academic Press, London, pp 253–293Google Scholar
  7. Cetin H, Tufan-Cetin O, Turk AO, Tay T, Candan M, Yanikoglu A, Sumbul H (2008) Insecticidal activity of major lichen compounds, (−)- and (+)-usnic acid, against the larvae of house mosquito, Culex pipiens L. Parasitol Res 102:1277–1279CrossRefGoogle Scholar
  8. Cohen PA, Towers GHN (1995a) Anthraquinones and phenanthroperylenequinones from Nephroma laevigatum. J Nat Prod 58:520CrossRefGoogle Scholar
  9. Cohen PA, Towers GHN (1995b) The anthraquinones of Heterodermia obscurata. Phytochemistry 40:911CrossRefGoogle Scholar
  10. Cohen PA, Hudson JB, Towers GHN (1996) Antiviral activities of anthraquinones, bianthrones and hypericin derivatives from lichens. Experientia 52:180–183CrossRefGoogle Scholar
  11. Drake MG, Bivins-Smith ER, Proskocil BJ et al (2016) Human and mouse eosinophils have antiviral activity against parainfluenza virus. Am J Respir Cell Mol Biol 55(3):387–394CrossRefGoogle Scholar
  12. Ebrahim HY, Elsayed HE, Mohyeldin MM et al (2016) Norstictic acid inhibits breast cancer cell proliferation, migration, invasion, and in vivo invasive growth through targeting C-met. Phytother Res 30:557–566CrossRefGoogle Scholar
  13. Emmerich R, Giez I, Lange OL, Proksch P (1993) Toxicity and antifeedant activity of lichen compounds against the polyphagous herbivorous insect Spodoptera littoralis. Phytochemistry 33:1389–1394CrossRefGoogle Scholar
  14. Esimone CO, Grunwald T, Wildner O, Nchinda G, Tippler B, Proksch P, Uberla K (2005) In vitro pharmacodynamic evaluation of antiviral medicinal plants using a vector-based assay technique. J Appl Microbiol 99(6):1346–1355CrossRefGoogle Scholar
  15. Esimone CO, Ofokansi KC, Adikwu MU, Ibezim EC, Abonyi DO, Odaibo GN, Olaleye DO (2007) In vitro evaluation of the antiviral activity of extracts from the lichen Parmelia perlata (L.) Ach. against three RNA viruses. J Infect Dev Ctries 1(3):315–320CrossRefGoogle Scholar
  16. Esimone CO, Eck G, Duong TN, Uberla K, Proksch P, Grunwald T (2008) Potential anti-respiratory syncytial virus lead compounds from Aglaia species. Pharmazie 63:1–6Google Scholar
  17. Esimone CO, Grunwald T, Nworu CS, Kuate S, Proksch P, Uberla K (2009) Broad spectrum anti-viral fractions from the lichen Ramalina farinacea (L.) Ach. Chemotherapy 55:119–126CrossRefGoogle Scholar
  18. Farrar JF (1976) The lichen as an ecosystem: observation and experiment. In: Brown DH, Hawksworth DL, Bailey RH (eds) Lichenology: progress and problems, Special volume – The Systematics Association, vol 8. Academic Press, London, pp 385–406Google Scholar
  19. Fazio AT, Adler MT, Bertoni MD, Sepulveda CS, Damonte EB, Maier MS (2007) Lichen secondary metabolites from the cultured lichen mycobionts of Teloschistes chrysophthalmus and Ramalina celastri and their antiviral activities. Z Naturforsch 62:543–549CrossRefGoogle Scholar
  20. Gautam R, Saklani A, Jachak SM (2007) Indian medicinal plants as a source of antimycobacterial agents. J Ethnopharmacol 110:200–234CrossRefGoogle Scholar
  21. Halama P, Van Haluwin C (2004) Antifungal activity of lichen extracts and lichenic acids. BioControl 49:95–107CrossRefGoogle Scholar
  22. Harvey AL (2008) Natural products in drug discovery. Drug Discov Today 13:894–901CrossRefGoogle Scholar
  23. Hawksworth DL, Honegger R (1994) The lichen thallus: a symbiotic phenotype of nutritionally specialized fungi and its response to gall producers. In: Williams MAJ (ed) Plant galls, Special volume – The Systematics Association, vol 49. Clarendon Press, Oxford, pp 77–98Google Scholar
  24. Hidalgo ME, Fernandez E, Quilhot W, Lissi E (1994) Antioxidant activity of depsides and depsidones. Phytochemistry 37:1585–1587CrossRefGoogle Scholar
  25. Hirabayashi K, Iwata S, Ito M, Shigeta S, Narui T, Mori T, Shibata S (1989) Inhibitory effect of a lichen polysaccharide sulfate, GE-3-S, on the replication of human immunodeficiency virus (HIV) in vitro. Chem Pharm Bull 37:2410–2412CrossRefGoogle Scholar
  26. Honegger R (1991) Functional aspects of the lichen symbioses. Annu Rev Plant Physiol Plant Mol Biol 42:553–578CrossRefGoogle Scholar
  27. Hong JM, Suh SS, Kim TK et al (2018) Anti-cancer activity of lobaric acid and lobarstin extracted from the Antarctic lichen Stereocaulon alpnum. Molecules 23:658.  https://doi.org/10.3390/molecules23030658. eCollection 2018 MarCrossRefPubMedCentralGoogle Scholar
  28. Jassim SAA, Naji MA (2003) Novel anti-viral agents: a medicinal plant perspective. J Appl Microbiol 95:412–427CrossRefGoogle Scholar
  29. Jha BN, Shrestha M, Pandey DP et al (2017) Investigation of antioxidant, antimicrobial and toxicity activities of lichens from high altitude regions of Nepal. BMC Complement Altern Med 17:282. eCollection 2017CrossRefGoogle Scholar
  30. Karagöz A, Aslan A (2005) Antiviral and cytotoxic activity of some lichen extracts. Biol Bratis 60:281–286Google Scholar
  31. Kirk PM, Cannon PF, Minter DW, Stalpers JA (eds) (2008) Dictionary of the fungi, 10th edn. CAB International, WallingfordGoogle Scholar
  32. Kohlmann R, Schwannecke S, Tippler B, Ternette N, Temchura V, Tenbusch M, Überla K, Grunwald T (2009) Protective efficacy and immunogenicity of an adenoviral vector vaccine encoding the codon-optimized F protein of respiratory syncytial virus. J Virol 83(23):12601–12610CrossRefGoogle Scholar
  33. Kott V, Barbini L, Cruanes M et al (1999) Anti-viral activity in Argentine medicinal plants. J Ethnopharmacol 64:79–84CrossRefGoogle Scholar
  34. Kumar J, Dhar P, Tayade AB et al (2014) Antioxidant capacities, phenolic profile and cytotoxic effects of saxicolous lichens from trans-Himalayan cold desert of Ladakh. PLoS One 9:e98696CrossRefGoogle Scholar
  35. Kwon IS, Yim JH, Lee HK et al (2016) Lobaric acid inhibits VCAM-1 expression in TNF-α-stimulated vascular smooth muscle cells via modulation of NF-ΰB and MAPK signaling pathways. Biomol Ther (Seoul) 24:25–32CrossRefGoogle Scholar
  36. Lai D, Odimegwu DC, Esimone C, Grunwald T, Proksch P (2013) Phenolic compounds with in vitro activity against respiratory syncytial virus from the Nigerian lichen Ramalina farinacea. Planta Med 79(15):1440–1446CrossRefGoogle Scholar
  37. Legouin B, Lohézic-Le Dévéhat F, Ferron S et al (2017) Specialized metabolites of the lichen Vulpicida pinastri act as photoprotective agents. Molecules 22:1162.  https://doi.org/10.3390/molecules22071162. eCollection 2017 JulCrossRefPubMedCentralGoogle Scholar
  38. Li F, Ma C, Wang J (2015) Inhibitors targeting the influenza virus hemagglutinin. Curr Med Chem 22:1361–1382CrossRefGoogle Scholar
  39. Lisicka E (2008) Lichens on an acrylic-coated aluminium roof. Graph Scr 20:9–12Google Scholar
  40. Lumbsch HT (1998) Taxonomic use of metabolic data in lichen-forming fungi. In: Frisvad JC, Bridge PD, Arora DK (eds) Chemical fungal taxonomy. Marcel Dekker, New York, pp 345–387Google Scholar
  41. Mayer M, O’Neill MA, Murry KE, Santos-Magalhaes NS, Carneiro-Leao AMA, Thompson AM, Appleyard VCL (2005) Usnic acid: a non-genotoxic compound with anti-cancer properties. Anti-Cancer Drugs 16:805–809CrossRefGoogle Scholar
  42. Molnar K, Farkas E (2010) Current results on biological activities of lichen secondary metabolites: a review. Z Naturforsch 65c:157–173CrossRefGoogle Scholar
  43. Motohashi Y, Igarashi M, Okamatsu M et al (2013) Antiviral activity of stachyflin on influenza A viruses of different hemagglutinin subtypes. Virol J 10:118.  https://doi.org/10.1186/1743-422X-10-118 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Nash TH III (ed) (2008) Lichen biology, 2nd edn. Cambridge University Press, CambridgeGoogle Scholar
  45. Neamati N, Hong H, Mazumder A, Wang S, Sunder S, Nicklaus MC, Milne GWA, Proksa B, Pommier Y (1997) Depsides and depsidones as inhibitors of HIV-1 integrase: discovery of novel inhibitors through 3D database searching. J Med Chem 40:942–951CrossRefGoogle Scholar
  46. Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335CrossRefGoogle Scholar
  47. Odimegwu DC (2018) Low-dose Sekikaic acid modulates host immunity and protects cells from Respiratory Syncytial Virus infection. Biotechnol J Int 21(2):1–10CrossRefGoogle Scholar
  48. Odimegwu DC, Okoye FBC, Nworu CS, Esimone CO (2018) Anti-respiratory syncytial virus activities of leaf extracts of Alchornea cordifolia and Alchornea floribunda. Afr J Pharm Pharmacol 12(8):97–105CrossRefGoogle Scholar
  49. Omarsdottir S, Óladóttir AK, Árnadóttir T, Ingólfsdóttir K (2006) Antiviral compounds from Icelandic lichens. Planta Med 72.  https://doi.org/10.1055/s-2006-949742
  50. Paluszczak J, Kleszcz R, Studzińska-Sroka E et al (2018) Lichen-derived caperatic acid and physodic acid inhibit Wnt signaling in colorectal cancer cells. Mol Cell Biochem 441:109–124CrossRefGoogle Scholar
  51. Paudel B, Bhattarai HD, Koh HY et al (2011) Ramalin, a novel nontoxic antioxidant compound from the Antarctic lichen Ramalina terebrata. Phytomedicine 18:1285–1290CrossRefGoogle Scholar
  52. Pengsuparp T, Cai L, Constant H, Fong HHS, Lin LZ, Kinghorn AD, Pezzuto JM, Cordell GA, Ingolfsdöttir K, Wagner H, Hughes SH (1995) Mechanistic evaluation of new plant-derived compounds that inhibit HIV-1 reverse transcriptase. J Nat Prod 58:1024–1031CrossRefGoogle Scholar
  53. Perry NB, Benn MH, Brennan NJ, Burgess EJ, Ellis G, Galloway DJ, Lorimer SD, Tangney RS (1999) Antimicrobial, antiviral and cytotoxic activity of New Zealand lichens. Lichenologist 31(6):627–636CrossRefGoogle Scholar
  54. Ranković B, Mišić M (2007) Antifungal activity of extracts of the lichens Alectoria sarmentosa and Cladonia rangiferina. Mikol Fitopatol 41:276–281Google Scholar
  55. Ranković B, Mišić M (2008) The antimicrobial activity of the lichen substances of the lichens Cladonia furcata, Ochrolechia androgyna, Parmelia caperata and Parmelia conspersa. Biotechnol Biotechnol Equip 22:1013–1016CrossRefGoogle Scholar
  56. Ranković B, Mišić M, Sukdolak S (2008) The antimicrobial activity of substances derived from the lichens Physcia aipolia, Umbilicaria polyphylla, Parmelia caperata and Hypogymnia physodes. World J Microbiol Biotechnol 24:1239–1242CrossRefGoogle Scholar
  57. Ronalds CJ, Hardiman AE, Griffiths PD (1983) Hotting up the complement fixation test. J Hyg (Lond) 90:127–134CrossRefGoogle Scholar
  58. Russo A, Piovano M, Lombardo L, Garbarino J, Cardile V (2008) Lichen metabolites prevent UV light and nitric oxide-mediated plasmid DNA damage and induce apoptosis in human melanoma cells. Life Sci 83:468–474CrossRefGoogle Scholar
  59. Schmeda-Hirschmann G, Tapia A, Lima B et al (2008) A new antifungal and antiprotozoal depside from the Andean lichen Protousnea poeppigii. Phytother Res 22:349–355CrossRefGoogle Scholar
  60. Schreiner S, Wimmer P, Sirma H, Everett RD, Blanchette P, Groitl P, Dobner T (2010) Proteosome-dependent degradation of Daxx by the Viral E1B-55K protein in human adenovirus-infected cells. J Virol 84(14):7029–7038CrossRefGoogle Scholar
  61. Seaward MRD (2008) Environmental role of lichens. In: Nash TH III (ed) Lichen biology, 2nd edn. Cambridge University Press, Cambridge, pp 274–298CrossRefGoogle Scholar
  62. Semple SJ, Reynolds GD, O’Leary GD, Flower RLP (1998) Screening of Australian medicinal plants for anti-viral activity. J Ethnopharmacol 60:163–172CrossRefGoogle Scholar
  63. Seo C, Sohn JH, Park SM et al (2008a) Usimines A-C, bioactive usnic acid derivatives from the Antarctic lichen Stereocaulon alpinum. J Nat Prod 71:710–712CrossRefGoogle Scholar
  64. Seo C, Yim JH, Lee HK et al (2008b) Stereocalpin A, a bioactive cyclic depsipeptide from the Antarctic lichen Stereocaulon alpinum. ChemInform 49:29–31Google Scholar
  65. Sindambiwe JB, Calomme M, Cos P et al (1999) Screening of seven selected Rwandan medicinale plants for antimicrobial and anti-viral activities. J Ethnopharmacol 65:71–77CrossRefGoogle Scholar
  66. Sloan E, Tatham MH, Groslambert M, Glass M, Orr A, Hay RT, Everett RD (2015) Analysis of the SUMO2 Proteome during HSV-1 Infection. PLoS Pathog 11(7):e1005059.  https://doi.org/10.1371/journal.ppat.1005059 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Sokolov DN, Zarubaev VV, Shtro AA et al (2012) Anti-viral activity of (−)- and (+)-usnic acids and their derivatives against influenza virus A(H1N1)2009. Bioorg Med Chem Lett 22:7060–7064CrossRefGoogle Scholar
  68. Stocker-Worgotter E (2008) Metabolic diversity of lichen-forming ascomycetous fungi: culturing, polyketide and shikimate metabolite production, and PKS genes. Nat Prod Rep 25:188–200CrossRefGoogle Scholar
  69. Stubler D, Buchenauer H (1996) Antiviral activity of the glucan lichenan (poly-β{1 → 3, 1 →4} Danhydroglucose) 1. Biological activity in tobacco plants. J Phytopathol 144:37–43CrossRefGoogle Scholar
  70. Studzinska-Sroka E, Galanty A, Bylka W (2017) Atranorin - an interesting lichen secondary metabolite. Mini Rev Med Chem 17:1633–1645CrossRefGoogle Scholar
  71. Suh SS, Kim TK, Kim JE et al (2017) Anticancer activity of ramalin, a secondary metabolite from the antarctic lichen Ramalina terebrata, against colorectal cancer cells. Molecules 22:1361.  https://doi.org/10.3390/molecules22081361. eCollection 2017 AugCrossRefPubMedCentralGoogle Scholar
  72. Tavalai N, Papior P, Rechter S, Stamminger T (2008) Nuclear domain 10 components promyelocytic leukemia protein and hDaxx independently contribute to an intrinsic antiviral defense against human cytomegalovirus infection. J Virol 82:126–137CrossRefGoogle Scholar
  73. Ternette N, Tippler B, Uberla K, Grunwald T (2007) Immunogenicity and efficacy of codon optimized DNA vaccines encoding the F-protein of respiratory syncytial virus. Vaccine 25:7271–7279CrossRefGoogle Scholar
  74. Thadhani VM, Karunaratne V (2017) Potential of lichen compounds as antidiabetic agents with antioxidative properties: a review. Oxid Med Cell Longev 2017:2079697CrossRefGoogle Scholar
  75. Tian Y, Li YL, Zhao FC (2017) Secondary metabolites from polar organisms. Mar Drugs 15:28.  https://doi.org/10.3390/md15030028. eCollection 2017 MarCrossRefPubMedCentralGoogle Scholar
  76. Turk AO, Yilmaz M, Kivanc M, Turk H (2003) The antimicrobial activity of extracts of the lichen Cetraria aculeata and its protolichesterinic acid constituent. Z Naturforsch 58c:850–854CrossRefGoogle Scholar
  77. Voss EG, Burdet HM, Chaloner WG, Demoulin V, Hiepko P, Mcneill J, Meikle RD, Nicolson DH, Rollins RC, Silva PC, Greuter W (1983) International code of botanical nomenclature (Sydney Code). Regnum Veg 111:1–472Google Scholar
  78. Vu TH, Le Lamer AC, Lalli C et al (2015) Depsides: lichen metabolites active against hepatitis C virus. PLoS One 10:e0120405CrossRefGoogle Scholar
  79. Wang X, Chi X, Wang M (2011) Structural characteristics and antiviral activity of multiple peptides derived from MDV glycoproteins B and H. Virol J 8:190CrossRefGoogle Scholar
  80. Wood S, Huffman J, Weber N, Andersen D, North J, Murray B, Sidwell R, Hughes B (1990) Antiviral activity of naturally occurring anthraquinones and anthraquinone derivatives. Planta Med 56:65–52CrossRefGoogle Scholar
  81. Xu M, Heidmarsson S, Olafsdottir ES et al (2016) Secondary metabolites from cetrarioid lichens: chemotaxonomy, biological activities and pharmaceutical potential. Phytomedicine 23:441–459CrossRefGoogle Scholar
  82. Yamamoto Y, Kinoshita Y, Kurokawa T, Yoshimura I, Ahmadjian V, Yamada Y (1995) Cell growth and pigment production in suspension cultures of a mycobiont isolated from the lichen Cladonia cristatella. Can J Bot 73:590–594CrossRefGoogle Scholar
  83. Yang Y, Park SY, Nguyen TT et al (2015) Lichen secondary metabolite, physciosporin, inhibits lung cancer cell motility. PLoS One 10:e0137889CrossRefGoogle Scholar
  84. Zhou R, Yang Y, Park SY et al (2017) The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis. Sci Rep 7:8136. E Collection 2017CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Damian C. Odimegwu
    • 1
  • Kenneth Ngwoke
    • 2
  • Chika Ejikeugwu
    • 2
  • Charles O. Esimone
    • 2
    Email author
  1. 1.Faculty of Pharmaceutical SciencesUniversity of NigeriaNsukkaNigeria
  2. 2.Faculty of Pharmaceutical SciencesNnamdi Azikiwe UniversityAwkaNigeria

Personalised recommendations