Names | |
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IUPAC name 2,6-Diacetyl-7,9-dihydroxy-8,9b-dimethyldibenzo[b,d]furan-1,3(2H,9bH)-dione | |
Other names
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Identifiers | |
3D model (JSmol) | |
ChEBI | |
ChEMBL | |
ChemSpider | |
ECHA InfoCard | 100.004.310 |
PubChem CID | |
UNII |
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CompTox Dashboard (EPA) | |
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Properties | |
C18H16O7 | |
Molar mass | 344.319 g·mol−1 |
Melting point | 204 °C (399 °F; 477 K) |
<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). |
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.
Usnic acid is a polyketide biosynthesized via methylphloroacetophenone as an intermediate. [7]
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.
Usnic acid has been found to have adrenergic activity in both frog and earthworm nerve junction models in preliminary research. [13]
It 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]
Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump.
Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.
Hepatotoxicity implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.
An imidazopyridine is a nitrogen containing heterocycle that is also a class of drugs that contain this same chemical substructure. In general, they are GABAA receptor agonists, however recently proton pump inhibitors, aromatase inhibitors, NSAIDs and other classes of drugs in this class have been developed as well. Despite usually being similar to them in effect, they are not chemically related to benzodiazepines. As such, GABAA-agonizing imidazopyridines, pyrazolopyrimidines, and cyclopyrrones are sometimes grouped together and referred to as "nonbenzodiazepines." Imidazopyridines include:
Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build up in the liver, a condition called cholestasis. Further slow damage to the liver tissue can lead to scarring, fibrosis, and eventually cirrhosis.
Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts, which normally allow bile to drain from the gallbladder. Affected individuals may have no symptoms or may experience signs and symptoms of liver disease, such as yellow discoloration of the skin and eyes, itching, and abdominal pain.
Fatty liver disease (FLD), also known as hepatic steatosis and steatotic liver disease (SLD), is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complications may include cirrhosis, liver cancer, and esophageal varices.
Ursodeoxycholic acid (UDCA), also known as ursodiol, is a secondary bile acid, produced in humans and most other species from metabolism by intestinal bacteria. It is synthesized in the liver in some species, and was first identified in bile of bears of genus Ursus, from which its name derived. In purified form, it has been used to treat or prevent several diseases of the liver or bile ducts.
Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are:
Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack or reduction of digestive enzymes made by the pancreas. EPI can occur in humans and is prevalent in many conditions such as cystic fibrosis, Shwachman–Diamond syndrome, different types of pancreatitis, multiple types of diabetes mellitus, advanced renal disease, older adults, celiac disease, IBS-D, IBD, HIV, alcohol-related liver disease, Sjogren syndrome, tobacco use, and use of somatostatin analogues.
Metabolic dysfunction–associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a type of chronic liver disease. This condition is diagnosed when there is excessive fat build-up in the liver, and at least one metabolic risk factor. When there is also increased alcohol intake, the term MetALD, or metabolic dysfunction and alcohol associated/related liver disease is used, and differentiated from alcohol-related liver disease (ALD) where alcohol is the predominant cause of the steatotic liver disease. The terms non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis have been used to describe different severities, the latter indicating the presence of further liver inflammation. NAFL is less dangerous than NASH and usually does not progress to it, but this progression may eventually lead to complications, such as cirrhosis, liver cancer, liver failure, and cardiovascular disease.
Acute fatty liver of pregnancy is a rare life-threatening complication of pregnancy that occurs in the third trimester or the immediate period after delivery. It is thought to be caused by a disordered metabolism of fatty acids by mitochondria in the fetus, caused by long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. This leads to decreased metabolism of long chain fatty acids by the feto-placental unit, causing subsequent rise in hepatotoxic fatty acids in maternal plasma. The condition was previously thought to be universally fatal, but aggressive treatment by stabilizing the mother with intravenous fluids and blood products in anticipation of early delivery has improved prognosis.
Bentazepam is a thienodiazepine which is a benzodiazepine analog.
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is a condition of the liver in which the normal functioning tissue, or parenchyma, is replaced with scar tissue (fibrosis) and regenerative nodules as a result of chronic liver disease. Damage to the liver leads to repair of liver tissue and subsequent formation of scar tissue. Over time, scar tissue and nodules of regenerating hepatocytes can replace the parenchyma, causing increased resistance to blood flow in the liver's capillaries—the hepatic sinusoids—and consequently portal hypertension, as well as impairment in other aspects of liver function. The disease typically develops slowly over months or years.
Methasterone, also known as methyldrostanolone and known by the nickname Superdrol, is a synthetic and orally active anabolic–androgenic steroid (AAS) which was never marketed for medical use. It was sold legally for 9 years as a body building supplement. Because of this lengthy time being legal it has more studies and references than most other designer steroids.
Bile acid malabsorption (BAM), known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic diarrhea. It has also been called bile acid-induced diarrhea, cholerheic or choleretic enteropathy, bile salt diarrhea or bile salt malabsorption. It can result from malabsorption secondary to gastrointestinal disease, or be a primary disorder, associated with excessive bile acid production. Treatment with bile acid sequestrants is often effective. It is recognised as a disability in the United Kingdom under the Equality Act 2010.
Thomas D. Schiano is an American specialist in liver transplantation, intestinal transplantation and in the diagnosis and treatment of acute and chronic liver disease. He serves as associate editor for the journals Hepatology and Liver Transplantation and has published more than 200 peer-reviewed articles and abstracts and more than 20 book chapters.
Obeticholic acid (OCA), sold under the brand name Ocaliva, is a semi-synthetic bile acid analogue which has the chemical structure 6α-ethyl-chenodeoxycholic acid. It is used as a medication used to treat primary biliary cholangitis. Intercept Pharmaceuticals Inc. hold the worldwide rights to develop OCA outside Japan and China, where it is licensed to Dainippon Sumitomo Pharma.
Aramchol is an investigational drug being developed by Galmed Pharmaceuticals as a first-in-class, potentially disease modifying treatment for nonalcoholic steatohepatitis, or NASH, a more advanced condition of non-alcoholic fatty liver disease.
Odevixibat, sold under the brand name Bylvay, is a medication for the treatment of progressive familial intrahepatic cholestasis. It is taken by mouth. Odevixibat is a reversible, potent, selective inhibitor of the ileal bile acid transporter (IBAT). It was developed by Albireo Pharma.
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: CS1 maint: date and year (link)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.