Glycyrrhiza glabra (Licorice Root) - Comprehensive Profile

Taxonomy & Botany

• Botanical name: Glycyrrhiza glabra L.
• Family: Fabaceae (Leguminosae)
• Common names: Licorice, Liquorice, Mulethi (Hindi), Yastimadhu (Ayurveda), Gan Cao (Traditional Chinese Medicine - though TCM primarily uses G. uralensis)
• Etymology: From Greek glykys (sweet) + rhiza (root)
• Plant part used: Roots and rhizomes (harvested after 3-4 years)
• Origin: Native to Mediterranean region and southwestern Asia
• Major cultivation zones: Turkey, Greece, Iran, China (~70% of worldwide production)
• Note: G. glabra is distinct from G. inflata (Chinese licorice) and G. uralensis. The key difference: G. glabra is rich in glabridin, while G. inflata contains licochalcone A.

Phytochemistry (Active Constituents)

Primary bioactive compounds (Wu et al., J Adv Res 2025; PMID 39551128):

Structural pharmacology highlight (Medical Physiology textbook, Boron & Boulpaep):

Glycyrrhizic acid = glycyrrhetinic acid conjugated to two glucuronic acid moieties. Glycyrrhetinic acid inhibits 11β-hydroxysteroid dehydrogenase (11β-HSD), the enzyme that converts cortisol into the inactive cortisone. This leads to cortisol acting as a mineralocorticoid at the renal mineralocorticoid receptor (MR), causing sodium retention, potassium loss, and hypertension - the basis of "pseudohyperaldosteronism."

Mechanism of Action (Organ-by-Organ)

1. Adrenal / Endocrine Axis

• 11β-HSD inhibition → cortisol accumulates in kidney → activates MR → Na+ retention, K+ loss, hypertension
• This is the primary mechanism of licorice-induced hypertension and hypokalemia
• Glycyrrhizin also inhibits 15-hydroxyprostaglandin dehydrogenase in gastric mucosa → raises mucosal prostaglandins → gastroprotection + expectorant effects

2. Anti-inflammatory

• Glabridin inhibits NF-κB signaling and COX-2 activity
• Glycyrrhizin inhibits phospholipase A2 and prostaglandin synthesis
• Reduces TNF-α, IL-6, IL-1β (Basumatary et al., Inflammopharmacology 2026; PMID 42371378)

3. Gastrointestinal (Mucosal Protection)

• Enhanced mucus secretion via prostaglandin E2 upregulation
• Stimulation of epithelial cell proliferation
• Anti-H. pylori activity (isoliquiritigenin)
• Intestinal barrier enhancement and microbiota regulation

4. Hepatoprotection

• Glycyrrhizin reduces hepatocyte inflammation and fibrosis markers
• Meta-analysis (Giangrandi et al., Phytother Res 2024; PMID 39079711): 15 RCTs (n=1,367) showed licorice significantly reduced ALT by 15.63 U/L (95% CI: -25.08 to -6.18; p=0.001) and AST by 7.37 U/L (95% CI: -13.13 to -1.61; p=0.01) in primary liver disease patients. Purified glycyrrhizic acid compounds were most effective.

5. Skin / Dermatology (Dermatology 5e textbook, Wolff):

• Glabridin → inhibits tyrosinase → suppresses melanin synthesis → skin-lightening / hyperpigmentation treatment
• Anti-irritant and anti-inflammatory properties
• Anti-elastase activity → anti-aging
• Anti-tyrosinase activity
• Clinical use: rosacea, atopic dermatitis, sensitive skin OTC preparations
• Used in anti-aging cosmeceuticals

6. Antiviral

• Glycyrrhizin inhibits viral replication (HSV, SARS-CoV-2, HIV, Influenza A)
• Interferes with viral envelope proteins and host receptor binding

7. Anticancer (Preclinical)

• Glabridin and isoliquiritigenin induce apoptosis in cancer cell lines (breast, colorectal, prostate)
• Anti-angiogenic effects via VEGF pathway suppression
• Current evidence is primarily preclinical; no confirmed clinical anti-cancer indication

Clinical Applications - Evidence Grading

2025 Clinical Trial Highlight (GutGard):

Pharmacokinetics

• Glycyrrhizin is poorly absorbed orally in native form; gut bacteria hydrolyze it to 18β-glycyrrhetinic acid, which is the primary active species
• Peak plasma concentration of glycyrrhetinic acid: ~4-6 hours post-ingestion
• Half-life: ~10-15 hours (variable with dose)
• Enterohepatic recirculation occurs
• Glabridin is lipophilic - high tissue distribution

Dosage Forms

Adverse Effects & Toxicity

Glycyrrhizin-related (dose-dependent, from whole extract):

1. Pseudohyperaldosteronism (most significant)
   • Hypokalemia, sodium retention, hypertension, edema
   • Can cause arrhythmias and heart failure at high doses (Dermatology 5e textbook)
   • Linked to stroke (case reports)
2. Hypertension - dose-related; documented with chronic use
3. Hypokalemia - can be severe; causes muscle weakness, rhabdomyolysis
4. Congestive heart failure exacerbation
5. Kidney syndromes: Comprehensive Clinical Nephrology 7th ed. lists Glycyrrhiza spp. under herbal-induced hypertension and potential renal tubular effects
6. Drug interactions: Warfarin, antihypertensives, corticosteroids, thiazide diuretics (additive K+ loss), loop diuretics, digoxin (hypokalaemia increases toxicity risk)

Special populations:

• Contraindicated in pregnancy (stimulates prostaglandins, potential uterotonic)
• Avoid in hypertension, heart failure, hypokalemia, kidney disease, liver cirrhosis
• Safe upper limit: 100 mg glycyrrhizin/day for adults (European regulation)
• The EU Safety Assessment flags 100-200 mg/day glycyrrhizin as the threshold for clinically relevant blood pressure effects

Traditional Medicine Systems

Recent Research Directions (2024-2026)

1. Gut microbiome modulation: G. glabra polysaccharides increase beneficial Bifidobacterium and Lactobacillus populations, reduce Clostridium spp. - potential prebiotic application (2026 review, PMID 42371378)
2. Synthetic biology: Metabolic engineering to biosynthesize glycyrrhizin and glabridin in yeast/bacteria - addressing wild plant overexploitation (Wu et al. J Adv Res 2025, PMID 39551128)
3. Nanodelivery systems: Glabridin-loaded phytosomes and PLGA nanoparticles are improving bioavailability for skin conditions
4. Anti-SARS-CoV-2 activity: Glycyrrhizin inhibits viral protease 3CLpro and ACE2 binding in preclinical models (Gasmi et al. Curr Pharm Des 2024, PMID 38685809)
5. Oncology (preclinical): Isoliquiritigenin targets PI3K/AKT/mTOR pathway in colorectal and lung cancer cell lines (Imtiaz et al. Biomolecules 2025, PMID 40149916)
6. Licorice fruit extract: 2025 Scientific Reports study found G. glabra fruit (not just root) modulates oxidative stress and apoptotic markers in PC12 cells - expanding the usable plant part

Conservation Status

Key References

• Medical Physiology (Boron & Boulpaep) - 11β-HSD mechanism
• Dermatology 5e (Wolff et al.) - Skin applications
• Comprehensive Clinical Nephrology 7th ed. - Renal risks
• Maudsley Prescribing Guidelines 15th ed. - Peony-Glycyrrhiza Decoction for hyperprolactinemia
• Giangrandi et al. Phytother Res 2024 - Liver meta-analysis (PMID 39079711)
• Basumatary et al. Inflammopharmacology 2026 - Gut health review (PMID 42371378)
• Wu et al. J Adv Res 2025 - Species classification and synthetic biology (PMID 39551128)