Usnic acid is a naturally occurring dibenzofuran derivative found in several lichen species with the formula C18H16O7. It was first isolated by German scientist W. Knop in 1844[2] and first synthesized between 1933 and 1937 by Curd and Robertson.[3] Usnic acid was identified in many genera of lichens including Usnea, Cladonia, Hypotrachyna, Lecanora, Ramalina, Evernia, Parmelia and Alectoria. Although it is generally believed that usnic acid is exclusively restricted to lichens, in a few unconfirmed isolated cases the compound was found in kombucha tea and non-lichenized ascomycetes.[4][5]
At normal conditions, usnic acid is a bitter, yellow, solid substance.[6] It is known to occur in nature in both the d- and l-forms as well as a racemic mixture. Salts of usnic acid are called usnates (e.g. copper usnate).
Usnic acid is a secondary metabolite in lichens whose role has not been completely elucidated. It is believed that usnic acid protects the lichen from adverse effects of sunlight exposure and deters grazing animals with its bitter taste.
Biosynthesisedit
Usnic acid is a polyketide biosynthesized via methylphloroacetophenone as an intermediate.[7]
Proposed biosynthesis for usnic acid
Safetyedit
Usnic acid and its salts are idiosyncratically associated with severe hepatotoxicity and liver failure.[8][9] Daily oral intake of 300–1350 mg over a period of weeks has led to severe hepatotoxicity in a number of persons.[10][11]
Sodium usnate was one ingredient in a product called "Lipokinetix" that was claimed to induce weight loss via an increase in metabolic rate. Lipokinetix has been the topic of an FDA warning in the USA[12] due to potential hepatotoxicity, although it is unclear yet if any toxicity would be attributable to the aforementioned salt. Lipokinetix also contained norephedrine (PPA), caffeine, yohimbine and 3,5-diiodothyronine.
Pharmacologyedit
Usnic acid has been found to have adrenergic activity in both frog and earthworm nerve junction models in preliminary research.[13]
^ abcdeO'Neil, Maryadele J.; Merck Sharp and Dohme Research Laboratories, eds. (2001). The Merck index: an encyclopedia of chemicals, drugs, and biologicals (13th ed.). Whitehouse Station, NJ: Merck. p. 1762. ISBN978-0-911910-13-1.{{cite book}}: CS1 maint: date and year (link)
^Knop, W (1844). "Chemisch-physiologische Untersuchung uber die Flechten". Annalen der Chemie und Pharmacie. 49 (2): 103–124. doi:10.1002/jlac.18440490202.
^Robertson, A.; Curd, F. H. (1933). "277. Usnic acid. Part III. Usnetol, usnetic acid, and pyrousnic acid". Journal of the Chemical Society (Resumed): 1173. doi:10.1039/jr9330001173.
^Cocchietto, Moreno; Skert, Nicola; Nimis, Pier; Sava, Gianni (2002). "A review on usnic acid, an interesting natural compound". Naturwissenschaften. 89 (4): 137–146. Bibcode:2002NW.....89..137C. doi:10.1007/s00114-002-0305-3. ISSN 0028-1042. PMID 12061397. S2CID 11481018.
^Blanc, Philippe J. (1996). "Characterization of the tea fungus metabolites". Biotechnology Letters. 18 (2): 139–142. doi:10.1007/BF00128667. ISSN 0141-5492. S2CID 34822312.
^Michael Ash; Irene Ash (2004). Handbook of preservatives. Synapse Info Resources. p. 5856. ISBN978-1-890595-66-1. Retrieved 5 August 2010.
^Taguchi, Heihachiro; Sankawa, Ushio; Shibata, Shoji (1969). "Biosynthesis of Natural Products. VI. Biosynthesis of Usnic Acid in Lichens. (1). A General Scheme of Biosynthesis of Usnic Acid". Chemical & Pharmaceutical Bulletin. 17 (10): 2054–2060. doi:10.1248/cpb.17.2054. PMID 5353559.
^Chitturi, Shivakumar; Farrell, Geoffrey C. (2008). "Hepatotoxic slimming aids and other herbal hepatotoxins". Journal of Gastroenterology and Hepatology. 23 (3): 366–373. doi:10.1111/j.1440-1746.2008.05310.x. PMID 18318821. S2CID 23840983.
^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". Canadian Journal of Gastroenterology. 25 (3): 157–60. doi:10.1155/2011/174978. PMC3076034. PMID 21499580.
^Hsu, LM; Huang, YS; Chang, FY; Lee, SD (Jul 2005). "'Fat burner' herb, usnic acid, induced acute hepatitis in a family". Journal of Gastroenterology and Hepatology. 20 (7): 1138–9. doi:10.1111/j.1440-1746.2005.03855.x. PMID 15955234. S2CID 6717430.
^Sanchez, William; Maple, John T.; Burgart, Lawrence J.; Kamath, Patrick S. (2006). "Severe Hepatotoxicity Associated with Use of a Dietary Supplement Containing Usnic Acid". Mayo Clinic Proceedings. 81 (4): 541–544. doi:10.4065/81.4.541. PMID 16610575.
^"Safety Alerts for Human Medical Products > Lipokinetix". MedWatch: The FDA Safety Information and Adverse Event Reporting Program. U.S. Food and Drug Administration. November 20, 2001. Retrieved 5 December 2012. FDA has received multiple reports of persons who developed liver injury or liver failure while using Lipokinetix. The product contains norephedrine (also known as phenylpropanolamine or PPA), caffeine, yohimbine, diiodothyronine, and sodium usniate.
^Harris N. J. (1961), Honors Thesis, Clark University, Worcester, Massachusetts
Seeking to Fight Fat, She Lost Her Liver, New York Times, March 4, 2003
January 01, 1970
usnic, acid, naturally, occurring, dibenzofuran, derivative, found, several, lichen, species, with, formula, c18h16o7, first, isolated, german, scientist, knop, 1844, first, synthesized, between, 1933, 1937, curd, robertson, identified, many, genera, lichens, . Usnic acid is a naturally occurring dibenzofuran derivative found in several lichen species with the formula C18H16O7 It was first isolated by German scientist W Knop in 1844 2 and first synthesized between 1933 and 1937 by Curd and Robertson 3 Usnic acid was identified in many genera of lichens including Usnea Cladonia Hypotrachyna Lecanora Ramalina Evernia Parmelia and Alectoria Although it is generally believed that usnic acid is exclusively restricted to lichens in a few unconfirmed isolated cases the compound was found in kombucha tea and non lichenized ascomycetes 4 5 Usnic acid Names IUPAC name 2 6 Diacetyl 7 9 dihydroxy 8 9b dimethyldibenzo b d furan 1 3 2H 9bH dione Other names UsneineUsninic acidUsniacin Identifiers CAS Number 125 46 2 racemic Y7562 61 0 R Y6159 66 6 S Y 3D model JSmol Interactive image ChEBI CHEBI 38319 N ChEMBL ChEMBL242022 N ChemSpider 5444 Y ECHA InfoCard 100 004 310 PubChem CID 5646 UNII 0W584PFJ77 Y663456969I R Y5HYW08F205 S Y CompTox Dashboard EPA DTXSID0040123 InChI InChI 1S C18H16O7 c1 6 14 22 12 8 3 20 16 13 15 6 23 18 4 10 25 16 5 9 21 11 7 2 19 17 18 24 h5 11 22 23H 1 4H3 YKey CUCUKLJLRRAKFN UHFFFAOYSA N YInChI 1 C18H16O7 c1 6 14 22 12 8 3 20 16 13 15 6 23 18 4 10 25 16 5 9 21 11 7 2 19 17 18 24 h5 11 22 23H 1 4H3Key CUCUKLJLRRAKFN UHFFFAOYAS SMILES CC1 C C C2C C1O C3 C CC O C C3 O C O C O2 C C O C O Properties Chemical formula C 18H 16O 7 Molar mass 344 319 g mol 1 Melting point 204 C 399 F 477 K Solubility in water lt 0 001 g L 25 C 1 Solubility in acetone 0 077 g L 1 Solubility in ethyl acetate 0 088 g L 1 Solubility in furfural 0 732 g L 1 Solubility in furfuryl alcohol 0 121 g L 1 Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references At normal conditions usnic acid is a bitter yellow solid substance 6 It is known to occur in nature in both the d and l forms as well as a racemic mixture Salts of usnic acid are called usnates e g copper usnate Contents 1 Biological role in lichens 2 Biosynthesis 3 Safety 4 Pharmacology 5 Analytics 6 References 7 External linksBiological role in lichens editUsnic acid is a secondary metabolite in lichens whose role has not been completely elucidated It is believed that usnic acid protects the lichen from adverse effects of sunlight exposure and deters grazing animals with its bitter taste Biosynthesis editUsnic acid is a polyketide biosynthesized via methylphloroacetophenone as an intermediate 7 nbsp Proposed biosynthesis for usnic acidSafety editUsnic acid and its salts are idiosyncratically associated with severe hepatotoxicity and liver failure 8 9 Daily oral intake of 300 1350 mg over a period of weeks has led to severe hepatotoxicity in a number of persons 10 11 Sodium usnate was one ingredient in a product called Lipokinetix that was claimed to induce weight loss via an increase in metabolic rate Lipokinetix has been the topic of an FDA warning in the USA 12 due to potential hepatotoxicity although it is unclear yet if any toxicity would be attributable to the aforementioned salt Lipokinetix also contained norephedrine PPA caffeine yohimbine and 3 5 diiodothyronine Pharmacology editUsnic acid has been found to have adrenergic activity in both frog and earthworm nerve junction models in preliminary research 13 Analytics editIt is possible to determine the content of usnic acid in lichen extract using reversed polarity capillary zone electrophoresis or high performance liquid chromatography analysis 14 References edit a b c d e O Neil Maryadele J Merck Sharp and Dohme Research Laboratories eds 2001 The Merck index an encyclopedia of chemicals drugs and biologicals 13th ed Whitehouse Station NJ Merck p 1762 ISBN 978 0 911910 13 1 a href Template Cite book html title Template Cite book cite book a CS1 maint date and year link Knop W 1844 Chemisch physiologische Untersuchung uber die Flechten Annalen der Chemie und Pharmacie 49 2 103 124 doi 10 1002 jlac 18440490202 Robertson A Curd F H 1933 277 Usnic acid Part III Usnetol usnetic acid and pyrousnic acid Journal of the Chemical Society Resumed 1173 doi 10 1039 jr9330001173 Cocchietto Moreno Skert Nicola Nimis Pier Sava Gianni 2002 A review on usnic acid an interesting natural compound Naturwissenschaften 89 4 137 146 Bibcode 2002NW 89 137C doi 10 1007 s00114 002 0305 3 ISSN 0028 1042 PMID 12061397 S2CID 11481018 Blanc Philippe J 1996 Characterization of the tea fungus metabolites Biotechnology Letters 18 2 139 142 doi 10 1007 BF00128667 ISSN 0141 5492 S2CID 34822312 Michael Ash Irene Ash 2004 Handbook of preservatives Synapse Info Resources p 5856 ISBN 978 1 890595 66 1 Retrieved 5 August 2010 Taguchi Heihachiro Sankawa Ushio Shibata Shoji 1969 Biosynthesis of Natural Products VI Biosynthesis of Usnic Acid in Lichens 1 A General Scheme of Biosynthesis of Usnic Acid Chemical amp Pharmaceutical Bulletin 17 10 2054 2060 doi 10 1248 cpb 17 2054 PMID 5353559 Chitturi Shivakumar Farrell Geoffrey C 2008 Hepatotoxic slimming aids and other herbal hepatotoxins Journal of Gastroenterology and Hepatology 23 3 366 373 doi 10 1111 j 1440 1746 2008 05310 x PMID 18318821 S2CID 23840983 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 Canadian Journal of Gastroenterology 25 3 157 60 doi 10 1155 2011 174978 PMC 3076034 PMID 21499580 Hsu LM Huang YS Chang FY Lee SD Jul 2005 Fat burner herb usnic acid induced acute hepatitis in a family Journal of Gastroenterology and Hepatology 20 7 1138 9 doi 10 1111 j 1440 1746 2005 03855 x PMID 15955234 S2CID 6717430 Sanchez William Maple John T Burgart Lawrence J Kamath Patrick S 2006 Severe Hepatotoxicity Associated with Use of a Dietary Supplement Containing Usnic Acid Mayo Clinic Proceedings 81 4 541 544 doi 10 4065 81 4 541 PMID 16610575 Safety Alerts for Human Medical Products gt Lipokinetix MedWatch The FDA Safety Information and Adverse Event Reporting Program U S Food and Drug Administration November 20 2001 Retrieved 5 December 2012 FDA has received multiple reports of persons who developed liver injury or liver failure while using Lipokinetix The product contains norephedrine also known as phenylpropanolamine or PPA caffeine yohimbine diiodothyronine and sodium usniate Harris N J 1961 Honors Thesis Clark University Worcester Massachusetts Kreft Samo Strukelj Borut 2001 Reversed polarity capillary zone electrophoretic analysis of usnic acid Electrophoresis 22 13 2755 2757 doi 10 1002 1522 2683 200108 22 13 lt 2755 AID ELPS2755 gt 3 0 CO 2 6 PMID 11545403 S2CID 24341350 External links editSeeking to Fight Fat She Lost Her Liver New York Times March 4 2003 Retrieved from https en wikipedia org w index php title Usnic acid amp oldid 1210020505, wikipedia, wiki, book, books, library,
