Chinese licorice
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| Summary | |
|---|---|
| Binomial | Glycyrrhiza uralensis |
| Family | Fabaceae |
| Native range | Northern China, Mongolia, Siberia, and Central Asia; wild stands in Xinjiang, Gansu, Inner Mongolia, and Manchuria; commercial supply largely from cultivated stands in northern and northwestern China. |
| Pharmacy | |
| Pharmacology | |
Chinese licorice (Glycyrrhiza uralensis Fisch.) is a perennial leguminous herb of the north Chinese steppe, the botanical source of gan cao (甘草, literally "sweet herb"), one of the most widely prescribed medicinals in the entire Chinese Materia Medica. Gan cao occupies a role in classical Chinese medicine without parallel in Western pharmacology: it is the defining harmonizer of formulas (调和诸药, tiáo hé zhū yào), an herb added to approximately sixty percent of all classical formulae not primarily for a specific therapeutic action of its own but to moderate the potency of harsh or toxic herbs, unify the divergent properties of a formula's ingredients, and protect the stomach and spleen from irritating constituents. The closely related Mediterranean species G. glabra (Western licorice) is the historical centroid of Ayurvedic, Unani, and European herbal licorice use; the two species share essentially the same glycyrrhizin-mediated pharmacology and the same pseudohyperaldosteronism safety profile, described in full at Western licorice. Both species are routinely substituted in commerce without pharmacopoeia distinction.
History and traditional use
Chinese medicine (primary centroid)
The earliest written record of gan cao is in the Shennong Ben Cao Jing (神农本草经, Divine Farmer's Classic of Materia Medica), the foundational Chinese pharmacopoeia compiled approximately between the first and second centuries of the common era.[citation needed] The Shennong Ben Cao Jing categorized all 365 medicinal substances into three tiers: 120 upper herbs (上品, shàng pǐn), considered tonic and safe for prolonged use; 120 middle herbs, with specific therapeutic actions and moderate safety considerations; and 125 lower herbs, potent or toxic and reserved for acute conditions. Gan cao was classified as an upper herb, the most favorable designation in the text, a judgment that prefigured its two-thousand-year career as the universal harmonizing tonic base of Chinese formula construction.
The feature of gan cao that defines its clinical identity, and that has no close analog in Western pharmacological thinking, is its role as the harmonizer of formulas (调和诸药, tiáo hé zhū yào). Bensky, Clavey, and Stoger document gan cao's presence in approximately sixty percent of all classical Chinese herbal formulae,[1] a frequency no other single herb approaches, reflecting a function performed at the formula level rather than the organ-system level. Bensky identifies three distinct harmonizing roles that collectively account for this ubiquity.[1] First, gan cao moderates the toxicity and harshness of potent formula ingredients: where aconite (fu zi, a potent yang-warming root with a narrow therapeutic window), coptis (huang lian, intensely bitter and cold), or other drastic herbs appear, gan cao is the standard buffer, softening action and preventing the formula from overshooting its therapeutic purpose. Second, it harmonizes herbs of divergent thermal properties, flavors, and organ tropisms, preventing the "qi conflict" that TCM theory associates with unmediated confrontations between cold and hot, or ascending and descending, formula components. Third, it protects the stomach and spleen from the irritating effects of harsh ingredients, supporting patient tolerability through extended decoction courses. So thoroughgoing was this mediating function in the view of later TCM physicians that gan cao acquired the court honorific 国老 (guó lǎo, "Elder Statesman" or "Grand Councillor of the Nation"), comparing the herb's role in a formula to that of a senior official who mediates among warring ministers, integrates competing interests, and supports the sovereign's governing intention without seeking prominence for its own office.[1]
Zhang Zhongjing compiled the Shang Han Lun (伤寒论, Treatise on Cold Damage Disorders) approximately 210 CE; together with its companion the Jin Gui Yao Lue (金匮要略, Essential Prescriptions of the Golden Cabinet), it codified the classical formula architecture that remains foundational in contemporary TCM practice.[citation needed] Gan cao appears in a large proportion of the Shang Han Lun's one hundred and thirteen prescriptions. Four formulae from this text are of particular clinical significance and continue in active contemporary use:
Gan Cao Tang (甘草汤, Licorice Decoction) is the simplest formula: sheng gan cao as the sole herb, at full therapeutic dose, for sore throat and fire-toxicity patterns of the throat. It exemplifies gan cao in its direct anti-toxicity function rather than in the harmonizing role.[1]
Zhi Gan Cao Tang (炙甘草汤, Honey-Fried Licorice Decoction), also known as Fumai Tang (复脉汤, Restore the Pulse Decoction), is a nine-ingredient formula combining honey-fried licorice as the principal herb with Rehmannia glutinosa (di huang), Ophiopogon japonicus (mai men dong), Colla Corii Asini (e jiao, donkey-hide gelatin), Cannabis sativa seed (huo ma ren), dried ginger (gan jiang), cinnamon twig (gui zhi; the same herb as Cassia cinnamon in TCM usage), jujube (da zao), and sake. It is prescribed specifically for heart palpitations (心悸, xīn jì) and irregularly or regularly irregular pulse arising from deficiency of heart yin and heart yang.[citation needed] Zhi Gan Cao Tang is the most specific TCM cardiac-rhythm prescription in the Shang Han Lun and remains a subject of contemporary pharmacological and small-scale clinical research.
Shao Yao Gan Cao Tang (芍药甘草汤, Peony and Licorice Decoction) pairs white peony root (bai shao, Paeonia lactiflora) with honey-fried gan cao in a two-herb formula prescribed for muscular spasm and cramping, particularly abdominal spasm and lower-limb cramps. The combination has attracted modern pharmacognosy investigation: paeoniflorin, the principal active glycoside of white peony, and glycyrrhizin appear to produce antispasmodic effects in animal models that exceed either constituent alone, with paeoniflorin and glycyrrhetinic acid proposed as synergistic components acting through distinct but complementary antispasmodic pathways.[citation needed]
Si Jun Zi Tang (四君子汤, Four Gentlemen Decoction) combines ginseng (ren shen, Panax ginseng), white atractylodes (bai zhu, Atractylodes macrocephala), poria (fu ling, Wolfiporia cocos), and honey-fried licorice. It is the foundational spleen-qi tonic of TCM, the structural core from which a large family of derivative tonifying and digestive-support formulae is built, including Liu Jun Zi Tang (Six Gentlemen), Xiang Sha Liu Jun Zi Tang, and numerous others.[citation needed] Gan cao's role in Si Jun Zi Tang is primarily harmonizing and stomach-protective rather than directly tonifying; the principal tonifying agents are ginseng and white atractylodes, with gan cao integrating their divergent properties and protecting the stomach from the full impact of concentrated qi-supplementing herbs.
Li Shizhen's Ben Cao Gang Mu (本草纲目, Compendium of Materia Medica), completed in 1578 and published in 1596, gave gan cao its most comprehensive classical Chinese treatment, cataloguing morphological varieties, regional origins, harvesting protocols, processing methods (with particular attention to the honey-frying distinction), flavors, thermal properties, organ tropisms, formulaic combinations, and the guó lǎo honorific as a tradition tracing to the Han dynasty.[citation needed] Li Shizhen's synthesis made the Ben Cao Gang Mu the de facto reference standard for East Asian herbal medicine from the Ming dynasty onward.
Western herbal and Ayurvedic use (brief)
G. uralensis has no significant independent tradition in Ayurvedic or Unani medicine; the yashtimadhu (sweet stick) of Ayurveda, the asl-us-sus of Unani medicine, and the glykyrrhiza of the Greco-Roman and medieval European herbal traditions are rooted in G. glabra, the Mediterranean species. G. uralensis enters Western herbal and Ayurvedic practice primarily through commercial substitution: international licorice root trade routinely mixes or substitutes the two species, as dried root from the two is morphologically indistinguishable in commerce and the pharmacological properties are sufficiently comparable for pharmacopoeial equivalence. The complete traditions of Western herbal, Ayurvedic, Unani, and Greco-Roman licorice practice are documented at Western licorice.
Preparations
Sheng gan cao (生甘草, raw dried root): unprocessed dried sliced root used in TCM decoction for fire-toxicity conditions (throat swellings, carbuncles, heat patterns), lung-dryness cough, and the universal formula-harmonizing role. This is also the standard commercial source material for Western herbal extracts and pharmaceutical-grade glycyrrhizin extraction.
Zhi gan cao (炙甘草, honey-fried root): root stir-fried with liquid honey until fragrant and golden-brown; TCM processing theory holds that honey-frying intensifies tonifying and warmth-generating properties while moderating bitterness and astringency. Specified for spleen-qi tonification, heart palpitations (particularly in the Zhi Gan Cao Tang formula), and all indications where a warming-tonifying rather than cooling-clearing action is required.
Standardized root extract: concentrated extract standardized to 18 to 25 percent glycyrrhizin content, available as solid extract or liquid concentrate; both G. uralensis and G. glabra are sourced commercially for standardized extracts, frequently without species designation on product labels.
TCM granule extract: spray-dried or freeze-dried root extract in granule form for contemporary TCM granule-prescription practice, allowing formula assembly without traditional decoction; commercially available as sheng gan cao or zhi gan cao granules.
Deglycyrrhizinated licorice (DGL): available in Western clinical herbal practice as a preparation from which glycyrrhizin has been removed, retaining demulcent and mucosal-protective activity without the pseudohyperaldosteronism risk. Western market DGL preparations are predominantly derived from G. glabra material; G. uralensis-sourced DGL exists but is less commonly available in Western markets. The full DGL discussion, including clinical evidence, dose, and chronic-use appropriateness, is at Western licorice.
Pharmacokinetics
Glycyrrhizin is poorly absorbed intact from the gastrointestinal tract; rate-limiting absorption involves bacterial beta-glucuronidase hydrolysis in the large intestine, producing 18-beta-glycyrrhetinic acid with a lag of two to four hours between oral ingestion and rising plasma 18β-GA levels. Individual variation in gut microbiome composition generates substantial inter-individual variability in 18β-GA plasma exposure at equivalent oral glycyrrhizin doses, which partly explains the observed case-to-case variability in pseudohyperaldosteronism susceptibility.
18-Beta-glycyrrhetinic acid: half-life approximately 7 to 8 hours; primarily hepatic metabolism; biliary excretion with enterohepatic recirculation reported, potentially prolonging effective exposure with repeated daily dosing.
The full pharmacokinetic discussion, including DGL pharmacokinetics and the plasma-level considerations underlying the pseudohyperaldosteronism dose-response, is at Western licorice.
Experience
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Problems
TCM indications (primary)
Spleen qi deficiency: fatigue, diminished appetite, loose stools, and lassitude; honey-fried gan cao as a constituent of tonifying formulae, principally Si Jun Zi Tang and its extensive derivative family; the most frequently invoked TCM indication in formula construction.[1]
Heart palpitations and irregularly irregular pulse from deficiency of heart yin and heart yang: the specific indication of the Zhi Gan Cao Tang formula; among the more physiologically specific classical TCM cardiac-rhythm indications and a subject of contemporary pharmacological and small-scale clinical investigation, including case reports of formula modifications for both bradyarrhythmia and tachyarrhythmia.[1][2]
Lung dryness and cough: raw gan cao in wind-heat or lung-dryness patterns; gan cao moistens the lung channel and moderates the drying effect of other herbs in respiratory formulae.[1]
Fire toxicity: carbuncles, boils, and sore throat with heat characteristics; raw gan cao as Gan Cao Tang alone or combined with other heat-clearing herbs; one of the direct therapeutic indications in which gan cao functions as the principal herb rather than as a harmonizer.[1]
Lower-limb and abdominal muscular spasm: Shao Yao Gan Cao Tang (white peony and honey-fried licorice); the most-studied specific two-herb-pair indication for gan cao, with pharmacological evidence of paeoniflorin-glycyrrhizin antispasmodic synergy.[1]
Universal harmonizing and formula-integrating role: the indication accounting for the majority of gan cao prescriptions; not condition-specific but formula-architecture-specific; see Traditional uses above for the mechanism and significance.
Western clinical indications (condensed; full evidence base at Western licorice)
Western clinical research on licorice does not systematically distinguish G. uralensis from G. glabra; commercial preparations are often from mixed or unspecified species. The evidence base for peptic ulcer and mucosal protection (deglycyrrhizinated licorice preparations), chronic hepatitis (intravenous Stronger Neo-Minophagen C glycyrrhizin compound in Japanese clinical practice), respiratory catarrh (Commission E approved indication), and adrenal-supportive use is described in full at Western licorice.
Titration and dosing
TCM decoction dose: 2 to 12 g dried root per day (raw or honey-fried) in multi-herb decoction. Harmonizing doses, which account for the majority of gan cao prescriptions, are typically 2 to 6 g per day; doses in which gan cao is the principal therapeutic herb (as in Gan Cao Tang) may reach 9 to 12 g per day. Single-herb throat formula (Gan Cao Tang): 4 to 9 g.[1]
Western clinical extract dose: standardized extract equivalent to 5 to 15 g dried root daily; maximum continuous course four to six weeks without reassessment per Commission E guidance. Same limit as G. glabra.
Glycyrrhizin intake limit: 100 mg glycyrrhizin per day maximum for chronic use per the European Union Scientific Committee on Food opinion SCF/CS/ADD/EDUL/225 Final (2003), the same guidance applicable to both G. uralensis and G. glabra.
Effects
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Interactions
The interaction profile of G. uralensis is identical to that of G. glabra; the shared glycyrrhizin content and shared 11-beta-HSD2 inhibition mechanism produce the same clinically relevant pharmacodynamic interactions regardless of species. Full interaction details are at Western licorice; the following is a clinical summary.
Antihypertensive medicines: whole-licorice preparations raise blood pressure through sodium and water retention (the pseudohyperaldosteronism mechanism), directly antagonizing antihypertensive treatment; concurrent use should be avoided or blood pressure monitored closely with readiness to adjust antihypertensive doses.
Potassium-depleting medicines (loop diuretics, thiazide diuretics, corticosteroids): additive hypokalemia risk; the combination carries increased risk of clinically significant potassium depletion, muscle weakness, cardiac arrhythmia, and, at severe depletion, respiratory muscle compromise. Serum potassium monitoring is warranted in any patient combining licorice with these agents.
Cardiac glycosides (digoxin): licorice-induced hypokalemia increases myocardial sensitivity to cardiac glycoside toxicity; the combination of chronic licorice use and digoxin therapy requires concurrent potassium monitoring.
Exogenous corticosteroids: 11-beta-HSD2 inhibition by 18β-GA may amplify the mineralocorticoid effects of concurrent exogenous corticosteroid therapy, accelerating fluid retention and raising blood pressure.
A note specific to TCM formula practice: at the standard harmonizing dose (2 to 6 g daily for a short course of four weeks or less), the probability of clinically significant pharmacodynamic interaction in most patients is low. The interaction concern becomes clinically important at chronic high-dose use and in patients taking antihypertensives, diuretics, or cardiac glycosides concurrently.
DGL preparations: negligible pharmacodynamic interaction risk from the glycyrrhizin-mediated pathway; DGL is the preparation of choice for any chronic use requiring avoidance of these interactions.
Monitoring
Whole-licorice use (any form of G. uralensis root or extract containing significant glycyrrhizin) for more than four weeks: obtain baseline blood pressure and serum potassium before initiating; recheck monthly during ongoing use. Discontinue and reassess if systolic blood pressure rises more than 10 to 15 mmHg from baseline, serum potassium falls below 3.5 mmol/L, or peripheral edema develops.
For patients taking concurrent antihypertensive medicines or cardiac glycosides, lower the monitoring threshold: check blood pressure and potassium after two weeks of use rather than four.
DGL preparations: no monitoring required beyond routine clinical follow-up appropriate to the underlying condition being managed.
Patient counseling
The pseudohyperaldosteronism risk that applies to Western licorice (G. glabra) applies equally to Chinese licorice (G. uralensis) and to any TCM formula containing gan cao. A patient told by a conventional physician to avoid licorice for blood pressure or potassium reasons should apply that restriction to gan cao in TCM decoctions and patent medicines. The two species are pharmacologically interchangeable with respect to this risk; a patient's conventional prescriber may not know that a TCM formula contains licorice under the name "gan cao" and will benefit from the information.
The harmonizing role accounts for the majority of gan cao prescriptions and typically places it at a lower dose (2 to 6 g daily) than its use as a primary therapeutic herb. Most patients on short-course multi-herb formulae at harmonizing doses will not experience clinical pseudohyperaldosteronism. The risk rises with increasing dose, increasing duration (months rather than weeks), and pre-existing clinical vulnerability: baseline hypertension, concurrent diuretic use, and low dietary potassium intake each shift the threshold downward.
Patients who need a chronic licorice-based preparation for mucosal protection, peptic ulcer, or gastritis should be directed to deglycyrrhizinated licorice (DGL), which removes the glycyrrhizin while retaining demulcent and mucosal-protective activity. DGL does not carry the mineralocorticoid risk and does not require blood pressure or potassium monitoring; see Western licorice for the full DGL discussion including dose, formulation, and comparison with whole licorice.
Commercial licorice root products (confectionery, chewable tablets, licorice-extract beverages) may contain G. uralensis, G. glabra, or both, often without species designation and without declared glycyrrhizin content. Patients using such products as a therapeutic practice should be asked about quantity, frequency, and glycyrrhizin content where possible; "licorice root extract" on a label does not specify species or dose.
The guó lǎo (国老, Elder Statesman) characterization of gan cao is a useful explanatory frame for patients: the herb is not added to a formula to fix one thing but to make the entire formula work more safely and effectively together. Patients who ask why their TCM formula contains licorice even though they are not being treated for a licorice-specific condition can be offered this framing as an accurate and culturally grounded explanation.
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References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 Bensky D, Clavey S, Stoger E. Chinese Herbal Medicine: Materia Medica. 3rd ed. Eastland Press, 2004. Section on Glycyrrhiza uralensis (Gan Cao, 甘草).
- ↑ Chen WG, Ba ZM. "Prof. ZHANG Yi's experience in treating severe arrhythmia." J Tradit Chin Med 2010;30(1):47-50. PMID 20397463.