{"id":43038,"date":"2018-09-14T14:45:45","date_gmt":"2018-09-14T13:45:45","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=43038"},"modified":"2018-09-21T16:01:37","modified_gmt":"2018-09-21T15:01:37","slug":"jeffrey-aronson-when-i-use-a-word-liquorice-and-glycyrrhetinic-acid","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2018\/09\/14\/jeffrey-aronson-when-i-use-a-word-liquorice-and-glycyrrhetinic-acid\/","title":{"rendered":"Jeffrey Aronson: When I use a word . . . Liquorice and glycyrrhetinic acid"},"content":{"rendered":"<p><a href=\"https:\/\/blogs.bmj.com\/bmj\/files\/2014\/12\/jeffrey_aronson.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignleft wp-image-32935\" src=\"https:\/\/blogs.bmj.com\/bmj\/files\/2014\/12\/jeffrey_aronson-223x300.jpg\" alt=\"jeffrey_aronson\" width=\"122\" height=\"146\" \/><\/a><span style=\"font-weight: 400\">As I described <\/span><a href=\"https:\/\/blogs.bmj.com\/bmj\/2018\/08\/31\/jeffrey-aronson-when-i-use-a-word-non-drugs\"><span style=\"font-weight: 400\">two weeks ago<\/span><\/a><span style=\"font-weight: 400\">, phenylbutazone was the first marketed compound to be later classified as a non-steroidal anti-inflammatory drug. However, the first drug to be so <\/span><a href=\"https:\/\/blogs.bmj.com\/bmj\/2018\/09\/07\/jeffrey-aronson-when-i-use-a-word-non-steroidal-anti-inflammatory-drugs-origin-of-the-term\"><span style=\"font-weight: 400\">described<\/span><\/a><span style=\"font-weight: 400\"> seems to have been glycyrrhetinic acid, now no longer used as an anti-inflammatory drug.<\/span><\/p>\n<p><span style=\"font-weight: 400\">The IndoEuropean root DLKU, sweet, gives us words such as the saccharide dulcite or dulcose, the organ stop called dulciana and the musical instrument called the dulcimer, dulcet billet-doux, such as Don Quixote might have written to his imaginary love Dulcinea del Toboso, and the life he might have led with her, la dolce vita. The Greek derivative \u03b3\u03bb\u03c5\u03ba\u03cd\u03c2, sweet, gives us glycerol, glyceraldehyde, glycerine and nitroglycerine, glucose and glucoside, glycolysis and glycoside. Add \u03b3\u03bb\u03c5\u03ba\u03cd\u03c2 to \u1fe5\u03af\u03b6\u03b1, a root, and we get <\/span><i><span style=\"font-weight: 400\">Glycyrrhiza glabra<\/span><\/i><span style=\"font-weight: 400\"> (Spanish liquorice) and <\/span><i><span style=\"font-weight: 400\">Glycyrrhiza echinata<\/span><\/i><span style=\"font-weight: 400\"> (Italian liquorice), among others. \u201cLiquorice\u201d is a direct descendant of \u03b3\u03bb\u03c5\u03ba\u03cd\u03c1\u03c1\u03b9\u03b6\u03b1. In early times its spellings (e.g lycuryce) reflected its Greek origin, and it gained its modern spelling, with a <\/span><i><span style=\"font-weight: 400\">q<\/span><\/i><span style=\"font-weight: 400\">, from confusion with \u201cliquor\u201d, a different word altogether. Only in the UK does the spelling \u201cliquorice\u201d predominate in bioscience papers; elsewhere \u201clicorice\u201d is the preferred spelling (Table 1). The Italian word for liquorice, regolizia, and the French word r\u00e9glisse are formed by metathesis from the late Latin version liquiritia.<\/span><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-43039 alignnone\" src=\"https:\/\/blogs.bmj.com\/bmj\/files\/2018\/09\/aronson_liquorice.png\" alt=\"\" width=\"355\" height=\"83\" srcset=\"https:\/\/blogs.bmj.com\/bmj\/files\/2018\/09\/aronson_liquorice.png 355w, https:\/\/blogs.bmj.com\/bmj\/files\/2018\/09\/aronson_liquorice-300x70.png 300w\" sizes=\"auto, (max-width: 355px) 100vw, 355px\" \/><\/p>\n<p><b>Table 1.<\/b><span style=\"font-weight: 400\"> The frequencies with which the two variants \u201cliquorice\u201d and \u201clicorice\u201d are used in bioscience papers from addresses in the UK, USA, and the rest of the world (source PubMed); \u03c7<sup>2<\/sup>= 128, P&lt;10<sup>\u201326<\/sup><\/span><\/p>\n<p><span style=\"font-weight: 400\">Greek physicians thought that liquorice reduced thirst, and they used it to treat dropsy, even though it causes hyperaldosteronism and fluid retention. It has also been used to treat coughs and to disguise the taste of unpleasant medicines. Pliny mentioned glycyrrhiza in his <\/span><i><span style=\"font-weight: 400\">Naturalis Historia<\/span><\/i><span style=\"font-weight: 400\">, and others, such as Celsus, called it dulcis radix, which means the same thing, a sweet root. Dioscorides recommended it for \u201csharpness of the arteries\u201d, \u201cburning of the stomach\u201d, chest, liver, bladder, and kidney disorders, parasitic skin diseases, wounds, and pterygium. <\/span><\/p>\n<p><span style=\"font-weight: 400\">Liquorice has also been included as a component of many patent medicines over the years. For example, we learn from the BMA\u2019s publication <\/span><a href=\"http:\/\/www.bmj.com\/content\/339\/bmj.b5415\"><i><span style=\"font-weight: 400\">Secret Remedies<\/span><\/i><\/a><span style=\"font-weight: 400\"> (1909) that Dr Lauser\u2019s Cough Drops, a liquid formulation, contained, not what it said on the bottle, but liquorice, senna, aniseed, and ammonium chloride; Beecham\u2019s Cough Pills had similar contents plus a small amount of morphine; and Keating\u2019s Cough Lozenges contained morphine, liquorice, and ipecacuanha. Doan&#8217;s Backache Kidney Pills came in boxes of 40 kidney pills and four \u201cdinner\u201d pills; the <\/span><a href=\"https:\/\/blogs.bmj.com\/bmj\/2017\/12\/15\/jeffrey-aronson-when-i-use-a-word-dropsies\/\"><span style=\"font-weight: 400\">latter<\/span><\/a><span style=\"font-weight: 400\"> contained oil of peppermint, podophyllin, aloin, jalap resin, powdered capsicum, maize starch, acacia gum, extract of henbane, and powdered liquorice.<\/span><\/p>\n<p><span style=\"font-weight: 400\">A cachou is defined in the <\/span><i><span style=\"font-weight: 400\">Oxford English Dictionary<\/span><\/i><span style=\"font-weight: 400\"> as \u201cA sweetmeat, generally in the form of a pill, made of cashew-nut, extract of liquorice, etc., used by tobacco-smokers to sweeten the breath.\u201d The <\/span><i><span style=\"font-weight: 400\">Chambers English Dictionary<\/span><\/i><span style=\"font-weight: 400\"> (1988 edition, but not since) took a more cynical attitude: \u201c\u2026.used by some smokers in the hope of sweetening the breath.\u201d<\/span><\/p>\n<p><span style=\"font-weight: 400\">Glycyrrhizic acid, the active constituent of liquorice, is a conjugate of glucuronic acid and glycyrrhetinic acid, also known as enoxolone (Figure 1). When it was first introduced into clinical practice, it was as a <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/13071674\"><span style=\"font-weight: 400\">treatment<\/span><\/a><span style=\"font-weight: 400\"> for Addison\u2019s disease. It was then used to <\/span><a href=\"https:\/\/www.bmj.com\/content\/2\/4954\/1501.2\"><span style=\"font-weight: 400\">treat<\/span><\/a><span style=\"font-weight: 400\"> eczema and other skin conditions, starting in 1955, as described in a series of letters to <em>The BMJ<\/em>, with <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/13629167\"><span style=\"font-weight: 400\">variable results<\/span><\/a><span style=\"font-weight: 400\">, and was later <\/span><a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2133.1958.tb13285.x\"><span style=\"font-weight: 400\">said<\/span><\/a><span style=\"font-weight: 400\"> to be less effective than hydrocortisone.<\/span><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-43042 alignnone\" src=\"https:\/\/blogs.bmj.com\/bmj\/files\/2018\/09\/aronson_liquorice_2.png\" alt=\"\" width=\"815\" height=\"574\" srcset=\"https:\/\/blogs.bmj.com\/bmj\/files\/2018\/09\/aronson_liquorice_2.png 815w, https:\/\/blogs.bmj.com\/bmj\/files\/2018\/09\/aronson_liquorice_2-300x211.png 300w, https:\/\/blogs.bmj.com\/bmj\/files\/2018\/09\/aronson_liquorice_2-768x541.png 768w, https:\/\/blogs.bmj.com\/bmj\/files\/2018\/09\/aronson_liquorice_2-640x451.png 640w\" sizes=\"auto, (max-width: 815px) 100vw, 815px\" \/><\/p>\n<p><b>Figure 1.<\/b><span style=\"font-weight: 400\"> Structures of glycyrhizic acid, enoxolone (glycyrrhetinic acid), carbenoxolone, and, for comparison, hydrocortisone<\/span><\/p>\n<p><span style=\"font-weight: 400\">A paste of powdered succus liquiritiae was used to <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20291620\"><span style=\"font-weight: 400\">treat<\/span><\/a><span style=\"font-weight: 400\"> gastric ulceration in Holland in 1946. Then in 1962 Richard Doll and colleagues showed that carbenoxolone (glycyrrhetinic acid hydrogen succinate; Figure 1) was also <\/span><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0140673662925886\"><span style=\"font-weight: 400\">efficacious<\/span><\/a><span style=\"font-weight: 400\">. It had been <\/span><a href=\"https:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736(59)90611-7\/fulltext?code=lancet-site\"><span style=\"font-weight: 400\">synthesized<\/span><\/a><span style=\"font-weight: 400\"> in 1959 and was marketed by Biorex, the same company that had <\/span><a href=\"https:\/\/blogs.bmj.com\/bmj\/2018\/09\/07\/jeffrey-aronson-when-i-use-a-word-non-steroidal-anti-inflammatory-drugs-origin-of-the-term\"><span style=\"font-weight: 400\">advertised<\/span><\/a><span style=\"font-weight: 400\"> glycyrrhetinic acid as a non-steroidal anti-inflammatory agent in 1957. Curiously, the product known as Caved S was also supposed to be effective in curing peptic ulcers\u2014and that contained deglycyrrhized or deglycyrrhizinated liquorice, a fact that puzzled the unsceptical medical students of my day.<\/span><\/p>\n<p><span style=\"font-weight: 400\">But don\u2019t give up on medicinal liquorice. Although it <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/15579328\"><span style=\"font-weight: 400\">inhibits<\/span><\/a><span style=\"font-weight: 400\"> 11\u03b2-hydroxysteroid dehydrogenase and 17-20 lyase and lowers serum testosterone concentrations, it has been used as an aphrodisiac. In the Kama Sutra and its sequel, the Ananga Ranga, it is called madhuka kalka, madhu meaning honey. To get the best effect, follow this recipe: grind equal quantities of liquorice root, sesame seeds, and fennel seeds, boil them rapidly in water for 5 minutes, and drink the strained fluid. As I have pointed out <\/span><a href=\"https:\/\/www.bmj.com\/content\/344\/bmj.e1453\"><span style=\"font-weight: 400\">before<\/span><\/a><span style=\"font-weight: 400\">, perhaps liquorice can make you lickerish.<\/span><\/p>\n<p><em><strong>Jeffrey Aronson<\/strong>\u00a0is a clinical pharmacologist, working in the Centre for Evidence Based Medicine in Oxford&#8217;s Nuffield Department of Primary Care Health Sciences. He is also president emeritus of the British Pharmacological Society.<\/em><\/p>\n<p><strong>Competing interests:<\/strong>\u00a0None declared.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>As I described two weeks ago, phenylbutazone was the first marketed compound to be later classified as a non-steroidal anti-inflammatory drug. However, the first drug to be so described seems [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/bmj\/2018\/09\/14\/jeffrey-aronson-when-i-use-a-word-liquorice-and-glycyrrhetinic-acid\/\">More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":38359,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5762],"tags":[],"class_list":["post-43038","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-jeff-aronsons-words"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Jeffrey Aronson: When I use a word . . . 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