Skip to main navigation menu Skip to main content Skip to site footer

Review Articles

Early Access

Lichen-derived secondary metabolites: Ethnobotanical insights and pharmacological prospects

DOI
https://doi.org/10.14719/pst.12208
Submitted
10 October 2025
Published
05-02-2026

Abstract

Lichens, symbiotic associations of fungi and photosynthetic algae, are rich sources of bioactive compounds with significant ecological functions and considerable pharmacological potential. This review provides an integrated overview of the morphological, ethnobotanical, structural and functional diversity of lichen metabolites. Most lichen species produce structurally diverse secondary metabolites with antimicrobial, anticancer, antioxidant, anti-inflammatory and enzyme-inhibitory effects. Despite centuries of traditional use, challenges persist in isolating individual metabolites because of their complex thallus structure, low solubility and sensitivity to conventional extraction methods. However, modern advancements, including axenic cultivation, genome mining, molecular networking and next-generation analytical technologies, have enabled the discovery of previously undetectable metabolites and provided deeper insights into their biosynthetic pathways. Advancing lichen research by combining traditional knowledge with modern biotechnological innovations will be pivotal for identifying new, sustainable therapeutic molecules that meet emerging global healthcare demands.

References

  1. 1. Noh HJ, Park Y, Hong SG, Lee YM. Diversity and physiological characteristics of Antarctic lichens-associated bacteria. Microorganisms. 2021;9(3):607. https://doi.org/10.3390/microorganisms9030607
  2. 2. Spribille T, Resl P, Stanton DE, Tagirdzhanova G. Evolutionary biology of lichen symbioses. New Phytol. 2022;234(5):1566–82. https://doi.org/10.1111/nph.18048
  3. 3. Yuan X, Xiao S, Taylor TN. Lichen-like symbiosis 600 million years ago. Science. 2005;308(5724):1017–20.
  4. 4. Suryanarayanan TS, Thirunavukkarasu N. Endolichenic fungi: the lesser known fungal associates of lichens. Mycology. 2017;8(3):189–96. https://doi.org/10.1080/21501203.2017.1352048
  5. 5. Casale M, Bagnasco L, Giordani P, Mariotti MG, Malaspina P. NIR spectroscopy as a tool for discriminating between lichens exposed to air pollution. Chemosphere. 2015;134:355–60. https://doi.org/10.1016/j.chemosphere.2015.03.095
  6. 6. Dresler S, Baczewska I, Mykhailenko O, Zidorn C, Sowa I, Wojciak M, et al. Extraction of lichen bioactive compounds using volatile natural deep eutectic solvents and comparative analytical approaches. Sci Rep. 2025;15(1):22742. https://doi.org/10.1038/s41598-025-08069-0
  7. 7. Zhang W, Ran Q, Li H, Lou H. Endolichenic fungi: a promising medicinal microbial resource to discover bioactive natural molecules—an update. J Fungi. 2024;10(2):99. https://doi.org/10.3390/jof10020099
  8. 8. Ramya K, Thirunalasundari T. Lichens: a myriad hue of bioresources with medicinal properties. Int J Life Sci. 2017;5(3):387–93.
  9. 9. Bhagarathi LK, Maharaj G, DaSilva PN, Subramanian G. A review of the diversity of lichens and factors affecting their distribution in the neotropics. GSC Biol Pharm Sci. 2022;20(3):27–63. https://doi.org/10.30574/gscbps.2022.20.3.0348
  10. 10. Thakur M, Bhardwaj S, Kumar V, Rodrigo-Comino J. Lichens as effective bioindicators for monitoring environmental changes: a comprehensive review. Total Environ Adv. 2024;9:200085. https://doi.org/10.1016/j.teadva.2023.200085
  11. 11. Bao HY, Bau T. Advance in studies on chemical constituents and pharmacological activity of lichens in Usnea genus. China J Chin Mater Med. 2013;38(4):539–45.
  12. 12. Lichen. Wikipedia. https://en.wikipedia.org/wiki/Lichen
  13. 13. Crawford SD. Lichens used in traditional medicine. In: Rankovic B, editor. Lichen secondary metabolites: bioactive properties and pharmaceutical potential. Cham: Springer International Publishing; 2019. p. 31–97. https://doi.org/10.1007/978-3-030-16814-8_2
  14. 14. Manojlovic NT, Vasiljevic PJ, Maskovic PZ, Juskovic M, Bogdanovic-Dusanovic G. Chemical composition, antioxidant and antimicrobial activities of lichen Umbilicaria cylindrica (L.) Delise (Umbilicariaceae). J Evid Based Complementary Altern Med. 2012;2012:452431. https://doi.org/10.1155/2012/452431
  15. 15. Tripathi AH, Negi N, Gahtori R, Kumari A, Joshi P, Tewari LM, et al. A review of anticancer and related properties of lichen extracts and metabolites. Anticancer Agents Med Chem. 2022;22(1):115–42. https://doi.org/10.2174/1871520621666210322094647
  16. 16. Llano GA. Economic uses of lichens. Econ Bot. 1948;2(1):15–45.
  17. 17. Turkez H, Aydın E, Aslan A. Effects of lichenic extracts (Hypogymnia physodes, Ramalina polymorpha and Usnea florida) on human blood cells: cytogenetic and biochemical study. Iran J Pharm Res. 2012;11(3):889.
  18. 18. Thadhani VM, Karunaratne V. Potential of lichen compounds as antidiabetic agents with antioxidative properties: a review. Oxid Med Cell Longev. 2017;2017:2079697. https://doi.org/10.1155/2017/2079697
  19. 19. Silva CJA, Bomfim RR, Santos Estevam CD, Antoniolli AR, de Souza Araújo AA, Thomazzi SM. Pharmacological properties of lichen Cladonia clathrata. Pharm Biol. 2010;48(7):745–52. https://doi.org/10.3109/13880200903273914
  20. 20. Karagoz Y, Karagoz BO. Lichens in pharmacological action: what happened in the last decade? Eurasian J Med. 2022;54(Suppl 1):S195. https://doi.org/10.5152/eurasianjmed.2022.22335
  21. 21. Adenubi OT, Famuyide IM, McGaw LJ, Eloff JN. Lichens: an update on their ethnopharmacological uses and potential as sources of drug leads. J Ethnopharmacol. 2022;298:115657. https://doi.org/10.1016/j.jep.2022.115657
  22. 22. Rankovic B, Kosanic M. Biotechnological substances in lichens. In: Mandal SC, Nayak AK, editors. Natural bioactive compounds. Academic Press; 2021. p. 249–65. https://doi.org/10.1016/B978-0-12-820655-3.00012-4
  23. 23. Rankovic B, Kosanic M. Lichen secondary metabolites. Cham: Springer International Publishing; 2015. p. 202. https://doi.org/10.1007/978-3-319-13374-4_3
  24. 24. Boustie J, Grube M. Lichens—a promising source of bioactive secondary metabolites. Plant Genet Res. 2005;3(2):273–87. https://doi.org/10.1079/PGR200572
  25. 25. Goga M, Elecko J, Marcincinova M, Rucova D, Backorova M, Backor M. Lichen metabolites: an overview of some secondary metabolites and their biological potential. Co-Evol Second Metab. 2018:1–36. https://doi.org/10.1007/978-3-319-96397-6_57
  26. 26. Goga M, Balaz M, Daneu N, Elecko J, Tkacikova Ľ, Marcincinova M, et al. Biological activity of selected lichens and lichen-based Ag nanoparticles prepared by a green solid-state mechanochemical approach. Mater Sci Eng C. 2021;119:111640.
  27. 27. Santos-Sanchez NF, Salas-Coronado R, Hernandez-Carlos B, Villanueva-Canongo C. Shikimic acid pathway in biosynthesis of phenolic compounds. In: Plant physiological aspects of phenolic compounds. IntechOpen; 2019. https://doi.org/10.5772/intechopen.83815
  28. 28. Nguyen KH, Chollet-Krugler M, Gouault N, Tomasi S. UV-protectant metabolites from lichens and their symbiotic partners. Nat Prod Rep. 2013;30(12):1490–508. https://doi.org/10.1039/c3np70064j
  29. 29. Rankovic B, Kosanic M. Lichens as a potential source of bioactive secondary metabolites. In: Rankovic B, editor. Lichen secondary metabolites: bioactive properties and pharmaceutical potential. Cham: Springer International Publishing; 2019. p. 1–29. https://doi.org/10.1007/978-3-319-13374-4_1
  30. 30. Nishanth KS, Sreerag RS, Deepa I, Mohandas C, Nambisan B. Protocetraric acid: an excellent broad spectrum compound from the lichen Usnea albopunctata against medically important microbes. Nat Prod Res. 2015;29(6):574–7. https://doi.org/10.1080/14786419.2014.953500
  31. 31. Hamida RS, Ali MA, Abdelmeguid NE, Al-Zaban MI, Baz L, Bin-Meferij MM. Lichens—a potential source for nanoparticles fabrication: a review on nanoparticles biosynthesis and their prospective applications. J Fungi. 2021;7(4):291. https://doi.org/10.3390/jof7040291
  32. 32. White PA, Oliveira RC, Oliveira AP, Serafini MR, Araujo AA, Gelain DP, et al. Antioxidant activity and mechanisms of action of natural compounds isolated from lichens: a systematic review. Molecules. 2014;19(9):14496–527. https://doi.org/10.3390/molecules190914496
  33. 33. Rezanka T, Guschina IA. Macrolactone glycosides of three lichen acids from Acarospora gobiensis, a lichen of Central Asia. Phytochemistry. 2001;58(8):1281–7. https://doi.org/10.1016/S0031-9422(01)00388-0
  34. 34. Niu DL, Wang LS, Zhang YJ, Yang CR. Acroscyphus sphaerophoroides (lichenized Ascomycota, Caliciaceae) in Hengduanshan Mountains. Biochem Syst Ecol. 2008;36(5–6):423–9. https://doi.org/10.1016/j.bse.2008.01.009
  35. 35. Ingolfsdottir K. Usnic acid. Phytochemistry. 2002;61(7):729–36. https://doi.org/10.1016/S0031-9422(02)00383-7
  36. 36. Verma N, Behera BC, Makhija U. Antioxidant and hepatoprotective activity of a lichen Usnea ghattensis in vitro. Appl Biochem Biotechnol. 2008;151(2):167–81. https://doi.org/10.1007/s12010-008-8164-9
  37. 37. Meli MA, Desideri D, Cantaluppi C, Ceccotto F, Feduzi L, Roselli C. Elemental and radiological characterization of commercial Cetraria islandica (L.) Acharius pharmaceutical and food supplementation products. Sci Total Environ. 2018;613:1566–72. https://doi.org/10.1016/j.scitotenv.2017.08.320
  38. 38. Huang X, Ma J, Wei L, Song J, Li C, Yang H, et al. An antioxidant α-glucan from Cladina rangiferina (L.) Nyl. and its protective effect on alveolar epithelial cells from Pb2+- induced oxidative damage. Int J Biol Macromol. 2018;112:101–9. https://doi.org/10.1016/j.ijbiomac.2018.01.154
  39. 39. Saenz MT, Garcia MD, Rowe JG. Antimicrobial activity and phytochemical studies of some lichens from south of Spain. Fitoterapia. 2006;77(3):156–9. https://doi.org/10.1016/j.fitote.2005.12.001
  40. 40. Kekuda TP, Vinayaka KS, Swathi D, Suchitha Y, Venugopal TM, Mallikarjun N. Mineral composition, total phenol content and antioxidant activity of a macrolichen Everniastrum cirrhatum (Fr.) Hale (Parmeliaceae). J Chem. 2011;8(4):1886–94. https://doi.org/10.1155/2011/420673
  41. 41. Lee S, Suh YJ, Yang S, Hong DG, Ishigami A, Kim H, et al. Neuroprotective and anti-inflammatory effects of evernic acid in an MPTP-induced Parkinson’s disease model. Int J Mol Sci. 2021;22(4):2098. https://doi.org/10.3390/ijms22042098
  42. 42. Malhotra S, Subban RA, Singh A. Lichens—role in traditional medicine and drug discovery. Internet J Altern Med. 2008;5(2):1–5.
  43. 43. Gupta VK, Darokar MP, Saikia D, Pal A, Fatima A, Khanuja SP. Antimycobacterial activity of lichens. Pharm Biol. 2007;45(3):200–4. https://doi.org/10.1080/13880200701213088
  44. 44. Devkota S, Chaudhary RP, Werth S, Scheidegger C. Indigenous knowledge and use of lichens by the lichenophilic communities of the Nepal Himalaya. J Ethnobiol Ethnomed. 2017;13(1):15. https://doi.org/10.1186/s13002-017-0142-2
  45. 45. Marante FT, Castellano AG, Rosas FE, Aguiar JQ, Barrera JB. Identification and quantitation of allelochemicals from the lichen Lethariella canariensis: phytotoxicity and antioxidative activity. J Chem Ecol. 2003;29(9):2049–71. https://doi.org/10.1023/A:1025682318001
  46. 46. Lohezic-Le Devehat F, Legouin B, Couteau C, Boustie J, Coiffard L. Lichenic extracts and metabolites as UV filters. J Photochem Photobiol B. 2013;120:17–28. https://doi.org/10.1016/j.jphotobiol.2013.01.009
  47. 47. Siddiqi KS, Rashid M, Rahman A, Tajuddin, Husen A, Rehman S. Biogenic fabrication and characterization of silver nanoparticles using aqueous-ethanolic extract of lichen (Usnea longissima) and their antimicrobial activity. Biomater Res. 2018;22(1):23. https://doi.org/10.1186/s40824-018-0135-9
  48. 48. Thadhani VM, Choudhary MI, Ali S, Omar I, Siddique H, Karunaratne V. Antioxidant activity of some lichen metabolites. Nat Prod Res. 2011;25(19):1827–37. https://doi.org/10.1080/14786419.2010.529546
  49. 49. Emsen B, Togar B, Turkez H, Aslan A. Effects of two lichen acids isolated from Pseudevernia furfuracea (L.) Zopf in cultured human lymphocytes. Z Naturforsch C. 2018;73(7–8):303–12. https://doi.org/10.1515/znc-2017-0209
  50. 50. Russo A, Piovano M, Lombardo L, Garbarino J, Cardile V. Lichen metabolites prevent UV light- and nitric oxide-mediated plasmid DNA damage and induce apoptosis in human melanoma cells. Life Sci. 2008;83(13–14):468–74. https://doi.org/10.1016/j.lfs.2008.07.012
  51. 51. Luo H, Wei X, Yamamoto Y, Liu Y, Wang L, Jung JS, et al. Antioxidant activities of edible lichen Ramalina conduplicans and its free radical-scavenging constituents. Mycoscience. 2010;51(5):391–5. https://doi.org/10.1007/s10267-010-0048-5
  52. 52. Galanina IA, Sheard JW, Konoreva LA. A new saxicolous species, Rinodina jacutica (Physciaceae, lichenized Ascomycota) from the Republic of Sakha (Yakutia), Russia. Phytotaxa. 2022;564(1):121–6. https://doi.org/10.11646/phytotaxa.564.1.10
  53. 53. Torres-Benitez A, Ortega-Valencia JE, Jara-Pinuer N, Ley-Martínez JS, Velarde SH, Pereira I, et al. Antioxidant and antidiabetic potential of the Antarctic lichen Gondwania regalis ethanolic extract: metabolomic profile and in vitro and in silico evaluation. Antioxidants. 2025;14(3):298. https://doi.org/10.3390/antiox14030298
  54. 54. Poulsen-Silva E, Gordillo-Fuenzalida F, Atala C, Moreno AA, Otero MC. Bioactive lichen secondary metabolites and their presence in species from Chile. Metabolites. 2023;13(7):805. https://doi.org/10.3390/metabo13070805
  55. 55. Kim MS, Cho HB. Melanogenesis inhibitory effects of methanolic extracts of Umbilicaria esculenta and Usnea longissima. J Microbiol. 2007;45(6):578–82.
  56. 56. Jayalal U, Divakar PK, Joshi S, Oh SO, Kim JA, Hur JS. Overview of Xanthoparmelia taxa from South Korea including the description of two new species (Parmeliaceae, Ascomycota). Phytotaxa. 2014;181(2):96. https://doi.org/10.11646/phytotaxa.181.2.3
  57. 57. Guedes BN, Krambeck K, Durazzo A, Lucarini M, Santini A, Oliveira MB, et al. Natural antibiotics against antimicrobial resistance: sources and bioinspired delivery systems. Braz J Microbiol. 2024;55(3):2753–66. https://doi.org/10.1007/s42770-024-01410-1
  58. 58. Aschenbrenner IA, Cernava T, Berg G, Grube M. Understanding microbial multi-species symbioses. Front Microbiol. 2016;7:180. https://doi.org/10.3389/fmicb.2016.00180
  59. 59. Ren M, Jiang S, Wang Y, Pan X, Pan F, Wei X. Discovery and excavation of lichen bioactive natural products. Front Microbiol. 2023;14:1177123. https://doi.org/10.3389/fmicb.2023.1177123
  60. 60. Calchera A, Dal Grande F, Bode HB, Schmitt I. Biosynthetic gene content of the “perfume lichens” Evernia prunastri and Pseudevernia furfuracea. Molecules. 2019;24(1):203. https://doi.org/10.3390/molecules24010203
  61. 61. Pradhan S, Dash S, Parida S, Sahoo B, Rath B. Antioxidant and antimicrobial activities and GC/MS-based phytochemical analysis of two traditional lichen species Trypethellium virens and Phaeographis dendritica. J Genet Eng Biotechnol. 2023;21(1):41. https://doi.org/10.1186/s43141-023-00490-0
  62. 62. Zizovic I, Ivanovic J, Misic D, Stamenic M, Djordjevic S, Kukic-Markovic J, et al. SFE as a superior technique for isolation of extracts with strong antibacterial activities from lichen Usnea barbata L. J Supercrit Fluids. 2012;72:7–14. https://doi.org/10.1016/j.supflu.2012.07.018
  63. 63. Bonny S, Hitti E, Boustie J, Bernard A, Tomasi S. Optimization of a microwave-assisted extraction of secondary metabolites from crustose lichens with quantitative spectrophotodensitometry analysis. J Chromatogr A. 2009;1216(45):7651–6. https://doi.org/10.1016/j.chroma.2009.09.009
  64. 64. Krug D, Muller R. Secondary metabolomics: the impact of mass spectrometry-based approaches on the discovery and characterization of microbial natural products. Nat Prod Rep. 2014;31(6):768–83. https://doi.org/10.1039/C3NP70127A
  65. 65. Xu M, Oppong-Danquah E, Wang X, Oddsson S, Abdelrahman A, Pedersen SV, et al. Novel methods to characterise spatial distribution and enantiomeric composition of usnic acids in four Icelandic lichens. Phytochemistry. 2022;200:113210. https://doi.org/10.1016/j.phytochem.2022.113210
  66. 66. Lagarde A, Mambu L, Mai PY, Champavier Y, Stigliani JL, Beniddir MA, et al. Chlorinated bianthrones from the cyanolichen Nephroma laevigatum. Fitoterapia. 2021;149:104811. https://doi.org/10.1016/j.fitote.2020.104811
  67. 67. Liao C, Piercey-Normore MD, Sorensen JL, Gough K. In situ imaging of usnic acid in selected Cladonia spp. by vibrational spectroscopy. Analyst. 2010;135(12):3242–8. https://doi.org/10.1039/c0an00533a
  68. 68. Macedo DC, Almeida FJ, Wanderley MS, Ferraz MS, Santos NP, Lopez AM, et al. Usnic acid: from an ancient lichen derivative to promising biological and nanotechnology applications. Phytochemistry Rev. 2021;20(3):609–30. https://doi.org/10.1007/s11101-020-09717-1

Downloads

Download data is not yet available.