Lichens represent a promising source of antimicrobial, cytotoxic and antioxidant agents. Their great pharmacological potential lies in the fact that they represent specific symbiotic organisms and thus possess natural roles allowing them to be highly adaptable to different environmental conditions. On the other hand, stated biological activities of lichens with prospective medicinal significance may be connected to their long-term use in traditional treatment of various ailments. Genus Usnea from the Parmeliaceae family is certainly one of the best studied in terms of chemical composition and biological properties of its extracts and/or isolated compounds. In the first part of the study, a detailed review of literature has been performed yielding a detailed report on the investigations of biological activities of the lichens belonging to this genus. In the second part of the study, chemical composition of the lichens from the genus was described and, additionally, a survey of the biological properties of the most representative secondary metabolites in these lichens has been reported. It could be concluded that the extracts and/or isolated compounds from the lichens belonging to the genus Usnea may be considered a valuable source of prospective drug candidates with potential clinical relevance.
Agar, G., Aslan, A., Sarioglu, E. K., Alpsoy, L., & Ceker, S. (2011). Protective activity of the methanol extract of Usnea longissima against oxidative damage and genotoxicity caused by aflatoxin B1 in vitro. Turk. J. Med. Sci, 41(6), 1043–1049.
Almeida, J. C. F., J.R.G.S., Q., J.S.S., Q.-J., L.J., & Santos, M. R. V. (2014). Antioxidant activity and mechanisms of action of natural compounds isolated from lichens: a systematic review. Molecules, 19, 14496–14527.
Araujo, A. A. S., & Silva, F. A. (2011). Redox properties and cytoprotective actions of atranorin, a lichen secondary metabolite. Toxicol. In Vitro, 25(2), 462–468.
Backorova, M., Backor, M., Mikes, J., Jendzelovsky, R., & Fedorocko, P. (2011). Variable responses of different human cancer cells to the lichen compounds parietin, atranorin, usnic acid and gyrophoric acid. Toxicol. in Vitro, 25(1), 37–44.
Barreto, R. S. S., Albuquerque-Junior, R. L. C., Pereira-Filho, R. N., Quintans, J. S. S., Barreto, A. S., DeSantana, J. M., Santana-Filho, V. J., Santos, M. R. V., Bonjardim, L. R., & Araujo, A. A. S. (2013). Evaluation of wound healing activity of atranorin, a lichen secondary metabolite, on rodents. Braz. J. Pharmacogn, 23(2), 310–319.
Bayir, Y., Odabasoglu, F., Cakir, A., Aslan, A., Suleyman, H., Halici, M., & Kazaz, C. (2006). The inhibition of gastric mucosal lesion, oxidative stress and neutrophil-infiltration in rats by the lichen constituent diffractaic acid. Phytomedicine, 13(8), 584–590.
Behera, B. C., Mahadik, N. A. M., & M. (2012). Antioxidative and cardiovascular-protective activities of metabolite usnic acid and psoromic acid produced by lichen species Usnea complanata under submerged fermentation. Pharm. Biol, 50(8), 968–979.
Behera, B. C., Verma, N., & Sonone, A. A. M. U. (2005). Antioxidant and antibacterial activities of lichen Usnea ghattensis in vitro. Biotechnol. Lett, 27(14), 991–995.
Behera, B. C., Verma, N., Sonone, A., & Makhija, U. (2006). Determination of antioxidative potential of lichen Usnea ghattensis in vitro. LWT–Food Sci. Technol, 39(1), 80–85.
Behera, B. C., Verma, S., N.A., & Makhija, U. (2005). Evaluation of antioxidant potential of the cultured mycobiont of a lichen Usnea ghattensis. Phytother. Res, 19(1), 58–64.
Bessadottir, M., Egilsson, M., M., E., E., M., I.H., O., M.H., O., S., & Ogmundsdottir, H. M. (2012). Proton-shuttling lichen compound usnic acid affects mitochondrial and lysosomal function in cancer cells. Plos One, 7(12), 51296.
Bezivin, C., Tomasi, S., Rouaud, I., Delcros, J. G., & Boustie, J. (2004). Cytotoxic activity of compounds from the lichen: Cladonia convoluta. Planta Med, 70(9), 874–877.
Brandao, L. F., Alcantara, G. B., Matos Mde, F., Bogo, D., Freitas Ddos, S., Oyama, N. M., & Honda, N. K. (2013). Cytotoxic evaluation of phenolic compounds from lichens against melanoma cells. Chem. Pharm. Bull, 61, 2 176-183.
Brisdelli, F., Perilli, M., Sellitri, D., Piovano, M., Garbarino, J. A., Nicoletti, M., Bozzi, A., Amicosante, G., & Celenza, G. (2013). Cytotoxic activity and antioxidant capacity of purified lichen metabolites: an in vitro study. Phytother. Res, 27(3), 431–437.
Bugni, T. S., Andjelic, C. D., Pole, A. R., Rai, P., Ireland, C. M., & Barrows, L. R. (2009). Biologically active components of a Papua New Guinea analgesic and anti-inflammatory lichen preparation. Fitoterapia, 80(5), 270–273.
Burlando, B., Ranzato, E., Volante, A., Appendino, G., Pollastro, F., & Verotta, L. (2009). Antiproliferative effects on tumour cells and promotion of keratinocyte wound healing by different lichen compounds. Planta Med, 75(6), 607–613.
Campanella, L., Delfini, M., Ercole, P., Iacoangeli, A., & Risuleo, G. (2002). Molecular characterization and action of usnic acid: a drug that inhibits proliferation of mouse polyomavirus in vitro and whose main target is RNA transcription. Biochimie, 84(4), 329–334.
Candan, M., Yilmaz, M., Tay, T., Erdem, M., & Turk, A. O. (2007). Antimicrobial activity of extracts of the lichen Parmelia sulcata and its salazinic acid constituent. Z. Naturforsch. C: J. Biosci, 62(7–8), 619–621.
Cansaran, D., Kahya, D., Yurdakulola, E., & Atakol, O. (2006). Identification and quantitation of usnic acid from the lichen Usnea species of Anatolia and antimicrobial activity. Z. Naturforsch., C: J. Biosci, 61(11–12), 773–776.
Cardarelli, M., Serino, G., Campanella, L., Ercole, P., Cicco Nardone, F., Alesiani, O., & Rossiello, F. (1997). Antimitotic effects of usnic acid on different biological systems. Cell. Mol. Life Sci, 53(8), 667–672.
Ceker, S., Orhan, F., Kizil, H. E., Alpsoy, L., Gulluce, M., Aslan, A., & Agar, G. (2013). Genotoxic and antigenotoxic potentials of two Usnea species. Toxicol. Ind. Health.
Choudhary, M. I., Azizuddin, J., S., & Atta-ur-Rahman. (2005). Bioactive phenolic compounds from a medicinal lichen, Usnea longissima. Phytochemistry, 66(19), 2346–2350.
Clerc, P. (1998). Species concepts in the genus Usnea (lichenized Ascomycetes. Lichenologist, 30(4–5), 321–340.
Einarsdottir, E., Groeneweg, J., Bjornsdottir, G. G., Harethardottir, G., Omarsdottir, S., Ingolfsdottir, K., & Ogmundsdottir, H. M. (2010). Cellular mechanisms of the anticancer effects of the lichen compound usnic acid. Planta Med, 76(10), 969–974.
Engel, K., Schmidt, U., Reuter, J., Weckesser, S., Simon-Haarhaus, B. C., & Schempp, M. (2007). Usnea barbata extract prevents ultraviolet-B induced prostaglandin E2 synthesis and COX-2 expression in HaCaT keratinocytes. J. Photochem. Photobiol., B, 89(1), 9–14.
Fiscus, S. A. (1972). A survey of the chemistry of the Usnea florida group in North America. Bryologist, 75(3), 299–304.
Fournet, A., Ferreira, M. E., Arias, A., Ortiz, S., Inchausti, A., Yaluff, G., Quilhot, W., Fernandez, E., & Hidalgo, M. E. (1997). Activity of compounds isolated from Chilean lichens against experimental cutaneous leishmaniasis. Comp. Biochem. Physiol. Part C: Pharmacol. Toxicol. Endocrinol, 116(1), 51–54.
Gollapudi, S. R., Telikepalli, H., Jampani, H. B., Mirhom, Y. W., Drake, S. D., Bhattiprolu, K. R., Vander Velde, D., & Mitscher, L. A. (1994). Alectosarmentin, a new antimicrobial dibenzofuranoid lactol from the lichen, Alectoria sarmentosa. J. Nat. Prod, 57(7), 934–938.
Gomez-Serranillos, M. P., Fernandez-Moriano, C., Gonzalez-Burgos, E., Divakarb, P. K., & Crespo, A. (2014). Parmeliaceae family: phytochemistry, pharmacological potential and phylogenetic features. RSC Adv, 4, 59017–59047.
Gupta, V. K., Verma, S., Gupta, S., Singh, A., Pal, A., Srivastava, S. K., Srivastava, P. K., Singh, S. C., & Darokar, M. P. (2012). Membrane-damaging potential of natural L-(-)-usnic acid in Staphylococcus aureus. Eur. J. Clin. Microbiol. Infect. Dis, 31(12), 3375–3383.
Hager. (1979). Handbuch der pharmazeutischen praxis, Bd. 6, Teil C.
Halici, M., Odabasoglu, F., Suleyman, H., Cakir, A., Aslan, A., & Bayir, Y. (2005). Effects of water extract of Usnea longissima on antioxidant enzyme activity and mucosal damage caused by indomethacin in rats. Phytomedicine, 12(9), 656–662.
Han, D., Matsumaru, K., Rettori, D., & Kaplowitz, N. (2004). Usnic acid-induced necrosis of cultured mouse hepatocytes: inhibition of mitochondrial function and oxidative stress. Biochem. Pharmacol, 67(3), 439–451.
Honda, N. K., Pavan, F. R., Coelho, R. G., Andrade Leite, S. R., Micheletti, A. C., Lopes, T. I., Misutsu, M. Y., Beatriz, A., Brum, R. L., & Leite, C. Q. (2010). Antimycobacterial activity of lichen substances. Phytomedicine, 17(5), 328–332.
Ingolfsdottir, K., Chung, G. A., Skulason, V. G., Gissurarson, S. R., & Vilhelmsdottir, M. (1998). Antimycobacterial activity of lichen metabolites in vitro. Eur. J. Pharm. Sci, 6(2), 141–144.
Ivanova, V., Backor, M. D., H.M., & Graefe, U. (2010). Molecular structural studies of lichen substances with antimicrobial, antiproliferative, and cytotoxic effects from Parmelia subrudecta. Prep. Biochem. Biotechnol, 40(4), 377–388.
Jayaprakasha, G. K., & Rao, L. J. (2000). Phenolic constituents from the lichen Parmotrema stuppeum (Nyl.) Hale and their antioxidant activity. Z. Naturforsch. C: J. Biosci, 55(11–12), 1018–1022.
Jin, J. Q., Li, C. Q., & He, L. C. (2008). Down-regulatory effect of usnic acid on nuclear factor-kappaB-dependent tumour necrosis factor-alpha and inducible nitric oxide synthase expression in lipopolysaccharide-stimulated macrophages RAW 264.7. Phytother. Res, 22(12), 1605–1609.
Kim, M. S., & Cho, H. B. (2007). Melanogenesis inhibitory effects of methanolic extracts of Umbilicaria esculenta and Usnea longissima. J. Microbiol, 45(6), 578–582.
Kohlhardt-Floehr, C., Boehm, F., Troppens, S., Lademann, J., & Truscott, T. G. (2010). Prooxidant and antioxidant behavior of usnic acid from lichens under UVB-light irradiation–studies on human cells. J. Photochem. Photobiol B, 101(1), 97–102.
Kokubun, T., Shiu, W. K. P., & Gibbons, S. (2007). Inhibitory activities of lichen-derived compounds against methicillin- and multidrug-resistant Staphylococcus aureus. Planta Med, 73(2), 176–179.
Kosanic, M., Manojlovic, N., Jankovic, S. S., T., & Rankovic, B. (2013). Evernia prunastri and Pseudoevernia furfuraceae lichens and their major metabolites a antioxidant, antimicrobial and anticancer agents. Food Chem. Toxicol, 53, 112–118.
Kosanić, M., Ranković, B., Stanojković, T., Rančić, A., & Manojlović, N. (2014). Cladonia lichens and their major metabolites as possible natural antioxidant, antimicrobial and anticancer agents. LWT Food Sci. Technol, 59(1), 518–525.
Kumar, K. C., & Muller, K. (1999a). Lichen metabolites. 1. Inhibitory action against leukotriene B4 biosynthesis by a non-redox mechanism. J. Nat. Prod, 62(6), 817–820.
Kumar, K. C., & Muller, K. (1999b). Lichen metabolites. 2. Antiproliferative and cytotoxic activity of gyrophoric, usnic, and diffractaic acid on human keratinocyte growth. J. Nat. Prod, 62(6), 821–823.
Lee, K. A., & Kim, M. S. (2005). Antiplatelet and antithrombotic activities of methanol extract of Usnea longissima. Phytother. Res, 19(12), 1061–1064.
Lohezic-LeDevehat, F., Tomasi, S., Elix, J. A., Bernard, A., Rouaud, I., Uriac, P., & Boustie, J. (2007). Stictic acid derivatives from the lichen Usnea articulata and their antioxidant activities. J. Nat. Prod, 70(7), 1218–1220.
Luo, H., Yamamoto, Y., Kim, J. A., Jung, J. S., Koh, Y. J., & Hur, J. (2009). Lecanoric acid, a secondary lichen substance with antioxidant properties from Umbilicaria antarctica in maritime Antarctica (King George Island. Polar. Biol, 32(7), 1033–1040.
Madamombe, I. T., & Afolayan, A. J. (2003). Evaluation of antimicrobial activity of extracts from South African Usnea barbata. Pharm. Biol, 41(3), 199–202.
Manojlovic, N., Rankovic, B., Kosanic, M., Vasiljevic, P., & Stanojkovic, T. (2012). Chemical composition of three Parmelia lichens and antioxidant, antimicrobial and cytotoxic activities of some their major metabolites. Phytomedicine, 19(13), 1166–1172.
Martins, M. C. B., Lima, M. J. G., Silva, F. P., Azevedo-Ximenes, E., Silva, N. H., & Pereira, E. C. (2010). Cladia aggregata (lichen) from Brazilian northeast: chemical characterization and antimicrobial activity. Braz. Arch. Biol. Technol, 53(1), 115–122.
Molnar, K., & Farkas, E. (2010). Current results on biological activities of lichen secondary metabolites: a review. Z. Naturforsch, 65(3–4), 157–173.
Odabasoglu, F., Aslan, A., Cakir, A., Suleyman, H., Karagoz, Y., Bayir, Y., & Halici, M. (2005). Antioxidant activity, reducing power and total phenolic content of some lichen species. Fitoterapia, 76(2), 216–219.
Odabasoglu, F., Aslan, A., Cakir, A., Suleyman, H., Karagoz, Y., Halici, M. A. B., & Y. (2004). Comparison of antioxidant activity and phenolic content of three lichen species. Phytother. Res, 18(11), 938–941.
Odabasoglu, F., Cakir, A., Suleyman, H., Aslan, A., Bayir, Y., Halici, M., & Kazaz, C. (2006). Gastroprotective and antioxidant effects of usnic acid on indomethacin-induced gastric ulcer in rats. J. Ethnopharmacol, 103(1), 59–65.
Odabasoglu, F., Yildirim, O. S., Aygun, H., Halici, Z., Halici, M., Erdogan, F., Cadirci, E., Cakir, A., Okumus, Z., Aksakal, B., Aslan, A., Unal, D., & Bayir, Y. (2012). Diffractaic acid, a novel proapoptotic agent, induces with olive oil both apoptosis and antioxidative systems in Ti-implanted rabbits. Eur. J. Pharmacol, 674(2–3), 171–178.
Ohmura, Y. (2012). A synopsis of the lichen genus Usnea (Parmeliaceae, Ascomycota) in Taiwan. Mem. Natl. Mus. Nat. Sci, 48, 91–137.
Papadopoulou, P., Tzakou, O., Vagias, C., Kefalas, P., & Roussis, V. (2007). Beta-orcinol metabolites from the lichen Hypotrachyna revoluta. Molecules, 12(5), 997–1005.
Paudel, B., Datta Bhattarai, H., Prasad Pandey, D., Seoun Hur, J., Gyu Hong, S., Kim, I. C., & Han Yim, J. (2012). Antioxidant, antibacterial activity and brine shrimp toxicity test of some mountainous lichens from Nepal. Biol. Res, 45(4), 387–391.
Paz, G. A., Raggio, J., Gomez-Serranillos, M. P., Palomino, O. M., Gonzalez-Burgos, E., Carretero, M. E., & Crespo, A. (2010). HPLC isolation of antioxidant constituents from Xanthoparmelia spp. J. Pharm. Biomed. Anal, 53(2), 165–171.
Polat, Z., Aydin, E., Turkez, H., & Aslan, A. (2016). In vitro risk assessment of usnic acid compound. Toxicol. Ind. Health, 32(3), 468–475.
Rankovic, B., & Kosanic, M. (2015). Lichens as a potential source of bioactive secondary metabolites. In Lichen secondary metabolites bioactive properties and pharmaceutical potential (pp. 1–26).
Rankovic, B., Kosanic, M., Stanojkovic, T., Vasiljevic, P., & Manojlovic, N. (2012). Biological activities of Toninia candida and Usnea barbata together with their norstictic acid and usnic acid constituents. Int. J. Mol, Sci.13(11, 14707–14722.
Rankovic, B., Misic, 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(7), 1239–1242.
Rezanka, T., & Sigler, K. (2007). Hirtusneanoside, an unsymmetrical dimeric tetrahydroxanthone from the lichen Usnea hirta. J. Nat. Prod, 70(9), 1487–1491.
Rukayadi, Y., Shim, J. S., & Hwang, J. K. (2008). Screening of Thai medicinal plants for anticandidal activity. Mycoses, 51(4), 308–312.
Safak, B., Ciftci, I. H., Ozdemir, M., Kiyildi, N., Cetinkaya, Z., Aktepe, O. C., Altindis, M., & Asik, G. (2009). In vitro anti-Helicobacter pylori activity of usnic acid. Phytother. Res, 23(7), 955–957.
Schmeda-Hirschmann, G., Tapia, A., Lima, B., Pertino, M., Sortino, M., Zacchino, S., Arias, A. R., & Feresin, G. E. (2008). A new antifungal and antiprotozoal depside from the Andean lichen Protousnea poeppigii. Phytother. Res, 22(3), 349–355.
Shrestha, G., & Clair, L. L. (2013). Lichens: a promising source of antibiotic and anticancer drugs. Phytochem. Rev, 12(1), 229–244.
Singh, G., Divakar, P. K., Dal Grande, F., Otte, J., Parnmen, S., Wedin, M., Crespo, A., Lumbsch, H. T., & Schmitt, I. (2013). The sister-group relationships of the largest family of lichenized fungi, Parmeliaceae (Lecanorales, Ascomycota. Fungal Biol, 117(10), 715–721.
Srivastava, P., Upreti, D. K., Dhole, T. N., Srivastava, A. K., & Nayak, M. T. (2013). Antimicrobial property of extracts of Indian lichen against human pathogenic bacteria. Interdiscip. Perspect. Infect. Dis, ID709348.
Sultana, N., & Afolayan, A. J. (2011). A new depsidone and antibacterial activities of compounds from Usnea undulata Stirton. J. Asian Nat. Prod. Res, 13(12), 1158–1164.
Swinscow, T. D. V., & Krog, H. (1979). The fruticose species of Usnea subgenus Usnea in east Africa. Lichenologist, 11(3), 207–252.
Thadhani, V. M., Choudhary, M. I., Ali, S., Omar, I., Siddique, H., & Karunaratne, V. (2011). Antioxidant activity of some lichen metabolites. Nat. Prod. Res, 25(19), 1827–1837.
Toledo Marante, F. J., Garcıa Castellano, A., Estevez Rosas, F., Quintana Aguiar, J., & Bermejo Barrera, J. (2003). Identification and quantitation of allelochemicals from the lichen Lethariella canariensis: phytotoxicity and antioxidative activity. J. Chem. Ecol, 29(9), 2049–2071.
Turk, H., Yilmaz, M., Tay, T., Turk, A. O., & Kivanc, M. (2006). Antimicrobial activity of extracts of chemical races of the lichen Pseudevernia furfuracea and their fusidic acid, chlor atranorin, atranorin, and olivetolic acid constituents. Z. Naturforsch. C: J. Biosci, 61(7–8), 499–507.
Valencia-Islas, N., Zambrano, A., & Rojas, J. L. (2007). Ozone reactivity and free radical scavenging behavior of phenolic secondary metabolites in lichens exposed to chronic oxidant air pollution from Mexico City. J. Chem. Ecol, 33(8), 1619–1634.
Verma, N., Behera, B. C., & Makhija, U. (2008). Antioxidant and hepatoprotective activity of a lichen Usnea ghattensis in vitro. Appl. Biochem. Biotechnol, 151(2–3), 167–181.
Vijayan, P., Raghu, C., Ashok, G., Dhanaraj, S. A., & Suresh, B. (2004). Antiviral activity of medicinal plants of Nilgiris. Indian J. Med. Res, 120(1), 24–29.
Vilegas, W. (2004). Intermediate reactive oxygen and nitrogen from macrophages induced by Brazilian lichens. Fitoterapia, 75(5), 473–479.
V.P., Z., & L.P., C. (2012). Biopharmaceutical potential of lichens. 50(6), 778–798.
Weckesser, S., Engel, K., Simon-Haarhaus, B., Wittmer, A., Pelz, K., & Schempp, C. M. (2007). Screening of plant extracts for antimicrobial activity against bacteria and yeasts with dermatological relevance. Phytomedicine, 14(7–8), 508–516.
Yamamoto, Y., Miura, Y., Kinoshita, Y., Higuchi, M., Yamada, Y., Murakami, A., Ohigashi, H., & Koshimizu, K. (1995). Screening of tissue cultures and thalli of lichens and some of their active constituents for inhibition of tumour promoter-induced Epstein-Barr Virus activation. Chem. Pharm. Bull, 43(8), 1388–1390.
Zugic, A. R., Jeremic, I. P., Isakovic, A. J., Arsic, I. A., Savic, S. D., & Tadic, V. M. (2016). Evaluation of Anticancer and Antioxidant Activity of a Commercially Available CO2 Supercritical Extract of Old Man’s Beard (Usnea barbata). 11(1).
Zugic, A. R., Lukic, M. Z., Tasic-Kostov , M. Z., Tadic, V. M., Arsic, I. A., Misic, D. R., Petrovic , S. D., & Savic, S. D. (2015). Alkyl polyglucoside-stabilized emulsion as a prospective vehicle for Usnea barbata CO2-supercritical extract: Assessing stability, safety and efficiency of a topical formulation. 69(6), 703–712.
(1994). Analysis of Usnea fasciata crude extracts with antineoplastic activity. Tokai J. Exp. Clin. Med, 19(1–2), 47–52.
(2013). A new pseudodepsidone from the Antarctic lichen Stereocaulon alpinum and its antioxidant, antibacterial activity. J. Antibiot, 66(9), 559–561.
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