Glycyrrhiza glabra
This article is copyright 2021 by Eric Yarnell, ND, RH(AHG). If you want to share this information, link to this page. This information is intended for health care providers trained in herbal medicine and not the lay public.
Fear Not!One of the most shocking things in modern herbal medicine is that many herbal prescribers have allowed themselves to be made afraid of the most useful herbs in the entire materia medica. Based on many things, there is simply no contest, Glycyrrhiza (licorice) is a pre-eminent herbal medicine, yet far too many are irrationally afraid to prescribe it. The medicinal species in this genus have a huge range of incredibly valuable actions and are massively important in herbal traditions across Eurasia, North Africa, and the Middle East (where they are native), and their use has spread globally. The goal of this article is to help eliminate fear-based herbal medicine and instead to turn it to knowledge-based herbal medicine. Fear of licorice must be banished!
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Glycyrrhiza glabra growing at Bastyr University, Kenmore, WA
(photo by E. Yarnell)
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"Because it is without doubt the most commonly used Chinese herb, with a moderating, harmonious nature that mitigates the harsh actions of other herbs, it is very much like a wise elder statesman, and is thus also known as the national elder (國老 gúo lǎo)." –Bensky, et al. 2004 (emphasis added)
The Medicines
There are three species of Glycyrrhiza definitively used as medicine, reviewed in the table below. These are distinctive from all others species in the genus (of which there are a total of 20) in that they contain substantial amounts of glycyrrhizoside (what most people call glycyrrhizin, also called glycyrrhizic acid or glycyrrhizinic acid). Most common names of licorice, including in Greek (γλυκόριζα), English, Japanese, Korean, and Chinese, mean "sweet root," reflecting the distinctive sweet taste of glycyrrhizoside (an unusual property among triterpenoid saponins, which most often taste soapy).
| Latin binomial | Common name(s) | Native bioregion |
| Glycyrrhiza glabra | licorice, liquorice | Central Asia, Southern Europe, Middle East, India |
| Glycyrrhiza inflata | Chinese licorice, 脹果甘草 zhàng guǒ gān cǎo (Chinese), カンゾウ kanzō (Japanese), 감초 gamcho (Korean) | China |
| Glycyrrhiza uralensis | Chinese licorice, 甘草 gān cǎo (Chinese), カンゾウ kanzō (Japanese), 감초 gamcho (Korean) | East Asia |
In all cases it is the root that is used as medicine. In East Asian medicine, it is also common to use both dry- and honey-fried root.
Glycyrrhiza uralensis roots for sale in an herb market in Seoul, Korea (photo by E. Yarnell)
An Herbal Polycrest
Medicinal Glycyrrhiza spp have a dazzling array of medicinal uses (Wang, et al. 2020; Jiang, et al. 2020; Hosseinzadeh and Nassiri-Asl 2015). Its major clinical actions are listed below. These are based on traditional use and, where cited, human clinical trials (actions demonstrated solely in animal or in vitro studies are not listed).
- Immunomodulator (regulates immune function) (Brush, et al. 2006)
- Inflammation modulator (regulates inflammation)
- Adaptogen (helps the mind/body adapt to excessive stress)
- Formula synergizer (used to help herbs in a formula mix and work together, and be well absorbed)
- Antifibrotic
- Corrigent (flavoring agent, though some people dislike it, so always ask before adding to a formula)
- Phytoestrogenic
- Antiviral
- Hepatoprotective
- Against cancer chemotherapy agents (Ni, et al. 2009)
- Against ethanol (Chigurupati, et al. 2016 and 2018)
- Insulin sensitizing (Alizadeh, et al. 2018; Hioki, et al. 2004)
- Nephroprotective
- Erythropoietic (Sheng, et al. 1994; Jin, et al. 1992)
- Anti-Helicobacter pylori (Hajiaghamohammadi, et al. 2016; Rahnama, et al. 2013)
- Anti-androgen (Armanini, et al. 2003 and 2004; Takahashi, et al. 1988; negative trial: Josephs, et al. 2001)
The list of conditions in which it has shown benefit in human clinical trials are given below (note that only clinical trials including whole oral or topical use of licorice alone or in herbal formulas are listed here, not isolated constituents given by any route). Formulas that are mentioned by name are explicated in more detail later in this monograph.
Clinical Trial-Supported Indications for Whole Licorice
- Adenomyosis:
- To offset menopausal symptoms during use of GnRH superagonist drugs (Tanaka 2001)
- To treat dysmenorrhea and overcome infertility: as Shao Yao Gan Cao Tang, alternated in a biphasic fashion with Dang Gui Shao Yao Tang (Tanaka 2003)
- Antipsychotic drug adjunct, Peony and Licorice Decoction:
- See Hyperprolactinemia below
- To offset extrapyramidal symptoms (Ota, et al. 2015)
- To counteract amenorrhea (Yamada, et al. 1999)
- Aphthous ulcers:
- ethanol extract + diphenhydramine elixir 3 ml 3 min swish qid superior to diphenhydramine alone (Akbari, et al. 2020)
- mucoadhesive patches qd (Martin, et al. 2008)
- Chronic kidney disease:
- See also Hyperkalemia in the glycyrrhizoside section below
- For anemia: Asian licorice + Panax ginseng (Asian ginseng) + Astragalus propinquus (astragalus) + Cinnamomum cassia (cassia cinnamon) (Jin, et al. 1992)
- For symptomatic relief: Asian licorice + Panax ginseng (Asian ginseng) + Astragalus propinquus (astragalus) + Cinnamomum cassia (cassia cinnamon) + Rheum palmatum (rhubarb) (Sheng, et al. 1994)
- Colonoscopy adjunct, to suppress spasms: direct spraying of Shao Yao Gan Cao Tang on the colonic mucosa (Ai, et al. 2006)
- Cough, idiopathic, chronic: licorice pastille 300 mg tid (Ghaemi, et al. 2020).
- CoVid-19 pneumonia:
- Clinical trial underway in Iran (Safa, et al. 2020).
- Dental caries:
- To prevent by correcting oral dysbiosis: licorice lollipops (meta-analysis: Tharakan, et al. 2020)
- Dysmenorrhea: see adenomyosis and endometriosis
- Dyspepsia, functional:
- Iberogast formula (Madisch, et al. 2004)
- Endometriosis:
- To treat dysmenorrhea and overcome infertility: as Shao Yao Gan Cao Tang, alternated in a biphasic fashion with Dang Gui Shao Yao Tang (Tanaka 2003)
- To offset menopausal symptoms during use of GnRH superagonist drugs (Tanaka 2001)
- Endoscopic retrograde cholangiopancreatography (ERCP) adjunct, to suppress spasms: direct spraying of Shao Yao Gan Cao Tang on the colonic mucosa (Sakai, et al. 2009)
- Familial Mediterranean fever:
- To reduce symptom severity and to reduce frequency, duration, and severity of acute flare-ups: licorice + Andrographis paniculata (andrographis) herb + Eleutherococcus senticosus (eleuthero) root + Schisandra chinensis (schisandra) fruit (Amaryan, et al. 2003)
- Gastritis due to Helicobacter pylori infection:
- To improve symptoms and reduce severity of infection: licorice + Lactobacillus paracasei HP7-fermented milk (Yoon, et al. 2019)
- Hyperprolactinemia due to antipsychotic drugs:
- Peony and Licorice Decoction (Man, et al. 2016; Yamada, et al. 1996 and 1997)
- Positive meta-analysis of Peony and Licorice Decoction (Zheng, et al. 2018)
- Superior to bromocriptine (Yuan, et al. 2008)
- Influenza, seasonal:
- Licorice + Ephedra sinica (ma huang) stem + Cinnamomum cassia (cassia cinnamon) branch + Prunus armeniaca (apricot) seed, as effective as neuraminidase inhibitor drugs (Nabeshima, et al. 2012)
- Melasma:
- Licorice + Bellis perennis (English daisy) extract + Phyllanthus emblica (emblic myrobalan) fruit, 7% topical cream bid (Costa, et al. 2010)
- Menopausal hot flashes:
- To decrease frequency and duration (but not severity), licorice 1140 mg capsule qd (Menati, et al. 2014)
- Metabolic liver disease (non-alcoholic fatty liver):
- Licorice aqueous extract 2 g qd (Hajiaghamohammadi, et al. 2012)
- Licorice + Panax pseudoginseng (Himalayan ginseng) root + Eucommia ulmoides (du zhong) bark + Reynoutria multiflora (he shou wu) prepared root (Chande, et al. 2006)
- Muscle cramps, Peony and Licorice Decoction:
- Due to cirrhosis of the liver (Kumada, et al. 1999)
- Due to hemodialysis (Hyodo, et al. 2006; Hinoshita, et al. 2003)
- Due to spinal stenosis (Takao, et al. 2015)
- Oral mucositis due to radiation therapy:
- Oral aqueous extract bid (Najafi, et al. 2017)
- Mucoadhesive film qd, as effective as triamcinolone (Ghalayani, et al. 2017)
- Powder 5 g mixed in honey along with 500 mg capsules bid (Mamgain, et al. 2020; Das, et al. 2011)
- Parkinson's disease:
- To reduce symptom severity: 5 ml licorice syrup bid (Petramfar, et al. 2020)
- Peptic ulcer, Helicobacter pylori status not determined:
- Crude licorice (Revers 1946 and 1948)
- Peptic ulcer due to Helicobacter pylori infection:
- Licorice 500 mg tid x 30 d + amoxicillin 500 mg tid x 15 d + metronidazole 250 mg qid x 15 d + omeprazole 20 mg bid x 30 d (Rahnama, et al. 2013)
- Licorice extract 380 mg tid + clarithromycin 500 mg bid + amoxicillin 1 g qd + omeprazole 20 mg bid x 15 d (Hajiaghamohammadi, et al. 2016)
- Polycystic ovarian syndrome:
- Licorice + Paeonia lactiflora (white peony) + Hypericum perforatum (St. John's wort) + Cinnamomum verum (true cinnamon) + Tribulus terrestris (caltrop vine) (Arentz, et al. 2017)
- Shao Yao Gan Cao Tang to reduce androgens and increase pregnancy rates (Takahashi, et al. 1988)
- Ulcerative colitis:
- In complex Chinese herbal formulas, both orally and rectally (He, et al. 2012; Zhou, et al. 2012)
- Ureteral colic:
- As Shao Yao Gan Cao Tang, almost all stones ≤5 mm pass within 60 days, comparable to pharmaceutical spasmolytics (Washizuka, et al. 1983)
- Vaginal atrophy due to menopause:
- Licorice cream 2% intravaginally qd x 8 wk (Sadeghi, et al. 2019)
Oral use of deglycyrrhizinated licorice has been associated with benefit in patients with the conditions listed below. The removal of glycyrrhizoside from licorice clearly and dramatically reduces its utility, and so this product should be reserved only for those patients who absolutely cannot tolerate whole licorice, and who have one of the gastrointestinal issues noted below.
Clinical Trial-Supported Indications for DGL
- Dyspepsia, functional (Raveendra, et al. 2011)
- Gastroesophageal reflux (Setright 2017)
- Peptic ulcer (Revers 1952)
- DGL + bismuth + magnesium and sodium carbonate + frangula bark, as effective as raniditine (Morgan, et al. 1987, 1985a, 1985b and 1982)
- DGL + bismuth + magnesium and sodium carbonate + frangula bark, as effective as raniditine (Morgan, et al. 1987, 1985a, 1985b and 1982)
Additionally, glycyrrhizoside (glycyrrhizin) used orally (such as in the formula called Compound Glycyrrhizin, described in detail in a separate section) and intravenously (particularly in the formula known as Stronger Neo-Minophagen C or SNMC, described in detail in a separate section), has been documented to help people with a number of conditions, listed below.
Clinical Trial-Supported Indications for Glycyrrhizoside
- Alopecia areata:
- In adults: Compound Glycyrrhizin (Yang, et al. 2012)
- In children: Compound Glycyrrhizin + total glycosides of Paeonia lactiflora (white peony) root without bark (Yang, et al. 2013)
- Aplastic anemia:
- Glycyrrhizoside + cyclosporin (Ren, et al. 2013)
- Autoimmune hepatitis:
- IV glycyrrhizoside (Fujiwara, et al. 2013; Yasui, et al. 2011)
- Bullous pemphigoid, infantile:
- Compound Glycyrrhizin (Xu, et al. 2020)
- Eczema, chronic, in adults:
- Compound Glycyrrhizin + topical mometasone 0.1% (Xu, et al. 2020)
- Hepatitis B:
- IV SNMC and oral glycyrrhozide (Chen, et al. 2014; Zhang, et al. 2002; Wang 1984)
- Subacute liver failure, largely due to hepatitis B (Acharya, et al. 1993)
- SNMC safe and effective in pregnant women with HBV (Sun, et al. 2010)
- Hepatitis C
- Combined with interferon for cirrhosis (Iwabuchi, et al. 1994)
- 52-week trial showing reduced necroinflammation and ALT levels in interferon non-responders (Manns, et al. 2012)
- Largely negative trial using SNMC (Orlent, et al. 2006)
- Very long-term use (median 10.1 yr) approximately halved the rate of hepatocellular carcinoma in chronic HCV patients (Arase, et al. 1997).
- Retrospective analysis found that SNMC use was associated with a 40% reduction in hepatocellular cancer rates in chronic HCV patients compared to no such treatment, a significant reduction (Ikeda, et al. 2006).
- Hepatitis, cytomegalovirus, pediatric:
- Compound Glycyrrhizin (Shi, et al. 2010
- HIV infection/AIDS:
- To prevent progression to AIDS and treat liver dysfunction (Mori, et al. 1990)
- To raise CD4+ lymphocyte counts: Compound Glycyrrhizin (Yao, et al. 2006)
- Hyperkalemia due to end-stage renal failure:
- Glycyrrhetinic acid 500 mg twice daily (!!!) (Farese, et al. 2009)
- Infectious mononucleosis with liver involvement:
- Compound Glycyrrhizin (Cao, et al. 2006)
- Liver diseases, general, chronic, to lower serum transaminases:
- Compound Glycyrrhizin and magnesium isoglycyrrhizinate equally effective (Mao et al. 2009)
- Liver transplant adjunct:
- To reduce serum bilirubin and improve survival: diammonium glycyrrhizinate + matrine (an alkaloid from Sophora flavescens) (Xu, et al. 2009)
- Metabolic liver disease, pediatric:
- Compound Glycyrrhizin (Li, et al. 2017)
- Primary biliary cirrhosis:
- IV glycyrrhizoside (Fujiwara, et al. 2013)
- Psoriasis, erythrodermic, with bullous pemphigoid:
- Compound Glycyrrhin + methotrexate (Si, et al. 2014)
- Psoriasis vulgaris:
- Compound Glycyrrhizin + conventional medications (Yu, et al. 2017
- Pyoderma gangrenosum, complication ulcerative colitis:
- Compound Glycyrrhizin IV + povidone iodine + kangfuxin solution + methylprednisolone + thalidomide (Niu, et al. 2020)
- Riehl's melanosis:
- Compound Glycyrrhizin + tranexamic acid (Xu, et al. 2019)
- Compound Glycyrrhiin + vitamin C + salicylic acid peels (Wang, et al. 2020)
- Vasculitis, eosinophilic, cutaneous, necrotizing:
- Compound Glycyrrhizin + corticosteroids (Li, et al. 2013)
- Vitiligo:
- Compound Glycyrrhizin + carbon dioxide laser + topical triamcinolone (Li, et al. 2019)
- Oral glycyrrhizin + UV-B phototherapy (Mou, et al. 2016)
Adverse Effects of Licorice
All glycyrrhizoside-containing species of licorice inhibit 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), which largely occurs in the kidneys. It is glycyrrhetinic acid, the aglycone of glycyrrhizoside, that is responsible for this inhibition. The function of this enzyme is to inactivate cortisol by converting it to cortisone. This is important in the kidneys because cortisol is a potent mineralocorticoid, as well as a glucocorticoid. But if cortisol were allowed to bind to aldosterone receptors in an uncontrolled fashion, it would cause havoc and completely obviate the entire renin-angiotensin-aldosterone system that regulates blood pressure.
The effect of glycyrrhetinic acid on cortisol in the kidneys. 11β-HSD = 11β-hydroxysteroid dehydrogenase; CR = corticosteroid receptor; MR = mineralocorticoid receptor.
By inhibiting 11βHSD2, licorice allows more cortisol to act as a mineralocorticoid in the kidneys. This leads to sodium retention and potassium wasting in the urine. Since water follows sodium, this also causes an increase in both vascular and extracellular fluid levels. This can result in hypertension and edema with sufficiently high and long-lasting dosing. If licorice, glyryrrhizoside, or glycyrrhetinic acid is not withdrawn (depending on what substance is causing the problem), severe hypokalemia and hypernatremia develop, which can result in rhabdomyolysis, acute renal failure, and even death. This is known as pseudohyperaldosteronism (as aldosterone is not actually elevated, cortisol is, and it is acting as a mineralocorticoid). Almost all such cases have been reported in people eating licorice candy in overdose or from used of isolated glycyrrhizoside, not from medical use of licorice (see table at end of this section).
For most people, it requires an intake of >100 mg of glycyrrhetinic acid per day more more for >2 weeks to develop the early signs of pseudohyperaldosteronism (such as hypertension, and minor but measurable declines in serum potassium and urine sodium, and increases in serum sodium and urine potassium). Some people are sensitive to lower doses than this, and others can tolerate more. One clinical trial found that just 75 mg glycyrrhetinic acid per day for two weeks was enough to cause hypertension in many previously healthy people (Sigurjónsdóttir, et al. 2001). Another found that it actually took 380 mg of glycyrrhetinic acid per day for two weeks to cause headache, hypertension, hypokalemia, edema, and/or weight gain (Bernardi, et al. 1994). A review of several other studies came to the conclusion that 95 mg of glycyrrhetinic acid per day was the level at which problems started to develop with chronic use (Boganen, et al. 2007). The 100 mg glycyrrhetinic acid cut-off recommended here is a somewhat conservative estimate between these two studies, and based on the author's experience that almost no one has developed problems at licorice doses providing <100 mg glycyrrhetinic acid per day. Licorice with a 5% glycyrrhetinic acid content (which would be extremely good quality) would contain 100 mg of glycyrrhetinic acid in 2 g of herb. In reality, most licorice has maybe 1–3% glycyrrhetinic acid, so then it would take 3–10 g of licorice per day to reach the 100 mg glycyrrhetinic acid level of concern.
These problems are easy to avoid in clinical medicine. First, only reasonable doses of licorice are used (generally providing less than 100 mg glycyrrhetinic acid per day). Second, patients are monitored, both by measuring their own blood pressure and assessing or edema, as well as periodic medical exams assessing these variables (as well as blood testing of serum and/or urine sodium and potassium levels when higher doses are being used, or in patients for whom more caution is warranted). Third, patients should be encouraged to eat high potassium, low sodium diets as much as possible. With these things in mind, licorice can be used quite safely. Note that hypertension is not an absolute contraindication to use of licorice, especially low doses. Enough licorice must be given to cause hypokalemia for licorice to exacerbate hypertension. Again, by careful dosing and monitoring, this should not happen clinically (and if it does, the licorice dose can be reduced until blood pressure is normalized).
Note that for patients with late-stage chronic kidney disease (CKD), including if they have hypertension, licorice is highly indicated for them. This is because it directly counters the problems of potassium accumulation due to insufficient ability to excrete potassium as the kidneys fail. As noted above, extremely high doses of glycyrhetinic acid (500 mg twice per day, or more than 10 times the hypertensive dose in people without late-stage CKD) are actually quite therapeutic in people in this situation (Farese, et al. 2009).
Reports of these problems are not noted in traditional Asian medical texts (except edema, if used to treat people who already had so-called damp conditions), despite widespread use of fairly high doses of licorice (Bensky, et al. 2014). It is plausible that this is because of several factors, including that the people taking licorice ate higher potassium diets (though excessive use of salt has long been a problem in Chinese and other Asian cultures).
For most people, it requires an intake of >100 mg of glycyrrhetinic acid per day more more for >2 weeks to develop the early signs of pseudohyperaldosteronism (such as hypertension, and minor but measurable declines in serum potassium and urine sodium, and increases in serum sodium and urine potassium). Some people are sensitive to lower doses than this, and others can tolerate more. One clinical trial found that just 75 mg glycyrrhetinic acid per day for two weeks was enough to cause hypertension in many previously healthy people (Sigurjónsdóttir, et al. 2001). Another found that it actually took 380 mg of glycyrrhetinic acid per day for two weeks to cause headache, hypertension, hypokalemia, edema, and/or weight gain (Bernardi, et al. 1994). A review of several other studies came to the conclusion that 95 mg of glycyrrhetinic acid per day was the level at which problems started to develop with chronic use (Boganen, et al. 2007). The 100 mg glycyrrhetinic acid cut-off recommended here is a somewhat conservative estimate between these two studies, and based on the author's experience that almost no one has developed problems at licorice doses providing <100 mg glycyrrhetinic acid per day. Licorice with a 5% glycyrrhetinic acid content (which would be extremely good quality) would contain 100 mg of glycyrrhetinic acid in 2 g of herb. In reality, most licorice has maybe 1–3% glycyrrhetinic acid, so then it would take 3–10 g of licorice per day to reach the 100 mg glycyrrhetinic acid level of concern.
These problems are easy to avoid in clinical medicine. First, only reasonable doses of licorice are used (generally providing less than 100 mg glycyrrhetinic acid per day). Second, patients are monitored, both by measuring their own blood pressure and assessing or edema, as well as periodic medical exams assessing these variables (as well as blood testing of serum and/or urine sodium and potassium levels when higher doses are being used, or in patients for whom more caution is warranted). Third, patients should be encouraged to eat high potassium, low sodium diets as much as possible. With these things in mind, licorice can be used quite safely. Note that hypertension is not an absolute contraindication to use of licorice, especially low doses. Enough licorice must be given to cause hypokalemia for licorice to exacerbate hypertension. Again, by careful dosing and monitoring, this should not happen clinically (and if it does, the licorice dose can be reduced until blood pressure is normalized).
Note that for patients with late-stage chronic kidney disease (CKD), including if they have hypertension, licorice is highly indicated for them. This is because it directly counters the problems of potassium accumulation due to insufficient ability to excrete potassium as the kidneys fail. As noted above, extremely high doses of glycyrhetinic acid (500 mg twice per day, or more than 10 times the hypertensive dose in people without late-stage CKD) are actually quite therapeutic in people in this situation (Farese, et al. 2009).
Reports of these problems are not noted in traditional Asian medical texts (except edema, if used to treat people who already had so-called damp conditions), despite widespread use of fairly high doses of licorice (Bensky, et al. 2014). It is plausible that this is because of several factors, including that the people taking licorice ate higher potassium diets (though excessive use of salt has long been a problem in Chinese and other Asian cultures).
| Citation | Patient(s) | Dose form and dose | Result(s) |
| Tourtellotte, et al. 1970 | 63-yo WF | Licorice candy 5 sticks/d for unknown period | Hypokalemic rhabdomyolysis exacerbated by oral chlorthalidone; full recovery with IV K+ |
| Nightingale, et al. 1981 | 25-yo WF | Licorice candy 1100 g/wk for unknown period | Hypokalemic rhabdomyolysis exacerbated by vomiting and diarrhea, full recovery with oral and IV K+ |
| Brouwers and van der Meulen 2001 | 41-yo WF | 3 L licorice tea/d (unknown duration) | Hypertension (misdiagnosed as "essential"), hypokalemia (exacerbated by HCTZ treatment of hypertension), complete recovery w/ licorice discontinuation |
| Hussain 2003 | 56-yo W?F | Licorice candy (Pontefract cakes) 200–400 g/d (~15 g licorice/d) | Hypertension, hypokalemic myopathy, complete recovery w/ licorice d/c and IV K+ |
| Yasue, et al. 2007 | 93-yo JF | 5 g/d G. uralensis from ninjintō and saikokeishitō x 7 yr | Hypertension, hypokalemic myopathy, rhabdomyolysis, complete recovery w/ licorice d/c and oral K+ and spironolactone |
| Tancevski, et al. 2008 | 54-yo WF | 750 g/d licorice candy x 2 wk | Hypokalemic tetraparesis, U wave on ECG, complete recovery w/ IV K+ |
| Kormann, et al. 2012 | 70-yo WF | "Licorice-rich tea" ~15 bags/day x ~2 wk | Hypokalemia, collapse, nasal fracture, VFib requiring defibrillation w/ IV K+, complete recovery |
| Nielsen , et al. 2012 | 50-yo WF | Unknown form, dose, or duration of licorice intake | Hypertension, hypokalemic myopathy, complete recovery w/ licorice d/c and oral K+ and spironolactone |
Table abbreviations: d = day; d/c = discontinuation; ECG = electrocardiograph; F = female; HCTZ = hydrochlorothiazide; IV = intravenous; J = Japanese; K+ = potassium. W = White
Herbal Formulas that Feature Glycyrrhiza
芍藥甘草湯 Sháo Yào Gān Cǎo Tāng (Shakuyaku-kanzo-tō, Peony and Licorice Decoction)
Both the Chinese and Japanese names of this formula mean "peony and licorice decoction." It was first described in the famous Chinese medical text known as 傷寒論 (伤寒论) Shāng hán lùn (Treatise on Cold Damage Disorders or Treatise on Cold Injury) by 张仲景 Zhāng Zhòng-Jǐng(ca. 150—219), known by his formal name of 张机 Zhāng Ji, around 220 CE (at the end of the Han dynasty).
This formula contains equal parts of Chinese licorice honey-fried root and Paeonia lactiflora (white peony) bark without root. As a decoction, generally 12 g of each herb are included per day. However, in the clinical trials for treating antipsychotic drug-induced hyperprolactinemia, doses of 22.5 g of each herb per day were used (Yuan, et al. 2008). Doses to reduce muscle cramping are as low as 1.25–3 g of each herb per day (Hyodo, et al. 2006; Hinoshita, et al. 2003).
This formula contains equal parts of Chinese licorice honey-fried root and Paeonia lactiflora (white peony) bark without root. As a decoction, generally 12 g of each herb are included per day. However, in the clinical trials for treating antipsychotic drug-induced hyperprolactinemia, doses of 22.5 g of each herb per day were used (Yuan, et al. 2008). Doses to reduce muscle cramping are as low as 1.25–3 g of each herb per day (Hyodo, et al. 2006; Hinoshita, et al. 2003).
Iberogast® (STW 5)
This is a proprietary German formula created in 1961 by the Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany. The rights to the formula are now owned by Bayer. It is a bit of an odd combination of bitters (that stimulate digestive activity) and carminatives (that inhibit it).
The main form in which the formula is sold, and as it has been studied, contains tinctures of Matricaria chamomilla (chamomile) flowers 20%, Iberis amara (bitter candytuft and the namesake of the formula) herb 15%, Glycyrrhiza glabra (licorice) root 10%, Angelica archangelica (garden angelica) root 10%, Silybum marianum (milk thistle) seed 10%, Chelidonium majus (celandine) herb, Carum carvi (caraway) fruit 10%, Melissa officinalis (lemonbalm) leaf 10%, and Mentha x piperita (peppermint) leaf 5% (Heinle, et al. 2006). Bitter candytuft is made with 50% ethanol; all the other tinctures with 30% ethanol. However, at least some studies (on a version of the formula dubbed STW 5-II) have used a simpler version containing only bitter candy, chamomile, peppermint, caraway, licorice, and lemonbalm (Madisch, et al. 2004). At least two studies suggest that bitter candytuft actually works at cross purposes to the other herbs in the formula, stimulating GI activity in the ileum when all the other herbs inhibit it, and stimulating IL-8 production while the rest of the formula inhibits it (Ammon, et al. 2006; Ulrich-Merzenich, et al. 2019).
The main form in which the formula is sold, and as it has been studied, contains tinctures of Matricaria chamomilla (chamomile) flowers 20%, Iberis amara (bitter candytuft and the namesake of the formula) herb 15%, Glycyrrhiza glabra (licorice) root 10%, Angelica archangelica (garden angelica) root 10%, Silybum marianum (milk thistle) seed 10%, Chelidonium majus (celandine) herb, Carum carvi (caraway) fruit 10%, Melissa officinalis (lemonbalm) leaf 10%, and Mentha x piperita (peppermint) leaf 5% (Heinle, et al. 2006). Bitter candytuft is made with 50% ethanol; all the other tinctures with 30% ethanol. However, at least some studies (on a version of the formula dubbed STW 5-II) have used a simpler version containing only bitter candy, chamomile, peppermint, caraway, licorice, and lemonbalm (Madisch, et al. 2004). At least two studies suggest that bitter candytuft actually works at cross purposes to the other herbs in the formula, stimulating GI activity in the ileum when all the other herbs inhibit it, and stimulating IL-8 production while the rest of the formula inhibits it (Ammon, et al. 2006; Ulrich-Merzenich, et al. 2019).
Formulas that Feature Glycyrrhizoside
Stronger Neo-Minophagen C
Made by the Minophagen Pharmaceutical Co. of Japan, this formula for intravenous injection contains glycyrrhozide, glycine, and cysteine. In the 20 ml ampoule, there are 40 mg glycyrrhizoside, 20 mg L-cysteine, and 400 mg glycine. Up to 100 ml of this solution can be injected safely on a daily basis. Blood pressure must be monitored regularly and patients should be vigorously encouraged to eat high potassium, low sodium diets.
Compound Glycyrrhizin
This formula is made by the Beijing Kawin Technology Co. of China. Each capsule contains glycyrrhizoside 25 mg, glycine 25 mg, and methionine 25 mg. A typical dose is 2–3 capsules three times daily. Blood pressure must be monitored regularly and patients should be vigorously encouraged to eat high potassium, low sodium diets.
Chemistry
Triterpenoid Glycosides
Glycyrrhizoside (by many called glycyrrhizin, see diagram) is a major component of medicinal species of Glycyrrhiza. This is a triterpenoid glycoside. Its glycone is made up of two glucuronic acid units. Its aglycone is known as triterpenoid 18β-glycyrrhetinic acid, which has a very potent sweet taste (Yang, et al. 2019). It has a naturally-occurring isomer, 18α-glycyrrhetinic acid.
In some countries (Turkey, Malaysia), glycyrrhizoside is an approved drug that goes by the name enoxolone.
In some countries (Turkey, Malaysia), glycyrrhizoside is an approved drug that goes by the name enoxolone.
Glycyrrhizoside (glycyrrhizin)
Flavonoids and Chalcones
Licorice is rich in numerous flavonoids and their glycosides, such as liquiritoside (often called liquiritin, with the flavonoid aglycone of liquiritigenin), and the closely related chalcones and their glycosides, such as isoliquiritoside (often called isoliquiritin, with the chalcone aglycone isoliquiritogenin). These molecules have a yellow hue and imbue licorice roots with their golden color. These are believed to be the main compounds responsible for the activity of DGL.
Isoflavones
Another variant of flavonoids important in the medicinal actions of licorice are the isoflavones and their glycosides. They are particularly responsible for the significant phytoestrogenic effects of licorice (Hajirahimkhan, et al. 2013; Thompson, et al. 2007). Glabridin, glabrene, and formononetin are major examples.
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