Western licorice: Difference between revisions

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| common_names = licorice (American English), liquorice (British English), Western licorice, European licorice, Mediterranean licorice, mulethi (Hindi), yashtimadhu (Sanskrit, "sweet stick"), madhuyashti (Sanskrit alternative form), asl-us-sus or irq al-sus (Arabic), sus (Arabic short form), mahek (Persian); the Greek genus name glycyrrhiza is from glykys (sweet) + rhiza (root)

| native_range = Mediterranean basin, Western Asia (eastern Mediterranean to Iran), and parts of southern Europe and North Africa; cultivated widely throughout the Mediterranean and in Spain, Italy, Greece, Turkey, Iran, Iraq, Syria, and the Caucasus

| cultivars = the principal commercial source is wild-harvested or semi-cultivated root from the Mediterranean, Caspian, and Central Asian populations; Spanish licorice (cultivated in Spain since the medieval period) and Italian licorice (Calabria) are the European commercial grades; Turkish and Iranian licorice supply the Middle Eastern and South Asian markets; related Glycyrrhiza uralensis (Chinese licorice, gan cao, the principal TCM licorice) and Glycyrrhiza inflata (Xinjiang licorice) are distinct species with their own articles

| cultivars = the principal commercial source is wild-harvested or semi-cultivated root from the Mediterranean, Caspian, and Central Asian populations; Spanish licorice (cultivated in Spain since the medieval period) and Italian licorice (Calabria) are the European commercial grades; Turkish and Iranian licorice supply the Middle Eastern and South Asian markets; related ''Glycyrrhiza uralensis'' (Chinese licorice, gan cao, the principal TCM licorice) and ''Glycyrrhiza inflata'' (Xinjiang licorice) are distinct species with their own articles

| parts_used = root and underground stolon (the rhizome and runners), dried and (in some forms) deglycyrrhizinated; the leaves and aerial parts are not used medicinally

| cultivation = hardy perennial herb to 1.5 m at flowering; deep tap-rooted with extensive horizontal stolon network; propagated by stolon division or seed; harvested at three to four years for medicinal root, with deep mechanical or hand-digging required

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| legal = unscheduled; food-use restrictions on glycyrrhizin content in many jurisdictions; the European Scientific Committee on Food (SCF) set an adult guidance upper limit of 100 mg glycyrrhizin per day for habitual consumption in 2003

| interactionsummary = the pseudohyperaldosteronism mechanism produces clinically significant interactions with potassium-depleting diuretics (loop diuretics, thiazides) where the combined hypokalemia is the principal risk; with cardiac glycosides (digoxin) where licorice-induced hypokalemia increases digoxin toxicity risk; with corticosteroids where glycyrrhetinic acid potentiates exogenous corticosteroid effect through 11-beta-HSD2 inhibition (relevant in patients on chronic prednisone or similar); and with antihypertensive medicines where the sodium-retention effect opposes blood-pressure control; chronic high-dose licorice is contraindicated in patients with hypertension, congestive heart failure, hypokalemia, renal disease, or hepatic cirrhosis with ascites; DGL (deglycyrrhizinated licorice) avoids these interactions and is the preparation of choice for any chronic use

| intro = '''Western licorice''' is the dried root and underground stolon of Glycyrrhiza glabra L., a perennial leguminous herb of the Fabaceae (Leguminosae) native to the Mediterranean basin and Western Asia and one of the oldest continuously used medicinal plants of the Eurasian materia medica. The genus name [[wikipedia:Glycyrrhiza|glycyrrhiza]] is from the Greek glykys (sweet) and rhiza (root), reflecting the principal phytochemical feature of the plant: the sweet triterpene saponin glycyrrhizin (also called glycyrrhizic acid) reaches 2 to 12 percent of the dry root by weight and is approximately fifty times sweeter than sucrose by mass, making licorice the sweetest of the major medicinal roots and the source of the candy, tobacco-flavoring, and beverage uses that have run alongside the medicinal use for centuries. The medicinal indications of Western licorice converge across multiple traditions on a stable cluster: digestive complaint and peptic ulcer (the principal modern Western-clinical indication, addressed by the deglycyrrhizinated licorice formulation that removes the pseudohyperaldosteronism risk while retaining demulcent activity); chronic cough and respiratory complaint; chronic hepatic disease (where intravenous glycyrrhizin has been a Japanese clinical practice for chronic viral hepatitis for several decades); and a broadly tonic, harmonizing, or rasayana role across the traditions. The load-bearing modern safety story is the pseudohyperaldosteronism syndrome produced by chronic high-dose glycyrrhizin intake, which inhibits the renal 11-beta-hydroxysteroid dehydrogenase type 2 enzyme and produces functional mineralocorticoid agonism with hypertension, hypokalemia, sodium retention, and edema. The Chinese licorice ([[Chinese licorice|Glycyrrhiza uralensis]]) is the principal licorice of the Chinese materia medica, where it is known as gan cao and serves as the harmonizing ingredient in approximately sixty percent of all classical Chinese herbal formulas; the TCM material lives on the [[Chinese licorice]] page, with the present article covering the Western, Ayurvedic, and Unani historical centroid of G. glabra.

| intro = '''Western licorice''' is the dried root and underground stolon of ''Glycyrrhiza glabra'' L., a perennial leguminous herb of the Fabaceae (Leguminosae) native to the Mediterranean basin and Western Asia and one of the oldest continuously used medicinal plants of the Eurasian materia medica. The genus name [[wikipedia:''Glycyrrhiza''|glycyrrhiza]] is from the Greek glykys (sweet) and rhiza (root), reflecting the principal phytochemical feature of the plant: the sweet triterpene saponin glycyrrhizin (also called glycyrrhizic acid) reaches 2 to 12 percent of the dry root by weight and is approximately fifty times sweeter than sucrose by mass, making licorice the sweetest of the major medicinal roots and the source of the candy, tobacco-flavoring, and beverage uses that have run alongside the medicinal use for centuries. The medicinal indications of Western licorice converge across multiple traditions on a stable cluster: digestive complaint and peptic ulcer (the principal modern Western-clinical indication, addressed by the deglycyrrhizinated licorice formulation that removes the pseudohyperaldosteronism risk while retaining demulcent activity); chronic cough and respiratory complaint; chronic hepatic disease (where intravenous glycyrrhizin has been a Japanese clinical practice for chronic viral hepatitis for several decades); and a broadly tonic, harmonizing, or rasayana role across the traditions. The load-bearing modern safety story is the pseudohyperaldosteronism syndrome produced by chronic high-dose glycyrrhizin intake, which inhibits the renal 11-beta-hydroxysteroid dehydrogenase type 2 enzyme and produces functional mineralocorticoid agonism with hypertension, hypokalemia, sodium retention, and edema. The Chinese licorice ([[Chinese licorice|''Glycyrrhiza'' uralensis]]) is the principal licorice of the Chinese materia medica, where it is known as gan cao and serves as the harmonizing ingredient in approximately sixty percent of all classical Chinese herbal formulas; the TCM material lives on the [[Chinese licorice]] page, with the present article covering the Western, Ayurvedic, and Unani historical centroid of ''G. glabra''.

| traditional_uses = The Mediterranean and Near Eastern origin of Western licorice is the historical centroid of the herb. Licorice root was recovered from the tomb of Tutankhamun (interred approximately 1323 BCE in the Valley of the Kings) among the grave goods, suggesting royal use in pharaonic Egypt; the herb appears in the Hippocratic corpus and earlier Greek references as glykyrrhiza, the sweet root, and [[wikipedia:Theophrastus|Theophrastus]] in his Enquiry into Plants of about 300 BCE classed the plant as "the Scythian root" and noted its use for thirst-quenching, cough, and chest complaints, with the characteristic observation that Scythian horsemen could go ten or twelve days without drinking by chewing on the root (a folk-pharmacological reading of the demulcent and water-retaining effect that anticipates the modern pseudohyperaldosteronism mechanism).<ref name="theophrastus-licorice">Hort AF (translator). ''Theophrastus: Enquiry into Plants'', Volume II, Books VI-IX. Loeb Classical Library. Cambridge, MA: Harvard University Press; 1916 (translation of c. 300 BCE original).</ref> [[wikipedia:Pedanius Dioscorides|Dioscorides]] in book three of his De Materia Medica of about 60 CE listed glykyrrhiza for thirst, dry cough, lung disease, stomach pain, urinary irritation, and as a sweetener and corrective for harsh-tasting medicines, the early documentation of the harmonizing role that would later be elaborated in Chinese medicine as the gan cao "harmonizer of formulas" role.<ref name="dioscorides-licorice">Beck LY (translator). ''Pedanius Dioscorides of Anazarbus: De Materia Medica''. Hildesheim: Olms-Weidmann; 2005 (translation of c. 60 CE original).</ref> [[wikipedia:Pliny the Elder|Pliny the Elder]] in book twenty-two of his Naturalis Historia continued the Greek tradition, naming the plant glycyrrhiza and listing it for cough, lung complaint, stomach disorders, and the sweetening of pharmaceutical preparations.<ref name="pliny-licorice">Bostock J, Riley HT (translators). Pliny the Elder: ''The Natural History''. London: Taylor and Francis; 1855.</ref>

The Islamic and Persian medical traditions documented licorice as asl-us-sus (Arabic, "root of the sus plant") or irq al-sus and as mahek (Persian), with the herb classed as warming in the second degree, moist in the second, sweet, and indicated for cough, hoarseness, chest complaint, gastric pain, urinary irritation, and as a corrective and sweetener in compound formulations. [[wikipedia:Avicenna|Avicenna]] in book two of his Canon of Medicine of about 1025 CE devoted an entry to asl-us-sus listing the indications and noting the harmonizing role of the herb in compound preparations of harsher simples;<ref name="avicenna-licorice">Gruner OC (translator). ''A Treatise on the Canon of Medicine of Avicenna, Incorporating a Translation of the First Book''. London: Luzac and Co.; 1930.</ref> the Unani tradition of South Asia incorporated licorice as one of the central simples and continues to use it in clinical practice to the present.

The Ayurvedic tradition is one of the two principal historical centroids of Glycyrrhiza glabra outside the Mediterranean, with the herb documented as yashtimadhu (Sanskrit, "sweet stick") in the Charaka Samhita and Sushruta Samhita and used continuously from the early centuries of the common era to the present.<ref name="charaka-yashtimadhu">Sharma PV (translator). ''Charaka Samhita: Text with English Translation''. Varanasi: Chaukhambha Orientalia; 1981.</ref> Yashtimadhu is classed as sweet (madhura rasa), cooling (sheeta virya), unctuous (snigdha), heavy (guru), kapha-vata-shamaka (pacifying the cold-and-damp and cold-and-windy doshas, although somewhat increasing kapha at large dose), and is classed as a medhya rasayana (mind-and-intellect rejuvenative) and as one of the foundational Ayurvedic rasayanas (tonic rejuvenatives).<ref name="williamson-yashtimadhu">Williamson EM. ''Major Herbs of Ayurveda''. Edinburgh: Churchill Livingstone; 2002.</ref> Classical indications include cough (kasa), respiratory complaint, throat irritation, gastric pain (amlapitta), peptic disease, mental fatigue and memory weakness (the medhya rasayana role), and as a corrective sweetener in many compound formulations. Yashtimadhukadi Ghrita is a classical ghee-based compound of yashtimadhu with other herbs, used for chronic respiratory and digestive complaint; yashtimadhu also appears in numerous churnas (powders) and kashayas (decoctions).

The Ayurvedic tradition is one of the two principal historical centroids of ''Glycyrrhiza glabra'' outside the Mediterranean, with the herb documented as yashtimadhu (Sanskrit, "sweet stick") in the Charaka Samhita and Sushruta Samhita and used continuously from the early centuries of the common era to the present.<ref name="charaka-yashtimadhu">Sharma PV (translator). ''Charaka Samhita: Text with English Translation''. Varanasi: Chaukhambha Orientalia; 1981.</ref> Yashtimadhu is classed as sweet (madhura rasa), cooling (sheeta virya), unctuous (snigdha), heavy (guru), kapha-vata-shamaka (pacifying the cold-and-damp and cold-and-windy doshas, although somewhat increasing kapha at large dose), and is classed as a medhya rasayana (mind-and-intellect rejuvenative) and as one of the foundational Ayurvedic rasayanas (tonic rejuvenatives).<ref name="williamson-yashtimadhu">Williamson EM. ''Major Herbs of Ayurveda''. Edinburgh: Churchill Livingstone; 2002.</ref> Classical indications include cough (kasa), respiratory complaint, throat irritation, gastric pain (amlapitta), peptic disease, mental fatigue and memory weakness (the medhya rasayana role), and as a corrective sweetener in many compound formulations. Yashtimadhukadi Ghrita is a classical ghee-based compound of yashtimadhu with other herbs, used for chronic respiratory and digestive complaint; yashtimadhu also appears in numerous churnas (powders) and kashayas (decoctions).

The Chinese tradition uses Glycyrrhiza uralensis (Chinese licorice) rather than G. glabra as the principal licorice of the materia medica; G. uralensis is the gan cao of the [[Chinese licorice|companion article]], where the TCM "harmonizer of formulas" role is documented in detail.<ref name="bensky-gan-cao">Bensky D, Clavey S, Stoger E. ''Chinese Herbal Medicine: Materia Medica, 3rd ed''. Seattle: Eastland Press; 2004.</ref> G. glabra has appeared in Chinese herbal practice as an import substitute for gan cao where uralensis was unavailable, and modern Chinese herbal pharmacies sometimes carry both species under the gan cao name without species discrimination, but the historical centroid of the Chinese tradition is firmly on uralensis.

The Chinese tradition uses ''Glycyrrhiza uralensis'' (Chinese licorice) rather than ''G. glabra'' as the principal licorice of the materia medica; ''G. uralensis'' is the gan cao of the [[Chinese licorice|companion article]], where the TCM "harmonizer of formulas" role is documented in detail.<ref name="bensky-gan-cao">Bensky D, Clavey S, Stoger E. ''Chinese Herbal Medicine: Materia Medica, 3rd ed''. Seattle: Eastland Press; 2004.</ref> ''G. glabra'' has appeared in Chinese herbal practice as an import substitute for gan cao where uralensis was unavailable, and modern Chinese herbal pharmacies sometimes carry both species under the gan cao name without species discrimination, but the historical centroid of the Chinese tradition is firmly on uralensis.

The medieval European tradition received licorice as the standard Mediterranean apothecary commodity and incorporated the herb into the European herbal pharmacopoeia continuously from the Greek inheritance through the medieval monastic and Renaissance traditions to the modern. [[wikipedia:Nicholas Culpeper|Nicholas Culpeper]] in The English Physitian of 1652 wrote of licorice as warming and moistening, prescribed for "hoarseness, wheezing, shortness of breath, and all the diseases of the breast and lungs," for thirst in fevers, and as a corrective sweetener in unpleasant-tasting compound preparations; Culpeper's description tracks the Greek and Islamic indications closely. The German Commission E approved Western licorice for catarrh of the upper respiratory tract and for gastric and duodenal ulcer (at doses of 5 to 15 g daily of root, providing 200 to 600 mg glycyrrhizin, for a duration not exceeding four to six weeks because of the pseudohyperaldosteronism risk at longer courses).<ref name="commission-e-licorice">Blumenthal M, Goldberg A, Brinckmann J (editors). ''Herbal Medicine: Expanded Commission E Monographs''. Newton, MA: Integrative Medicine Communications; 2000.</ref>

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The pseudohyperaldosteronism syndrome is the load-bearing modern safety story for whole licorice consumption and has been documented in a substantial case-report literature dating from the 1950s onward. The classical presentation is the licorice-candy headache and edema syndrome in heavy consumers of glycyrrhizin-containing licorice candy (or, less commonly, chronic medicinal use of whole licorice root preparations): hypertension, hypokalemia, sodium retention, edema, and in severe cases hypokalemic muscle weakness, paralysis, or cardiac arrhythmia. The Walker 1994 and van Uum 2005 reviews are standard references for the mechanism and the case literature.<ref name="walker-1994">Walker BR, Edwards CR. Licorice-induced hypertension and syndromes of apparent mineralocorticoid excess. ''Endocrinology and Metabolism Clinics of North America''. 1994 Jun;23(2):359-377. PMID 8070427.</ref><ref name="vanuum-2005">van Uum SH. Liquorice and hypertension. ''The Netherlands Journal of Medicine''. 2005 Apr;63(4):119-120. PMID 15869038.</ref> The European Scientific Committee on Food set an adult guidance upper limit of 100 mg glycyrrhizin per day for habitual consumption in 2003, equivalent to approximately 1 to 5 g of licorice root depending on cultivar and preparation; chronic intake above this threshold approaches the pseudohyperaldosteronism range in susceptible individuals and intake at multiple times this level reliably produces clinical syndromes in case-report populations.<ref name="scf-2003">European Commission Scientific Committee on Food. ''Opinion of the Scientific Committee on Food on Glycyrrhizinic Acid and its Ammonium Salt''. SCF/CS/ADD/EDUL/225 Final. Brussels: European Commission Health and Consumer Protection Directorate-General; 10 April 2003. (Sets 100 mg/day adult upper guidance for habitual glycyrrhizin intake.)</ref> Pregnancy carries a real preterm-birth signal at high glycyrrhizic acid intake: Finnish cohort studies have documented associations between heavy licorice candy consumption in pregnancy and preterm birth, with a dose-response pattern.<ref name="strandberg-2001">Strandberg TE, Järvenpää AL, Vanhanen H, McKeigue PM. Birth outcome in relation to licorice consumption during pregnancy. ''American Journal of Epidemiology''. 2001 Jun 1;153(11):1085-1088. PMID 11390327.</ref>

| traditional_geography =

| botany = Glycyrrhiza glabra is a perennial herbaceous legume of the Fabaceae reaching 1 to 1.5 m at flowering. The deep tap root extends 1 to 2 m into the soil and produces an extensive horizontal stolon network from which new aerial stems emerge; the harvested medicinal "root" is in fact a mixture of true root and underground stolon. The leaves are pinnate with 9 to 17 elliptic leaflets 3 to 6 cm long, smooth and somewhat sticky-glandular on the lower surface. The flowers are small (8 to 12 mm), pale lilac to violet, in axillary racemes, papilionaceous in the typical Fabaceae form; the fruit is a small flat oblong pod 1.5 to 3 cm long containing two to eight reniform brown seeds. The dried root of commerce is the cured peeled rhizome and stolon: yellow-brown to greyish-yellow, fibrous, somewhat woody, with a characteristic sweet aroma and intensely sweet taste. Distinguished from Glycyrrhiza uralensis (the Chinese licorice) by smaller leaflet size and a less branched root system; from Glycyrrhiza inflated (Xinjiang licorice) by the smooth (rather than inflated) seed pod. Whole-stick licorice is light yellow-brown internally and dark brown externally; powdered licorice is light yellow-brown. Whole and powdered preparations are largely indistinguishable from G. uralensis without species-specific chemical or microscopic analysis, with the consequence that "licorice" of unspecified species is often unidentifiable as glabra or uralensis after processing.

| botany = ''Glycyrrhiza glabra'' is a perennial herbaceous legume of the Fabaceae reaching 1 to 1.5 m at flowering. The deep tap root extends 1 to 2 m into the soil and produces an extensive horizontal stolon network from which new aerial stems emerge; the harvested medicinal "root" is in fact a mixture of true root and underground stolon. The leaves are pinnate with 9 to 17 elliptic leaflets 3 to 6 cm long, smooth and somewhat sticky-glandular on the lower surface. The flowers are small (8 to 12 mm), pale lilac to violet, in axillary racemes, papilionaceous in the typical Fabaceae form; the fruit is a small flat oblong pod 1.5 to 3 cm long containing two to eight reniform brown seeds. The dried root of commerce is the cured peeled rhizome and stolon: yellow-brown to greyish-yellow, fibrous, somewhat woody, with a characteristic sweet aroma and intensely sweet taste. Distinguished from ''Glycyrrhiza uralensis'' (the Chinese licorice) by smaller leaflet size and a less branched root system; from ''Glycyrrhiza'' inflated (Xinjiang licorice) by the smooth (rather than inflated) seed pod. Whole-stick licorice is light yellow-brown internally and dark brown externally; powdered licorice is light yellow-brown. Whole and powdered preparations are largely indistinguishable from ''G. uralensis'' without species-specific chemical or microscopic analysis, with the consequence that "licorice" of unspecified species is often unidentifiable as glabra or uralensis after processing.

| constituents = The principal medicinally active constituents of Western licorice are the '''glycyrrhizin''' fraction (the triterpene saponin) and the '''flavonoid''' fraction.

'''Glycyrrhizin''' (glycyrrhizic acid, the triterpene saponin) is 2 to 12 percent of the dried root by weight (variable by region, cultivar, and harvest age, with Iranian and Turkish roots typically at the higher end). Glycyrrhizin is the principal sweet compound, approximately fifty times sweeter than sucrose by mass, and the source of licorice's characteristic taste and of its candy and tobacco-flavoring uses. On oral administration glycyrrhizin is hydrolyzed in the intestinal lumen and colonic flora to its aglycone, '''glycyrrhetinic acid''' (also called enoxolone or glycyrrhetic acid), which is the active intracellular form. Glycyrrhetinic acid is the molecule that inhibits 11-beta-hydroxysteroid dehydrogenase type 2 and produces the pseudohyperaldosteronism effect, as well as the anti-inflammatory and other systemic effects of licorice. The pharmaceutical derivative '''carbenoxolone''' (glycyrrhetinic acid hydrogen succinate disodium) is a semisynthetic derivative produced by succinylation of glycyrrhetinic acid; carbenoxolone was approved for peptic ulcer in several countries in the 1960s and 70s and remains a research tool for 11-beta-HSD2 pharmacology.

The '''flavonoid''' fraction is approximately 1 to 2 percent of the dried root and includes the chalcone '''isoliquiritin''' and its aglycone '''isoliquiritigenin''', the flavanone '''liquiritin''' and its aglycone '''liquiritigenin''', and the isoflavones '''glabridin''' and '''licochalcone A''' (with glabridin distinctive of G. glabra and licochalcone A more characteristic of G. inflata). The flavonoids contribute the antioxidant, antimicrobial, and topical anti-inflammatory activity of licorice; glabridin and licochalcone A are the principal constituents of the modern licorice-derived topical preparations for atopic dermatitis. The flavonoid fraction is retained in deglycyrrhizinated licorice (DGL) preparations, providing the basis of DGL's gastroprotective and anti-ulcer activity in the absence of glycyrrhizin.

The '''flavonoid''' fraction is approximately 1 to 2 percent of the dried root and includes the chalcone '''isoliquiritin''' and its aglycone '''isoliquiritigenin''', the flavanone '''liquiritin''' and its aglycone '''liquiritigenin''', and the isoflavones '''glabridin''' and '''licochalcone A''' (with glabridin distinctive of ''G. glabra'' and licochalcone A more characteristic of ''G. inflata''). The flavonoids contribute the antioxidant, antimicrobial, and topical anti-inflammatory activity of licorice; glabridin and licochalcone A are the principal constituents of the modern licorice-derived topical preparations for atopic dermatitis. The flavonoid fraction is retained in deglycyrrhizinated licorice (DGL) preparations, providing the basis of DGL's gastroprotective and anti-ulcer activity in the absence of glycyrrhizin.

The non-active fractions include '''polysaccharides''' (contributing to the demulcent and immunomodulatory activity), '''asparagine''' and other amino acids (the licorice "honey-stick" sweetness extends beyond the glycyrrhizin contribution), '''coumarins''' (small amounts; not the warfarin class, no anticoagulant activity), and trace volatile oil (contributing to the characteristic aroma).

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| pharmacodynamics = The principal pharmacodynamic effect of glycyrrhizin and glycyrrhetinic acid is the inhibition of 11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2), the renal and colonic enzyme that normally protects the mineralocorticoid receptor from cortisol by converting cortisol to inactive cortisone in the immediate vicinity of the receptor. With 11-beta-HSD2 inhibited by glycyrrhetinic acid, local cortisol concentrations rise and cortisol (which has comparable affinity to aldosterone for the mineralocorticoid receptor and circulates at concentrations approximately one hundred times higher) binds and activates the receptor, producing functional mineralocorticoid agonism. The downstream effects are sodium retention with consequent water retention, potassium loss through the renal collecting duct, hypertension, edema, and (in severe cases) hypokalemic muscle weakness or paralysis and cardiac arrhythmia. The plasma renin and aldosterone are suppressed (the syndrome is called "pseudo-hyperaldosteronism" because the clinical picture mimics primary hyperaldosteronism while renin and aldosterone levels are low rather than elevated). The pseudohyperaldosteronism is the principal safety concern of whole licorice and the principal reason DGL exists as a preparation.

Glycyrrhetinic acid also potentiates exogenous corticosteroid effect through the same 11-beta-HSD2 inhibition mechanism and through some direct glucocorticoid receptor modulation, with clinical relevance in patients on chronic prednisone or similar corticosteroid medicines. The anti-inflammatory effect of licorice in respiratory and gastric complaint is partly attributable to this endogenous-cortisol-potentiation mechanism and partly to direct flavonoid anti-inflammatory activity. Glycyrrhizin and glycyrrhetinic acid have documented in vitro and limited in vivo antiviral activity against hepatitis B virus, hepatitis C virus, and herpes simplex virus, the empirical basis of the Japanese SNMC clinical practice. The flavonoid fraction (glabridin, licochalcone A, liquiritin) provides antioxidant activity, antimicrobial activity against several oral and gastric pathogens including Helicobacter pylori, and topical anti-inflammatory effects on atopic dermatitis lesions. The saponin and polysaccharide fractions contribute to the demulcent and expectorant effects.

Glycyrrhetinic acid also potentiates exogenous corticosteroid effect through the same 11-beta-HSD2 inhibition mechanism and through some direct glucocorticoid receptor modulation, with clinical relevance in patients on chronic prednisone or similar corticosteroid medicines. The anti-inflammatory effect of licorice in respiratory and gastric complaint is partly attributable to this endogenous-cortisol-potentiation mechanism and partly to direct flavonoid anti-inflammatory activity. Glycyrrhizin and glycyrrhetinic acid have documented in vitro and limited in vivo antiviral activity against hepatitis B virus, hepatitis C virus, and herpes simplex virus, the empirical basis of the Japanese SNMC clinical practice. The flavonoid fraction (glabridin, licochalcone A, liquiritin) provides antioxidant activity, antimicrobial activity against several oral and gastric pathogens including ''Helicobacter pylori'', and topical anti-inflammatory effects on atopic dermatitis lesions. The saponin and polysaccharide fractions contribute to the demulcent and expectorant effects.

| interactions = <pharmaInteractions/>

The clinically significant interactions of whole Western licorice (Glycyrrhiza glabra root and glycyrrhizin-containing preparations) are dominated by the pseudohyperaldosteronism mechanism and produce a cluster of medicine-class interactions that share the common feature of being amplified by licorice-induced hypokalemia or sodium retention.

The clinically significant interactions of whole Western licorice (''Glycyrrhiza glabra'' root and glycyrrhizin-containing preparations) are dominated by the pseudohyperaldosteronism mechanism and produce a cluster of medicine-class interactions that share the common feature of being amplified by licorice-induced hypokalemia or sodium retention.

'''Potassium-depleting diuretics''' (loop diuretics such as furosemide and bumetanide; thiazide diuretics such as hydrochlorothiazide and chlorthalidone): the combined hypokalemia is the principal risk, with case reports of severe hypokalemic muscle weakness and cardiac arrhythmia in patients on long-term diuretic therapy who add chronic licorice consumption. The combination is contraindicated at therapeutic-dose chronic licorice consumption; DGL avoids the interaction.

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Patients seeking the cortisol-sparing or mild adrenal-supportive use of licorice (a folk and complementary indication, not a primary clinical intervention) should be counseled that the effect is real but is the same mechanism that produces the pseudohyperaldosteronism syndrome at higher intake, and that the clinical management of any indication for adrenal supplementation should involve formal endocrine evaluation rather than empirical herbal supplementation.

| anecdotes =

| seealso = [[Chinese licorice]], [[Glycyrrhiza uralensis]], [[Ginger]], [[Marshmallow]], [[Slippery elm]], [[Comfrey]], [[Mullein]], [[Thyme]]

| seealso = [[Chinese licorice]], ''[[Glycyrrhiza uralensis]]'', [[Ginger]], [[Marshmallow]], [[Slippery elm]], [[Comfrey]], [[Mullein]], [[Thyme]]

| references = <references/>

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