Publication Cover
Natural Product Research
Formerly Natural Product Letters
Volume 29, 2015 - Issue 23
1,134
Views
105
CrossRef citations to date
0
Altmetric
Articles

Review of the biological properties and toxicity of usnic acid

, , , , , , , & show all
Pages 2167-2180 | Received 03 Oct 2014, Accepted 07 Jan 2015, Published online: 24 Feb 2015

References

  • Al-Bekairi  AM , Qureshi  S , Chaudhry  MA , Krishna  DR , Shah  AH . 1991. Mitodepressive, clastogenic and biochemical effects of (+)-usnic acid in mice. J Ethnopharmacol. 33:217–220. doi: 10.1016/0378-8741(91)90079-S.
  • BaČkorová  M , BaČkor  M , Mikeš  J , Jendželovský  R , FedoroČko  P . 2011. Variable responses of different human cancer cells to the lichen compounds parietin, atranorin, usnic acid and gyrophoric acid. Toxicol In Vitro. 25:37–44. doi: 10.1016/j.tiv.2010.09.004.
  • BaČkorová  M , Jendželovský  R , Kello  M , BaČkor  M , Mikeš  J , FedoroČko  P . 2012. Lichen secondary metabolites are responsible for induction of apoptosis in HT-29 and A2780 human cancer cell lines. Toxicol In Vitro. 26:462–468. doi: 10.1016/j.tiv.2012.01.017.
  • Behera  BC , Mahadik  N , Morey  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. 50:968–979. doi: 10.3109/13880209.2012.654396.
  • Bézivin  C , Tomasi  S , Rouaud  I , Delcros  JG , Boustie  J . 2004. Cytotoxic activity of compounds from the lichen: Cladonia convoluta . Planta Med. 70:874–877. doi: 10.1055/s-2004-827240.
  • Bissell  DM , Gores  GJ , Laskin  DL , Hoofnagle  JH . 2001. Drug-induced liver injury: mechanisms and test systems. Hepatology (Baltimore, MD). 33:1009–1013. doi: 10.1053/jhep.2001.23505.
  • Boelsterli  UA , Lim  PL . 2007. Mitochondrial abnormalities–a link to idiosyncratic drug hepatotoxicity?  Toxicol Appl Pharmacol. 220:92–107. doi: 10.1016/j.taap.2006.12.013.
  • Bomfim  RR , Araujo  AAS , Cuadros-Orellana  S , Melo  MGD , Quintans  LJ , Cavalcanti  SCH . 2009. Larvicidal activity of Cladonia substellata extract and usnic acid against Aedes aegypti and Artemia salina . Lat Am J Pharm. 28:580–584.
  • Brisdelli  F , Perilli  M , Sellitri  D , Piovano  M , Garbarino  JA , Nicoletti  M , Bozzi  A , Amicosante  G , Celenza  G . 2012. Cytotoxic activity and antioxidant capacity of purified lichen metabolites: an in vitro study. Phytother Res. 25:431–437.
  • Brisdelli  F , Perilli  M , Sellitri  D , Piovano  M , Garbarino  JA , Nicoletti  M , Bozzi  A , Amicosante  G , Celenza  G . 2013. Cytotoxic activity and antioxidant capacity of purified lichen metabolites: an in vitro study. Phytother Res: PTR. 27:431–437. doi: 10.1002/ptr.4739.
  • Bruno  M , Trucchi  B , Burlando  B , Ranzato  E , Martinotti  S , Akkol  EK , Süntar  I , Kele¸  H , Verotta  L . 2013. (+)-Usnic acid enamines with remarkable cicatrizing properties. Bioorg Med Chem. 21:1834–1843. doi: 10.1016/j.bmc.2013.01.045.
  • 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. 84:329–334. doi: 10.1016/S0300-9084(02)01386-X.
  • Cardarelli  M , Serino  G , Campanella  L , Ercole  P , De Cicco Nardone  F , Alesiani  O , Rossiello  F . 1997. Antimitotic effects of usnic acid on different biological systems. Cell Mol Life Sci. 53:667–672. doi: 10.1007/s000180050086.
  • Cocchietto  M , Skert  N , Nimis  PL , Sava  G . 2002. A review on usnic acid, an interesting natural compound. Die Naturwissenschaften. 89:137–146. doi: 10.1007/s00114-002-0305-3.
  • da Silva Santos  NP , Nascimento  SC , Wanderley  MS , Pontes-Filho  NT , da Silva  JF , de Castro  CM , Pereira  EC , da Silva  NH , Honda  NK , Santos-Magalhaes  NS . 2006. Nanoencapsulation of usnic acid: an attempt to improve antitumour activity and reduce hepatotoxicity. Eur J Pharm Biopharm. 64:154–160. doi: 10.1016/j.ejpb.2006.05.018.
  • De Carvalho  EAB , Andrade  PP , Silva  NH , Pereira  EC , Figueiredo  RCBQ . 2005. Effect of usnic acid from the lichen Cladonia substellata on Trypanosoma cruzi  in vitro: an ultrastructural study. Micron. 36:155–161. doi: 10.1016/j.micron.2004.09.003.
  • Durazo  FA , Lassman  C , Han  SHB , Saab  S , Lee  NP , Kawano  M , Saggi  B , Gordon  S , Farmer  DG , Yersiz  H , et al. 2004. Fulminant liver failure due to usnic acid for weight loss. Amer J Gastroenterol. 99:950–952. doi: 10.1111/j.1572-0241.2004.04165.x.
  • Dykens  JA , Jamieson  JD , Marroquin  LD , Nadanaciva  S , Xu  JJ , Dunn  MC , Smith  AR , Will  Y . 2008. In vitro assessment of mitochondrial dysfunction and cytotoxicity of nefazodone, trazodone, and buspirone. Toxicol Sci. 103:335–345. doi: 10.1093/toxsci/kfn056.
  • Dykens  JA , Will  Y . 2007. The significance of mitochondrial toxicity testing in drug development. Drug Disc Today. 12:777–785.
  • Elo  H , Matikainen  J , Pelttari  E . 2007. Potent activity of the lichen antibiotic (+)-usnic acid against clinical isolates of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus . Die Naturwissenschaften. 94:465–468. doi: 10.1007/s00114-006-0208-9.
  • Favreau  JT , Ryu  ML , Braunstein  G , Orshansky  G , Park  SS , Coody  GL , Love  LA , Fong  TL . 2002. Severe hepatotoxicity associated with the dietary supplement LipoKinetix. Ann Int Med. 136:590–595. doi: 10.7326/0003-4819-136-8-200204160-00008.
  • Fernandes  VA . 2013. Avaliação do efeito do tratamento com ácido úsnico sobre o perfil redox cardíaco e em parâmetros da função cardíaca na doença de Chagas. Federal University of Sergipe.
  • Foti  RS , Dickmann  LJ , Davis  JA , Greene  RJ , Hill  JJ , Howard  ML , Pearson  JT , Rock  DA , Tay  JC , Wahlstrom  JL , Slatter  JG . 2008. Metabolism and related human risk factors for hepatic damage by usnic acid containing nutritional supplements. Xenobiotica. 38:264–280. doi: 10.1080/00498250701802514.
  • Fournet  A , Ferreira  ME , deArias  AR , deOrtiz  ST , Inchausti  A , Yaluff  G , Quilhot  W , Fernandez  E , Hidalgo  ME . 1997. Activity of compounds isolated from Chilean lichens against experimental cutaneous leishmaniasis. Comp Biochem Phys C. 116:51–54.
  • 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. 12:656–662. doi: 10.1016/j.phymed.2004.06.021.
  • Halliwell  B . 2008. Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies?  Arch Biochem Biophys. 476:107–112. doi: 10.1016/j.abb.2008.01.028.
  • 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. 67:439–451. doi: 10.1016/j.bcp.2003.09.032.
  • Huang  Z , Zheng  G , Tao  J , Ruan  J . 2011. Anti-inflammatory effects and mechanisms of usnic acid. J Wuhan Univ Technol Mater. 26:955–959. doi: 10.1007/s11595-011-0344-8.
  • Ingólfsdóttir  K . 2002. Usnic acid[J]. Phytochemistry. 61:729–736.
  • Joseph  A , Lee  T , Moland  CL , Branham  WS , Fuscoe  JC , Leakey  JE , Allaben  WT , Lewis  SM , Ali  AA , Desai  VG . 2009. Effect of (+)-usnic acid on mitochondrial functions as measured by mitochondria-specific oligonucleotide microarray in liver of B6C3F1 mice. Mitochondrion. 9:149–158. doi: 10.1016/j.mito.2009.02.002.
  • Kohlhardt-Floehr  C , Boehm  F , Troppens  S , Lademann  J , Truscott  TG . 2010. Prooxidant and antioxidant behaviour of usnic acid from lichens under uvb-light irradiation – studies on human cells. J Photochem Photobiol B, Biol. 101:97–102. doi: 10.1016/j.jphotobiol.2010.06.017.
  • Kowaltowski  AJ , de Souza-Pinto  NC , Castilho  RF , Vercesi  AE . 2009. Mitochondria and reactive oxygen species. Free Rad Biol Med. 47:333–343. doi: 10.1016/j.freeradbiomed.2009.05.004.
  • Krishna  YR , Mittal  V , Grewal  P , Fiel  M , Schiano  T . 2011. Acute liver failure caused by ‘fat burners’ and dietary supplements: A case report and literature review. Can J Gastroenterol. 25:157–160.
  • Kumar  KC , Müller  K . 1999a. Lichen metabolites. 1. Inhibitory action against leukotriene b 4 biosynthesis by a non-redox mechanism. J Nat Prod. 62:817–820. doi: 10.1021/np9803777.
  • Kumar kc  KC , Müller  K . 1999b. Lichen metabolites. 2. Antiproliferative and cytotoxic activity of gyrophoric, usnic, and diffractaic acid on human keratinocyte growth. J Nat Prod. 62:821–823. doi: 10.1021/np980378z.
  • Lauterwein  M , Oethinger  M , Belsner  K , Peters  T , Marre  R . 1995. In vitro activities of the lichen secondary metabolites vulpinic acid, (+)-usnic acid, and ( − )-usnic acid against aerobic and anaerobic microorganisms. Antimicrob Agents Chemother. 39:2541–2543. doi: 10.1128/AAC.39.11.2541.
  • Lee  WM . 2003. Drug-induced hepatotoxicity. New Engl J Med. 349:474–485. doi: 10.1056/NEJMra021844.
  • Lira  MCB , Siqueira-Moura  MP , Rolim-Santos  HML , Galetti  FCS , Simioni  AR , Santos  NP , Do Egito  EST , Silva  CL , Tedesco  AC , Santos-Magalhaes  NS . 2009. In vitro uptake and antimycobacterial activity of liposomal usnic acid formulation. J Liposome Res. 19:49–58.
  • Lisci  M , Monte  M , Pacini  E . 2003. Lichens and higher plants on stone: a review. Int Biodeterior Biodegrad. 51:1–17. doi: 10.1016/S0964-8305(02)00071-9.
  • Manojlovic  NT , Vasiljevic  PJ , Maskovic  PZ , Juskovic  M , Bogdanovic-Dusanovic  G . 2012. Chemical composition, antioxidant, and antimicrobial activities of lichen Umbilicaria cylindrica (L.) Delise (Umbilicariaceae). Evid Based Complement Alternat Med. 2012:1–8. doi: 10.1155/2012/452431.
  • Mayer  M , O'Neill  MA , Murray  KE , Santos-Magalhães  NS , Carneiro-Leão  AM , Thompson  AM , Appleyard  VC . 2005. Usnic acid: a non-genotoxic compound with anti-cancer properties. Anti-cancer Drugs. 16:805–809. doi: 10.1097/01.cad.0000175588.09070.77.
  • Melo  MG , dos Santos  JPA , Serafini  MR , Caregnato  FF , de Bittencourt Pasquali  MA , Rabelo  TK , da Rocha  RF , Quintans  L, Jr. , de Souza Araújo  AA , da Silva  FA , Fonseca Moreira  JC, , Gelain  PN . 2011. Redox properties and cytoprotective actions of atranorin, a lichen secondary metabolite. Toxicol In Vitro. 25:462–468. doi: 10.1016/j.tiv.2010.11.014.
  • Mendonça  SCS . 2009. Efeito do ácido úsnico obtido do líquen Cladonia substellata Vainio sobre a contratilidade do átrio esquerdo de cobaia (Cavia porcellus). Federal of Sergipe University.
  • Mitchell  JC , Shibata  S.   1969. Immunologic activity of some substances derived from Lichenized Fungi. J Investigative Dermatology. 52:517–520. 10.1038/jid.1969.88.
  • Neff  GW , Reddy  KR , Durazo  FA , Meyer  D , Marrero  R , Kaplowitz  N . 2004. Severe hepatotoxicity associated with the use of weight loss diet supplements containing ma huang or usnic acid. J Hepatol. 41:1062–1064. doi: 10.1016/j.jhep.2004.06.028.
  • Nunes  PS , Albuquerque  Jr., RLC , Cavalcante  DRR , Dantas  MDM , Cardoso  JC , Bezerra  SMS , Souza  JCC , Serafini  MR , Quitans  Jr., LJ , Bonjardim  LR , Araújo  AS . 2011. Collagen-based films containing liposome-loaded usnic acid as dressing for dermal burn healing. J Biomed Biotechnol. 2011:1–9. doi: 10.1155/2011/761593.
  • 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. 103:59–65. doi: 10.1016/j.jep.2005.06.043.
  • Okuyama  E , Umeyama  K , Yamazaki  M , Kinoshita  Y , Yamamoto  Y . 1995. Usnic acid and diffractaic acid as analgesic and antipyretic components of usnea diffracta. Planta Med. 61:113–115. doi: 10.1055/s-2006-958027.
  • O'Neill  MA , Mayer  M , Murray  KE , Rolim-Santos  HM , Santos-Magalhães  NS , Thompson  AM , Appleyard  VC . 2010. Does usnic acid affect microtubules in human cancer cells?  Brazil J Biol. 70:659–664. doi: 10.1590/S1519-69842010005000013.
  • Pires  RH , Lucarini  R , Mendes-Giannini  MJS . 2012. Effect of usnic acid on Candida orthopsilosis and C. parapsilosis . Antimicrob Agents Chemother. 56:595–597. doi: 10.1128/AAC.05348-11.
  • Pramyothin  P . 1986. Isolated liver cell preparations. J Natl Res Council. 18:1–9.
  • Pramyothin  P , Janthasoot  W , Pongnimitprasert  N , Phrukudom  S , Ruangrungsi  N.   2004. Hepatotoxic effect of (+)usnic acid from UsneasiamensisWainio in rats, isolated rat hepatocytes and isolated rat liver mitochondria. J Ethnopharmacol. 90:381–387.
  • Rabelo  TK , Zeidán-Chuliá  F , Vasques  LM , dos Santos  JPA , da Rocha  RF , Pasquali  MAdB , Rybarczyk-Filho  JL , Araújo  AAS , Moreira  JCF , Gelain  DP . 2012. Redox characterization of usnic acid and its cytotoxic effect on human neuron-like cells (SH-SY5Y). Toxicol In Vitro. 26:304–314. doi: 10.1016/j.tiv.2011.12.003.
  • Rafanelli  S , Bacchillga  R , Stanganelli  I , Rafanelli  A . 1995. Contact dermatitis from usnic acid in vaginal ovules. Contact Dermatitis. 33:271–271. doi: 10.1111/j.1600-0536.1995.tb00484.x.
  • Ramos  DF , da silva  PEA . 2010. Antimycobacterial activity of usnic acid against resistant and susceptible strains of Mycobacterium tuberculosis and non-tuberculous mycobacteria. Pharm Biology. 48:260–263. doi: 10.3109/13880200903085490.
  • Rancan  F , Rosan  S , Boehm  K , Fernández  E , Hidalgo  ME , Quihot  W , Rubio  C , Boehm  F , Piazena  H , Oltmanns  U . 2002. Protection against UVB irradiation by natural filters extracted from lichens. J Photochem Photobiol B. 68:133–139. doi: 10.1016/S1011-1344(02)00362-7.
  • Ribeiro-Costa  RM , Alves  AJ , Santos  NP , Nascimento  SC , Gonçalves  EC , Silva  NH , Honda  NK , Santos-Magalhães  NS . 2004. In vitro and in vivo properties of usnic acid encapsulated into PLGA-microspheres. J Microencapsul. 21:371–384. doi: 10.1080/02652040410001673919.
  • Rice-Evans  CA , Miller  NJ , Bolwell  PG , Bramley  PM , Pridham  JB . 1995. The relative antioxidant of plant-derived polyphenolic flavonoids. Free Rad Res. 22:375–383. doi: 10.3109/10715769509145649.
  • Riella  KR , Marinho  RR , Santos  JS , Pereira-Filho  RN , Cardoso  JC , Albuquerque-Junior  RL , Thomazzi  SM . 2012. Anti-inflammatory and cicatrizing activities of thymol, a monoterpene of the essential oil from Lippia gracilis, in rodents. J Ethnopharmacol. 143:656–663. doi: 10.1016/j.jep.2012.07.028.
  • Sahu  SC , O'Donnell, Jr, MW , Sprando  RL . 2012. Interactive toxicity of usnic acid and lipopolysaccharides in human liver HepG2 cells. J Appl Toxicol. 32:739–749. doi: 10.1002/jat.2768.
  • Salo  H , Hannuksela  M , Hausen  B . 1981. Lichen picker's dermatitis (cladonia alpestris (l) rab.). Contact Dermatitis. 7:9–13. doi: 10.1111/j.1600-0536.1981.tb03951.x.
  • Sanchez  W , Maple  JT , Burgart  LJ , Kamath  PS . 2006. Severe hepatotoxicity associated with use of a dietary supplement containing usnic acid. Mayo Clin Proc. 81:541–544. doi: 10.4065/81.4.541.
  • Santos  NPS , Nascimento  SC , Wanderley  MSO , Pontes-Filho  NT , Silva  JF , Castro  CMMB , Pereira  EC , Silva  NH , Honda  NK , Santos-Magalhães  NS . 2006. Nanoencapsulation of usnic acid: An attempt to improve antitumour activity and reduce hepatotoxicity. Eur J Pharm Biopharm. 64:154–160.
  • Scalbert  A , Johnson  IT , Saltmarsh  M . 2005. Polyphenols: antioxidants and beyond. Am J Clin Nutr. 81:215S–217S.
  • Segatore  B , Bellio  P , Setacci  D , Brisdelli  F , Piovano  M , Garbarino  JA , Nicoletti  M , Amicosante  G , Perilli  M , Celenza  G . 2012. In vitro interaction of usnic acid in combination with antimicrobial agents against methicillin-resistant Staphylococcus aureus clinical isolates determined by FICI and δe model methods. Phytomedicine. 19:341–347. doi: 10.1016/j.phymed.2011.10.012.
  • Seifried  HE , Anderson  DE , Fisher  EI , Milner  JA . 2007. A review of the interaction among dietary antioxidants and reactive oxygen species. J Nutr Biochem. 18:567–579. doi: 10.1016/j.jnutbio.2006.10.007.
  • Sheu  M , Simpson  EL , Law  SV , Storrs  FJ . 2006. Allergic contact dermatitis from a natural deodorant: a report of 4 cases associated with lichen acid mix allergy. J Amer Acad Dermatol. 55:332–337. doi: 10.1016/j.jaad.2004.12.043.
  • Sokolov  DN , Zarubaev  VV , Shtro  AA , Polovinka  MP , Luzina  OA , Komarova  NI , Salakhutdinov  NF , Kiselev  OI . 2012. Anti-viral activity of ( − )- and (+)-usnic acids and their derivatives against influenza virus A(H1N1)2009. Bioorg Med Chem Lett. 22:7060–7064. doi: 10.1016/j.bmcl.2012.09.084.
  • Song  Y , Dai  F , Zhai  D , Dong  Y , Zhang  J , Lu  B , Luo  J , Liu  M , Yi  Z . 2012. Usnic acid inhibits breast tumor angiogenesis and growth by suppressing VEGFR2-mediated AKT and ERK1/2 signaling pathways. Angiogenesis. 15:421–432. doi: 10.1007/s10456-012-9270-4.
  • Sonko  BJ , Schmitt  TC , Guo  L , Shi  Q , Boros  LG , Leakey  JE , Beger  RD . 2011. Assessment of usnic acid toxicity in rat primary hepatocytes using 13c isotopomer distribution analysis of lactate, glutamate and glucose. Food Chem Toxicol. 49:2968–2974. doi: 10.1016/j.fct.2011.07.047.
  • Su  Z-Q , Mo  Z-Z , Liao  J-B , Feng  X-X , Liang  Y-Z , Zhang  X , Liu  Y-H , Chen  X-Y , Chen  Z-W , Su  Z-R , Lai  X-P . 2014. Usnic acid protects LPS-induced acute lung injury in mice through attenuating inflammatory responses and oxidative stress. Inter Immunopharmacology  22: 371–378.
  • Takai  M , Uehara  Y , Beisler  JA . 1979. Usnic acid derivatives as potential antineoplastic agents. J Med Chem. 22:1380–1384. doi: 10.1021/jm00197a019.
  • Thune  PO , Solberg  YJ . 1980. Photosensitivity and allergy to aromatic lichen acids, compositae oleoresins and other plant substances. Compositae oleoresins and other plant substances. Contact Dermatitis. 6:81–87. doi: 10.1111/j.1600-0536.1980.tb03911.x.
  • Vijayakumar  CS , Viswanathan  S , Reddy  MK , Parvathavarthini  S , Kundu  AB , Sukumar  E . 2000. Anti-inflammatory activity of (+)-usnic acid. Fitoterapia. 71:564–566. doi: 10.1016/S0367-326X(00)00209-4.
  • Yellapu  RK , Mittal  V , Grewal  P , Fiel  M , Schiano  T . 2011. Acute liver failure caused by ‘fat burners’ and dietary supplements: a case report and literature review. Can J Gastroenterol. 25:157–160.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.