Usnic acid biological activity: history, evaluation and usage

Ahlam Abdulaziz Alahmadi


Since Usnic acid (UA) was isolated from lichen metabolite in 1844, a lot of studies were conducted on it and now it became commercially available in the market. Its wide availability in different lichen species, being isolated easily, and high purity of the isolated product make it an excellent base for producing new pharmaceuticals. In this review the different usage of UA was summarized. It was utilized as an antioxidant, anti-proliferative, antimicrobial and antiprotozoal, larvicidal and insecticidal, antifungal, antiviral, algicidal, anti-inflammatory, pain-relieving and antipyretic agent. Many adverse effects were associated with using usnic acid, especially at high dose, including; hepatotoxicity, genotoxicity, allergenicity, side effects on the cardiovascular system and adipocytes of fatty tissue. This review aimed to throw the light on the updated biological activities, effectiveness and safety and usage of usnic acid during the last decade.


Animal, Cytotoxicity, Human, Hepatotoxicity, Lichen, Nephrotoxicity, Neurotoxicity, Usnic Acid

Full Text:



Raizada N, Sachdeva KS, Sreenivas A, Vadera B, Gupta RS, Parmar M, et al. Feasibility of decentralised deployment of Xpert MTB/RIF test at lower level of health system in India. PLoS One. 2014;26;9(2):e89301.

Maciąg-Dorszyńska M1, Węgrzyn G, Guzow-Krzemińska B. Antibacterial activity of lichen secondary metabolite usnic acid is primarily caused by inhibition of RNA and DNA synthesis. 2014;353(1):57-62. Available at:"FEMS Microbiol Lett.

Luzina OA, Salakhutdinov NF. Biological activity of usnic acid and its derivatives: Part 2. effects on higher organisms. Molecular and physicochemical aspects. Russian Journal of Bioorganic Chemistry. 2016;1;42(3):249-68.

Guo L, Shi Q, Fang JL, Mei N, Ali AA, Lewis SM, et al. Review of usnic acid and Usnea barbata toxicity. J of Env Sci and Heal, Part C. 2008;26(4):317-38.

Castle H, Kubsch F. The production of usnic, didymic, and rhodocladonic acids by the fungal component of the lichen Cladonia cristatella. Archives of biochemistry. 1949;23(1):158-60.

Taguchi H, Sankawa U, Shibata S. Biosynthesis of natural products. VII. Biosynthesis of usnic acid in lichens. Seasonal variation observed in usnic acid biosynthesis. Chemical and Pharmaceutical Bulletin. 1969;17(10):2061-4.

Bjerke JW, Elvebakk A, Domínguez E, Dahlback A. Seasonal trends in usnic acid concentrations of Arctic, alpine and Patagonian populations of the lichen Flavocetraria nivalis. Phytochemistry. 2005;66(3):337-44.

Curd FN, Robertson AJ. Usnic Acid. Part I. Derivatives of methylphloroglucinol. Chem. Soc. 1933;0:437-44.

Komiya T, Shibata S. Formation of Lichen Substances by Mycobionts of Lichens. Isolation of (+) Usnic Acid and Salazinic Acid from Mycobionts of Ramalina spp. Chemical and Pharmaceutical Bulletin. 1969;17(6):1305-6.

Krishna DR, Ramana DV, Mamidi NV. In vitro protein binding and tissue distribution of D(+) usnic acid. Drug Metabol Drug Interact. 1995;12:53-63.

Krishna DR, Venkataramana D. Pharmacokinetics of D(+)-usnic acid in rabbits after intravenous and oral administration. Drug Metab Dispos. 1992;20:909-11.

Foti RS, Dickmann LJ, Davis JA, Greene RJ, Hill JJ, Howard ML, et al. Metabolism and related human risk factors for hepatic damage by usnic acid containing nutritional supplements. Xenobiotica. 2008;38:264-80.

Sahu SC, Amankwa‐Sakyi M, O'Donnell MW, Sprando RL. Effects of usnic acid exposure on human hepatoblastoma HepG2 cells in culture. J Appl Toxicol. 2012;32(9):722-30.

Johnson RB, Feldott G, Lardy HA. The mode of action of the antibiotic, usnic acid. Arch. Biochem. 1950;28(3):317-23.

Pramyothin P, Janthasoot W, Pongnimitprasert N, Phrukudom S, Ruangrungsi N. Hepatotoxic effect of (+) usnic acid from Usnea siamensis Wainio in rats, isolated rat hepatocytes and isolated rat liver mitochondria. J Ethnopharmacol. 2004;90:381-87.

Han D, Matsumaru K, Rettori D, Kaplowitz N. Usnic acid-induced necrosis of cultured mouse hepatocytes: inhibition of mitochondrial function and oxidative stress. Biochem Pharmacol. 2004;67:439-51.

Al-Ahmadi AA, Al-Robai AA, Abo-Khatwa AN, Ali SS. Assessment of Usnic Acid (Lichen Usnea Articulata Extract) Safety on Lipid Profile, Adipocytes Morphology and Liver Functions in Adult Male Rats. JKAU: Med. Sci. 2013;20(2):45-65.‎

Shtro AA, Zarubaev VV, Luzina OA, Sokolov DN, Kiselev OI, Salakhutdinov NF. Novel derivatives of usnic acid effectively inhibiting reproduction of influenza A virus. Bioorganic & medicinal chemistry. 2014;22(24):6826-36.

Joseph A, Lee T, Moland CL, Branham WS, Fuscoe JC, Leakey JE, et al. Effect of (+)-usnic acid on mitochondrial functions as measured by mitochondria-specific oligonucleotide microarray in liver of B6C3F 1 mice. Mitochondrion. 2009;9(2):149-58.

Odabasoglu F, Cakir A, Suleyman H, Aslan A, Bayir Y, Halici M, et al. Gastroprotective and antioxidant effects of usnic acid on indomethacin-induced gastric ulcer in rats. J Ethnopharmacol. 2006;103(1):59-65.

Rabelo TK, Zeida´n-Chulia´ F, Vasques LM, dos Santos JPA, da Rocha RF, Pasquali MAdB, et al. Redox characterization of usnic acid and its cytotoxic effect on human neuron-like cells (SH-SY5Y). Toxicol In Vitro. 2012;26:304-14.

Kohlhardt-Floehr C, Boehm F, Troppens S, Lademann J, Truscott TG. Prooxidant and antioxidant behaviour of usnic acid from lichens under UVB-light irradiation–studies on human cells. Journal of Photochemistry and Photobiology B: Biology. 2010;101(1):97-102.

Takai M, Uehara Y, Beisler JA. Usnic acid derivatives as potential antineoplastic agents. J Med Chem. 1979;22:1380-84.

Cardarelli M, Serino G, Campanella L, Ercole P, De Cicco NF, Alesiani O, et al. Antimitotic effects of usnic acid on different biological systems. Cell Mol Life Sci. 1997;53:667-72.

Kristmundsdottir T, Aradottir HA, Ingolfsdottir K, Ogmundsdottir HM. Solubilization of the lichen metabolite (+)-usnic acid for testing in tissue culture. J Pharm Pharmacol. 2002;54:1447-52.

Mayer M, O’Neill MA, Murray KE, Santos-Magalha˜es NS, Carneiro-Lea˜o AM, Thompson AM, et al. Usnic acid: a non-genotoxic compound with anti-cancer properties. Anti-cancer Drugs. 2005;16(8)805-9.

O’Neill MA, Mayer M, Murray KE, Rolim-Santos HM, Santos-Magalha˜es NS, Thompson AM, et al. Does usnic acid affect microtubules in human cancer cells? Brazil J Biol. 2010;70:659-64.

Brisdelli F, Perilli M, Sellitri D, Piovano M, Garbarino JA, Nicoletti M, et al. Cytotoxic activity and antioxidant capacity of purified lichen metabolites: an in vitro study. Phytotherapy research. 2013;27(3):431-7.

Ingolfsdottir K. Usnic acid. Phytochemistry. 2002;61:729-36.

Ramos DF, Almeida da Silva PE. Antimycobacterial activity of usnic acid against resistant and susceptible strains of Mycobacterium tuberculosis and non-tuberculous mycobacteria. Pharm Biol. 2010;48(3):260-3.

Frankos VH. NTP nomination for usnic acid and Usnea barbata. 2004. Available at:

Francolini I, Norris P, Piozzi A, Donelli G, Stoodley P. Usnic acid, a natural antimicrobial agent able to inhibit bacterial biofilm formation on polymer surfaces. Antimicrob Agents Chemother. 2004;48:4360-65.

Gupta VK, Verma S, Gupta S, Singh A, Pal A, Srivastava SK, et al. Membrane-damaging potential of natural L-(−)-usnic acid in Staphylococcus aureus. Eur J Clin Microbiol Infect Dis. 2012 Dec;31(12):3375-83.

De Carvalho EA, Andrade PP, Silva NH, Pereira, EC, Fiqueiredo RC. Effect of usnic acid from the lichen Cladonia substellata on Trypanosoma cruzi in vitro: an ultrastructural study, Micron. 2005;36(2):155-61.

Luzina OA, Salakhutdinov NF. Biological activity of usnic acid and its derivatives: Part 1. Activity against unicellular organisms. Russian J Bioorg Chemis. 2016;42(2):115-32.

Emmerich R, Giez I, Lange OL, Proksch P. Toxicity and antifeedant activity of lichen compounds against the polyphagous herbivorous insect Spodoptera littoralis. Phytochemistry. 1993;33(6):1389-94.

Polovinka MP, Salakhutdinov NF, Luzina OA, Glupov VV, Serebrov VV, Dubovskii IM, et al. Patent no. 2328493, Byull. Izobret. 2008:19.

Nikolić V, Stanković M, Nikolić L, Nikolić G, Ilić-Stojanović S, Popsavin M, et al. Inclusion complexes with cyclodextrin and usnic acid. Journal of Inclusion Phenomena and Macrocyclic Chemistry. 2013;76(1-2):173-82.

Bomfim RR, Araújo AA, Cuadros-Orellana S, Melo MG, Quintans-Junior LJ, Cavalcanti SC, et al. Larvicidal activity of Cladonia substellata extract and usnic acid against Aedes aegypti and Artemia salina. Latin Ame J of Pha. 2009;28(4):580-4.

Broksa B, Sturdikova M, Pronayova N, Liptaj T. (-)-Usnic acid and its derivatives. Their inhibition of fungal growth and enzyme activity. Die Pharmazie. 1996;51(3):195-6.

Cocchietto M, Skert N, Nimis P, Sava G. A review on usnic acid, an interesting natural compound. Natur wissenschaften. 2002;89(4):137-46.

Campanella L, Delfini M, Ercole P, Iacoangeli A, Risuleo G. 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. 2002;84(4):329-34.

Schimmer O, Lehner H. Untersuchungen zur Wirkung von Usninsäure auf die Grünalge Chlamydomonas reinhardii. Archives of Microbiology. 1973;93(2):145-54.

Vijayakumar CS, Viswanathan S, Reddy MK, Parvathavarthini S, Kundu AB, Sukumar E. Anti-inflammatory activity of (+)-usnic acid. Fitoterapia. 2000;71:564-566.55

Sahu SC, O'Donnell MW, Sprando RL. Interactive toxicity of usnic acid and lipopolysaccharides in human liver HepG2 cells. J Appl Toxicol. 2012;32(9):739-49.

Huang Z, Zheng G, Tao J, Ruan J. Anti-inflammatory effects and mechanisms of usnic acid. Journal of Wuhan University of Technology-Materials Science Edition. 2011;26(5):955-9.

Okuyama E, Umeyama K, Yamazaki M, Kinoshita Y, Yamamoto Y. Usnic acid and diffractaic acid as analgesic and antipyretic components of Usnea diffracta. Planta Med. 1995;61:113-5.

Riella KR, Marinho RR, Santos JS, Pereira-Filho RN, Cardoso JC, Albuquerque-Junior RL, Thomazzi SM. Anti-inflammatory and cicatrizing activities of thymol, a monoterpene of the essential oil from Lippia gracilis, in rodents. J of Eth. 2012;143(2):656-63.

Rancan F, Rosan S, Boehm K, Fernández E, Hidalgo ME, Quihot W, et al. Protection against UVB irradiation by natural filters extracted from lichens. Journal of Photochemistry and Photobiology B: Biology. 2002;68(2):133-9.

Favreau JT, Ryu ML, Braunstein G, Orshansky G, Park SS, Coody GL, et al. Severe hepatotoxicity associated with the dietary supplement LipoKinetix. Annals of internal medicine. 2002;136(8):590-5.

Neff GW, Reddy KR, Durazo FA, Meyer D, Marrero R, Kaplowitz N. Severe hepatotoxicity associated with the use of weight loss diet supplements containing ma huang or usnic acid. J Hepatol. 2004;41(6):1062-4.

Sanchez W, Maple JT, Burgart LJ, Kamath PS. Severe hepatotoxicity associated with use of a dietary supplement containing usnic acid. In Mayo Clinic Proceedings. 2006;81(4):541-4.

Yellapu RK, Mittal V, Grewal P, Fiel M, Schiano T. Acute liver failure caused by ‘fat burners’ and dietary supplements: a case report and literature review. Can J Gastroenterol. 2011;25:157-60.

Leandro LF, Munari CC, Sato VL, Alves JM, de Oliveira PF, Mastrocola DF, et al. Assessment of the genotoxicity and antigenotoxicity of (+)-usnic acid in V79 cells and Swiss mice by the micronucleus and comet assays. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 2013;753(2):101-6.

Al-Ahmadi AA, Ayuob NN, Ali SS, Al-Robai AA, Abo-Khatwa NA. Effect of (+)-Usnic Acid as a Fat Burner on the Rat Hepatocyte; Correlated Histological and Biochemical in vivo Study. J Anim Vet Adv. 2012;11(9):1368-77.

Ivanova V, Bačkor M, Dahse HM, Graefe U. Molecular structural studies of lichen substances with antimicrobial, antiproliferative, and cytotoxic effects from Parmelia subrudecta. Preparative biochemistry & biotechnology. 2010 Sep;40(4):377-88.

Thune PO, Solberg YJ. Photosensitivity and allergy to aromatic lichen acids, Compositae oleoresins and other plant substances. Contact Dermatitis. 1980;6(2):81-7.

Mitchell JC, Shibata S. Immunologic Activity of Some Substances Derived from Lichenized Fungi** From the Division of Dermatology, Department of Medicine, The University of British Columbia. J Invest Dermatol. 1969;52(6):517-20k.